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[1]

TÍTULO / TITLE:  - Phase II Trial of Erlotinib Plus Concurrent Whole-Brain Radiation Therapy for Patients With Brain Metastases From Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2011.40.1174

AUTORES / AUTHORS:  - Welsh JW; Komaki R; Amini A; Munsell MF; Unger W; Allen PK; Chang JY; Wefel JS; McGovern SL; Garland LL; Chen SS; Holt J; Liao Z; Brown P; Sulman E; Heymach JV; Kim ES; Stea B

INSTITUCIÓN / INSTITUTION:  - James W. Welsh, Ritsuko Komaki, Arya Amini, Mark F. Munsell, Wyatt Unger, Pamela  K. Allen, Joe Y. Chang, Jeffrey S. Wefel, Susan L. McGovern, Su S. Chen, Zhongxing Liao, Paul Brown, Erik Sulman, John V. Heymach, and Edward S. Kim, The  University of Texas MD Anderson Cancer Center, Houston TX; and Linda L. Garland,  Jamie Holt, and Baldassarre Stea, The Arizona Cancer Center, Tucson, AZ.

RESUMEN / SUMMARY:  - PURPOSEBrain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the  EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt  to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety. PATIENTS AND METHODSEligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once  per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week,  to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility.ResultsForty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n =  36). No increase in neurotoxicity was detected, and no patient experienced grade  >/= 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status,  median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations. CONCLUSIONErlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.

 

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[2]

TÍTULO / TITLE:  - An eHealth system supporting palliative care for patients with non-small cell lung cancer: A randomized trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2013 Jan 25. doi: 10.1002/cncr.27939.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27939

AUTORES / AUTHORS:  - Gustafson DH; Dubenske LL; Namkoong K; Hawkins R; Chih MY; Atwood AK; Johnson R; Bhattacharya A; Carmack CL; Traynor AM; Campbell TC; Buss MK; Govindan R; Schiller JH; Cleary JF

INSTITUCIÓN / INSTITUTION:  - Center for Health Enhancement Systems Studies, University of Wisconsin-Madison, Madison, Wisconsin. dhgustaf@wisc.edu.

RESUMEN / SUMMARY:  - BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed  to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale. RESULTS: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d  = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study. CONCLUSIONS: The current results  indicated that an online support system may reduce patient symptom distress. The  effect on survival bears further investigation. Cancer 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 American Cancer Society.

 

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[3]

TÍTULO / TITLE:  - Palliative Radiation Therapy Practice in Patients With Metastatic Non-Small-Cell  Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.7954

AUTORES / AUTHORS:  - Chen AB; Cronin A; Weeks JC; Chrischilles EA; Malin J; Hayman JA; Schrag D

INSTITUCIÓN / INSTITUTION:  - Aileen B. Chen, Dana-Farber Cancer Institute and Brigham and Women’s Hospital; Angel Cronin, Jane C. Weeks, and Deborah Schrag, Dana-Farber Cancer Institute, Boston, MA; Elizabeth A. Chrischilles, University of Iowa, Iowa City, IA; Jennifer Malin, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA; and James A. Hayman, University of Michigan Health System, Ann Arbor, MI.

RESUMEN / SUMMARY:  - PURPOSERandomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic  cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODSFrom patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients  with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression.ResultsOf 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest. CONCLUSIONWhen palliative  RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery.

 

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[4]

TÍTULO / TITLE:  - Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease-free survival of surgically resected non-small-cell-lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2056-y

AUTORES / AUTHORS:  - Ludovini V; Flacco A; Bianconi F; Ragusa M; Vannucci J; Bellezza G; Chiari R; Minotti V; Pistola L; Tofanetti FR; Siggillino A; Baldelli E; Sidoni A; Daddi N; Puma F; Varella-Garcia M; Crino L

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, S. Maria Della Misericordia Hospital, 1, G. Dottori Street, 06132, Perugia, Italy, ludoviniv@hotmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: Insulin-like growth factor 1 receptor (IGF1R) represents a novel molecular target in non-small-cell-lung cancer (NSCLC). IGF1R and epidermal growth factor receptor (EGFR) activation are essential to mediate tumor cell survival, proliferation, and invasion. This study investigates the prognostic role of IGF1R and EGFR in surgically resected NSCLC. MATERIALS AND METHODS: IGF1R and EGFR copy number gain (CNG) were tested by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC) in 125 stage I-II-IIIA NSCLC patients. RESULTS: Fourty-six tumors (40.3 %) were IGF1R FISH-positive (FISH+), and 76 (67.2 %) were EGFR FISH+. Tumors with concomitant IGF1R/EGFR FISH+ were observed in 34 cases (30.1 %). IGF1R and EGFR FISH+ were associated with SCC histology (p = 0.01 and p = 0.04, respectively). IGF1R and EGFR protein over-expression (IHC+) were detected in 45 (36.0 %) and 69 (55.2 %)  cases, respectively. Tumors with concomitant IGF1R/EGFR IHC+ were detected in 31  (24.8 %) patients. IGF1R/EGFR FISH+ and IGF1R/EGFR IHC+ were significantly associated (chi(2) = 4.02, p = 0.04). Patients with IGF1R/EGFR FISH+ and IGF1R/EGFR IHC+ were associated with shorter disease-free survival (DFS) (p = 0.05 and p = 0.05, respectively). Patients with concomitant IGF1R/EGFR FISH+/IHC+ had a worse DFS and overall survival (p = 0.005 and p = 0.01, respectively). The  multivariate model confirmed that IGF1R/EGFR FISH+/IHC+ (hazard ratio (HR), 4.08; p = 0.01) and tumor stage (II-III vs I) (HR, 4.77; p = 0.003) were significantly  associated with worse DFS. CONCLUSIONS: IGF1R/EGFR FISH+ correlates with IGF1R/EGFR IHC+. IGF1R/EGFR FISH+/IHC+ is an independent negative prognostic factor for DFS in early NSCLC. These features may have important implications for future anti-IGF1R therapeutic approaches.

 

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[5]

TÍTULO / TITLE:  - Symptom and Quality of Life Benefit of Afatinib in Advanced Non-Small-Cell Lung Cancer Patients Previously Treated with Erlotinib or Gefitinib: Results of a Randomized Phase IIb/III Trial (LUX-Lung 1).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):229-37. doi: 10.1097/JTO.0b013e3182773fce.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182773fce

AUTORES / AUTHORS:  - Hirsh V; Cadranel J; Cong XJ; Fairclough D; Finnern HW; Lorence RM; Miller VA; Palmer M; Yang JC

INSTITUCIÓN / INSTITUTION:  - *McGill University Health Center, Montreal, Canada; daggerHopital Tenon-APHP and  University Paris 6, Paris, France; double daggerBoehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut; section signUniversity of Colorado, Denver, Colorado; ||Memorial Sloan-Kettering Cancer Center, New York, New York; paragraph signKeele University, Keele, United Kingdom; and #National Taiwan University, Taipei, Taiwan.

RESUMEN / SUMMARY:  - BACKGROUND: : Patient-reported symptom and health-related quality of life (HRQoL) benefit of afatinib, a novel, irreversible, ErbB Family Blocker, was investigated in a double-blind, randomized, phase IIb/III trial (LUX-Lung 1). METHODS: : Five  hundred and eighty-five patients with lung adenocarcinoma (stage IIIb/IV), who had progressed after chemotherapy (1-2 lines) and at least 12 weeks of erlotinib  or gefitinib, were randomized (2:1) to receive either afatinib plus best supportive care (BSC) or placebo plus BSC. Symptom and HRQoL benefit were measured using the lung cancer-specific European Organisation for Research and Treatment of Cancer (QLQ-C30/LC13) and EuroQol (EQ-5D) questionnaires. Non-small-cell lung cancer-related symptoms (cough, dyspnea, and pain) were prespecified using three preplanned analyses (percentage of patients improved/worsened/stable, change in scores over time, and time to deterioration of scores). RESULTS: : Compared with patients on placebo, a significantly higher  proportion of afatinib-treated patients showed an improvement in cough (p < 0.0001), dyspnea (p = 0.006), and pain (p < 0.0001). Afatinib also significantly  improved the mean scores over time for cough (p < 0.0001), dyspnea (p = 0.0161),  and pain (p = 0.0056); significantly delayed the time to deterioration for cough  (p < 0.001); and showed a trend in delaying dyspnea (p = 0.170) and pain (p = 0.287). Consistent with the adverse-event profile of afatinib, a significantly (p < 0.05) higher proportion of afatinib-treated patients showed worsening of diarrhea, sore mouth, dysphagia, and appetite scores. However, compared with placebo, afatinib significantly (p < 0.05) improved QoL assessed with the EQ-5D questionnaire and global health status/QoL, physical functioning, and fatigue, which were assessed with the European Organisation for Research and Treatment of  Cancer questionnaires. CONCLUSION: : In the LUX-Lung 1 trial, the addition of afatinib to BSC significantly improved non-small-cell lung cancer-related symptoms (cough, dyspnea, and pain), fatigue, physical functioning, and HRQoL and significantly delayed time to deterioration of cough.

 

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[6]

TÍTULO / TITLE:  - Overall and Cancer-Specific Survival of Patients With Breast, Colon, Kidney, and  Lung Cancers With and Without Chronic Lymphocytic Leukemia: A SEER Population-Based Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.4449

AUTORES / AUTHORS:  - Solomon BM; Rabe KG; Slager SL; Brewer JD; Cerhan JR; Shanafelt TD

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - PURPOSEChronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the disease  course of these cancers once they occur. PATIENTS AND METHODSAll patients with cancers of the breast (n = 579,164), colorectum (n = 412,366), prostate (n = 631,616), lung (n = 489,053), kidney (n = 95,795), pancreas (n = 82,116), and ovary (n = 61,937) reported to the SEER program from 1990 to 2007 were identified. Overall survival (OS; death resulting from any cause) and cancer-specific survival were examined, comparing patients with and without pre-existing CLL. Cancer-specific survival was evaluated for each tumor type in a site-specific manner (eg, death resulting from breast cancer in a patient with breast cancer).ResultsPatients with cancers of the breast (hazard ratio [HR], 1.70; P < .001), colorectum (HR, 1.65; P < .001), kidney (HR, 1.54; P < .001), prostate (HR, 1.92; P < .001), or lung (HR, 1.19; P < .001) had inferior OS if they had a pre-existing diagnosis of CLL after adjusting for age, sex, race, and  disease stage. These results for OS remained significant for patients with cancers of the breast, colorectum, and prostate after excluding or censoring CLL-related deaths. Cancer-specific survival was also inferior for patients with  cancers of the breast (HR, 1.41; P = .005) and colorectum (HR, 1.46; P < .001) who had pre-existing CLL after adjusting for age, sex, race, and disease stage. CONCLUSIONInferior OS and cancer-specific survival was observed for several common cancers in patients with pre-existing CLL. Additional studies are needed to determine the optimal management of these malignancies in patients with CLL and whether more aggressive screening or alternative approaches to adjuvant therapy are needed.

 

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[7]

TÍTULO / TITLE:  - Lung Cancer Screening With Low-Dose Computed Tomography After the National Lung Screening Trial. The Debate is Still Open.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Bronconeumol. 2013 Jan 11. pii: S0300-2896(12)00287-6. doi: 10.1016/j.arbres.2012.10.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.arbres.2012.10.003

AUTORES / AUTHORS:  - Ruano-Ravina A; Perez Rios M; Fernandez-Villar A

INSTITUCIÓN / INSTITUTION:  - Area de Medicina Preventiva y Salud Publica, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, España; CIBER de Epidemiologia y Salud Publica, CIBERESP, España. Electronic address: alberto.ruano@usc.es.

RESUMEN / SUMMARY:  - The aim of this article is to highlight some concerns regarding lung cancer screening with CT through a thorough analysis of scientific literature. The publication of the National Lung Screening Trial in 2011 has revealed that CT screening of smokers and ex-smokers in three annual rounds reduces lung cancer mortality a 20% when compared with thorax x-ray screening. The first limitation of this screening modality is its lack of downstaging in successive screening rounds compared with the initial round. Also, lung cancer screening with CT has a low positive predictive value, similar to the percentage of unnecessary surgeries performed in false positives. Another problem is that, at present, the burden of  lung cancer overdiagnosis is not known. It is to be expected that if overdiagnosis occurs when thorax x-ray screening is used it will be greater when  using CT. CT, even at low doses, exposes patients to high levels of radiation. Dealing with positive nodules entails an even higher radiation dose and the number of cancer cases induced by radiation in patients screened with CT is not known. Lastly, published studies on lung cancer CT screening are vastly heterogeneous. They include different age groups, different types of smokers and  ex-smokers and different tomogram thickness, making the results hardly comparable. In this context we do not recommend lung cancer screening with CT for smokers or ex-smokers outside of the context of individual counseling.

 

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[8]

TÍTULO / TITLE:  - A randomised multicentre phase II study with cisplatin/docetaxel vs oxaliplatin/docetaxel as first-line therapy in patients with advanced or metastatic non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 17. doi: 10.1038/bjc.2012.555.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.555

AUTORES / AUTHORS:  - Atmaca A; Al-Batran SE; Werner D; Pauligk C; Guner T; Koepke A; Bernhard H; Wenzel T; Banat AG; Brueck P; Caca K; Prasnikar N; Kullmann F; Gunther Derigs H; Koenigsmann M; Dingeldein G; Neuhaus T; Jager E

INSTITUCIÓN / INSTITUTION:  - Department of Hematology and Oncology, Institute of Clinical Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, 60488 Frankfurt am Main, Germany.

RESUMEN / SUMMARY:  - Background:This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment.Methods:Patients were randomly assigned to receive either cisplatin 75 mg m(-2) and docetaxel 75 mg m(-2) every 3 weeks or oxaliplatin 85 mg m(-2) and docetaxel 50 mg m(-2) every 2 weeks. The primary end  point was response rate, and secondary end points were toxicity, time to progression and overall survival.Results:A total of 88 patients (median age: 65 (39-86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17-43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs  27%), any grade leukopenia (84% vs 61%) and grade ¾ leukopenia (44% vs 14%) and neutropenia (56% vs 27%).Conclusion:Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel.British Journal of Cancer advance online publication, 17 January 2013; doi:10.1038/bjc.2012.555 www.bjcancer.com.

 

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TÍTULO / TITLE:  - Different sizes of centrilobular ground-glass opacities in chest high-resolution  computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cardiovasc Pathol. 2013 Jan 9. pii: S1054-8807(12)00154-8. doi: 10.1016/j.carpath.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.carpath.2012.12.002

AUTORES / AUTHORS:  - Miura A; Akagi S; Nakamura K; Ohta-Ogo K; Hashimoto K; Nagase S; Kohno K; Kusano K; Ogawa A; Matsubara H; Toyooka S; Oto T; Ohtsuka A; Ohe T; Ito H

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Centrilobular ground-glass opacity (GGO) is one of the characteristic findings in chest high-resolution computed tomography (HRCT) of patients with pulmonary veno-occlusive disease (PVOD) and patients with pulmonary capillary hemangiomatosis (PCH). However, clinical differential diagnosis of these two diseases is difficult and has not been established. In order to clarify their differences, we compared the sizes of GGOs in chest HRCT and the sizes of capillary assemblies in pulmonary vascular casts between patients diagnosed pathologically with PVOD and PCH. METHODS: We evaluated chest HRCT images for four patients with idiopathic pulmonary arterial hypertension (IPAH), three patients with PVOD and three patients with PCH, and we evaluated pulmonary vascular casts of lung tissues obtained from those patients at lung transplantation or autopsy. RESULTS: Centrilobular GGOs in chest HRCT were observed in patients with PVOD and patients with PCH but not in patients with IPAH. We measured the longest diameter of the GGOs. The size of centrilobular GGOs was significantly larger in patients with PCH than in patients with PVOD (5.60+/-1.43 mm versus 2.51+/-0.79 mm, P<.01). We succeeded in visualization of the 3-dimensional structures of pulmonary capillary vessels obtained from the same patients with PVOD and PCH undergoing lung transplantation or autopsy and measured the diameters of capillary assemblies. The longest diameter of capillary assemblies was also significantly larger in patients with PCH than in patients with PVOD (5.44+/-1.71 mm versus 3.07+/-1.07 mm, P<.01). CONCLUSION: Measurement  of the sizes of centrilobular GGOs in HRCT is a simple and useful method for clinical differential diagnosis of PVOD and PCH.

 

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[10]

TÍTULO / TITLE:  - The complex relationship between lung tumor volume and survival in patients with  non-small cell lung cancer treated by definitive radiotherapy: A prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiother Oncol. 2013 Jan 16. pii: S0167-8140(12)00531-2. doi: 10.1016/j.radonc.2012.12.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2012.12.003

AUTORES / AUTHORS:  - Ball DL; Fisher RJ; Burmeister BH; Poulsen MG; Graham PH; Penniment MG; Vinod SK; Krawitz HE; Joseph DJ; Wheeler GC; McClure BE

INSTITUCIÓN / INSTITUTION:  - Peter MacCallum Cancer Centre, Melbourne, Australia; The University of Melbourne, Parkville, Australia. Electronic address: david.ball@petermac.org.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung  cancer (NSCLC) treated by definitive radiotherapy. MATERIALS AND METHODS: Multicenter prospective observational study. Patient eligibility: pathologically  proven stage I-III non-small cell lung cancer planned for definitive radiotherapy (minimum 50Gy in 20 fractions) using CT-based contouring. Volumes of the primary  tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage. RESULTS: There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR=1.060 (per doubling); 95% CI 1.01-1.12; P=0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR=1.029, 95% CI, 0.96-1.10, P=0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18months but not beyond. CONCLUSIONS: In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy.

 

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[11]

TÍTULO / TITLE:  - Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: A randomised phase II study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2012 Dec 5. pii: S0959-8049(12)00891-X. doi: 10.1016/j.ejca.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.11.007

AUTORES / AUTHORS:  - Bar-Sela G; Wollner M; Hammer L; Agbarya A; Dudnik E; Haim N

INSTITUCIÓN / INSTITUTION:  - Division of Oncology, Rambam Health Care Campus, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: g_barsela@rambam.health.gov.il.

RESUMEN / SUMMARY:  - INTRODUCTION: Mistletoe preparations, such as iscador, are common complementary medications. This randomised phase II study of iscador combined with carboplatin-containing regimens was conducted in chemotherapy-naive advanced non-small-cell lung cancer (NSCLC) patients to assess its influence on chemotherapy-related side-effects and QoL. METHODS: Patients with advanced NSCLC  were randomised to receive chemotherapy alone or chemotherapy plus iscador thrice weekly until tumour progression. Chemotherapy consisted of 21-day cycles of carboplatin combined with gemcitabine or pemetrexed. RESULTS: Seventy-two patients (control: 39; iscador: 33) were enrolled in the study. Most (65%) were in stage IV, and 62% had squamous histology. Median overall survival in both groups was 11months. Median TTP was 4.8months for the controls and 6months in the iscador arm (p=NS). Differences in grade 3-4 haematological toxicity were not significant but more control patients had chemotherapy dose reductions (44% versus 13%, p=0.005), grade 3-4 non-haematological toxicities (41% versus 16%, p=0.043) and hospitalisations (54% versus 24%, p=0.016). CONCLUSION: No effect of iscador could be found on quality of life or total adverse events. Nevertheless,  chemotherapy dose reductions, severe non-haematological side-effects and hospitalisations were less frequent in patients treated with iscador, warranting  further investigation of iscador as a modifier of chemotherapy-related toxicity.

 

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[12]

TÍTULO / TITLE:  - Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds616

AUTORES / AUTHORS:  - Wang HM; Liao ZX; Komaki R; Welsh JW; O’Reilly MS; Chang JY; Zhuang Y; Levy LB; Lu C; Gomez DR

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.

RESUMEN / SUMMARY:  - BackgroundPreclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor.Patients and methodsWe retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the  association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival  (DFS), and overall survival (OS).ResultsIn univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of  aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P =  0.63).ConclusionBeta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

 

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[13]

TÍTULO / TITLE:  - Antibiotic-refractory sinusitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. 2012 Dec 12;308(22):2399-400. doi: 10.1001/jama.2012.91077.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jama.2012.91077

AUTORES / AUTHORS:  - Munoz J; Kuriakose P

INSTITUCIÓN / INSTITUTION:  - Henry Ford Hospital, Department of Hematology and Oncology, 2799 W Grand Blvd, Detroit, MI 48202, USA. javier.munoz@me.com

 

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[14]

TÍTULO / TITLE:  - Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Dev. 2013 Jan 15;27(2):197-210. doi: 10.1101/gad.203208.112. Epub 2013 Jan  15.

            ●● Enlace al texto completo (gratuito o de pago) 1101/gad.203208.112

AUTORES / AUTHORS:  - Watanabe H; Francis JM; Woo MS; Etemad B; Lin W; Fries DF; Peng S; Snyder EL; Tata PR; Izzo F; Schinzel AC; Cho J; Hammerman PS; Verhaak RG; Hahn WC; Rajagopal J; Jacks T; Meyerson M

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;

RESUMEN / SUMMARY:  - The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma and analyzed DNA-binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas.

 

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[15]

TÍTULO / TITLE:  - Epidermal growth factor receptor mutation and treatment outcome of mediastinoscopic N2 positive non-small cell lung cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 20. pii: S0169-5002(12)00631-9. doi: 10.1016/j.lungcan.2012.11.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.010

AUTORES / AUTHORS:  - Ahn HK; Choi YL; Han JH; Ahn YC; Kim K; Kim J; Shim YM; Um SW; Kim H; Kwon OJ; Sun JM; Ahn JS; Park K; Ahn MJ

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University  School of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - Epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) is a strong predictive factor for a favorable response to EGFR tyrosine kinase inhibitors, however, its prognostic role in locally advanced stage is unclear. The aim of this study was to analyze the association of EGFR mutational  status and clinical outcome after neoadjuvant chemoradiotherapy (CRT) followed by surgical resection in mediastinoscopically proven N2(+) NSCLC patients. We retrospectively identified 168 patients diagnosed between 1998 and 2006. EGFR mutational status was identified in 107 patients. Response and survival after neoadjuvant CRT followed by surgery were compared according to EGFR mutational status. 83 patients (77.6%) were found to have wild type EGFR, while exon 19 deletions or L858R missense mutations in the EGFR gene were detected in 19 patients. There was no significant difference in overall survival; however, the 5-year PFS rate in EGFR mutant patients (8.4%) were significantly lower than in the EGFR wild-type patients (33.6%; p=0.005). In multivariate analysis, EGFR mutation was a significant prognostic factor for a higher risk of distant recurrence/progression than the EGFR wild type (HR=7.183, p=0.005). In locally advanced mediastinoscopic N2-positive NSCLC, EGFR mutation was associated with more frequent distant relapses and worse 5-year PFS rate after neoadjuvant CRT followed by surgery, which might suggest that systemic control might be important in patients with the EGFR mutation. Therefore, the role of TKI for adjuvant EGFR  TKI to decrease disease recurrence in distant sites should be further investigated.

 

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[16]

TÍTULO / TITLE:  - A randomized controlled trial of postthoracotomy pulmonary rehabilitation in patients with resectable lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):214-21. doi: 10.1097/JTO.0b013e318279d52a.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318279d52a

AUTORES / AUTHORS:  - Stigt JA; Uil SM; van Riesen SJ; Simons FJ; Denekamp M; Shahin GM; Groen HJ

INSTITUCIÓN / INSTITUTION:  - *Department of Pulmonology, Isala Klinieken, Zwolle, The Netherlands; Departments of daggerPhysiotherapy, double daggerAnesthesiology, section signMedical Social Work, and ||Thoracic Surgery, Isala Klinieken, Zwolle, The Netherlands; and paragraph signDepartment of Pulmonology, University Medical Center Groningen, The Netherlands.

RESUMEN / SUMMARY:  - INTRODUCTION: : Little is known about the effects of rehabilitation for patients  with lung cancer after thoracotomy. The primary objective of this study was to evaluate the effect of a multidisciplinary rehabilitation program on quality of life (QOL) and secondary objectives were to determine its effects on pain and exercise capacity and the feasibility of combining rehabilitation with adjuvant chemotherapy. METHODS: : Patients who had undergone a thoracotomy for lung cancer were randomized between rehabilitation and usual care. Rehabilitation consisted of twice-weekly training for 12 weeks starting 1 month after hospital discharge,  scheduled visits to pain specialists, and medical social work. QOL and pain were  measured with validated questionnaires at baseline and after 1, 3, 6, and 12 months. Exercise tolerance was assessed at baseline and after 3 months with a 6-minute walking distance test. RESULTS: : The study closed prematurely because of the introduction of video-assisted thoracoscopic surgery. Of 57 randomized patients, 49 patients (23 active and 26 control) were analyzed. QOL was not significantly different between groups, although, the active group reported more  pain after 3 and 6 months and more limitations because of physical problems after 3 months. In the active group, 6-minute walking distance improved by 35 m from preoperative baseline, as opposed to the control group that showed a decline by 59 m (p = 0.024 for difference). Patients treated with adjuvant chemotherapy showed decreased attendance at training sessions. CONCLUSION: : Rehabilitation did not result in a better QOL. Exercise tolerance improved at the cost of more pain and more limitations because of physical problems. We suggest that rehabilitation is better postponed for 3 to 4 months after hospital discharge.

 

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[17]

TÍTULO / TITLE:  - A phase I trial of gefitinib and nimotuzumab in patients with advanced non-small  cell lung cancer (NSCLC).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 19. pii: S0169-5002(12)00638-1. doi: 10.1016/j.lungcan.2012.11.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.017

AUTORES / AUTHORS:  - Kim SH; Shim HS; Cho J; Jeong JH; Kim SM; Hong YK; Sung JH; Ha SJ; Kim HR; Chang H; Kim JH; Tania C; Cho BC

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College  of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Nimotuzumab (TheraCIM(®)) is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with minimal skin toxicity. Combining a different class of anti-EGFR drug with gefitinib is a new strategy to overcome intrinsic and acquired resistance to gefitinib. The aim of this phase I  trial was to determine recommended phase II dose (RPIID) and the safety of gefitinib and nimotuzumab combination treatment. METHODS: Patients with advanced/metastatic NSCLC were treated with escalating doses of weekly nimotuzumab (100mg or 200mg, IV) and fixed doses of daily gefitinib (250mg/day, PO) until disease progression or unacceptable toxicity. We planned to enroll 10 additional patients at RPIID to ascertain the safety of treatment. EGFR mutations and KRAS mutations were analyzed from available tumor samples. RESULTS: A total of 16 patients were enrolled (3 in 100mg cohort, 13 in 200mg cohort). Six patients (37.5%) were female, and 5 (31.3%) were never smokers. Adenocarcinoma was the major histologic type (13 patients, 81.3%). Treatment was well-tolerated  without dose-limiting toxicity (DLT). Four patients (25.0%) experienced grade 2 skin toxicity (1 in 100mg cohorts, 3 in 200mg cohort). Other common grade ½ toxicities were fatigue (37.5%) and diarrhea (25.0%). Among 16 evaluable patients, four patients (25.0%) achieved partial response and 7 patients (43.8%)  had stable disease. Two of 4 responders had EGFR mutation (exon 19 deletion). CONCLUSIONS: Dual agent molecular targeting of EGFR with nimotuzumab and gefitinib in patients with advanced NSCLC is well-tolerated. The RPIID for nimotuzumab is 200mg weekly IV and for gefitinib 250mg/day PO. Based upon this phase I trial, we are planning to conduct a randomized phase II trial comparing gefitinib and nimotuzumab with gefitinib alone in patients with advanced NSCLC.

 

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[18]

TÍTULO / TITLE:  - Low-dose human atrial natriuretic peptide for the prevention of postoperative cardiopulmonary complications in chronic obstructive pulmonary disease patients undergoing lung cancer surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs646

AUTORES / AUTHORS:  - Nojiri T; Inoue M; Maeda H; Takeuchi Y; Sawabata N; Shintani Y; Yamamoto K; Okumura M

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Toyonaka, Osaka, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: Lung cancer patients with chronic obstructive pulmonary disease are at an increased risk of respiratory and cardiovascular complications after pulmonary resection. The objective of the present study was to evaluate the clinical effects of low-dose human atrial natriuretic peptide (hANP) on postoperative cardiopulmonary complications in untreated chronic obstructive pulmonary disease patients undergoing lung cancer surgery. METHODS: Of 824 patients who underwent an elective pulmonary resection procedure for lung cancer  in two specialized thoracic centres between 2008 and 2011, 202 consecutive patients who had airflow limitation before surgery were included in this retrospective study. The results were compared between patients who did and those who did not receive hANP during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. Postoperative haemodynamics, white blood cell (WBC) counts and C-reactive protein (CRP) levels  were also examined. Furthermore, propensity score matching analysis was used to reduce treatment selection bias from patient characteristics. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower  in the hANP group than in the control group (14 vs 36%, P < 0.01). The propensity score matching analysis confirmed the significantly decreased frequency of postoperative cardiopulmonary complications in the hANP group. Patients in the hANP group showed significantly lower WBC counts and serum CRP levels postoperatively. CONCLUSIONS: Treatment with hANP during the perioperative period had a prophylactic effect against postoperative cardiopulmonary complications in  chronic obstructive pulmonary disease patients undergoing lung cancer surgery. TRIAL REGISTRATION NUMBER: JPRN-UMIN000003631.

 

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[19]

TÍTULO / TITLE:  - The expression of Axl receptor tyrosine kinase influences the tumour phenotype and clinical outcome of patients with malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 29. doi: 10.1038/bjc.2013.9.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.9

AUTORES / AUTHORS:  - Pinato DJ; Mauri FA; Lloyd T; Vaira V; Casadio C; Boldorini RL; Sharma R

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Medicine, Imperial Center for Translational and Experimental Medicine, Imperial College London, Du Cane Road, W12 0HS London, UK.

RESUMEN / SUMMARY:  - Background:Recent preclinical studies identified Axl, a tyrosine kinase receptor  implicated in tumour progression and epithelial-to-mesenchymal transition, as a putative therapeutic target in malignant pleural mesothelioma (MPM), an invariably fatal malignancy with limited treatment options. Here, we studied the  expression of Axl and its ligand Gas-6 (growth arrest signal-6) in primary specimens of MPM, correlating their expression levels with tumour phenotype and clinical outcomes.Methods:Two independent cohorts of consecutive patients diagnosed with MPM were studied: a derivation cohort composed of 63 cases and a validation set of 35 cases. Clinical variables including patients’ demographics,  tumour stage, histotype, performance status (PS), Axl and Gas-6 staining were tested for predicting overall survival (OS) using univariate and multivariate analyses.Results:In the derivation cohort, Axl (P=0.001) but not Gas-6 overexpression (P=0.35) emerged as a univariate prognostic factor for OS, together with stage (P=0.05), PS (P<0.001) hypoalbuminaemia (P<0.001) and anaemia (P<0.001). Multivariate analyses confirmed Axl overexpression (P=0.01), PS (P=0.01), hypoalbuminaemia (P<0.001) and anaemia (P=0.04) as independent predictors of OS. The prognostic role of Axl overexpression was externally validated in an independent cohort (P=0.03).Conclusion:Overexpression of Axl is found in the majority of MPM specimens and influences patient’s survival independently from other established prognostic factors. Such information may support patient selection for future trials.British Journal of Cancer advance online publication, 29 January 2013; doi:10.1038/bjc.2013.9 www.bjcancer.com.

 

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[20]

TÍTULO / TITLE:  - Characteristics of Lung Cancers Detected by Computer Tomography Screening in the  Randomized NELSON Trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Respir Crit Care Med. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1164/rccm.201209-1651OC

AUTORES / AUTHORS:  - Horeweg N; van der Aalst CM; Thunnissen E; Nackaerts K; Weenink C; Groen HJ; Lammers JW; Aerts JG; Scholten ET; van Rosmalen J; Mali W; Oudkerk M; de Koning HJ

INSTITUCIÓN / INSTITUTION:  - Department of Public Health, Erasmus MC, Rotterdam, Netherlands.

RESUMEN / SUMMARY:  - RATIONALE: The NELSON trial is with 15,822 participants the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening and an increasing length of the screening interval are particular features of the NELSON trial. OBJECTIVES: To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of the screen-detected lung cancers, and to compare this across screening rounds, between genders and with other screening trials METHODS: All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the genders and with other screening trials. MEASUREMENTS AND MAIN RESULTS: In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. 70.8% of the lung cancers were diagnosed at stage I, 8.1% at stage IIIB-IV and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology or tumor localization across the screening rounds. Women  were diagnosed at a significantly more favorable cancer stage than men. Compared  to other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV. CONCLUSIONS: Despite stringent criteria for a positive screening, an increasing length of the screening interval and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is a prerequisite for the effectiveness of our screening strategy.

 

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[21]

TÍTULO / TITLE:  - Inhaled tiotropium to prevent postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Today. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00595-012-0481-5

AUTORES / AUTHORS:  - Nojiri T; Inoue M; Yamamoto K; Maeda H; Takeuchi Y; Nakagiri T; Shintani Y; Minami M; Sawabata N; Okumura M

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2 (L5) Yamadaoka, Suita, Osaka, 565-0871, Japan, nojirit@thoracic.med.osaka-u.ac.jp.

RESUMEN / SUMMARY:  - PURPOSE: A new diagnosis of chronic obstructive pulmonary disease is often made during the evaluation of patients requiring lung cancer surgery. The objective of the present study was to evaluate the clinical effects of inhaled tiotropium on the postoperative cardiopulmonary complications in patients with untreated chronic obstructive pulmonary disease requiring lung cancer surgery. METHODS: A retrospective study involving 104 consecutive patients with moderate to severe chronic obstructive pulmonary disease who underwent a lobectomy for lung cancer at two specialized thoracic centers between April 2008 and October 2011 was performed. The results were compared between patients who did and did not receive inhaled tiotropium during the perioperative period. The primary endpoint was the  incidence of postoperative cardiopulmonary complications. The postoperative white blood cell counts and C-reactive protein levels as biomarkers of inflammation were also examined. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower in the tiotropium group than in the control group (18 vs. 48 %, P = 0.001). Patients in the tiotropium group also showed significantly lower white blood cell counts and C-reactive protein levels postoperatively. CONCLUSIONS: Inhaled tiotropium treatment during the perioperative period had a prophylactic effect on postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

 

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[22]

TÍTULO / TITLE:  - Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):450. doi: 10.1007/s12032-012-0450-2. Epub 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0450-2

AUTORES / AUTHORS:  - Tateishi K; Ichiyama T; Hirai K; Agatsuma T; Koyama S; Hachiya T; Morozumi N; Shiina T; Koizumi T

INSTITUCIÓN / INSTITUTION:  - First Department of Internal Medicine, Shinshu University, Matsumoto City, Japan.

RESUMEN / SUMMARY:  - The clinical efficacy and outcomes of gefitinib therapy as a first-line treatment for elderly patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations were analyzed retrospectively. We analyzed chemotherapy-naive NSCLC patients aged 75 years or older who had EGFR mutations (exon 19 deletion mutation or L858R), who were initially treated with gefitinib (250 mg) once daily in Nagano Prefecture. A total of 55 patients (16 men, 39 women) with a median age of 81.1 years (range; 75-94 years) treated between April 2007 and July 2012 were analyzed. The overall response rate and disease control rate were 72.7 % (95 % confidence interval (CI); 59.5-82.9 %) and 92.7 % (95 % CI; 82.0-97.6 %), respectively. Median progression-free survival and overall survival from the start of gefitinib treatment were 13.8 months (95 % CI; 9.9-18.8 months) and 29.1 months (95 % CI; 22.4 months-not reached), respectively. Two-year survival rate was 59.5 % (95 % CI; 41.0-78.0 %). Major grade 3 toxicities were skin rash (1.8 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (7.3 %). First-line treatment with gefitinib for elderly EGFR-mutated NSCLC patients was effective and well tolerated. The results suggest that first-line gefitinib should be considered as  a preferable standard treatment in elderly patients with advanced NSCLC harboring EGFR mutations.

 

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[23]

TÍTULO / TITLE:  - Higher Expression of Receptor Tyrosine Kinase Axl, and Differential Expression of its Ligand, Gas6, Predict Poor Survival in Lung Adenocarcinoma Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2795-3

AUTORES / AUTHORS:  - Ishikawa M; Sonobe M; Nakayama E; Kobayashi M; Kikuchi R; Kitamura J; Imamura N; Date H

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan, mishi@kuhp.kyoto-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Downstream activation through receptor tyrosine kinases (RTKs) plays  important roles in carcinogenesis. In this study, we assessed the clinical involvement of Axl, an RTK, and its ligand, Gas6, in surgically treated lung adenocarcinoma. METHODS: Axl and Gas6 mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in completely resected lung adenocarcinoma tissues (n = 88) and were evaluated for correlation with clinicopathologic features and patient survival. RESULTS: Higher expressions of Axl mRNA/protein and Gas6 protein were significantly related to worse clinicopathological features and prognosis (5-year overall survival rates: Axl mRNA low: 72.3 %, high: 49.7 %, P = 0.047; Axl protein low: 77.5 %, high: 38.6 %, P < 0.001; and Gas6 protein low: 70.5 %, high: 48 %, P = 0.042). On the contrary, higher Gas6 mRNA expression was related to better clinicopathological features and prognosis (5-year overall  survival rates: Gas6 mRNA low: 59.2 %, high: 81.8 %, P = 0.054). Multivariate analysis suggests that high Axl mRNA expression may be an independent factor for  poor patient prognosis (P = 0.04). CONCLUSIONS: In lung adenocarcinoma, Axl and Gas6 expression levels were associated with tumor advancement and patient survival, thus rendering them as reliable biomarkers and potential targets for treatment of lung adenocarcinoma.

 

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[24]

TÍTULO / TITLE:  - Evaluation of the safety and efficacy of combination chemotherapy with vinorelbine and platinum agents for patients with non-small cell lung cancer with interstitial lung disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5475-80.

AUTORES / AUTHORS:  - Okuda K; Hirose T; Oki Y; Murata Y; Kusumoto S; Sugiyama T; Ishida H; Shirai T; Nakashima M; Yamaoka T; Ohnishi T; Ohmori T

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo  142-8666, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Acute chemotherapy-associated exacerbation of interstitial lung disease (ILD) can occur in patients with non-small cell lung cancer (NSCLC). The  safety and efficacy of cytotoxic chemotherapy has not yet been established for NSCLC with ILD. Thus, patients with advanced NSCLC with ILD usually receive only  best supportive care. The aim of this study was to assess the safety and efficacy profiles of the combination chemotherapy of vinorelbine and a platinum agent in patients with advanced NSCLC with ILD. PATIENTS AND METHODS: Nineteen patients with advanced NSCLC with ILD treated with vinorelbine and a platinum agent, either cisplatin or carboplatin, were retrospectively reviewed to examine acute exacerbation of ILD, toxicity, response rate, and survival time. Additionally, possible predictive factors for acute chemotherapy-associated exacerbation of ILD were analyzed. RESULTS: The response rate was 42.1%, the progression-free survival time was 4.4 months, the median survival time was 7.4 months, and the one-year survival rate was 36.8%. Neutropenia was the most frequent grade 3 to 4  toxicity and it occurred in 63.2% of patients. Acute chemotherapy-associated exacerbation of ILD occurred in three patients (15.8%) and caused the death of one of these patients (5.3%). No variables were identified as being predictive factors for acute chemotherapy-associated exacerbation of ILD. CONCLUSION: The combination chemotherapy with vinorelbine and a platinum agent can be considered  as a treatment option for patients with advanced NSCLC with ILD, with careful management after sufficient evaluation of the risks and the benefits.

 

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[25]

TÍTULO / TITLE:  - TORCH Study: How Much Longer Should We Continue to Use Erlotinib in Unselected Patients With Non-Small-Cell Lung Cancer?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 10;31(2):288-9. doi: 10.1200/JCO.2012.46.2648. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.46.2648

AUTORES / AUTHORS:  - Lorusso V; Silvestris N; Marech I

INSTITUCIÓN / INSTITUTION:  - Medical Oncology, Istituto Tumori Giovanni Paolo II, Istituto di Ricovero e Cure  a Carattere Scientifico, National Cancer Research Center, Oncologico, Bari, Italy; vitolorusso@inwind.it.

 

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[26]

TÍTULO / TITLE:  - Electronic Prompt to Improve Outpatient Code Status Documentation for Patients With Advanced Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.2203

AUTORES / AUTHORS:  - Temel JS; Greer JA; Gallagher ER; Jackson VA; Lennes IT; Muzikansky A; Park ER; Pirl WF

INSTITUCIÓN / INSTITUTION:  - All authors: the Massachusetts General Hospital, Boston, MA.

RESUMEN / SUMMARY:  - PURPOSERates of documentation of end-of-life care preferences in the medical record remain low, even among patients with incurable malignancies. We therefore  conducted a two-phase study to develop and assess the effect of electronic prompts to encourage oncology clinicians to document code status in the outpatient electronic health record (EHR) of patients with advanced lung cancers. PATIENTS AND METHODSTo determine the optimal delivery, content, and timing of the electronic prompt, we first facilitated focus groups with oncology clinicians at  an affiliated medical center. Given this feedback, we developed e-mail reminders  timed to the start of each new chemotherapy regimen. Between July 2009 and January 2011, 102 eligible patients with incurable lung cancer were approached, and 100 agreed to participate. We compared e-mail prompt participants (EPPs) with a cohort of 100 consecutive historical controls who began therapy for incurable lung cancer at least 1 year before the start of this study. The primary outcome measure was clinician documentation of code status in the EHR.ResultsEPPs were similar to historical controls, with no significant differences in demographic or clinical characteristics. At 1-year follow-up, 33.7% (n = 33/98) of EPPs had a code status documented in the outpatient EHR compared with 14.5% (n = 12/83) of historical controls (P = .003). Mean time to code status documentation was significantly shorter in EPPs (8.6 months [95% CI, 7.6 to 9.5]) compared with controls (10.5 months [95% CI, 9.8 to 11.3]; P = .004). CONCLUSIONe-mail prompts  may improve the rate and timing of code status documentation in the EHR and warrant further investigation.

 

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[27]

TÍTULO / TITLE:  - Clinical Outcomes of Thoracoscopic Lobectomy for Patients With Clinical N0 and Pathologic N2 Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2012 Dec 19. pii: S0003-4975(12)02485-X. doi: 10.1016/j.athoracsur.2012.10.083.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.10.083

AUTORES / AUTHORS:  - Zhong C; Yao F; Zhao H

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Shanghai Chest Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.

RESUMEN / SUMMARY:  - BACKGROUND: We compared the surgical outcomes in patients with clinical N0 and pathologic N2 (cN0-pN2) non-small cell lung cancer (NSCLC) who underwent video-assisted thoracoscopic surgery (VATS) lobectomy and open thoracotomy to evaluate the role of VATS lobectomy for cN0-pN2 disease. METHODS: Between March 2006 and August 2011, 1,456 patients with clinical N0 NSCLC disease underwent lobectomy with systematic node dissection (SND) at Shanghai Chest Hospital. Of those patients, 157 were shown to have cN0-pN2 NSCLC. Of those, 67 patients underwent VATS lobectomy, and 90 patients underwent open lobectomy. SND was performed in all 157 patients. Clinicopathologic factors, local recurrence rates, and survival rates were compared. RESULTS: The two groups were similar in age, sex, and pulmonary function. The VATS approach was associated with significantly  shorter chest tube duration and postoperative stay than was the thoracotomy approach. Operative mortality, morbidity, and recurrence did not differ between the two groups. There was no significant difference between the two types of operation in numbers of total lymph nodes removed (17.4 +/- 6.1 in the VATS group vs 18.1 +/- 7.2 in the open group, p = 0.78) and mediastinal lymph nodes removed  (11.7 +/- 5.6 in the VATS group vs 12.0 +/- 5.1 in the open group, p = 0.84). Similarly, the two groups were not significantly different with regard to stations of total lymph nodes removed (7.6 +/- 1.9 in the VATS group vs 7.8 +/- 2.3 in the open group, p = 0.81) and mediastinal lymph nodes removed (4.5 +/- 1.1 in the VATS group vs 4.7 +/- 1.3 in the open group, p = 0.71). The rates of overall survival and disease-free 5-year survival were not significantly different between the two groups. CONCLUSIONS: The clinical outcomes of thoracoscopic lobectomy were comparable to those of thoracotomy for patients with cN0-pN2 NSCLC. Single-station N2 is a good prognostic factor for disease-free survival in these patients.

 

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[28]

TÍTULO / TITLE:  - Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2013 Jan 18. doi: 10.1002/cncr.27754.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27754

AUTORES / AUTHORS:  - Harada H; Miyamoto K; Yamashita Y; Nakano K; Taniyama K; Miyata Y; Ohdan H; Okada M

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan; Department of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Even after early detection and curative resection of early stage non-small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes. METHODS: Using the methylation-specific polymerase chain reaction assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. The clinical relevance of BRCA1 methylation status was evaluated in terms of outcome of the disease. RESULTS: Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (P = .0197) and that patients with  BRCA1 methylation demonstrated significantly poorer recurrence-free survival compared to those without (P = .0139). Cox’s proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence-free survival (P = .0155). CONCLUSIONS: Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC. Considering that BRCA1 plays a role in chemotherapy-induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information that is clinically relevant to tailored adjuvant therapy. Cancer 2013. © 2013 American Cancer Society.

 

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[29]

TÍTULO / TITLE:  - Dynamic contrast-enhanced CT to assess metabolic response in patients with advanced non-small cell lung cancer and stable disease after chemotherapy or chemoradiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Radiol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-012-2755-0

AUTORES / AUTHORS:  - Hwang SH; Yoo MR; Park CH; Jeon TJ; Kim SJ; Kim TH

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul, 135-720, Republic of Korea.

RESUMEN / SUMMARY:  - OBJECTIVES: To compare tumour enhancement patterns measured using dynamic contrast-enhanced (DCE)-CT with tumour metabolism measured using positron emission tomography (PET)-CT in patients with non-small cell lung cancer (NSCLC)  and stable disease after chemotherapy or chemoradiotherapy. METHODS: After treatment, 75 NSCLC tumours in 65 patients who had stable disease on DCE-CT according to Response Evaluation Criteria in Solid Tumour (RECIST) were evaluated using PET-CT. On DCE-CT, relative enhancement ratios (RER) of tumour at 30, 60, 90, 120 s and 5 min after injection of contrast material were measured. Metabolic responses of tumours were classified into two groups according to the maximum standardized uptake value (SUVmax) by PET-CT: complete metabolic response (CR) with an SUVmax of less than 2.5, and noncomplete metabolic response (NR) with an  SUVmax of at least 2.5. RESULTS: Using the optimal RER(60) cutoff value of 43.7 % to predict NR of tumour gave 95.7 % sensitivity, 64.2 % specificity, and 82.1 % positive and 95.0 % negative predictive values. After adjusting for tumour size,  the odds ratio for NR in tumour with an RER(60) of at least 43.7 % was 70.85 (95  % CI = 7.95-630.91; P < 0.05). CONCLUSIONS: Even when disease was stable according to RECIST, DCE-CT predicted hypermetabolic status of residual tumour in patients with NSCLC after treatment. KEY POINTS : * Dynamic contrast-enhanced CT  (DCE-CT) can provide useful metabolic information about non-small cell lung cancer. * NSCLC lesions, even grossly stable after treatment, show various metabolic states. * DCE-CT enhancement patterns correlate with tumour metabolic status as shown by PET. * DCE-CT helps to assess hypermetabolic NSCLC as stable disease after treatment.

 

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[30]

TÍTULO / TITLE:  - Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2013 Jan 14. doi: 10.1038/onc.2012.514.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.514

AUTORES / AUTHORS:  - Tsai HY; Yang YF; Wu AT; Yang CJ; Liu YP; Jan YH; Lee CH; Hsiao YW; Yeh CT; Shen CN; Lu PJ; Huang MS; Hsiao M

INSTITUCIÓN / INSTITUTION:  - 1] Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan [2] Genomics Research Center, Academia Sinica, Taipei, Taiwan.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer deaths and is the most occurring malignancy worldwide. Unraveling the molecular mechanisms involved in lung tumorigenesis will greatly improve therapy. During early tumorigenesis, rapid proliferating tumor cells require increased activity of endoplasmic reticulum (ER) for protein synthesis, folding and secretion, thereby are subjected to ER stress. Ribosome-binding protein 1 (RRBP1) was originally identified as a ribosome-binding protein located on the rough ER and associated with unfolding protein response (UPR). In this report, we investigated the role of RRBP1 in lung cancer. RRBP1 was highly expressed in lung cancer tissue, as compared with adjacent normal tissues as assessed by immunohistochemistry (IHC) using lung cancer tissue array (n=87). Knockdown of RRBP1 by short-hairpin RNAs caused ER stress and significantly reduced cell viability and tumorigenicity. This effect was associated with a significant reduction in the expression of glucose-regulated protein 78 (GRP78). UPR regulator GRP78, an anti-apoptotic protein that is widely upregulated in cancer, has a critical role in chemotherapy resistance in some cancers. According to our results, cells with a higher level of RRBP1 were more resistant to ER stress. Ectopic expression of RRBP1 alleviated apoptosis that was induced by the ER-stress agent tunicamycin, 2-deoxy-D-glucose  (2DG) or doxorubicin via enhancing GRP78 protein expression. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies using the database GSE10072. Our results also indicated that RRBP1 may involve in the regulation of mRNA stability of UPR components including ATF6 and GRP78. Taken together, RRBP1 could alleviate ER stress and help cancer cell survive. RRBP1 is  critical for tumor cell survival, which may make it a useful target in lung cancer treatment and a candidate for the development of new targeted therapeutics.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.514.

 

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[31]

TÍTULO / TITLE:  - Reducing the time before consulting with symptoms of lung cancer: a randomised controlled trial in primary care.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Gen Pract. 2013 Jan;63(606):47-54. doi: 10.3399/bjgp13X660779.

            ●● Enlace al texto completo (gratuito o de pago) 3399/bjgp13X660779

AUTORES / AUTHORS:  - Smith S; Fielding S; Murchie P; Johnston M; Wyke S; Powell R; Devereux G; Nicolson M; Macleod U; Wilson P; Ritchie L; Lee AJ; Campbell NC

INSTITUCIÓN / INSTITUTION:  - Environmental and occupational medicine and consultant respiratory physician, Institute of Medical Sciences, UK.

RESUMEN / SUMMARY:  - BACKGROUND: Most individuals with lung cancer have symptoms for several months before presenting to their GP. Earlier consulting may improve survival. AIM: To evaluate whether a theory-based primary care intervention increased timely consulting of individuals with symptoms of lung cancer. DESIGN AND SETTING: Open  randomised controlled trial comparing intervention with usual care in two general practices in north-east Scotland. METHOD: Smokers and ex-smokers aged >/=55 years were randomised to receive a behavioural intervention or usual care. The intervention comprised a single nurse consultation at participants’ general practice and a self-help manual. The main outcomes were consultations within target times for individuals with new chest symptoms (</=3 days haemoptysis, </=3 weeks other symptoms) in the year after the intervention commenced, and intentions about consulting with chest symptoms at 1 and 6 months. RESULTS: Two hundred and twelve participants were randomised and 206 completed the trial. The  consultation rate for new chest symptoms in the intervention group was 1.19 (95%  confidence interval [CI] = 0.92 to 1.53; P = 0.18) times higher than in the usual-care group and the proportion of consultations within the target time was 1.11 (95% CI = 0.41 to 3.03; P = 0.83) times higher. One month after the intervention commenced, the intervention group reported intending to consult with chest symptoms 31 days (95% CI = 7 to 54; P = 0.012) earlier than the usual care  group, and at 6 months this was 25 days (95% CI = 1.5 to 48; P = 0.037) earlier.  CONCLUSION: Behavioural intervention in primary care shortened the time individuals at high risk of lung disease intended to take before consulting with  new chest symptoms (the secondary outcome of the study), but increases in consultation rates and the proportions of consultations within target times were  not statistically significant.

 

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[32]

TÍTULO / TITLE:  - Clinical Impact of Immune Microenvironment in Stage I Lung Adenocarcinoma: Tumor  Interleukin-12 Receptor beta2 (IL-12Rbeta2), IL-7R, and Stromal FoxP3/CD3 Ratio Are Independent Predictors of Recurrence.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Feb 1;31(4):490-8. doi: 10.1200/JCO.2012.45.2052. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.45.2052

AUTORES / AUTHORS:  - Suzuki K; Kadota K; Sima CS; Nitadori J; Rusch VW; Travis WD; Sadelain M; Adusumilli PS

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; adusumip@mskcc.org.

RESUMEN / SUMMARY:  - PURPOSE Mounting evidence suggests that tumor-infiltrating immune cells have prognostic value for patients with solid organ malignancies. Our aim was to investigate the prognostic significance of the immune microenvironment in patients with stage I lung adenocarcinoma (ADC). PATIENTS AND METHODS Using tissue microarray and immunohistochemistry, we investigated eight types of tumor-infiltrating immune cells in the tumor nest and tumor-associated stroma as  well as tumor expression of five cytokines in a uniform cohort of 956 patients with stage I lung ADC (478 each in training and validation cohorts). Results Although a high density of stromal forkhead box P3 (FoxP3) -positive cells was associated with shorter recurrence-free probability (RFP; P = .043), the relative proportion of stromal FoxP3 to CD3 was a stronger predictor of recurrence (5-year RFP, 85% for high v 77% for low ratio; P = .004). High expression of tumor interleukin-12 receptor beta2 (IL-12Rbeta2) was associated with better outcome (5-year RFP, 90% for high v 80% for low expression; P = .026), whereas high expression of tumor IL-7R was associated with worse outcome (5-year RFP, 76% for  high v 86% for low expression; P = .001). In multivariate analysis, these immune  markers were independently associated with recurrence. Although IL-7R remained significant for poor overall survival, all the markers remained prognostic for recurrence in patients with stages IA and IB disease as well as for patients with tumors </= 2 cm. CONCLUSION Our investigation confirms the biologic and prognostic significance of the tumor immune microenvironment for patients with stage I lung ADC and provides support for its use to stratify clinical outcome and immunotherapeutic interventions.

 

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[33]

TÍTULO / TITLE:  - Lung cancer screening gets risk-specific.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Cancer Inst. 2013 Jan 2;105(1):1-2. doi: 10.1093/jnci/djs631. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djs631

AUTORES / AUTHORS:  - Peres J

INSTITUCIÓN / INSTITUTION:  - kristine.crane@oup.com.

 

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[34]

TÍTULO / TITLE:  - Pleural Plaques and the Risk of Pleural Mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Cancer Inst. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djs513

AUTORES / AUTHORS:  - Pairon JC; Laurent F; Rinaldo M; Clin B; Andujar P; Ameille J; Brochard P; Chammings S; Ferretti G; Galateau-Salle F; Gislard A; Letourneux M; Luc A; Schorle E; Paris C

INSTITUCIÓN / INSTITUTION:  - Affiliations of authors: INSERM, U955, Creteil, France (JCP, PA); Universite Paris-Est Creteil, France (JCP, PA); Centre Hospitalier Intercommunal, Service de pneumologie et pathologie professionnelle, Creteil, France (JCP, PA); Centre cardiothoracique INSERM 1045, Bordeaux, France (FL); Centre INSERM 897, Bordeaux, France (MR, PB); Universite Segalen Bordeaux, CHU de Bordeaux, France (FL, MR, PB); Cancers et Populations, INSERM U1086, France (BC, FGS); CHU Caen, Service de sante au travail et pathologie professionnelle, Caen, France (BC, ML); MESOPATH National Reference Center (FGS); Faculte de Medecine de Caen, France (BC, ML, FGS); AP-HP, Hopital Raymond Poincare, Unite de pathologie professionnelle, Garches, France (JA); Institut Interuniversitaire de Medecine du Travail de Paris-Ile de France, Paris, France (SC); INSERM U823, Grenoble, France (GF); Universite J Fourrier, Grenoble, France (GF); CHU Grenoble, Clinique universitaire de radiologie et imagerie medicale, Grenoble, France (GF); CHU Rouen, Service des maladies professionnelles, Rouen, France (AG); INSERM U954, Nancy, France (AL, CP); Universite de Lorraine, Faculte de Medecine de Nancy, Nancy, France (CP); CHU Nancy, Nancy, France (AL, CP); ERSM Rhone-Alpes, Lyon, France (ES).

RESUMEN / SUMMARY:  - BackgroundThe association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association  between pleural plaques on computed tomography (CT) scan and the risk of pleural  mesothelioma in a follow-up study of asbestos-exposed workers.MethodsRetired or unemployed workers previously occupationally exposed to asbestos were invited to  participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical  tests were two-sided.ResultsA total of 17 incident cases of pleural mesothelioma  were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos).ConclusionThe presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

 

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[35]

TÍTULO / TITLE:  - Solid tumors versus mixed tumors with a ground-glass opacity component in patients with clinical stage IA lung adenocarcinoma: Prognostic comparison using  high-resolution computed tomography findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Cardiovasc Surg. 2012 Dec 12. pii: S0022-5223(12)01396-7. doi: 10.1016/j.jtcvs.2012.11.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2012.11.019

AUTORES / AUTHORS:  - Tsutani Y; Miyata Y; Yamanaka T; Nakayama H; Okumura S; Adachi S; Yoshimura M; Okada M

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE: This study aimed to compare malignant behavior and prognosis between solid tumors and mixed tumors with a ground-glass opacity component on high-resolution computed tomography. METHODS: We examined 436 of 502 consecutive  patients with clinical stage IA adenocarcinoma who had undergone preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography; 66 patients with tumors with pure ground-glass opacity components were excluded. Tumor type (solid, n = 137; mixed, n = 299) and surgical results were analyzed for all patients and their matched pairs. RESULTS: In all patients, solid tumors showed a significantly greater association (P < .001) with lymphatic, vascular, and pleural invasion and lymph node metastasis compared with mixed tumors. The disease-free survival was also worse in patients  with solid tumors (P = .0006). Analysis of 97 pairs matched for solid component size confirmed that solid tumors were significantly associated with lymphatic, vascular, and pleural invasion (P = .008, P = .029, P = .003, respectively) and poor prognosis. When maximum standardized uptake value and solid component size were matched (n = 79), the differences in pathologic prognostic parameters and disease-free survivals between patients with solid and mixed tumors disappeared.  CONCLUSIONS: Solid tumors exhibit more malignant behavior and have a poorer prognosis compared with mixed tumors, even when the solid component size is the same in both tumor types. However, differences in malignant behavior can be identified using maximum standardized uptake values determined by F-18-fluorodeoxyglucose positron emission tomography/computed tomography.

 

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[36]

TÍTULO / TITLE:  - Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated  With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Nov 29. pii: S0360-3016(12)03653-X. doi: 10.1016/j.ijrobp.2012.10.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.003

AUTORES / AUTHORS:  - Reymen B; Van Loon J; van Baardwijk A; Wanders R; Borger J; Dingemans AM; Bootsma G; Pitz C; Lunde R; Geraedts W; Lambin P; De Ruysscher D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology (MAASTRO clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: bart.reymen@maastro.nl.

RESUMEN / SUMMARY:  - PURPOSE: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. METHODS AND MATERIALS: Analysis of our prospective database with stage I  to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). RESULTS: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 +/- 152 cc (7.5-895 cc). Isolated elective nodal failure  occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. CONCLUSIONS: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

 

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[37]

TÍTULO / TITLE:  - Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):19-30. doi: 10.1097/JTO.0b013e31827628ff.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827628ff

AUTORES / AUTHORS:  - Christoph DC; Asuncion BR; Hassan B; Tran C; Maltzman JD; O’Shannessy DJ; Wynes MW; Gauler TC; Wohlschlaeger J; Hoiczyk M; Schuler M; Eberhardt WE; Hirsch FR

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Medical Oncology, University of Colorado Denver, Aurora, Colorado 80045, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Folate receptor alpha (FRA) regulates cellular uptake of folates and antifolates. Information about FRA protein expression in metastatic non-small-cell lung cancer (NSCLC) is limited. We investigated FRA as a biomarker for pemetrexed-based chemotherapy and compared it with thymidylate synthase (TS), the main target of pemetrexed. METHODS: Pretreatment tumor specimens from 207 patients with advanced NSCLC were assessed for FRA and TS protein expression by immunohistochemistry using the H-score (range, 0-300) and correlated to patients’ clinicopathological data, radiographic response, progression-free survival (PFS), and overall survival (OS). RESULTS: Low total (cytoplasmic and nuclear) TS protein expression (H-score < 210) was associated with improved PFS (median: 5.6  versus 3.5 months; hazard ratio [HR] = 0.6379, p = 0.0131) and prolonged OS (median: 22.5 versus 11.5 months; HR = 0.5680,p = 0.0107). An association between lower TS levels and response to pemetrexed-based therapy was found-mean H-score 187 +/- 5, median 180 for responders versus mean H-score 201 +/- 4, median 210, for non-responders, p = 0.0244. High intracellular FRA expression (H-score >/=110) was associated with prolonged OS (28.9 versus 11.7 months, HR = 0.5316, p = 0.0040) and a trend for association with PFS (5.6 versus 4.1 months, HR = 0.7395, p = 0.0801) was noted. Membranous FRA expression was seen in 83% of patients, moreover, high membranous expression (H-score >/=20) was associated with improved PFS (5.6 versus 3.7 months, HR = 0.6445, p = 0.0306) and OS (22.1 versus 11.5 months, HR = 0.5378, p = 0.0131). CONCLUSIONS: A large number of NSCLC patients have high expression of FRA and/or a low level of TS expression. Expression levels of FRA and TS were associated with clinical benefit from pemetrexed therapy.

 

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[38]

TÍTULO / TITLE:  - Randomized phase II trial of sulindac for lung cancer chemoprevention.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 19. pii: S0169-5002(12)00632-0. doi: 10.1016/j.lungcan.2012.11.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.011

AUTORES / AUTHORS:  - Limburg PJ; Mandrekar SJ; Aubry MC; Ziegler KL; Zhang J; Yi JE; Henry M; Tazelaar HD; Lam S; McWilliams A; Midthun DE; Edell ES; Rickman OB; Mazzone P; Tockman M; Beamis JF; Lamb C; Simoff M; Loprinzi C; Szabo E; Jett J

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic, Rochester, MN, United States. Electronic address: limburg.paul@mayo.edu.

RESUMEN / SUMMARY:  - INTRODUCTION: Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (>/=30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). METHODS: At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. RESULTS: Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92). CONCLUSIONS: Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg  bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.

 

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[39]

TÍTULO / TITLE:  - A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non-Small-Cell Lung Cancer Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2321

AUTORES / AUTHORS:  - Tang H; Xiao G; Behrens C; Schiller J; Allen J; Chow CW; Suraokar M; Corvalan A; Mao JH; White M; Wistuba II; Minna JD; Xie Y

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Sciences, University of Texas Southwesten Medical Center.

RESUMEN / SUMMARY:  - PURPOSE: Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non-small-cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC. EXPERIMENTAL DESIGN: An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC. RESULTS: Using a cohort of 442 Stage I-III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set which robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four  microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (N=90 and N=176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: hazard ratio=0.34, p=0.017; JBR.10 clinical trial data: hazard ratio=0.36, p=0.038), while the predicted non-benefit group showed no survival benefit for two datasets (hazard ratio=0.80, p=0.70; hazard ratio= 0.91, p=0.82). CONCLUSIONS: This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non-small-cell lung cancer will have a survival benefit with ACT.

 

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[40]

TÍTULO / TITLE:  - A functional copy number variation in WWOX gene is associated with lung cancer risk in Chinese.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Mol Genet. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt019

AUTORES / AUTHORS:  - Yang L; Liu B; Huang B; Deng J; Li H; Yu B; Qiu F; Cheng M; Wang H; Yang R; Yang X; Zhou Y; Lu J

INSTITUCIÓN / INSTITUTION:  - The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.

RESUMEN / SUMMARY:  - WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that has been reported to lose function due to genetic alterations in several cancers. WWOX maps to the common chromosomal fragile site FRA16D and several copy number variations (CNVs) were found within this gene. In this study, we investigated the association between the CNVs of WWOX and lung cancer risk in four independent case-control studies, which are on 2942 lung cancer cases and 3074 cancer-free controls of southern, eastern and northern Chinese. A common CNV-67048 was genotyped by the Taqman real-time PCR, and its biological effect was accessed with protein expression and sequencing assays. We found that in comparison to the common 2-copy genotype, the carriers of loss variant genotypes (1-copy or 0-copy) had a significantly increased risk of lung cancer (adjusted OR=1.39, 95% C.I.=1.24-1.55, P=9.01x10(-9)) in a dose-response manner (P(trend)=1.12x10(-10)), and the WWOX protein expressions in lung cancer tissues were significantly lower  (P=0.036), accompanying a higher rate of exons absence (P=0.021) in subjects with loss genotypes of CNV-67048. Our data suggest that the loss genotypes of CNV-67048 in WWOX predispose their carriers to lung cancer; this might be related with altered WWOX gene expression and exons absence in them.

 

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[41]

TÍTULO / TITLE:  - Unresectable Lung Malignancy: Combination Therapy with Segmental Pulmonary Arterial Chemoembolization with Drug-eluting Microspheres and Radiofrequency Ablation in 17 Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12120198

AUTORES / AUTHORS:  - Gadaleta CD; Solbiati L; Mattioli V; Rubini G; Fazio V; Goffredo V; Vinciarelli G; Gadaleta-Caldarola G; Canniello E; Armenise F; D’Aluisio L; Gaudiano A; Ranieri G; Goldberg SN

INSTITUCIÓN / INSTITUTION:  - Interventional Radiology and Medical Oncology Unit and Department of Critical Area and Surgery, National Cancer Research Centre Istituto Tumori Giovanni Paolo  II Bari, Viale Orazio Flacco 65, 70124 Bari, Italy; Department of Radiology, Ospedale Generale, Busto Arsizio, Italy; Nuclear Medicine Unit, University of Bari, Bari, Italy.

RESUMEN / SUMMARY:  - Purpose:To evaluate the feasibility, safety, and effectiveness of combining segmental pulmonary arterial chemoembolization (SPACE) and percutaneous radiofrequency (RF) ablation in patients with unresectable lung neoplasms or patients with resectable neoplasms who refused surgery and to compare the local tumor progression (LTP) rate with that in previous studies of RF ablation alone.Materials and Methods:After institutional review board approval and informed consent, 17 patients with primary and metastatic lung cancer were enrolled in this prospective study. Between January 2008 and February 2011, 20 nodules (median diameter, 3.0 cm; range, 2.0-5.0 cm) were treated during 19 sessions. Antineoplastic agents loaded on 50-100-microm microspheres were selectively infused into specific pulmonary arteries. Percutaneous computed tomography (CT)-guided RF ablation of lung nodules was performed 48 hours after SPACE. Follow-up consisted of enhanced CT 48 hours after combination treatment was completed, after 30 days, and every 3 months thereafter. Fluorine 18 fluorodeoxyglucose positron emission tomography was performed 3 months after combination therapy and then every 6 months. The t test was used to compare groups.Results:Technical success was achieved in 100% of cases. Ventilation-lung  single photon emission computed tomography showed a wide area without ventilation in the lung parenchyma treated with SPACE. The LTP rate was 21% (three of 14 nodules) in 3-5-cm-diameter tumors and 0% (zero of six nodules) in tumors of 3 cm or smaller in diameter. Complete response was achieved in 65% (11 of 17) of patients at minimum follow-up of 6 months. Overall, treatment was well tolerated. Major complications were pneumothorax in five of 19 sessions (26%) and one bronchopleural fistula (one of 19, 5%). No treatment-related changes in general lung function were noted.Conclusion:Combination therapy with RF ablation after SPACE to treat unresectable lung tumors is technically feasible, safe, and effective and may represent an advantage over RF ablation alone.© RSNA, 2012.

 

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[42]

TÍTULO / TITLE:  - GTV differentially impacts locoregional control of non-small cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWEL trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiother Oncol. 2013 Jan 16. pii: S0167-8140(12)00540-3. doi: 10.1016/j.radonc.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2012.12.008

AUTORES / AUTHORS:  - Soliman M; Yaromina A; Appold S; Zips D; Reiffenstuhl C; Schreiber A; Thames HD; Krause M; Baumann M

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and OncoRay - Center for Radiation Research in Oncology, Technische Universitat Dresden, Germany; Department of Oncology, Alexandria University, Egypt.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the impact of fractionation schedule on the size of the gross tumour volume (GTV) effect on tumour control after radiotherapy of NSCLC. MATERIAL AND METHODS: A subgroup analysis on 163 patients treated in a randomized phase III trial of CHARTWEL (continuous hyperfractionated accelerated radiotherapy-weekend less) vs conventional radiotherapy was performed. The influence of GTV and other baseline factors on local failure (LF), disease-free survival (DFS), distant metastases (DM), and overall survival (OS) was estimated  using the Cox Proportional Hazards model. RESULTS: Superior local control was achieved by CHARTWEL compared to conventional radiotherapy (HR 0.54, p=0.015). The hazard of LF increased with increasing GTV for both conventional fractionation and CHARTWEL, however the increase for the latter was less pronounced and not significant. CONCLUSION: Highly accelerated CHARTWEL treatment was significantly more effective than conventional radiotherapy for locoregional  control of NSCLC. GTV had a significant effect on locoregional control after conventional fractionation, an effect that was not significant with CHARTWEL. This is the first study to demonstrate that the magnitude of the time factor of fractionated radiotherapy increases with tumour volume.

 

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[43]

TÍTULO / TITLE:  - Mutant surfactant A2 proteins associated with familial pulmonary fibrosis and lung cancer induce TGF-beta1 secretion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21064-9. doi: 10.1073/pnas.1217069110. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1217069110

AUTORES / AUTHORS:  - Maitra M; Cano CA; Garcia CK

INSTITUCIÓN / INSTITUTION:  - Eugene McDermott Center for Human Growth and Development and Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75229.

RESUMEN / SUMMARY:  - Mutations in the genes encoding the lung surfactant proteins are found in patients with interstitial lung disease and lung cancer, but their pathologic mechanism is poorly understood. Here we show that bronchoalveolar lavage fluid from humans heterozygous for a missense mutation in the gene encoding surfactant  protein (SP)-A2 (SFTPA2) contains more TGF-beta1 than control samples. Expression of mutant SP-A2 in lung epithelial cells leads to secretion of latent TGF-beta1,  which is capable of autocrine and paracrine signaling. TGF-beta1 secretion is not observed in lung epithelial cells expressing the common SP-A2 variants or other misfolded proteins capable of increasing cellular endoplasmic reticulum stress. Activation of the unfolded protein response is necessary for maximal TGF-beta1 secretion because gene silencing of the unfolded protein response transducers leads to an approximately 50% decrease in mutant SP-A2-mediated TGF-beta1 secretion. Expression of the mutant SP-A2 proteins leads to the coordinated increase in gene expression of TGF-beta1 and two TGF-beta1-binding proteins, LTBP-1 and LTBP-4; expression of the latter is necessary for secretion of this cytokine. Inhibition of the TGF-beta autocrine positive feedback loop by a pan-TGF-beta-neutralizing antibody, a TGF-beta receptor antagonist, or LTBP gene  silencing results in the reversal of TGF-beta-mediated epithelial-to-mesenchymal  transition and cell death. Because secretion of latent TGF-beta1 is induced specifically by mutant SP-A2 proteins, therapeutics targeted to block this pathway may be especially beneficial for this molecularly defined subgroup of patients.

 

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[44]

TÍTULO / TITLE:  - Role of EGFR SNPs in survival of advanced lung adenocarcinoma patients treated with Gefitinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gene. 2013 Jan 9. pii: S0378-1119(12)01646-0. doi: 10.1016/j.gene.2012.12.087.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2012.12.087

AUTORES / AUTHORS:  - Zhang L; Yuan X; Chen Y; Du XJ; Yu S; Yang M

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

RESUMEN / SUMMARY:  - AIM: As a novel molecularly targeting agent for non-small-cell lung cancer (NSCLC), Gefitinib can block its tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Genetic variations in EGFR may affect its protein function or expression and lead to diverse outcomes in NSCLC patients after Gefitinib therapy. Therefore, this prospective study examined whether EGFR single nucleotide polymorphisms (SNPs) are associated with different survival time in advanced lung adenocarcinoma patients treated with Gefitinib. METHODS: One hundred and twenty-eight patients with stage IIIB or IV lung adenocarcinoma receiving Gefitinib target therapy between 2008 and 2010 were recruited in this study. Six EGFR haplotype-tagging SNPs were genotyped by the Sequenom MassArray system. Survival by different genotypes was compared using Kaplan-Meier methods.  Cox proportional hazards models were applied to estimate the effect of prognostic factors on overall survival (OS) and progression-free survival (PFS). RESULTS: After the median 16.6months of follow-up, the unfavorable EGFR rs2293347AA or GA  genotype was significantly correlated with shorter OS (AA vs. GG: 2.0 vs. 21.0months; hazard ratio (HR)=2.44, 95% confidence interval (CI)=1.06-5.56; P=0.036; GA vs. GG: 15.0 vs. 21.0months; HR=1.75, 95%CI=1.08-2.86, P=0.025) compared with the favorable rs2293347GG genotype. The prognostic significance of  EGFR rs4947492 polymorphism on OS also existed (GG carriers vs. AA carriers: median OS=24.6 vs. 14.9months, HR=0.29, 95%CI=0.10-0.83, P=0.021). No significant associations were found among other EGFR SNPs and survival. CONCLUSION: EGFR rs2293347 and rs4947492 SNPs might be potential predictive markers of OS in advanced lung adenocarcinoma patients treated with Gefitinib.

 

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[45]

TÍTULO / TITLE:  - Video-assisted vs open mediastinal lymphadenectomy for Stage I non-small-cell lung cancer: results of a prospective randomized trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs668

AUTORES / AUTHORS:  - Palade E; Passlick B; Osei-Agyemang T; Gunter J; Wiesemann S

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Medical Center Freiburg, Freiburg, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: Since the introduction of video-assisted lobectomy for non-small-cell lung cancer (NSCLC) into clinical practice, it has been discussed controversially whether mediastinal lymphadenectomy can be performed as effectively as an open procedure via thoracotomy. Therefore, we address this issue in a prospective randomized trial conducted in our institution. METHODS: In total, 66 patients with completely staged clinical Stage I NSCLC were included and randomized either into a video-assisted group (n = 34) or into the conventional lobectomy group (n  = 32). The video-assisted thoracoscopic (VATS) lobectomy was performed by using a 4- to 5-cm utility incision in the fourth or fifth intercostal space and two additional 10-mm ports without rib spreading. The conventional lobectomy was done via an anterolateral thoracotomy. Lymph nodes were classified according to the International Association for the Study of Lung Cancer classification; for right-sided tumours, lymph nodes number 2R, 4R, 7, 8, 9, 10, 11 and 12 were dissected, and for left-sided tumours, lymph nodes number 5, 6, 7, 8, 9, 10, 11 and 12. For the subsequent analyses, lymph nodes were grouped into different zones consisting of Zone 1 (2R and 4R), Zone 2 (7), Zone 3 (8R and 9R), Zone 4 (10R, 11R and 12R), Zone 5 (4L), Zone 6 (5 and 6), Zone 7 (8L and 9L) and Zone 8  (10L, 11L and 12L). RESULTS: Both groups were comparable with respect to different clinical pathological parameters (age, tumour size and comorbidity). In the video-assisted group, 2 patients were excluded due to conversion to an open thoracotomy. The number of mediastinal lymph nodes removed was as follows: VATS (right side) 24.0 lymph nodes/patient, open right-sided 25.2 lymph nodes/patient, VATS (left side) 25.1 lymph nodes/patient and open left-sided 21.1 lymph nodes/patient. With respect to the zones mentioned above, we found the following  results: VATS vs open (mean number of lymph nodes/patient): Zone 1: 9 vs 8.5; Zone 2: 6.3 vs 5.6; Zone 3: 2.4 vs 3.2; Zone 4: 6.5 vs 6.9; Zone 5: 0 vs 0.5; Zone 6: 3.2 vs 3.7; Zone 7: 4.6 vs 3.2 and Zone 8: 10.5 vs 8.9. There were no statistically significant differences between the procedures, either with respect to the overall number of lymph nodes or with respect to the number of lymph nodes in each zone. CONCLUSIONS: Mediastinal lymph node dissection can be performed as  effectively by the video-assisted approach as by the open thoracotomy approach. Furthermore, the video-assisted approach allows a better visualization of different lymph node zones.

 

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[46]

TÍTULO / TITLE:  - CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 15;73(2):571-82. doi: 10.1158/0008-5472.CAN-12-0263. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-0263

AUTORES / AUTHORS:  - Saintigny P; Massarelli E; Lin S; Ahn YH; Chen Y; Goswami S; Erez B; O’Reilly MS; Liu D; Lee JJ; Zhang L; Ping Y; Behrens C; Solis Soto LM; Heymach JV; Kim ES; Herbst RS; Lippman SM; Wistuba II; Hong WK; Kurie JM; Koo JS

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Thoracic/Head & Neck Medical Oncology, Radiation Oncology, Biostatistics and Applied Mathematics, Bioinformatics and Computational Biology, Pathology, and Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas; Section of Medical Oncology,  Yale Cancer Center, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.

RESUMEN / SUMMARY:  - CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small-molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC.  Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in  52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a  cluster driven by CXCL5 and associated with smoking, poor prognosis, and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. Cancer Res; 73(2); 571-82. ©2012 AACR.

 

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[47]

TÍTULO / TITLE:  - A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non-Small Cell Lung Cancer with a KRAS Mutation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-1779

AUTORES / AUTHORS:  - Dingemans AM; Mellema WW; Groen HJ; van Wijk A; Burgers SA; Kunst PW; Thunnissen E; Heideman DA; Smit EF

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Department of Pulmonary Diseases and GROW- School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht; Departments of Pulmonology and Pathology, VU University Medical Center; Department of Thoracic Oncology, Netherlands Cancer Institute; Department of Pulmonology, Academic Medical Center, Amsterdam; and Department of Pulmonology, University Medical Center Groningen, Groningen, the Netherlands.

RESUMEN / SUMMARY:  - PURPOSE: Sorafenib inhibits the Ras/Raf pathway, which is overactive in cancer patients with a KRAS mutation. We hypothesized that patients with non-small cell  lung cancer (NSCLC) with KRAS mutation will benefit from treatment with sorafenib.EXPERIMENTAL DESIGN: In this phase II study, patients with KRAS-mutated, stage IIIb or IV NSCLC that progressed after at least one platinum-containing regimen were treated with sorafenib. Treatment consisted of sorafenib 400 mg twice daily until disease progression or unacceptable toxicity.  Pretreatment serum from each patient was obtained to predict outcome using a proteomic assay (VeriStrat). Primary endpoint was disease control rate (DCR) at 6 weeks.RESULTS: Fifty-nine patients were entered between May 2010 and February 2011. Fifty-seven patients started sorafenib. Mean age was 58.5 (SD = +/-8.1) years, 16 male/41 female, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1/2 24/30/3. At 6 weeks, 5 partial response, 25 stable disease, and 27 progressive disease were observed; DCR was 52.6%. Median duration of treatment was 9 weeks. The median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 5.3 months. Patients with a prediction of good prognosis according to VeriStrat serum proteomics assay showed a significantly superior PFS [HR, 1.4; 95% confidence interval (CI), 1.0-1.9] but not OS (HR, 1.3; 95% CI, 0.9-1.7). Sorafenib-related grade III/IV toxicity was reported in 10 patients (17.5%); all but one patient experienced grade III skin toxicity (14.0%) or grade III gastrointestinal toxicity (8.8%).CONCLUSION: Treatment with sorafenib has relevant clinical activity in patients with NSCLC harboring KRAS mutations. Further randomized study with this agent is warranted as single-agent  or combination therapy. Clin Cancer Res; 19(3); 1-9. ©2012 AACR.

 

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[48]

TÍTULO / TITLE:  - Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease  in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 19. pii: S0360-3016(12)03769-8. doi: 10.1016/j.ijrobp.2012.11.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.011

AUTORES / AUTHORS:  - Feddock J; Arnold SM; Shelton BJ; Sinha P; Conrad G; Chen L; Rinehart J; McGarry RC

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky. Electronic address: jmfedd0@uky.edu.

RESUMEN / SUMMARY:  - PURPOSE: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. METHODS AND MATERIALS: Patients without metastatic disease and with radiologic evidence of limited residual disease (</=5 cm) within the site of the  primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy x 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy x 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade >/=3 radiation pneumonitis (RP). RESULTS: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP.  Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. CONCLUSIONS: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy .

 

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[49]

TÍTULO / TITLE:  - Association of Depression and Anxiety on Quality of Life, Treatment Adherence, and Prognosis in Patients with Advanced Non-small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2793-5

AUTORES / AUTHORS:  - Arrieta O; Angulo LP; Nunez-Valencia C; Dorantes-Gallareta Y; Macedo EO; Martinez-Lopez D; Alvarado S; Corona-Cruz JF; Onate-Ocana LF

INSTITUCIÓN / INSTITUTION:  - Thoracic Oncology Clinic, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico, ogar@servidor.unam.mx.

RESUMEN / SUMMARY:  - BACKGROUND: Symptoms of depression and anxiety are common in patients with lung cancer and may produce an impact on both health-related quality of life (HRQL) and survival. The aim of the present study was to evaluate the association of depression and anxiety on HRQL, treatment adherence, and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: This is a prospective study of  patients with stage IIIB or IV NSCLC. Depression and anxiety were measured using  the hospital anxiety and depression scale, the International Neuropsychiatric Interview, and the HRQL with the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Instruments were applied before treatment and repeated at 3 and 6 months. Lack of treatment adherence was considered as patients who stopped going to their consultation appointments. RESULTS: A total of 82 patients were included. At the  initial evaluation, depression and anxiety were found in 32.9 and 34.1 % of patients, respectively. Depression was associated with feminine gender (p = 0.034) and poor performance status (p = 0.048). Depression and anxiety showed an  association with HRQL. Patients with depression showed median overall survival of 6.8 months, whereas that for nondepressed patients was 14 months (hazard ratio [HR], 1.9; 95 % confidence interval (95 % CI), 1.03-3.7; p = 0.042). The 58 % of  patients with depression had poor treatment adherence versus 42 % of patients without depression (p = 0.004). CONCLUSIONS: Depression and anxiety were present  in one-third of patients with recently diagnosed NSCLC. Depression and anxiety were associated with decreased HRQL scales, and depression was independently associated with treatment adherence and with poor prognosis.

 

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[50]

TÍTULO / TITLE:  - Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcome in Resected Non-Small Cell Lung Cancer Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827a7e7a

AUTORES / AUTHORS:  - Ragusa M; Vannucci J; Ludovini V; Bianconi F; Treggiari S; Tofanetti FR; Flacco A; Colella R; Sidoni A; Crino L; Puma F

INSTITUCIÓN / INSTITUTION:  - *Thoracic Surgery Unit parallelInstitute of Pathological Anatomy and Histology, University of Perugia Medical School daggerMedical Oncology Division, S. Maria della Misericordia Hospital double daggerDepartment of Electronic and Information Engineering, University of Perugia, Perugia section signThoracic Surgery Unit, S. Camillo Forlanini Hospital, Roma, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES:: Surgery yields best results for non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC.  Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC. METHODS:: We analyzed the clinical characteristics and outcome data for 230 patients who underwent resection at our institution for stage I to III NSCLC. The tumors were assessed for both EGFR (exons 18 to 21) and KRAS (exons 2 and 3) mutations by nested polymerase chain reaction and sequenced in both sense and antisense direction. Kaplan-Meier estimates of overall survival and disease-free  survival were calculated for clinical and biological variables using Cox model. RESULTS:: EGFR and KRAS mutations were detected in 22 (9.6%) and 39 (16.9%) patients, respectively. In the whole population, both EGFR and KRAS mutations were significantly correlated with adenocarcinoma (ADC). Overall, EGFR mutations  were more frequent in women (P<0.0001) and in nonsmokers (P<0.0001). In the ADC/BAC group, KRAS mutations were more frequent in man (P<0.02) and EGFR mutations (exon 19 deletion and L858R) demonstrated a tendency towards worse disease-free survival (P=0.056). No difference in outcome was seen between patients harboring KRAS mutations compared with KRAS wild type. CONCLUSIONS:: EGFR and KRAS mutations are frequent in ADCs and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.

 

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[51]

TÍTULO / TITLE:  - Oncogenic driver mutations in patients with non-small-cell lung cancer at various clinical stages.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2012 Dec 30.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds626

AUTORES / AUTHORS:  - Zhou JX; Yang H; Deng Q; Gu X; He P; Lin Y; Zhao M; Jiang J; Chen H; Lin Y; Yin W; Mo L; He J

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Ningbo University School of Medicine, Ningbo.

RESUMEN / SUMMARY:  - BackgroundOncogenic driver mutations are responsible for the initiation and maintenance of non-small-cell lung cancer (NSCLC). Elucidation of driver mutation occurrence in NSCLC has important clinical implications.Patients and methodsNSCLC at various clinical stages were studied for their oncogenic mutations and their association with patients’ disease-free survival (DFS).ResultsOf 488 patients with NSCLC, 28 had EML4-ALK fusions. Female, young age (<60 years old), and nonsmoker patients had significant greater mutation frequencies than male, old age (>/=60 years old), and smoker patients, respectively (P<0.05). Of 392 patients with NSCLC, 13 had PIK3CA mutations and 3 had MEK1 mutations. EML4-ALK,  PIK3CA, and MEK1 mutations were mutually exclusive. EML4-ALK fusion was found to  be of coexistence with EGFR and KRAS mutations in two cases. In stage IA NSCLC, EML4-ALK-positive patients had longer DFS than EML4-ALK-negative patients (P = 0.04). However, in stage IIIA NSCLC, EML4-ALK-positive patients had poorer DFS than EML4-ALK-negative patients (P < 0.01). Moreover, multivariate analysis indicated that in stage IIIA NSCLC EML4-ALK fusion was the only significant indicator for poor DFS (P < 0.001). Furthermore, tumors with EML4-ALK fusions had significantly higher levels of ERCC1, a molecule with a key role in platinum drug efficacy, than tumors without EML4-ALK fusions.ConclusionEML4-ALK, PIK3CA, and MEK1 mutations occurred in NSCLC with various distinct clinicopathological characteristics. EML4-ALK fusions could serve as a significant prognostic indicator for locally advanced NSCLC.

 

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[52]

TÍTULO / TITLE:  - High expression of FOXC1 is associated with poor clinical outcome in non-small cell lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0629-3

AUTORES / AUTHORS:  - Wei LX; Zhou RS; Xu HF; Wang JY; Yuan MH

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Tangdu Hospital, Fourth Military Medical University, No. 1, Xinsi Rd, Xi’an, 710038, China.

RESUMEN / SUMMARY:  - The aim of this study was to detect FOXC1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Expressional levels of FOXC1 mRNA and protein in 30 cases of NSCLC and corresponding non-tumor tissue samples were examined by quantitative real-time PCR and Western blotting. Immunohistochemistry was performed to detect the expression of FOXC1 in 125 NSCLC tissues. We found that the expression levels of  FOXC1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level FOXC1 expression was correlated with  poor tumor differentiation, tumor-node-metastasis stage, and lymph node metastasis. Patients with high expression levels of FOXC1 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high FOXC1 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of FOXC1 may play an important  role in the progression of NSCLC, and FOXC1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

 

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[53]

TÍTULO / TITLE:  - Phase I Clinical and Pharmacokinetic Study of Bi-weekly Carboplatin/Paclitaxel Chemotherapy in Elderly Patients with Advanced Non-small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):261-6.

AUTORES / AUTHORS:  - Tsubata Y; Okimoto T; Miura K; Karino F; Iwamoto S; Tada M; Honda T; Hamaguchi S; Ohe M; Sutani A; Kuraki T; Hamada A; Isobe T

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Division of Medical Oncology & Respiratory Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. isobeti@med.shimane-u.ac.jp.

RESUMEN / SUMMARY:  - Aim: We evaluated the pharmacokinetics and quality of life of elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with bi-weekly carboplatin and paclitaxel chemotherapy, and determined the maximum tolerated dose (MTD) of this treatment. PATIENTS AND METHODS: Eligible patients had histologically- or cytologically-proven inoperable NSCLC, age of 70 years or older, no prior treatment, and Eastern Cooperative Oncology Group performance status 0-2. Paclitaxel was administered in combination with carboplatin under a bi-weekly schedule. We determined the plasma concentrations of both drugs during  therapy. RESULTS: The median patient age was 80 years. Using carboplatin at AUC 3, the MTD of paclitaxel was 100 mg/m(2). Both hematological and non-hematological toxicities were mostly mild and manageable. Although paclitaxel is predominantly metabolized in the liver, clearance was decreased in patients with lower estimated glomerular filtration rate. CONCLUSION: Bi-weekly treatment, as described here, is feasible for elderly patients as a conventional regimen, particularly in the outpatient setting, due to its lower toxicity.

 

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[54]

TÍTULO / TITLE:  - Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15;108(1):179-82. doi: 10.1038/bjc.2012.575. Epub 2012 Dec  20.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.575

AUTORES / AUTHORS:  - Henson KE; McGale P; Taylor C; Darby SC

INSTITUCIÓN / INSTITUTION:  - Clinical Trial Service Unit (CTSU), University of Oxford, Richard Doll Building,  Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.

RESUMEN / SUMMARY:  - Background:Radiation-related heart disease and lung cancer can occur following radiotherapy for breast cancer but the duration of any mortality risk is uncertain.Methods:Mortality ratios, by laterality of breast cancer, were estimated using Poisson regression for 558 871 women recorded with breast cancer  during 1973-2008 in the Surveillance, Epidemiology and End Results (SEER) cancer  registries and followed until 01 January 2009.Results:For women diagnosed with breast cancer during 1973-1982 and given radiotherapy shortly afterwards, the cardiac mortality ratios, left-sided vs right-sided, were 1.19 (1.03-1.38), 1.35  (1.05-1.73), 1.64 (1.26-2.14) and 1.90 (1.52-2.37) at <10, 10-14, 15-19 and 20+ years since diagnosis (2p for trend: <0.001). The lung cancer mortality ratios, ipsilateral vs contralateral, in these women were 1.05 (0.57-1.94), 2.04 (1.28-3.23) and 3.87 (2.19-6.82) at <10, 10-19 and 20+ years, respectively, (2p for trend: 0.002). For women irradiated during 1983-92 there was evidence of radiation-related mortality for lung cancer, but not for heart disease. For women irradiated since 1993 there is, as yet, little evidence of any radiation-related  mortality.Conclusion:In this population, the radiation-related risks were larger  in the third decade after exposure than during the first two decades.

 

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[55]

TÍTULO / TITLE:  - Napsin A is differentially expressed in sclerosing hemangiomas of the lung.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec;136(12):1580-4. doi: 10.5858/arpa.2011-0486-OA.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2011-0486-OA

AUTORES / AUTHORS:  - Schmidt LA; Myers JL; McHugh JB

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109-0054, USA. lindschm@med.umich.edu

RESUMEN / SUMMARY:  - CONTEXT: Sclerosing hemangiomas (SH) are lung tumors characterized by surface cuboidal cells and round stromal cells. The cell of origin remains controversial, though immunohistochemical and ultrastructural studies suggest primitive respiratory epithelium. Napsin A, a human aspartic proteinase found primarily in  type II pneumocytes and alveolar macrophages, is emerging as a helpful immunohistochemical marker in characterizing the origin of lung neoplasms, and may be of use in evaluating SH. OBJECTIVE: To evaluate napsin A immunohistochemical staining in SH to further characterize the cell of origin. DESIGN: Six cases of SH were stained for napsin A, as well as thyroid transcription factor 1 and cytokeratin in selected cases. RESULTS: Surface and round cells were positive for thyroid transcription factor 1 in all cases stained with this marker. Cytokeratins were positive in surface cells in all cases stained with this marker; 2 cases had focal cytokeratin staining in round cells.  Round cells had focal napsin A staining in 1 case (17%); surface cells were napsin positive in all cases. CONCLUSIONS: The observation of thyroid transcription factor 1 positivity in both surface and round cells in all SH suggests primitive respiratory epithelium as the cell of origin of SH. Our napsin A findings support this, with positivity in surface cells of all tumors (100%), and focal round cell staining in only 1 (17%). In fact, surface cells may represent entrapped type II pneumocytes, which normally express napsin A in a granular cytoplasmic pattern, similar to surface cells. The coexpression of thyroid transcription factor 1 and napsin A also introduces a caveat in differentiating primary pulmonary adenocarcinomas from SH in small biopsy specimens.

 

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[56]

TÍTULO / TITLE:  - Timeliness of cancer care from diagnosis to treatment: a comparison between patients with breast, colon, rectal or lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Qual Health Care. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1093/intqhc/mzt003

AUTORES / AUTHORS:  - Li X; Scarfe A; King K; Fenton D; Butts C; Winget M

INSTITUCIÓN / INSTITUTION:  - 1Cancer Care, Alberta Health Services, Edmonton, Alberta, Canada.

RESUMEN / SUMMARY:  - OBJECTIVE: /st>The purpose of this study was to assess the value in measuring specific time intervals across cancer sites to identify potentially important variation in the timeliness of cancer care that may inform needed changes and/or  improvements in coordination of care. DESIGN: /st>Retrospective population-level  study. Demographic and treatment information were obtained from the Alberta Cancer Registry. Date of oncologist-consult was obtained from cancer medical records. SETTING: /st>Alberta, Canada. PARTICIPANTS: /st>All patients diagnosed in 2005 with breast, colon, rectal or lung cancer who were residents of Alberta,  Canada. MAIN OUTCOME MEASURES: /st>(i) Number of days from diagnosis to first treatment by treatment modality and cancer site, (ii) number of days from surgery to post-surgery consultation and subsequent treatment and (iii) relationship between clinical and demographic factors and the cancer-specific provincial median time for outcome measures (i) and (ii). RESULTS: /st>Time from diagnosis to surgery, if first treatment, was approximately 4 months for lung cancer compared with 1-2 months for breast and colorectal cancers. Factors associated with this time interval for breast and colorectal cancers was stage at diagnosis  but was region of residence for lung cancer. CONCLUSIONS: /st>Important variation within and across cancer sites identified in the care intervals evaluated in this study provides relevant information to inform local areas for improvement. Comparisons of these intervals across healthcare systems may also provide insights into strengths of different models for coordinating care.

 

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[57]

TÍTULO / TITLE:  - The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care - an observational analysis on non-small-cell lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Support Care Cancer. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-012-1711-5

AUTORES / AUTHORS:  - Ihbe-Heffinger A; Paessens B; Berger K; Shlaen M; Bernard R; von Schilling C; Peschel C

INSTITUCIÓN / INSTITUTION:  - Hospital Pharmacy Department, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675, Munchen, Germany, Angela.Ihbe-Heffinger@lrz.tum.de.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate frequency and severity of adverse drug reactions (ADRs) and  its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. RESULTS: A total  of 120 consecutive NSCLC patients (mean age, 63.0 +/- 8.4 (SD) years; men, 64.2 %; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3 %; tumour stage III/IV, 85 %; history of comorbidity, 93.3 %) receiving 130 CT lines were evaluated. 80 % of CT lines were associated with grade 3 or 4 ADRs, 22.3 % developed potential life-threatening complications, 77.7 % were associated with at least one hospital stay (inpatient, 63.9 %; outpatient/day clinic 39.2 %, ICU  6.9 %), with a mean cumulative number of 12.8 (+/-14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to <euro>3,366 (<euro>1,406) and were found to be higher for first-line compared to second-line  treatment: <euro>3,677 (<euro>1,599) vs. <euro>2,475 (<euro>518). TMC-TL were particularly high in CT lines with ICU care <euro>12,207 (<euro>9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with  ICU care accounted for 25 % of total expenses (<euro>109,861 out of <euro>437,580). CONCLUSIONS: In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients’ clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.

 

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[58]

TÍTULO / TITLE:  - Functional polymorphisms in NFkappaB1/IkappaBalpha predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Genet. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00439-013-1264-9

AUTORES / AUTHORS:  - Huang D; Yang L; Liu Y; Zhou Y; Guo Y; Pan M; Wang Y; Tan Y; Zhong H; Hu M; Lu W; Ji W; Wang J; Ran P; Zhong N; Zhou Y; Lu J

INSTITUCIÓN / INSTITUTION:  - School of Public Health, The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou, 510182, China.

RESUMEN / SUMMARY:  - Lung inflammation is the major pathogenetic feature for both chronic obstructive  pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFkappaB) and its inhibitor (IkappaB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFkappaB/IkappaB confer consistent risks for COPD and lung cancer. Four putative functional SNPs (NFkappaB1: -94del>insATTG; NFkappaB2: -2966G>A; IkappaBalpha: -826C>T, 2758G>A)  were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the -94ins ATTG variants (ins/del + ins/ins)  in NFkappaB1 conferred an increased risk of COPD (OR 1.27, 95 % CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline (P = 0.015). The 2758AA variant in IkappaBalpha had an increased risk of lung cancer (OR 1.53, 95  % CI 1.30-1.80) by decreasing IkappaBalpha expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the -94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for -2966G>A and -826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFkappaB1 (-94del>ins ATTG) or IkappaBalpha (2758G>A) to predict risk of COPD or lung cancer.

 

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[59]

TÍTULO / TITLE:  - Combined Treatment With Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Ligands and Gamma Radiation Induces Apoptosis by PPARgamma-Independent Up-Regulation of Reactive Oxygen Species-Induced Deoxyribonucleic Acid Damage Signals in Non-Small Cell Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Jan 16. pii: S0360-3016(12)03838-2. doi: 10.1016/j.ijrobp.2012.11.040.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.040

AUTORES / AUTHORS:  - Han EJ; Im CN; Park SH; Moon EY; Hong SH

INSTITUCIÓN / INSTITUTION:  - Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: To investigate possible radiosensitizing activities of the well-known peroxisome proliferator-activated receptor (PPAR)gamma ligand ciglitazone and novel PPARgamma ligands CAY10415 and CAY10506 in non-small cell lung cancer (NSCLC) cells. METHODS AND MATERIALS: Radiosensitivity was assessed using a clonogenic cell survival assay. To investigate the mechanism underlying PPARgamma ligand-induced radiosensitization, the subdiploid cellular DNA fraction was analyzed by flow cytometry. Activation of the caspase pathway by combined PPARgamma ligands and gamma-radiation treatment was detected by immunoblot analysis. Reactive oxygen species (ROS) were measured using 2,7-dichlorodihydrofluorescein diacetate and flow cytometry. RESULTS: The 3 PPARgamma ligands induced cell death and ROS generation in a PPARgamma-independent manner, enhanced gamma-radiation-induced apoptosis and caspase-3-mediated poly (ADP-ribose) polymerase (PARP) cleavage in vitro. The combined PPARgamma ligand/gamma-radiation treatment triggered caspase-8 activation, and this initiator caspase played an important role in the combination-induced apoptosis. Peroxisome proliferator-activated receptor-gamma ligands may enhance the gamma-radiation-induced DNA damage response, possibly by  increasing gamma-H2AX expression. Moreover, the combination treatment significantly increased ROS generation, and the ROS scavenger N-acetylcysteine inhibited the combined treatment-induced ROS generation and apoptotic cell death. CONCLUSIONS: Taken together, these results indicated that the combined treatment  of PPARgamma ligands and gamma-radiation synergistically induced DNA damage and apoptosis, which was regulated by ROS.

 

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[60]

TÍTULO / TITLE:  - Docetaxel plus cisplatin and bevacizumab for untreated patients with advanced/metastatic non-squamous non-small-cell lung cancer: a multicenter phase  II study of the Hellenic Oncology Research Group.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2037-1

AUTORES / AUTHORS:  - Kentepozidis N; Kotsakis A; Soultati A; Agelaki S; Christophylakis C; Agelidou M; Chelis L; Papakotoulas P; Vamvakas L; Zafiriou Z; Samonis G; Georgoulias V

INSTITUCIÓN / INSTITUTION:  - Hellenic Oncology Research Group (HORG), 55, Lombardou Str, 114 74, Athens, Greece, kentenik@hotmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting. METHODS: Chemotherapy-naive patients (n = 48) with measurable, histologically confirmed non-squamous, IIIB (wet)/IV NSCLC, and PS 0-2 were eligible. Patients received D (75 mg/m(2) IV), C (80 mg/m(2) IV), and B (15 mg/kg IV) every 3 weeks. Maintenance of bevacizumab was not mandatory. RESULTS: Complete and partial responses were achieved in two (4.2 %) and 14 (29.2 %) patients, respectively [overall response rate: 33.3 %; 95 % CI = 20.0-46.7 %], whereas stable disease was documented in 14 [disease control rate = 62.5 %; 95 % CI = 48.8-76.2 %]. The  median progression-free survival was 4.4 months and the median overall survival 13.3 months. Treatment-related grade 3 or 4 hematologic adverse events were leukopenia, neutropenia, and anemia in 8.4, 18.7, and 2.1 % of the patients, respectively. Febrile neutropenia occurred in three (6.3 %) patients. Bleeding was documented in 4 % of the patients, thrombotic episodes in 8 %, and proteinuria in 3 %. There was one treatment-related death. CONCLUSIONS: Frontline DCB in patients with advanced non-squamous NSCLC is an active regimen with manageable toxicity and merits to be further investigated.

 

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[61]

TÍTULO / TITLE:  - Gratitude in the Setting of Stage IV Lung Cancer: How Innovative Caregivers Help  the Success of Treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Intern Med. 2013 Jan 1;158(1):71-2. doi: 10.7326/0003-4819-158-1-201301010-00016.

            ●● Enlace al texto completo (gratuito o de pago) 7326/0003-4819-158-1-201301010-00016

AUTORES / AUTHORS:  - Webster NJ

 

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[62]

TÍTULO / TITLE:  - Survival difference in NSCLC and SCLC patients with diabetes mellitus according to the first-line therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):367. doi: 10.1007/s12032-012-0367-9. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0367-9

AUTORES / AUTHORS:  - Nakazawa K; Kurishima K; Tamura T; Ishikawa H; Satoh H; Hizawa N

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-city, Ibaraki, Japan.

RESUMEN / SUMMARY:  - The aim of this study was to examine the survival difference between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients with diabetes mellitus (DM) according to the first-line therapy. All patients with lung cancer  diagnosed at our hospitals between April 1999 and March 2011 were retrospectively analyzed. The definition of DM was strictly determined and included fasting plasma glucose and HbA1c levels. The patients were divided into 2 groups: those with DM (DM group) and those without DM (non-DM group). For each treatment type,  the survival of these 2 groups was evaluated. For NSCLC patients overall, the difference in survival between the DM group and the non-DM group was not significant (p = 0.112). However, in surgically treated NSCLC patients, the difference in survival between the 2 groups was significant (p = 0.022). In chemotherapy-treated NSCLC patients, the difference in survival between the 2 groups was not significant (p = 0.942). On the other hand, for SCLC patients overall, the difference in survival between the DM group and the non-DM group was significant (p = 0.012). In chemotherapy-treated SCLC patients, the difference in survival between the 2 groups was significant (p = 0.026). The influence of DM may differ between NSCLC and SCLC patients. At the current treatment level for unresectable NSCLC, the influence of DM might not be the same for NSCLC patients  treated with surgery as for SCLC patients treated with chemotherapy. Elucidation  of the mechanism by which hyperglycemia influences the progression of lung cancer will improve survival in lung cancer patients with DM.

 

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[63]

TÍTULO / TITLE:  - The Noncoding RNA MALAT1 Is a Critical Regulator of the Metastasis Phenotype of Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2850

AUTORES / AUTHORS:  - Gutschner T; Hammerle M; Eissmann M; Hsu J; Kim Y; Hung G; Revenko A; Arun G; Stentrup M; Gross M; Zornig M; Macleod AR; Spector DL; Diederichs S

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Helmholtz-University-Group “Molecular RNA Biology & Cancer,” German Cancer Research Center DKFZ & Institute of Pathology; Institute of Pathology, University Hospital Heidelberg, Heidelberg; Georg-Speyer-Haus, Frankfurt am Main, Germany; ISIS Pharmaceuticals, Carlsbad, California; and Cold  Spring Harbor Laboratory, Cold Spring Harbor, New York.

RESUMEN / SUMMARY:  - The long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant transcript 2), is a highly conserved nuclear noncoding RNA (ncRNA) and a predictive marker for metastasis development in lung cancer. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements using zinc finger nucleases. The achieved 1,000-fold MALAT1 silencing provides a unique loss-of-function model. Proposed mechanisms of action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft. Antisense oligonucleotides (ASO) blocking MALAT1 prevent metastasis formation after tumor implantation. Thus, targeting MALAT1 with ASOs provides a potential therapeutic approach to prevent lung cancer metastasis with this ncRNA serving as both predictive marker and therapeutic target. Finally, regulating gene expression, but not alternative splicing, is the critical function of MALAT1 in lung cancer metastasis. In summary, 10 years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis. Cancer Res; 73(3); 1-10. ©2012 AACR.

 

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[64]

TÍTULO / TITLE:  - KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2754-z

AUTORES / AUTHORS:  - Guan JL; Zhong WZ; An SJ; Yang JJ; Su J; Chen ZH; Yan HH; Chen ZY; Huang ZM; Zhang XC; Nie Q; Wu YL

INSTITUCIÓN / INSTITUTION:  - Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

RESUMEN / SUMMARY:  - BACKGROUND: The prognostic and predictive value of KRAS mutations in patients with lung cancer is controversial. Biases in disease stage, treatment regimen, small-scale patient studies, and biomarker status have led to inconsistent results in previous reports. METHODS: The KRAS and EGFR genes were examined in 1935 consecutive patients with non-small cell lung cancer. All patients were divided into KRAS mutation (KRAS group), EGFR mutation (EGFR group), and KRAS/EGFR wild type (WT group) groups. Randomly selected cases were paired with patients with the KRAS mutation, the EGFR mutation, and KRAS/EGFR wild type patients according to tumor, node, metastasis stage, time of first visit within 1 year, and pathology. Progression-free survival (PFS) and overall survival were evaluated by Kaplan-Meier and Cox models. RESULTS: The KRAS mutation rate for lung adenocarcinoma was 5.90 %. The overall survival was 14.47, 20.57, and 42.73  months for the KRAS group, WT group, and EGFR group, respectively (P < 0.001). Multivariate analysis indicated that KRAS mutation status was an independent prognostic factor (hazard ratio 2.69, 95 % confidence interval 1.91-3.80, P < 0.001). No difference was found in PFS and tumor responsiveness between patients  with a KRAS mutation and those with wild type KRAS/EGFR for chemotherapy and EGFR tyrosine kinase inhibitors (TKI). PFS did not significantly differ for chemotherapy among the three groups (P = 0.270). CONCLUSIONS: KRAS mutation is a  poor prognosis factor, but it is not an independent predictor of response to EGFR-TKI or chemotherapy in patients with lung cancer.

 

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[65]

TÍTULO / TITLE:  - DICER1, DROSHA and miRNAs in patients with non-small cell lung cancer: implications for outcomes and histologic classification.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt022

AUTORES / AUTHORS:  - Diaz-Garcia CV; Agudo-Lopez A; Perez C; Lopez-Martin JA; Rodriguez-Peralto JL; de Castro J; Cortijo A; Martinez-Villanueva M; Iglesias L; Garcia-Carbonero R; Fresno-Vara JA; Gamez-Pozo A; Palacios J; Cortes-Funes H; Paz-Ares L; Agullo-Ortuno MT

INSTITUCIÓN / INSTITUTION:  - Oncology Department. Hospital Universitario 12 de Octubre, Madrid, 28041, España.

RESUMEN / SUMMARY:  - The clinical and functional significance of RNA interference machinery in lung cancer is poorly understood. Besides, microRNAs have the potential to serve both  as biomarkers and therapeutic agents, by personalizing diagnosis and therapy. In  this study, we investigated whether the expression levels of DICER1 and DROSHA, components of the RNA-interference machinery, can predict survival, and whether microRNA expression profiles can differentiate histologic subtypes in non-small cell lung cancer (NSCLC). Levels of DICER1, DROSHA and five different microRNAs was measured in NSCLC specimens (N=115) by qRT-PCR assay, and correlated with clinical outcomes. Low expression of DROSHA was associated with an increased median survival (154.2 vs 39.8 months; P=0.016). Also, high DROSHA expression was associated with decreased median survival in the following subgroups: adenocarcinoma (P=0.011), grade III tumors (P=0.038), and low stage patients (P=0.014). In multivariate analyses we found two independent predictors of reduced disease-specific survival: high DROSHA expression (HR=2.24; P=0.04), and  advanced tumor stage (HR=1.29; P=0.02). In general, the overall tumor miRNA expression was downregulated inour cohort compared to normal tissues. Expression  level of hsa-let-7a (P=0.005) and miR-16 (P=0.003) miRNA were significantly higher in squamous cell carcinoma than in adenocarcinoma samples. The present study supports the value of the expression profiling of the components of the miRNA-processing machinery in the prognosis of NSCLC patients, especially DROSHA  expression levels. In addition, differential expression of miRNAs, such as hsa-let-7a and miR-16 may be helpful tools in the histologic subclassification of NSCLC.

 

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[66]

TÍTULO / TITLE:  - The Impact of Clinical Outcomes According to EGFR Mutation Status in Patients with Locally Advanced Lung Adenocarcinoma Who Recieved Concurrent Chemoradiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31826e04f9

AUTORES / AUTHORS:  - Akamatsu H; Kaira K; Murakami H; Serizawa M; Koh Y; Ono A; Shukuya T; Tsuya A; Nakamura Y; Kenmotsu H; Naito T; Takahashi T; Endo M; Harada H; Nakajima T; Yamamoto N

INSTITUCIÓN / INSTITUTION:  - Divisions of *Thoracic Oncology daggerDrug Discovery and Development double daggerDiagnostic Radiology section signRadiation Oncology parallelDiagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES:: Among patients with locally advanced lung adenocarcinoma, the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations was unknown. In addition, it has not been fully evaluated about the role of these mutations treated with concurrent chemoradiotherapy (CCR). METHODS:: The clinical records of locally advanced lung adenocarcinoma patients treated with CCR at Shizuoka Cancer Center between September 2002 and December 2009 were reviewed. RESULTS:: Forty-four patients were eligible for this study. EGFR mutation was detected in 13 (29.5%) of 44 patients, and KRAS mutation was detected in 2 (6.5%) of 31 patients. Among EGFR mutation status known patients, overall response rate, median progression-free survival (PFS), and median survival time were 52.3%, 11.5 months, and 35.8 months, respectively. Overall response rate was significantly higher in EGFR mutant group than in EGFR wild-type group (76.9% vs. 41.9%, P=0.02), but this difference did not translate into a significant PFS benefit (9.6 vs. 13.2 mo, P=0.78). Locoregional relapse occured less frequently in patients with EGFR mutation than those with EGFR wild-type, but not significant (15.4% vs. 32.3%, P=0.46). Brain was the most frequent metastatic site of relapse in EGFR mutant group. CONCLUSIONS:: Among locally advanced lung adenocarcinoma, EGFR mutation was detected in 29.5% and KRAS mutation was detected in 6.5%. We were not able to detect a difference in PFS or overall survival between EGFR mutant and wild-type patients treated with conventional CCR. Locoregional relapse was approximately half in the EGFR mutant group compared with the EGFR wild-type  group; however, this finding did not reach statistical significance.

 

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[67]

TÍTULO / TITLE:  - Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 25. pii: S0169-5002(13)00005-6. doi: 10.1016/j.lungcan.2012.12.022.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.022

AUTORES / AUTHORS:  - Li Y; Tang H; Sun Z; Bungum AO; Edell ES; Lingle WL; Stoddard SM; Zhang M; Jen J; Yang P; Wang L

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People’s Republic of China; Department of Health Sciences Research, Mayo Clinic, College of Medicine, Rochester, MN, USA.

RESUMEN / SUMMARY:  - Lung adenocarcinoma is the most common type of primary lung cancer. The purpose of this study was to delineate gene expression patterns for survival prediction in lung adenocarcinoma. Gene expression profiles of 82 (discovery set) and 442 (validation set 1) lung adenocarcinoma tumor tissues were analyzed using a systems biology-based network approach. We also examined the expression profiles  of 78 adjacent normal lung tissues from 82 patients. We found a significant correlation of an expression module with overall survival (adjusted hazard ratio  or HR=1.71; 95% CI=1.06-2.74 in discovery set; adjusted HR=1.26; 95% CI=1.08-1.49 in validation set 1). This expression module contained genes enriched in the biological process of the cell cycle. Interestingly, the cell cycle gene module and overall survival association were also significant in normal lung tissues (adjusted HR=1.91; 95% CI, 1.32-2.75). From these survival-related modules, we further defined three hub genes (UBE2C, TPX2, and MELK) whose expression-based risk indices were more strongly associated with poor 5-year survival (HR=3.85, 95% CI=1.34-11.05 in discovery set; HR=1.72, 95% CI=1.21-2.46 in validation set 1; and HR=3.35, 95% CI=1.08-10.04 in normal lung set). The 3-gene prognostic result was further validated using 92 adenocarcinoma tumor samples (validation set 2); patients with a high-risk gene signature have a 1.52-fold increased risk  (95% CI, 1.02-2.24) of death than patients with a low-risk gene signature. These  results suggest that a network-based approach may facilitate discovery of key genes that are closely linked to survival in patients with lung adenocarcinoma.

 

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[68]

TÍTULO / TITLE:  - Prognosis in patients with non-small cell lung cancer who received erlotinib treatment and subsequent dose reduction due to skin rash.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onkologie. 2012;35(12):747-52. doi: 10.1159/000345039. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345039

AUTORES / AUTHORS:  - Takashima N; Kimura T; Watanabe N; Umemura T; Katsuno S; Arakawa K; Fukatsu M; Nakamura N; Nishiyama O; Kataoka K; Kondoh Y; Taniguchi H

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy, Tosei General Hospital, Seto, Aichi, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Severe skin rash as toxicity of erlotinib has been reported in relation to better response and survival. However, some patients require dose reduction due to skin toxicities, and their prognosis remains uncertain. We retrospectively evaluated the clinical course of non-small cell lung cancer patients receiving erlotinib at a reduced dose because of skin rash. PATIENTS AND METHODS: Among 76 patients treated with erlotinib, 55 patients who developed skin rash severer than grade 2 were divided into 2 groups: 24 patients treated with erlotinib with dose reduction because of skin rash (dose reduction group) and 31  patients without any dose reduction (non-dose reduction group). RESULTS: The median progression-free survival in the dose reduction and non-dose reduction groups was 341 and 70 days, respectively, and the median overall survival was 566 and 202 days, respectively (p < 0.001). In the dose reduction group, no smoking history, female sex, epidermal growth factor receptor gene mutation, and grade 3  skin rash were significant baseline factors. CONCLUSIONS: Patients who received erlotinib at a reduced dose following skin rash showed better survival than those without reduction. In cases of intolerable skin rash, patients may benefit from continuous treatment with a reduced dose of erlotinib.

 

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[69]

TÍTULO / TITLE:  - Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):630-5. doi: 10.1073/pnas.1220425110.  Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1220425110

AUTORES / AUTHORS:  - Chen CY; Jan YH; Juan YH; Yang CJ; Huang MS; Yu CJ; Yang PC; Hsiao M; Hsu TL; Wong CH

INSTITUCIÓN / INSTITUTION:  - Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.

RESUMEN / SUMMARY:  - The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing alpha1,6-fucosylation in mammals, has been observed in several malignant cancers  including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely  unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as  well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial-mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of beta-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.

 

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[70]

TÍTULO / TITLE:  - Impact of dendritic cell vaccines pulsed with Wilms’ tumour-1 peptide antigen on  the survival of patients with advanced non-small cell lung cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2012 Dec 11. pii: S0959-8049(12)00889-1. doi: 10.1016/j.ejca.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.11.005

AUTORES / AUTHORS:  - Takahashi H; Okamoto M; Shimodaira S; Tsujitani SI; Nagaya M; Ishidao T; Kishimoto J; Yonemitsu Y

INSTITUCIÓN / INSTITUTION:  - Seren Clinic Tokyo, Tokyo, Japan. Electronic address: bzr06263@nifty.com.

RESUMEN / SUMMARY:  - PURPOSE: Dendritic cell (DC)-based vaccines have been expected to serve as new therapeutic approaches for advanced non-small cell lung cancers (NSCLCs); however, their clinical outcomes have not been fully elucidated. We report a single-centre clinical study analysing factors affecting the survival of patients with advanced NSCLCs who received DC vaccines pulsed with or without Wilms’ tumour protein-1 (WT1) peptide. METHODS: Among 62 patients with previously treated inoperable or postoperatively relapsed NSCLCs who met the inclusion criteria, DCs from 47 (76%) patients who showed HLA-A2402/0201/0206 were pulsed with one or more corresponding WT1 peptide antigens. DC vaccines were intradermally injected biweekly. RESULTS: Clinical responses based on response evaluation criteria in solid tumours (RECIST) were found in 31 (50%) patients at  3months after the first DC vaccine (complete response: 1 (1.6%), partial response: 4 (6.5%), stable disease: 26 (41.9%)). Median survival time was 27months (82% in 1year and 54% in 2years) from initial diagnosis, and that was 12months (48% in 1year and 22% in 2years) from the first DC vaccination. Importantly, multivariate analyses revealed that only two factors, blood haemoglobin and the use of WT1 peptides, significantly affected the overall survival of patients from both initial diagnosis and first vaccination. CONCLUSIONS: This study is the first to suggest that DC vaccines pulsed with WT1  may hold a significant impact to prolong the overall survival of patients with advanced NSCLCs.

 

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[71]

TÍTULO / TITLE:  - Activating Germline R776H Mutation in the Epidermal Growth Factor Receptor Associated With Lung Cancer With Squamous Differentiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.1586

AUTORES / AUTHORS:  - van Noesel J; van der Ven WH; van Os TA; Kunst PW; Weegenaar J; Reinten RJ; Kancha RK; Duyster J; van Noesel CJ

INSTITUCIÓN / INSTITUTION:  - Academic Medical Center, Amsterdam, the Netherlands.

 

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[72]

TÍTULO / TITLE:  - EGFR polymorphisms, hormone replacement therapy and lung adenocarcinoma risk: analysis from a genome-wide association study in never-smoking women.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs385

AUTORES / AUTHORS:  - Chen KY; Hsiao CF; Chang GC; Tsai YH; Su WC; Chen YM; Huang MS; Hsiung CA; Chen CJ; Yang PC

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan  University Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan.

RESUMEN / SUMMARY:  - Hormone replacement therapy (HRT) and epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) have been reported as risk factors for lung cancer in never smokers. We investigate the interaction of EGFR SNPs and HRT for lung adenocarcinoma risk in never-smoking women. This study included 532 never-smoking female lung adenocarcinoma patients and 532 controls, with EGFR SNPs retrieved from a genome-wide association study. The associations of EGFR SNPs with the lung adenocarcinoma risk were estimated by multivariate-adjusted logistic regression. The Haploview program was used to select tagged EGFR SNPs interacted with HRT and construct haplotype blocks. The Benjamini and Hochberg method was used to reduce the multiple testing effects. Among 84 EGFR SNPs retrieved, 11 tagging EGFR SNPs showed an interaction with HRT and lung adenocarcinoma risk, which were mostly located near the tyrosine kinase domain. Eight of the tagged SNPs were in two haplotype blocks. The interactions between HRT and numbers of protective EGFR SNP genotypes are significant in both blocks (P for interaction = 0.0004 and 0.0032, respectively). A trend of decrease in lung adenocarcinoma risk was found in subjects with HRT harboring an increasing number of protective EGFR SNP genotypes in both blocks (P = 0.0032 and 0.0046, respectively). In conclusion, HRT use may modify the association of EGFR SNPs with lung adenocarcinoma risk. The EGFR SNPs have a cumulative effect on decreasing lung adenocarcinoma risk in never-smoking women with HRT use.

 

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[73]

TÍTULO / TITLE:  - Predictors of grade >/= 2 and grade >/= 3 radiation pneumonitis in patients with  locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.747696

AUTORES / AUTHORS:  - Dang J; Li G; Ma L; Diao R; Zang S; Han C; Zhang S; Yao L

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The First Hospital of China Medical University  , Shenyang , China.

RESUMEN / SUMMARY:  - Grade >/= 3 radiation pneumonitis (RP) is generally severe and life-threatening.  Predictors of grade >/= 2 are usually used for grade >/= 3 RP prediction, but it  is unclear whether these predictors are appropriate. In this study, predictors of grade >/= 2 and grade >/= 3 RP were investigated separately. The increased risk of severe RP in elderly patients compared with younger patients was also evaluated. Material and methods. A total of 176 consecutive patients with locally advanced non-small cell lung cancer were followed up prospectively after three-dimensional conformal radiotherapy. RP was graded according to Common Terminology Criteria for Adverse Events version 3.0. Results. Mean lung dose (MLD), mean heart dose, ratio of planning target volume to total lung volume (PTV/Lung), and dose-volume histogram comprehensive value of both heart and lung  were associated with both grade >/= 2 and grade >/= 3 RP in univariate analysis.  In multivariate logistic regression analysis, age and MLD were predictors of both grade >/= 2 RP and grade >/= 3 RP; receipt of chemotherapy predicted grade >/= 3  RP only; and sex and PTV/Lung predicted grade >/= 2 RP only. Among patients who developed high-grade RP, MLD and PTV/Lung were significantly lower in patients aged >/= 70 years than in younger patients (p < 0.05 for both comparisons). Conclusions. The predictors were not completely consistent between grade >/= 2 RP and grade >/= 3 RP. Elderly patients had a higher risk of severe RP than younger  patients did, possibly due to lower tolerance of radiation to the lung.

 

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[74]

TÍTULO / TITLE:  - Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor-Bearing Mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Immunol. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1202086

AUTORES / AUTHORS:  - Rega A; Terlizzi M; Luciano A; Forte G; Crother TR; Arra C; Arditi M; Pinto A; Sorrentino R

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano 84084, Italy;

RESUMEN / SUMMARY:  - The antitumor activity of LPS was first described by Dr. William Coley. However,  its role in lung cancer remains unclear. The aim of our study was to elucidate the dose-dependent effects of LPS (0.1-10 mug/mouse) in a mouse model of B16-F10-induced metastatic lung cancer. Lung tumor growth increased at 3 and 7 d  after the administration of low-dose LPS (0.1 mug/mouse) compared with control mice. This was associated with an influx of plasmacytoid dendritic cells (pDCs),  regulatory T cells, myeloid-derived suppressor cells, and CD8(+) regulatory T cells. In contrast, high-dose LPS (10 mug/mouse) reduced lung tumor burden and was associated with a greater influx of pDCs, as well as a stronger Th1 and Th17  polarization. Depletion of pDCs during low-dose LPS administration resulted in a  decreased lung tumor burden. Depletion of pDCs during high-dose LPS treatment resulted in an increased tumor burden. The dichotomy in LPS effects was due to the phenotype of pDCs, which were immunosuppressive after the low-dose LPS, and Th1- and T cytotoxic-polarizing cells after the high-dose LPS. Adoptive transfer  of T cells into nude mice demonstrated that CD8(+) T cells were responsible for pDC recruitment following low-dose LPS administration, whereas CD4(+) T cells were required for pDC influx after the high-dose LPS. In conclusion, our data suggest differential effects of low-dose versus high-dose LPS on pDC phenotype and tumor progression or regression in the lungs of mice.

 

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[75]

TÍTULO / TITLE:  - A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases: Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):e17-8. doi: 10.1097/JTO.0b013e31827690da.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827690da

AUTORES / AUTHORS:  - Riess JW; Nagpal S; Das M; Neal JW; Kim JW; Wakelee HA

INSTITUCIÓN / INSTITUTION:  - *Department of Medicine, Division of Oncology and daggerDepartment of Neurology,  Division of Neuro-Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California; and double daggerDepartment of Opthalmology, University of Southern California, Los Angeles, California.

 

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[76]

TÍTULO / TITLE:  - Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds629

AUTORES / AUTHORS:  - Yoshioka H; Okamoto I; Morita S; Ando M; Takeda K; Seto T; Yamamoto N; Saka H; Atagi S; Hirashima T; Kudoh S; Satouchi M; Ikeda N; Iwamoto Y; Sawa T; Nakanishi Y; Nakagawa K

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki.

RESUMEN / SUMMARY:  - BackgroundA phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC).Patients and methodsA total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral  S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented.ResultsThe updated analysis revealed a median OS of 15.2 months in the  carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713;  95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC.ConclusionsThese results establish the efficacy and safety of  carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.

 

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[77]

TÍTULO / TITLE:  - Survival of patients with or without symptoms undergoing potentially curative resections for primary lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Jan;95(1):276-84. doi: 10.1016/j.athoracsur.2012.09.051. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.09.051

AUTORES / AUTHORS:  - Sheel AR; McShane J; Poullis MP

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. Electronic address: andrea.sheel@nhs.net.

RESUMEN / SUMMARY:  - BACKGROUND: Numerous historical screening programs to detect lung cancer have been undertaken. With technologic advances, complimentary diagnostic tests have been developed; however, only the National Lung Cancer Trial has demonstrated increased survival. Following the success of this study, screening programs are being trialled in several countries. Screening should, in theory, reduce lung cancer deaths by identifying asymptomatic patients with earlier tumors. This study asked whether lung cancer patients who are asymptomatic at presentation have a better survival than those who present with symptoms. METHODS: This was a  retrospective analysis of a validated prospective thoracic surgery database from  a tertiary center in the Northwest of England. Included were 1,546 consecutive patients (826 men, 720 women) who received operative intervention for non-small cell lung cancer. The main outcome measures included 5-year survival and univariate and multivariate Cox regression analysis. RESULTS: Cancer stage, age,  and operation type were confirmed as being of prognostic importance, validating previous studies. Survival between asymptomatic or symptomatic patients did not differ significantly (p = 0.489), regardless of stage. The hazard ratios (with 95% confidence intervals) for variables associated with poorer outcome identified by Cox’s regression analysis were male sex, 1.34 (1.15 to 1.56); advancing age, 1.03 (1.02 to 1.04); advancing stage, 3.30 (2.69 to 4.04); and pneumonectomy, 1.24 (1.01 to 1.52). Symptoms were not a significant variable affecting survival  on multivariate analysis. CONCLUSIONS: This retrospective study from the Northwest of England showed that in our subset of lung cancer patients undergoing resection, asymptomatic patients with non-small cell lung cancer do not have improved survival, implying it is a systemic disease in many at diagnosis. Care should be taken when generalizing the results of the National Lung Screening Trial to all populations until further validation has been performed.

 

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[78]

TÍTULO / TITLE:  - Design of clinical studies: Adaptive randomization and progression-free survival  (PFS) as an endpoint in clinical studies of advanced non-small cell lung cancer (NSCLC).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Pharmacol Ther. 2013 Jan;51(1):84-6.

AUTORES / AUTHORS:  - Schrimpf D; Manegold C; Pilz LR

INSTITUCIÓN / INSTITUTION:  - Deutsches Krebsforschungszentrum (DKFZ), Department of Biostatistics, and University of Heidelberg, Medical Faculty Mannheim, Heidelberg, Germany.

 

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[79]

TÍTULO / TITLE:  - Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:49-56. doi: 10.3171/2012.7.GKS121071.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.7.GKS121071

AUTORES / AUTHORS:  - Ma LH; Li G; Zhang HW; Wang ZY; Dang J; Zhang S; Yao L; Zhang XM

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The First Affiliated Hospital of China Medical  University, Shenyang, China.

RESUMEN / SUMMARY:  - OBJECT: This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non-small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT). METHODS: One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117  patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated. RESULTS: The MST  for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and  the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier-estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates  at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p =  0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all  patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases). CONCLUSIONS: The overall survival results in the present study were similar to those in other  studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.

 

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[80]

TÍTULO / TITLE:  - Effect of Tumor Size on Prognosis in Patients Treated with Radical Radiotherapy or Chemoradiotherapy for Non-Small Cell Lung Cancer: An Analysis of the Staging Project Database of the International Association for the Study of Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827dc74d

AUTORES / AUTHORS:  - Ball D; Mitchell A; Giroux D; Rami-Porta R

INSTITUCIÓN / INSTITUTION:  - *Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia; daggerSir Peter MacCallum Department of Oncology, The University Of Melbourne, Parkville, Australia; double daggerCancer  Research and Biostatistics, Seattle, Washington; section signThoracic Surgery Service, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, and CIBERES-Lung Cancer Group, España.

RESUMEN / SUMMARY:  - BACKGROUND:: Analysis of the International Association for the Study of Lung Cancer database revealed that for patients with completely resected, node-negative, non-small-cell lung cancer (NSCLC), increasing tumor size was associated with worsening survival. This analysis was performed to determine the  effect of size on prognosis in patients in the same database but who were treated with radiotherapy or chemoradiotherapy. METHODS:: Patients were eligible if they  had pathologically confirmed NSCLC, no evidence of distant metastases, intended treatment was radical radiotherapy (minimum 50 Gy) or combined chemotherapy and radiotherapy, no surgery, and tumor diameter was available. RESULTS:: Eight hundred and sixty-eight patients were available for analysis. Patient characteristics were: sex (men) 65.3%; median age 64 years (range, 32-88); Eastern Cooperative Oncology Group performance status 0: 55%, 1: 33%, 2 or more:  5%; chemotherapy 74%; no chemotherapy 18%; weight loss less than 5 %: 70%, and more than 5%: 25%. Primary tumor size was categorized according to tumor, node, metastasis 7th edition. On univariate analysis, the following factors were prognostic for survival: age (continuous) (p = 0.0035); performance status of 1 or more (p = 0.0021); weight loss less than 5% (p < 0.0001); chemotherapy (p = 0.0189); and primary tumor size (continuous) (p = 0.0002). Sex and clinical nodal stage were not significant. On multivariate analysis, age and weight loss remained significant factors for survival, as was tumor size less than 3 cm. CONCLUSIONS:: In patients treated with radiotherapy with or without chemotherapy, tumor size less than 3 cm was associated with longer survival than larger tumors. Evidence of the effect of size on prognosis above this was weak. Five-year survival of more than 10% was observed in all four size categories.

 

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[81]

TÍTULO / TITLE:  - Aryl Hydrocarbon Receptor is a Target of 17-allylamino-17-demethoxygeldanamycin and Enhances its Anticancer Activity in Lung Adenocarcinoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Pharmacol. 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1124/mol.112.081646

AUTORES / AUTHORS:  - Chen PH; Chang JT; Li LA; Tsai HT; Shen MY; Lin PP

INSTITUCIÓN / INSTITUTION:  - 1 National Health Research Institutes;

RESUMEN / SUMMARY:  - We have demonstrated that aryl hydrocarbon receptor (AhR) is overexpressed in lung adenocarcinoma (AD). AhR is usually associated with heat shock protein 90 (Hsp90) in the cytoplasm. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, is currently under evaluation for its anticancer activity in clinical trials. Here, we investigated whether AhR plays a role in 17-AAG-mediated anticancer activity by functioning as a downstream target or by modulating its anticancer efficacy. AhR expression in lung AD cells was modulated by siRNA interference or overexpression. Tumor growth was determined with colony  formation in vitro or in vivo. Anticancer activity of 17-AAG was determined by measuring cell viability, cell cycle distribution and expression of cell cycle regulators. Proteins and mRNA levels were examined by immunoblotting and the real-time reverse transcription-polymerase chain reaction, respectively. In this  study, AhR overexpression positively modulated growth of lung AD cells, at least  partially, via RelA-dependent mechanisms. Although treatment with 17-AAG reduced  AhR levels and AhR-regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17-AAG. In addition, 17-AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1 and phosphorylated Rb levels in AhR-expressing lung AD cells. NAD(P)H:quinone oxidoreductase (NQO1), which is regulated by AhR, was shown to increase anticancer activity of 17-AAG in cells. Knockdown of NQO1 expression attenuated the reduction of cell cycle regulators by 17-AAG treatment in AhR overexpressed cells. We demonstrated that AhR protein not only functions as a downstream target of 17-AAG, but also enhances anticancer activity of 17-AAG in lung AD cells.

 

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[82]

TÍTULO / TITLE:  - Gefitinib Combined With Stereotactic Radiosurgery in Previously Treated Patients  With Advanced Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31826e071b

AUTORES / AUTHORS:  - Wang Z; Zhu XX; Wu XH; Li B; Shen TZ; Kong QT; Li J; Liu ZB; Jiang WR; Wang Y; Hou B

INSTITUCIÓN / INSTITUTION:  - Departments of *Radiation Oncology daggerDermatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

RESUMEN / SUMMARY:  - BACKGROUND:: Disease progression remains the major challenge in the management of advanced (stage IIIb or IV) non-small cell lung cancer (NSCLC) after the failure  of first-line or second-line chemotherapy, or even of targeted therapies such as  gefitinib. The current study evaluated the tolerability and efficacy of stereotactic body radiation therapy (SBRT) in combined with gefitinib as a second-line or third-line treatment in patients with advanced NSCLC. METHODS:: Fourteen advanced NSCLC patients showing disease progression after platinum-based chemotherapy regimens were recruited. Eligible patients started taking gefitinib  (250 mg/d) 7 days before SBRT and continued for 1 year until disease progression, unacceptable toxicity or withdrawal of consent. SBRT was delivered in median 3 fractions within 3 to 5 days. Treatment-associated toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v.3.0). Local control was assessed according to the Response Evaluation Criteria in Solid Tumors criteria and symptom assessments were measured by the Functional Assessment of Cancer Therapy-Lung instrument (V4.0). RESULTS:: With an overall median follow-up of 15.5 months (range, 4 to 27 mo), most patients were well tolerated with common side effects from grade 1 to 2. No grade 4 or higher toxicity was encountered. The clinical disease-related symptom improvement rate was reached 57.1% with the median duration of symptom improvement of 8.0 months.  The 1-year local control and overall survival (OS) rates were 83.9% and 69.6%, respectively. The median progression-free survival and OS were 7.0 and 19.0 months, respectively. CONCLUSIONS:: The SBRT combined with gefitinib is a promising treatment strategy for advanced (stage IIIb or IV) NSCLC after the failure of previously chemotherapy. This method improves local control and disease-related symptoms with tolerated toxicity, and even increases the progression-free survival and OS.

 

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[83]

TÍTULO / TITLE:  - Phase I study of pemetrexed and cisplatin with concurrent high-dose thoracic radiation after induction chemotherapy in patients with unresectable locally advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 15. pii: S0169-5002(12)00652-6. doi: 10.1016/j.lungcan.2012.12.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.007

AUTORES / AUTHORS:  - Mornex F; Peignaux K; Germain T; Wautot V; Chouaki N; Bourayou N; Tourani JM

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Centre Hospitalier Lyon-Sud, Pierre-Benite, France. Electronic address: francoise.mornex@chu-lyon.fr.

RESUMEN / SUMMARY:  - PURPOSE: This is a phase I, escalating-dose trial targeting exclusively patients  with non-small cell lung cancer (NSCLC), investigating pemetrexed and fixed-dose  cisplatin concurrently administered with high-dose radiotherapy (RT) after induction chemotherapy (CT). Primary objective was to determine the maximum tolerated dose and recommended phase II dose of pemetrexed. PATIENTS AND MATERIALS: Patients with unresected stage III NSCLC, planned V20</=35%, and FEV>/=1.3L, were treated every 21 days for 2 cycles (pemetrexed 500mg/m(2); cisplatin 75mg/m(2)), followed by 2 cycles of concurrent CT-RT: pemetrexed starting dose was 400mg/m(2), escalated up to 800mg/m(2) per 100mg/m(2) dose level (DL), cisplatin at 75mg/m(2) and RT at fixed dose of 66Gy/33 fractions. RESULTS: Nine of 10 enrolled patients (age range 46-68 years; 6 men; ECOG PS 0 [6 patients], PS 1 [4]; stage IIIA [1], IIIB [9]; 6 adenocarcinomas, 3 squamous cell carcinomas, 1 large cell carcinoma) were entered on 3 DLs. Dose escalation of pemetrexed was conducted up to 600mg/m(2) based on the independent safety monitoring board recommendation. One dose-limiting toxicity occurred at DL3: Grade 4 septic shock. Grade 3 related toxicities: 2 neutropenia at DL3, 2 lymphopenia per DL (3 recurrent), 2 leukopenia (1 recurrent) at DL3, 1 gastric pain (DL3), 1 nausea and 1 recurrent vomiting (DL2). No Grade ¾ radiation-related toxicities were observed. No toxic death was observed. Disease  control rate was 77.7% (1 CR, 4 PR, 2 SD). One-year survival rate was 90%. CONCLUSIONS: This phase I report of pemetrexed is dedicated to NSCLC with induction therapy and fixed high-dose RT. Pemetrexed at 500mg/m(2), concurrently  given with cisplatin and RT was well tolerated and appears to be the only third-generation agent that can likely be recommended safely at full dose in future trials with concurrent RT.

 

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[84]

TÍTULO / TITLE:  - miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 15;73(2):756-66. doi: 10.1158/0008-5472.CAN-12-2651. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2651

AUTORES / AUTHORS:  - Cai J; Wu J; Zhang H; Fang L; Huang Y; Yang Y; Zhu X; Li R; Li M

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Microbiology and Pharmacology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education; and Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

RESUMEN / SUMMARY:  - Deeper mechanistic understanding of lung adenocarcinoma (non-small cell lung carcinoma, or NSCLC), a leading cause of cancer-related deaths overall, may lead  to more effective therapeutic strategies. In analyzing NSCLC clinical specimens and cell lines, we discovered a uniform decrease in miR-186 (MIR186) expression in comparison with normal lung tissue or epithelial cell lines. miR-186 expression correlated with patient survival, with median overall survival time of 63.0 or 21.5 months in cases exhibiting high or low levels of miR-186, respectively. Enforced overexpression of miR-186 in NSCLC cells inhibited proliferation by inducing G(1)-S checkpoint arrest. Conversely, RNA interference-mediated silencing miR-186 expression promoted cell-cycle progression and accelerated the proliferation of NSCLC cells. Cyclin D1 (CCND1),  cyclin-dependent kinase (CDK)2, and CDK6 were each directly targeted for inhibition by miR-186 and restoring their expression reversed miR-186-mediated inhibition of cell-cycle progression. The inverse relationship between expression of miR-186 and its targets was confirmed in NSCLC tumor xenografts and clinical specimens. Taken together, our findings established a tumor-suppressive role for  miR-186 in the progression of NSCLC. Cancer Res; 73(2); 756-66. ©2012 AACR.

 

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[85]

TÍTULO / TITLE:  - Clinic-based depression screening in lung cancer patients using the PHQ-2 and PHQ-9 depression questionnaires: a pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Support Care Cancer. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-012-1712-4

AUTORES / AUTHORS:  - Randall JM; Voth R; Burnett E; Bazhenova L; Bardwell WA

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, No. 0987, La Jolla, San Diego, CA, 92093, USA, jrandall@ucsd.edu.

RESUMEN / SUMMARY:  - OBJECTIVES: This study aims to validate the ability to perform depression screening with the patient health questionnaire (PHQ)-2 and PHQ-9 depression modules in a busy, outpatient practice, and to evaluate the prevalence of depression among lung cancer outpatients at our institution. METHODS: In 2010, 64 patients in a thoracic malignancy clinic completed the Patient Health Questionnaire-2. Patients endorsing either one or both items were then given the  Patient Health Questionnaire-9, a nine-item depression assessment tool. Patients  with mild or worse depression were offered a referral to a mental health care provider. RESULTS: Eighteen of 64 patients (28 %) endorsed one or both items on the PHQ-2. Thirteen of 18 patients with a positive PHQ-2 screen completed the PHQ-9, with mean score of 10.2 (SD 3.91), suggesting moderate depression. PHQ-9 item 4, evaluating fatigue, was positive in 12 patients, and PHQ-9 item 9, evaluating suicidal ideation, was never reported. Only 1 of 18 patients with a positive PHQ-2 screen was being followed by a psychiatrist, and no patient accepted a new referral to a mental health provider. CONCLUSIONS: The PHQ-2 and PHQ-9 modules are an effective means of depression screening in a busy, outpatient clinic. A high prevalence of depression was reported; yet, suicidal ideation was not reported. Depression severity ranged from mild to severe. The most endorsed PHQ-9 item was fatigue, although it is uncertain if this reflects a symptom of depression, a sequela of lung cancer itself, or both. The lung cancer  patients in this sample who reported depression were unlikely to receive mental health services.

 

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[86]

TÍTULO / TITLE:  - Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Feb 15;85(4):583-94. doi: 10.1016/j.bcp.2012.12.001. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2012.12.001

AUTORES / AUTHORS:  - Tseng SC; Huang YC; Chen HJ; Chiu HC; Huang YJ; Wo TY; Weng SH; Lin YW

INSTITUCIÓN / INSTITUTION:  - Molecular Oncology Laboratory, Department of Biochemical Science and Technology,  National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan.

RESUMEN / SUMMARY:  - Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer  drug. On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC). High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy. In this current  study, paclitaxel was found to increase phosphorylation of mitogen-activated protein kinase (MAPK) kinase 3/6 (MKK3/6)-p38 MAPK as well as protein and mRNA levels of ERCC1 in H1650 and H1703 cells. Moreover, paclitaxel-induced ERCC1 protein and mRNA levels significantly decreased via the downregulation of p38 activity by either a p38 MAPK inhibitor SB202190 or p38 knockdown with specific small interfering RNA (siRNA). Specific inhibition of ERCC1 with siRNA was found  to enhance the paclitaxel-induced cytotoxic effect and growth inhibition. Furthermore, metformin was able to not only decrease the paclitaxel-induced p38 MAPK-mediated ERCC1 expression, but also augment the cytotoxic effect induced by  paclitaxel. Finally, expression of constitutive activate MKK6 or HA-p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity. Overall, our results suggest that inhibition of the p38 MAPK signaling by metformin coupled with paclitaxel therapy in human NSCLC cells may be a clinically useful combination, which however will require further validation.

 

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[87]

TÍTULO / TITLE:  - Molecular diagnosis and prognostic significance of lymph node micrometastasis in  patients with histologically node-negative non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0667-5

AUTORES / AUTHORS:  - Dai CH; Li J; Yu LC; Li XQ; Shi SB; Wu JR

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

RESUMEN / SUMMARY:  - Lymph node metastasis is a major prognostic factor in resected non-small cell lung cancer (NSCLC). However, 30-40 % rate of recurrence after performing complete resection in node-negative patients suggests that their nodal staging is suboptimal. We aimed to evaluate the molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with node-negative NSCLC.  Primary tumor samples from 62 patients with resected stage I-IIB NSCLC were screened for fragile histidine triad (FHIT) and CDKN2A mRNA deletion using reverse transcriptase polymerase chain reaction (RT-PCR). The molecular alternations were found in tumors of 49 patients. A total of 269 lymph nodes from these 49 NSCLC patients with FHIT or/and CDKN2A deletion tumors were examined. Fifteen positive-control nodes and ten negative-control nodes were also analyzed  for FHIT and CDKN2A mRNA deletion. Thirty-nine (22 %) and 22 (18 %) lymph nodes from the 49 patients with FHIT and CDKN2A mRNA deletion in primary tumor had FHIT and CDKN2A mRNA deletion, respectively. The types of FHIT and CDKN2A mRNA deletion in lymph nodes were identical with those in their primary tumors. By combination of two markers, 16 patients (32.7 %) were found to have nodal micrometastasis. Survival analysis showed that patients with nodal micrometastasis had reduced disease-free survival (P = 0.001) and overall survival (P = 0.002) rates. Multivariate analysis demonstrated that nodal micrometastasis was an independent predictor for worse prognosis. Thus, the detection of lymph node micrometastasis by FHIT and CDKN2A mRNA deletion RT-PCR will be helpful to predict the recurrence and prognosis of patients with completely resected stage I-IIB NSCLC.

 

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[88]

TÍTULO / TITLE:  - Computed Tomography RECIST Assessment of Histopathologic Response and Prediction  of Survival in Patients with Resectable Non-Small-Cell Lung Cancer after Neoadjuvant Chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):222-228.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182774108

AUTORES / AUTHORS:  - William WN Jr; Pataer A; Kalhor N; Correa AM; Rice DC; Wistuba II; Heymach J; Lee JJ; Kim ES; Munden R; Gold KA; Papadimitrakopoulou V; Swisher SG; Erasmus JJ

INSTITUCIÓN / INSTITUTION:  - *Departments of Thoracic/Head and Neck Medical Oncology, daggerThoracic and Cardiovascular Surgery, double daggerPathology, section signBiostatistics, and ||Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina; and paragraph signDepartment of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - INTRODUCTION:: This study’s objectives were to determine whether tumor response measured by computed tomography (CT) and evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) correlated with overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy and surgical resection. METHODS:: We measured primary tumor size on CT before and after neoadjuvant chemotherapy in 160 NSCLC patients who underwent surgical resection. The relationship between CT-measured response (RECIST) and histopathologic response (</= 10% viable tumor) and OS were assessed by Kaplan-Meier survival, univariable, and multivariable Cox proportional hazards regression. RESULTS:: There was a statistically significant association between CT-measured response (RECIST) and OS (p = 0.03). However, histopathologic response was a stronger predictor of OS (p = 0.002), with a more pronounced separation of the survival curves when compared with CT-measured response. In multivariable Cox regression analysis, only pathologic stage and histopathologic  response were significant predictors of OS. A 41% overall discordance rate was noted between CT RECIST response and histopathologic response. CT RECIST classified as nonresponders a subset of patients with histopathologic response (8 out of 30 points, 27%) who demonstrated prolonged survival after neoadjuvant chemotherapy. CONCLUSION:: We were unable to show that CT RECIST is a reliable predictor of OS in patients with NSCLC undergoing surgical resection after neoadjuvant chemotherapy. The failure of CT RECIST to predict long-term outcome may be because of the inability of CT imaging to consistently identify patients with histopathologic response. CT RECIST may have only a limited role as an efficacy endpoint after neoadjuvant chemotherapy in patients with resectable NSCLC.

 

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[89]

TÍTULO / TITLE:  - Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Pathol. 2012 Dec 21. pii: S0046-8177(12)00330-9. doi: 10.1016/j.humpath.2012.09.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.09.002

AUTORES / AUTHORS:  - Tsuta K; Mimae T; Nitta H; Yoshida A; Maeshima AM; Asamura H; Grogan TM; Furuta K; Tsuda H

INSTITUCIÓN / INSTITUTION:  - Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan. Electronic address: ktsuta@ncc.go.jp.

RESUMEN / SUMMARY:  - Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively. IGF-1R expression in non-small cell lung carcinoma was observed in 41.4% of samples and was more prevalent in SCC (69.3%) than in ADC (25.1%), large cell carcinoma (33.3%), and sarcomatoid carcinoma (12.2%) (P < .001). Among ADCs, most mucinous ADCs (75%) showed strong membranous staining with the IGF-1R antibody. Compared with protein expression, IGF-1R gene alteration was rare (8.4%). A statistically significant correlation between IGF-1R expression and positive IGF-1R BISH was observed (gamma = 0.762, P < .001). IGF-1R-positive tumors were more common in smokers (P = .004), and these tumors were larger (P = .006) than the IGF-1R-negative tumors. IGF-1R BISH positivity was not correlated with any clinicopathologic factor. IGF-1R expression and IGF-1R BISH positivity were not correlated with overall survival. IGF-1R is highly expressed in SCC and mucinous  ADC, although copy number alterations in the IGF-1R gene were rare. These findings may have important implications for future anti-IGF-1R therapeutic approaches.

 

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[90]

TÍTULO / TITLE:  - Association of thymidylate synthase gene 3’-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Biomed Sci. 2013 Jan 25;20(1):5.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1423-0127-20-5

AUTORES / AUTHORS:  - Wang X; Wang Y; Wang Y; Cheng J; Wang Y; Ha M

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC  specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3’-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. RESULTS: Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3’-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3’-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3’-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3’-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). CONCLUSIONS: This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3’-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene  polymorphisms should be further evaluated as prognostic markers for personalized  therapy in lung adenocarcinoma.

 

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[91]

TÍTULO / TITLE:  - Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis  and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):52-61. doi: 10.1097/JTO.0b013e3182769aa8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182769aa8

AUTORES / AUTHORS:  - Yoshizawa A; Sumiyoshi S; Sonobe M; Kobayashi M; Fujimoto M; Kawakami F; Tsuruyama T; Travis WD; Date H; Haga H

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. akyoshi@shinshu-u.ac.jp

RESUMEN / SUMMARY:  - INTRODUCTION: This study aimed to validate the utility of the new histological classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) for identifying the prognostic subtypes of adenocarcinomas in Japanese patients; correlations between the classification and the presence of EGFR or KRAS mutation status were also investigated. METHODS: We retrospectively reviewed 440 patients with lung adenocarcinoma, who underwent resection. The tumors were classified according to the IASLC/ATS/ERS classification. EGFR and KRAS mutations were detected using the established methods. RESULTS: Five-year disease-free survival rates were: 100% for adenocarcinoma in situ (n = 20) and minimally invasive adenocarcinoma (n = 33), 93.8% for lepidic-predominant adenocarcinoma (n = 36), 88.8% for invasive mucinous adenocarcinoma (n = 10), 66.7% for papillary-predominant adenocarcinoma (n = 179), 69.7% for acinar-predominant adenocarcinoma (n = 61), 43.3% for solid-predominant adencoarcinoma (n = 78), and 0% for micropapillary-predominant adenocarcinoma (n = 19). Multivariate analysis  revealed that the new classification was an independent predictor of disease-free survival. EGFR and KRAS mutations were detected in 90 cases (53.9%) and 21 cases  (13.3%), respectively; EGFR mutations were significantly associated with adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic- and papillary-predominant adenocarcinoma, and KRAS mutations adenocarcinomas with mucinous tumor subtypes. CONCLUSIONS: We found that the IASLC/ATS/ERS classification identified prognostic histologic subtypes of lung adenocarcinomas  among Japanese patients. Histologic subtyping and molecular testing for EGFR and  KRAS mutations can help predict patient prognosis and select those who require adjuvant chemotherapy.

 

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[92]

TÍTULO / TITLE:  - Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2080-6

AUTORES / AUTHORS:  - Du G; Yang Y; Zhang Y; Sun T; Liu W; Wang Y; Li J; Zhang H

INSTITUCIÓN / INSTITUTION:  - Institute of Pharmacy, Pharmacy College of Henan University, Jinming street, Kaifeng, 475004, Henan, China, kfdgj@sohu.com.

RESUMEN / SUMMARY:  - PURPOSE: Patients with advanced non-small-cell lung cancer (NSCLC) have poor survival, and platinum-based chemotherapy agents are the standard first-line chemotherapy agents for advanced NSCLC. This study aimed to identify predictive factors associated with the response to chemotherapy and survival in 258 patients with advanced NSCLC treated with platinum-based chemotherapy. METHODS: Stage IIIA-IV NSCLC patients diagnosed in Kaifeng second people’s hospital (Henan, China) between March 2002 and September 2011 were retrospectively reviewed. All of the patients had received platinum-based chemotherapy, and patients were followed up to date of death or last follow-up to obtain data of response to chemotherapy and survival. Potential prognostic factors such as gender, age, tumor size, tumor type, histologic stage, anemia, calcium levels, ECOG performance status (PS), thrombocytosis, TTF-1, p63, and connexin 43 were analyzed. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method and Cox regression model. RESULTS: A univariate analysis indicated that thrombocytosis and connexin  43 were found to be significant prognostic factors (p < 0.001) and ECOG PS, Hb levels, and p63 presented a tendency toward association with survival. Kaplan-Meier survival showed that the mean OS and PFS in chemotherapy responders  with connexin 43 >/=+2 were significantly longer than in chemotherapy responders  with connexin 43 </=1+. In contrast, thrombocytosis was associated with increased mortality and resistance to chemotherapy in chemotherapy responders. In addition, all 21 patients of the 5-year OS were from chemotherapy responders with connexin  43 >/=+2 or non-thrombocytosis. CONCLUSIONS: Thrombocytosis and connexin 43 absence may be reliable surrogate markers for the prediction of chemotherapy response and prognosis for patients with advanced NSCLC, and assessment of these  factors may identify a population of patients with advanced NSCLC that is likely  to have a prolonged life expectancy.

 

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[93]

TÍTULO / TITLE:  - Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chemotherapy. 2013 Jan 4;58(6):419-425.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345617

AUTORES / AUTHORS:  - Watanabe H; Ikesue H; Oshiro M; Nagata K; Mishima K; Takada A; Suetsugu K; Sueyasu M; Egashira N; Harada T; Takayama K; Nakanishi Y; Oishi R

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Background: Neutropenia is one of the most frequent and dose-limiting toxicities  in amrubicin (AMR) therapy. However, the predictive factors for the development of severe neutropenia in AMR therapy remain unknown. Methods: The subjects were 61 advanced lung cancer patients treated with AMR monotherapy. All data were retrospectively collected from the electronic medical record system. A stepwise logistic regression analysis was performed to identify risk factors for grade 3-4 neutropenia. Results: Of a total 61 patients, 50 were male and 11 were female. The median dose of AMR was 35.0 mg/m(2). The incidence of grade 3-4 neutropenia during the first course was 62%. In multivariate analysis, female gender (OR = 6.68; 95% CI 1.01-134.15; p = 0.049), higher AMR doses (40 mg/m(2) or more) (OR = 5.98; 95% CI 1.77-23.74; p = 0.003), and lower hematocrit values (OR = 2.04 per 5% decrease; 95% CI 1.04-4.38; p = 0.036) were significantly associated with severe neutropenia induced by AMR. Conclusion: The present results suggest that female gender, higher doses of AMR, and lower baseline hematocrit values are predictive factors associated with severe neutropenia induced by AMR in patients  with advanced lung cancer. Patients who have these predictive factors should be monitored carefully and considered for early granulocyte colony-stimulating factor support.

 

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[94]

TÍTULO / TITLE:  - Role of ERCC5 promoter polymorphisms in response to platinum-based chemotherapy in patients with advanced non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Drugs. 2013 Mar;24(3):300-5. doi: 10.1097/CAD.0b013e32835bd6ce.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835bd6ce

AUTORES / AUTHORS:  - He C; Duan Z; Li P; Xu Q; Yuan Y

INSTITUCIÓN / INSTITUTION:  - Tumor Etiology and Screening Department of Cancer Institute and General Surgery,  the First Affiliated Hospital of China Medical University/Key Laboratory of Cancer Control in Liaoning Province, Shenyang, China.

RESUMEN / SUMMARY:  - The ERCC5 gene plays an important role in the nucleotide excision repair pathway  that recognizes and removes platinum-DNA adducts. We aimed to examine whether ERCC5 promoter polymorphisms contribute toward intervariations in the platinum treatment response in patients with advanced non-small-cell lung cancer (NSCLC).  We evaluated the association between three tag-single nucleotide polymorphisms in the ERCC5 promoter region (rs2094258, rs751402, and rs2296147, respectively) and  the efficacy of chemotherapy in 228 advanced NSCLC patients. We found that the rs751402 AA genotype was associated with a better treatment response [AA vs. AG+GG: odds ratio (OR)=2.74, 95% confidence interval (CI) 1.04-7.26, P=0.036) in  all NSCLC patients, which was more evident in the subgroup of patients with squamous cell carcinoma (AA vs. GG: OR=6.40, 95% CI 1.15-35.50, P=0.043; AA vs. AG+GG: OR=6.12, 95% CI 1.15-32.52, P=0.019). No statistically significant association was found between rs2094258 and rs2296147 polymorphisms and treatment response. Our results suggested that the ERCC5 rs751402 AA genotype increased the chemotherapy response in advanced NSCLC, especially in patients with squamous cell carcinoma. Further and larger scale studies are still required to provide more comprehensive information on ERCC5 promoter variations in the clinical outcome of NSCLC patients treated with platinum regimens.

 

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[95]

TÍTULO / TITLE:  - Long-term results in patients with pathological complete response after induction radiochemotherapy followed by surgery for locally advanced non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs622

AUTORES / AUTHORS:  - Lococo F; Cesario A; Margaritora S; Dall’armi V; Mattei F; Romano R; Porziella V; Granone P

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Catholic University, Rome, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES: The outcome of locally advanced non-small-cell lung cancer (NSCLC) patients with pathological complete response (pCR)-pT0N0 -after induction chemoradiotherapy (IT) followed by surgery has, to date, only rarely been investigated. The long-term results in this highly selected subset of patients were evaluated and reported here to identify any predictive factors associated with prognosis. METHODS: From January 1992 to December 2009, 195 consecutive locally advanced (T1-T4/N0-2/M0) NSCLC patients underwent IT, and after clinical  restaging, 137 were operated upon with radical intent. Among these, 37 (19% of the overall and 27% of the surgical cohort) showed a pCR status and were included in this retrospective analysis. Survival rates and prognostic factors were analysed by the Kaplan-Meier, the log-rank and Cox regression analyses. RESULTS:  The mean age and male/female ratio were 61.9 +/- 9.8 years and 33/4, respectively. Before starting IT, the clinical staging was IIb in 2 (5%) patients, IIIa in 20 (54%) and IIIb in 15 (41%). Morbidity and 30-day mortality rates were 27 and 3%, respectively. The overall 3- and 5-year long-term survivals (LTSs) and disease-free survival (DFS) were 67 and 64% and 68 and 71%, respectively. Overall, 17 patients (46%) experienced a recurrence, occurring more frequently in a distant site (32%) than locally (19%). The analysis of the 5-year LTS suggests that (i) the initial single N2 station involvement (P = 0.010); (ii) the resection to a lesser extent than pneumonectomy (P = 0.005) and (iii) the adjuvant therapy (P = 0.005) are all positive prognostic factors. In particular,  a 5-year hazard ratio of 8.21 (95% confidence interval 2.16-31.16, P = 0.002) was estimated by Cox regression analysis for subjects who did not undergo adjuvant therapy vs those who did. CONCLUSIONS: After induction radiochemotherapy followed by surgery in locally advanced NSCLC, a pCR is achieved in a remarkable proportion of cases (27% in our experience). In such patients, a rewarding LTS (64% at 5 years) could be expected, especially when a single N2 station is involved at diagnosis or when an adjuvant treatment is administered. Nevertheless, recurrences after surgery are quite common (46%) and this evidence  deserves further investigations and deeper analysis.

 

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[96]

TÍTULO / TITLE:  - A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):79-88. doi: 10.1097/JTO.0b013e318274a85d.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318274a85d

AUTORES / AUTHORS:  - Dy GK; Mandrekar SJ; Nelson GD; Meyers JP; Adjei AA; Ross HJ; Ansari RH; Lyss AP; Stella PJ; Schild SE; Molina JR; Adjei AA

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: The purpose of this study was to assess the safety and efficacy of  gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib  as first-line therapy for advanced non-small-cell lung cancer. METHODS: A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. RESULTS: On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased  overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). CONCLUSIONS: The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.

 

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[97]

TÍTULO / TITLE:  - Influence of Comorbidity on Racial Differences in Receipt of Surgery Among US Veterans With Early-Stage Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Feb 1;31(4):475-81. doi: 10.1200/JCO.2012.44.1170. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.1170

AUTORES / AUTHORS:  - Williams CD; Stechuchak KM; Zullig LL; Provenzale D; Kelley MJ

INSTITUCIÓN / INSTITUTION:  - Durham VA Medical Center, 508 Fulton St (152), Durham, NC 27705; Christina.Williams4@va.gov.

RESUMEN / SUMMARY:  - PURPOSE It is unclear why racial differences exist in the frequency of surgery for lung cancer treatment. Comorbidity is an important consideration in selection of patients for lung cancer treatment, including surgery. To assess whether comorbidity contributes to the observed racial differences, we evaluated racial differences in the prevalence of comorbidity and their impact on receipt of surgery. PATIENTS AND METHODS A total of 1,314 patients (1,135 white, 179 black)  in the Veterans Health Administration diagnosed with early-stage non-small-cell lung cancer in 2007 were included. The effect of comorbidity on surgery was determined by using generalized linear models with a logit link accounting for patient clustering within Veterans Administration Medical Centers. Results Compared with whites, blacks had greater prevalence of hypertension, liver disease, renal disease, illicit drug abuse, and poor performance status, but lower prevalence of respiratory disease. The impact of most individual comorbidities on receipt of surgery was similar between blacks and whites, and comorbidity did not influence the race-surgery association in a multivariable analysis. The proportion of blacks not receiving surgery as well as refusing surgery was greater than that among whites. CONCLUSION Blacks had a greater prevalence of several comorbid conditions and poor performance status; however, the overall comorbidity score did not differ by race. In general, the effect of comorbidity on receipt of surgery was similar in blacks and whites. Racial differences in comorbidity do not fully explain why blacks undergo lung cancer surgery less often than whites.

 

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[98]

TÍTULO / TITLE:  - Successful Treatment with Crizotinib in Mechanically Ventilated Patients with ALK Positive Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):250-3. doi: 10.1097/JTO.0b013e3182746772.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182746772

AUTORES / AUTHORS:  - Ahn HK; Jeon K; Yoo H; Han B; Lee SJ; Park H; Lee MJ; Ha SY; Han JH; Sun JM; Ahn JS; Ahn MJ; Park K

INSTITUCIÓN / INSTITUTION:  - Divisions of *Hematology-Oncology and daggerPulmonology and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and Departments of double daggerMedicine and section signPathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Lung cancer is the most common solid tumor in critically ill cancer patients admitted to intensive care units and is associated with a poor prognosis. Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is active for  advanced non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements. We report three cases of NSCLC patients who required mechanical ventilation for respiratory failure and were successfully weaned from mechanical  ventilation after treatment with ALK inhibitors. These responses were accompanied by minimal toxicities and an overt improvement in performance status. These results suggest that ALK inhibitors may be safe and effective in critically ill patients on mechanical ventilation for respiratory failure resulting from EML4-ALK translocated NSCLC progression.

 

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[99]

TÍTULO / TITLE:  - Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):352. doi: 10.1007/s12032-012-0352-3. Epub 2012 Dec 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0352-3

AUTORES / AUTHORS:  - Zhang J; Huang SH; Li H; Li Y; Chen XL; Zhang WQ; Chen HG; Gu LJ

INSTITUCIÓN / INSTITUTION:  - Thoracic Surgery Department and Clinical Research Center for Thoracic Oncology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, China.

RESUMEN / SUMMARY:  - Recently, the prognostic value of cancer-related inflammatory response has been revealed. Previous studies showed that peripheral neutrophils and lymphocytes had significant impact on the prognosis of advanced and early-node-negative non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate  the prognostic value of preoperative lymphocyte and neutrophil counts in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy. Retrospective analyses were performed to examine the impact of preoperative peripheral lymphocyte and neutrophil counts on disease-free survival (DFS) and overall survival (OS) and to analyze the relationships of these factors to clinicopathological factors. A total of 142 patients with NSCLC were evaluated of which 57 (40.1 %) patients had local recurrence or metastasis. Multivariate analyses revealed that peripheral lymphocyte count was an independent favorable prognostic factor of DFS (hazard ratio 0.548; 95 % confidence interval 0.351-0.857; P = 0.008) but not OS (P = 0.164). The maximum logrank statistical value was 9.504 (P = 0.002) when the cutoff value of lymphocyte was 1,800 mm(-3). The median DFS was 318.0 days (95 % confidence interval 226.0-410.0) for lymphocyte </=1,800 mm(-3) group and 669.0 days (95 % confidence interval 0.0-1,431.0) for lymphocyte >1,800 mm(-3) group. Low lymphocyte count was related with lymphatic invasion (P = 0.012) and recurrence of NSCLC (P = 0.022). Peripheral neutrophil count had no impact on DFS or OS when analysis included all the 142 patients. Preoperative peripheral lymphocyte count, which is related with lymphatic invasion, is an independent favorable prognostic factor of DFS in patients with NSCLC who underwent lobectomy and lymph node dissection and adjuvant chemotherapy.

 

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[100]

TÍTULO / TITLE:  - Improving image-guided radiation therapy of lung cancer by reconstructing 4D-CT from a single free-breathing 3D-CT on the treatment day.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Phys. 2012 Dec;39(12):7694-709. doi: 10.1118/1.4768226.

            ●● Enlace al texto completo (gratuito o de pago) 1118/1.4768226

AUTORES / AUTHORS:  - Wu G; Lian J; Shen D

INSTITUCIÓN / INSTITUTION:  - BRIC and Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.

RESUMEN / SUMMARY:  - Purpose: One of the major challenges of lung cancer radiation therapy is how to reduce the margin of treatment field but also manage geometric uncertainty from respiratory motion. To this end, 4D-CT imaging has been widely used for treatment planning by providing a full range of respiratory motion for both tumor and normal structures. However, due to the considerable radiation dose and the limit  of resource and time, typically only a free-breathing 3D-CT image is acquired on  the treatment day for image-guided patient setup, which is often determined by the image fusion of the free-breathing treatment and planning day 3D-CT images. Since individual slices of two free breathing 3D-CTs are possibly acquired at different phases, two 3D-CTs often look different, which makes the image registration very challenging. This uncertainty of pretreatment patient setup requires a generous margin of radiation field in order to cover the tumor sufficiently during the treatment. In order to solve this problem, our main idea  is to reconstruct the 4D-CT (with full range of tumor motion) from a single free-breathing 3D-CT acquired on the treatment day.Methods: We first build a super-resolution 4D-CT model from a low-resolution 4D-CT on the planning day, with the temporal correspondences also established across respiratory phases. Next, we propose a 4D-to-3D image registration method to warp the 4D-CT model to  the treatment day 3D-CT while also accommodating the new motion detected on the treatment day 3D-CT. In this way, we can more precisely localize the moving tumor on the treatment day. Specifically, since the free-breathing 3D-CT is actually the mixed-phase image where different slices are often acquired at different respiratory phases, we first determine the optimal phase for each local image patch in the free-breathing 3D-CT to obtain a sequence of partial 3D-CT images (with incomplete image data at each phase) for the treatment day. Then we reconstruct a new 4D-CT for the treatment day by registering the 4D-CT of the planning day (with complete information) to the sequence of partial 3D-CT images  of the treatment day, under the guidance of the 4D-CT model built on the planning day.Results: We first evaluated the accuracy of our 4D-CT model on a set of lung  4D-CT images with manually labeled landmarks, where the maximum error in respiratory motion estimation can be reduced from 6.08 mm by diffeomorphic Demons to 3.67 mm by our method. Next, we evaluated our proposed 4D-CT reconstruction algorithm on both simulated and real free-breathing images. The reconstructed 4D-CT using our algorithm shows clinically acceptable accuracy and could be used  to guide a more accurate patient setup than the conventional method.Conclusions:  We have proposed a novel two-step method to reconstruct a new 4D-CT from a single free-breathing 3D-CT on the treatment day. Promising reconstruction results imply the possible application of this new algorithm in the image guided radiation therapy of lung cancer.

 

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[101]

TÍTULO / TITLE:  - 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging in malignant mesothelioma patients: Looking from outside is not enough.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb;79(2):187-90. doi: 10.1016/j.lungcan.2012.10.017. Epub 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.10.017

AUTORES / AUTHORS:  - Roca E; Laroumagne S; Vandemoortele T; Berdah S; Dutau H; Maldonado F; Astoul P

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hopital Nord, Marseille, France.

RESUMEN / SUMMARY:  - Malignant mesothelioma (MM) is an uncommon neoplasm with a poor prognosis usually associated with asbestos exposure. 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) has become an invaluable tool  for the diagnosis, staging, and prognosis of this severe disease as it combines both anatomic and functional information in a single imaging procedure, allowing  for improved management of this disease. For many authors, 18F-FDG-PET/CT is the  cornerstone of the pre-therapeutic evaluation of mesothelioma patients, particularly when multimodal therapy (including extra-pleural pneumonectomy or omentectomy) is considered. However, while characteristic patterns have been reported as predictive of macroscopic pleural or peritoneal involvement, false negative findings are possible, both for pleural and peritoneal mesothelioma, during the initial diagnosis or during the patient’s surveillance as illustrated  by this report of three cases of suspected MM with negative PET/CT. This report highlights the limitations of PET/CT in the diagnostic evaluation of MM and the importance of histopathological confirmation by thoracoscopy and/or laparoscopy,  which remain the most important diagnostic procedures in MM.

 

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[102]

TÍTULO / TITLE:  - Metabolic Response to Pegylated Arginine Deiminase in Mesothelioma With Promoter  Methylation of Argininosuccinate Synthetase.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.1784

AUTORES / AUTHORS:  - Szlosarek PW; Luong P; Phillips MM; Baccarini M; Ellis S; Szyszko T; Sheaff MT; Avril N

INSTITUCIÓN / INSTITUTION:  - Barts and The London School of Medicine; St Bartholomew’s Hospital, London, United Kingdom.

 

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[103]

TÍTULO / TITLE:  - Caspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non-Small Cell Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2621

AUTORES / AUTHORS:  - Yamaguchi H; Hsu JL; Chen CT; Wang YN; Hsu MC; Chang SS; Du Y; Ko HW; Herbst R; Hung MC

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Molecular and Cellular Oncology and Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center; Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Asia University, Taichung, Taiwan.

RESUMEN / SUMMARY:  - PURPOSE: Results of multiple clinical trials suggest that EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) exhibit negative effects on platinum-based chemotherapy in patients with lung cancer with wild-type (WT) EGFR, but the underlying molecular mechanisms are still uncertain. Studies that identify the mechanism of how TKIs negatively affect patients with WT EGFR are important for future development of effective strategies to target lung cancer. Thus, we returned to in vitro study to investigate and determine a possible explanation for this phenomenon.EXPERIMENTAL DESIGN: We investigated the effects of TKIs and  cisplatin on caspase-independent cell death (CID) and the role of CID in the efficacy of each drug and the combination. Furthermore, we studied the mechanism  by which EGFR signaling pathway is involved in CID. Finally, on the basis of the  identified mechanism, we tested the combinational effects of cisplatin plus suberoylanilide hydroxamic acid (SAHA) or erastin on CID.RESULTS: We found that gefitinib inhibited cisplatin-induced CID but not caspase-dependent apoptotic cell death. In WT EGFR cells, gefitinib not only inhibited CID but also failed to induce apoptosis, therefore compromising the efficacy of cisplatin. Inhibition of EGFR-ERK/AKT by gefitinib activates FOXO3a, which in turn reduces reactive oxygen species (ROS) and ROS-mediated CID. To overcome this, we showed that SAHA and erastin, the inducers of ROS-mediated CID, strongly enhanced the effect of cisplatin in WT EGFR cells.CONCLUSION: TKI-mediated inhibition of CID plays an important role in the efficacy of chemotherapy. Moreover, FOXO3a is a key factor  in the negative effects of TKI by eliminating cisplatin-induced ROS. Clin Cancer  Res; 1-10. ©2012 AACR.

 

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[104]

TÍTULO / TITLE:  - Advanced lung cancer patients’ experience with continuity of care and supportive  care needs.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Support Care Cancer. 2012 Dec 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-012-1673-7

AUTORES / AUTHORS:  - Husain A; Barbera L; Howell D; Moineddin R; Bezjak A; Sussman J

INSTITUCIÓN / INSTITUTION:  - Division of Palliative Care, University of Toronto, Temmy Latner Centre for Palliative Care, Mount Sinai Hospital, 60 Murray St., 4th Floor, Toronto, ON, Canada, M5T 3L9, amna.husain@utoronto.ca.

RESUMEN / SUMMARY:  - As cancer care becomes increasingly complex, the ability to coordinate this care  is more difficult for health care providers, patients and their caregivers alike. Despite the widely recognized need for improving continuity and coordination of care, the relationship of continuity of care with patient outcomes has yet to be  elucidated. Our study’s main finding is that the Continuity and Coordination subscale of the widely used Picker System of Ambulatory Cancer Care Survey is able to distinguish between lung cancer patients with unmet supportive care needs and those without. Specifically, this study shows a new association between this  widely implemented continuity and coordination survey and the ‘psychological needs’ domain, as well as the ‘health system and information’ domains of supportive care needs. The finding provides support for the idea that interventions to improve continuity may impact tangible indicators of patient care such as supportive care needs being met. The study focuses attention on continuity of care as an important aspect of optimizing outcomes in cancer care.

 

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[105]

TÍTULO / TITLE:  - Survival data in elderly patients with locally advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):449. doi: 10.1007/s12032-012-0449-8. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0449-8

AUTORES / AUTHORS:  - Domingues PM; Zylberberg R; da Matta de Castro T; Baldotto CS; de Lima Araujo LH

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Department and Thoracic Oncology Tumor Group, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil, pedromasson@ig.com.br.

RESUMEN / SUMMARY:  - Combined chemoradiation (CRT) is the standard therapy in locally advanced non-small cell lung cancer (NSCLC). Nevertheless, the best approach in the elderly population is still poorly defined. We retrospectively reviewed the charts of elderly (>/=65 years) patients with unresectable, locally advanced NSCLC, diagnosed at the Brazilian National Cancer Institute between 2003 and 2007. The primary outcome was overall survival (OS), measured from diagnosis until death. Palliative therapy (PT) included best supportive care radiation therapy (RT; </=40 Gy) and palliative chemotherapy. Among patients treated with radical RT, OS was measured from date of treatment beginning until death (OST). One hundred seventy-one patients were included, with median age of 71 years (range 65-90). Thirty-nine percent received PT, 32 % exclusive RT (>40 Gy), and 29 % CRT (concomitant or sequential). Patients treated with RT and CRT had better OS (median 13.7 months [95 % CI 10.9-16.4] and 15.5 months [95 % CI 13.0-17.9]) than PT (median 4.1 months [95 % CI 3.6-4.6]; p < 0.0001). In the multivariate analysis, RT (HR 0.28 [95 % CI 0.18-0.42]; p < 0.0001) and CRT (HR 0.17 [95 % CI  0.1-0.27]; p < 0.0001) were independently correlated to better survival in comparison with PT. Among patients receiving radical RT, the addition of chemotherapy was correlated to longer OST (median 13.8 [95 % CI 10.6-17.0] vs. 10.8 months [95 % CI 8.6-13.1]; p = 0.018). This benefit was confirmed in the multivariate analysis (HR 0.59 [95 % CI 0.36-0.97]; p = 0.039). Elderly patients  with locally advanced NSCLC derived significant survival benefit from radical RT  and CRT, suggesting that age should not be a contraindication for these aggressive therapeutic strategies.

 

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[106]

TÍTULO / TITLE:  - Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3190

AUTORES / AUTHORS:  - Lau JK; Brown KC; Thornhill BA; Crabtree CM; Dom AM; Witte TR; Hardman WE; McNees CA; Stover CA; Carpenter AB; Luo H; Chen YC; Shiflett BS; Dasgupta P

INSTITUCIÓN / INSTITUTION:  - Pharmacology, Physiology and Toxicology, Marshall University.

RESUMEN / SUMMARY:  - Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BACs) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChRs). In this study, we show that human BACs produce acetylcholine  (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3) and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by alpha7-, alpha3beta2-, and beta3-nAChRs, ChAT and VAChT pathways. We observed that nicotine upregulated ChAT and VAChT. Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the growth of human BACs. Vesamicol  induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or IGF-II-induced growth of human BAC’s. siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. We also observed that vesamicol inhibited Akt phosphorylation during cell death,  and overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Taken together, our results suggested that disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy.

 

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[107]

TÍTULO / TITLE:  - Chronic obstructive pulmonary disease and risk of lung cancer: the importance of  smoking and timing of diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):6-11. doi: 10.1097/JTO.0b013e318274a7dc.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318274a7dc

AUTORES / AUTHORS:  - Powell HA; Iyen-Omofoman B; Baldwin DR; Hubbard RB; Tata LJ

INSTITUCIÓN / INSTITUTION:  - Nottingham Respiratory Research Unit, University Of Nottingham, Nottingham, UK. helen.powell@nottingham.ac.uk

RESUMEN / SUMMARY:  - INTRODUCTION: The majority of cases of both lung cancer and chronic obstructive pulmonary disease (COPD) are attributable to cigarette smoking, but whether COPD  is an independent risk factor for lung cancer remains unclear. METHODS: We used The Health Improvement Network, a U.K. general practice database, to identify incident cases of lung cancer and controls matched on age, sex, and practice. Using conditional logistic regression, we assessed the effects of timing of first diagnoses of COPD, pneumonia, and asthma on the odds of lung cancer, adjusting for smoking habit. RESULTS: Of 11,888 incident cases of lung cancer, 23% had a prior diagnosis of COPD compared with only 6% of the 37,605 controls. The odds of lung cancer in patients who had COPD diagnosed within 6 months of their cancer diagnosis were 11-fold those of patients without COPD (odds ratio 11.47, 95% confidence interval 9.38-14.02). However, when restricted to earlier COPD diagnoses, with adjustment for smoking, the effect markedly diminished (for COPD  diagnoses >10 years before lung cancer diagnosis, odds ratio: 2.18, 95% confidence interval: 1.87-2.54). The pattern was similar for pneumonia. The effect of COPD on lung cancer remained after excluding patients who had a codiagnosis of asthma. CONCLUSION: A diagnosis of COPD is strongly associated with a diagnosis of lung cancer, however, this association is largely explained by smoking habit, strongly dependent on the timing of COPD diagnosis, and not specific to COPD. It seems unlikely, therefore, that COPD is an independent risk  factor for lung cancer.

 

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[108]

TÍTULO / TITLE:  - Can mutations of EGFR and KRAS in serum be predictive and prognostic markers in patients with advanced non-small cell lung cancer (NSCLC)?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):328. doi: 10.1007/s12032-012-0328-3. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0328-3

AUTORES / AUTHORS:  - Kim ST; Sung JS; Jo UH; Park KH; Shin SW; Kim YH

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Department of Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, South Korea.

RESUMEN / SUMMARY:  - The status of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations has been used widely in management of patients with non-small cell lung cancer (NSCLC). However, it may be difficult to get tumor tissues for analyzing the status of EGFR and KRAS mutation in large proportion of patients with advanced disease. We obtained pairs of tumor and serum samples from 57 patients with advanced NSCLC, between March 2006 and January 2009. EGFR mutation status from tumor samples and KRAS mutation status from serum samples were analyzed by genomic polymerase chain reaction and direct sequence, and EGFR mutation status from serum samples was determined by the peptide nucleic acid-locked nucleic acid PCR clamp. EGFR mutations were detected in the serum samples of 11 patients and in the tumor samples of 12 patients. Fourteen patients revealed (?) KRAS mutation in the serum sample. EGFR mutation status in the serum and tumor samples was consistent in 50 (87.7 %) of the 57 pairs (correlation index 0.62, p < 0.001). Only 5 of 57 (8.7 %) patients showed mutation of both EGFR and KRAS in serum sample. Twenty-two of 57 patients (38.5 %) received EGFR-TKIs as any line therapy. The response for EGFR-TKIs was significantly associated with EGFR mutations in both tumor samples and serum samples (p < 0.05). The status of KRAS  mutation in serum was not predictive for the response of EGFR-TKI (p > 0.05). There was no significant difference in OS according to the status of EGFR mutations in both serum and tumor samples (p > 0.05) and KRAS mutations in serum  samples (p > 0.05). The status of EGFR and KRAS mutation in serum was not prognostic in patients with advanced NSCLC. However, the clinical usefulness of EGFR mutation of serum as a selection marker for EGFR-TKIs sensitivity in NSCLC might be allowed, not KRAS mutation.

 

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[109]

TÍTULO / TITLE:  - Genetic Variations in TGFbeta1, tPA, and ACE and Radiation-Induced Thoracic Toxicities in Patients with Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):208-13. doi: 10.1097/JTO.0b013e318274592e.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318274592e

AUTORES / AUTHORS:  - Yuan ST; Ellingrod VL; Schipper M; Stringer KA; Cai X; Hayman JA; Yu J; Lawrence TS; Kong FM

INSTITUCIÓN / INSTITUTION:  - *Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R. China; daggerDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; double daggerDepartment of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan; and section signDepartment of Radiation Oncology, Veteran Affair Health Center, Ann Arbor, Michigan.

RESUMEN / SUMMARY:  - INTRODUCTION: : We hypothesized that radiation-induced thoracic toxicity (RITT) of the lung, esophagus and pericardium share a similar mechanism, and aimed to examine whether genetic variation of transforming growth factor-beta1 (TGFbeta1), tissue plasminogen activator (tPA) and angiotensin converting enzyme (ACE), are associated with RITT in patients with non-small-cell lung cancer (NSCLC). METHODS: : Patients with stage I-III NSCLC were enrolled and received radiotherapy (RT). Blood samples were obtained pre-RT and at 4 to 5 weeks during  RT, and plasma TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The DNA samples extracted from blood pre-RT were analyzed for the following frequent genetic variations: TGFbeta1 509C/T, tPA -7351 C/T, and ACE I/D. RITT score was defined as the sum of radiation-induced toxicity grades in esophagus, lung, and pericardium. RESULTS: : Seventy-six NSCLC patients receiving definitive RT were enrolled. Patients with TGFbeta1 509CC had higher mean grade of esophagitis (1.4 +/- 0.2 versus 0.8 +/- 0.2, p = 0.019) and RITT score (2.6 +/- 0.3 versus 1.6 +/- 0.3, p = 0.009) than T allele carriers. Although no significant relationship was observed between RITT and the tPA or ACE variants individually, patients with any high-risk alleles (tPA CC or ACE D or TGFbeta1 509CC) had significantly higher grade of developing combined RITT (p < 0.001). Patients with TGFbeta1 509CC had greater increase of plasma TGF beta1 levels at 4 to 5 weeks during RT than T allele carriers did (CC 1.2 +/- 0.2 versus T 0.7 +/-  0.1, p = 0.047). CONCLUSION: : This exploratory study demonstrated that sensitivity of radiation toxicity may be determined by genomic factors associated with TGFbeta1 and genes involved in TGFbeta1 pathway.

 

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[110]

TÍTULO / TITLE:  - Overexpression of ubiquitin-specific protease 22 predicts poor survival in patients with early-stage non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Histochem. 2012 Nov 30;56(4):e46. doi: 10.4081/ejh.2012.e46.

AUTORES / AUTHORS:  - Ning J; Zhang J; Liu W; Lang Y; Xue Y; Xu S

INSTITUCIÓN / INSTITUTION:  - The Third Affiliated Hospital of Harbin Medical University. shidong_xu@163.com.

RESUMEN / SUMMARY:  - Ubiquitin-specific protease 22 (USP22), a novel ubiquitin hydrolase, has been implicated in oncogenesis and cancer progression in various types of human cancer. However, the clinical significance of USP22 expression in non-small cell  lung cancer (NSCLC) has not been determined. In the present study, USP22 messenger RNA (mRNA) and protein levels were analyzed by quantitative real-time polymerase chain reaction (PCR) and western blot analysis in 30 cases of NSCLC and in corresponding non-tumor tissue samples. Furthermore, immunohistochemistry  was performed to detect USP22 protein expression in 86 primary tumor tissues derived from clinically annotated NSCLC cases at stage I-II. In our analysis we found that both USP22 mRNA and protein levels in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues and that there was a significant correlation between the expression of USP22 mRNA and protein (P=0.000, kappa=0.732). In addition, a high-level of USP22 expression was observed in 53.3% (39 out of 86) cases and it was correlated with large tumor size (P=0.029) and lymph node metastasis (P=0.026). Patients with tumors displaying a high-level of USP22 expression showed significantly shorter survival (P=0.006, log-rank test). Importantly, multivariate analysis showed that high USP22 protein expression was an independent prognostic factor for NSCLC patients  (P=0.003). In sum, our data suggest that USP22 plays an important role in NSCLC progression at the early stage, and that overexpression of USP22 in tumor tissues could be used as a potential prognostic marker for patients with early clinical stage of NSCLC.

 

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[111]

TÍTULO / TITLE:  - Interleukin 23 regulates proliferation of lung cancer cells in a concentration-dependent way in association with the interleukin-23 receptor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs384

AUTORES / AUTHORS:  - Li J; Zhang L; Zhang J; Wei Y; Li K; Huang L; Zhang S; Gao B; Wang X; Lin P

INSTITUCIÓN / INSTITUTION:  - Division of Geriatrics, Center for Medical Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China and.

RESUMEN / SUMMARY:  - A proinflammatory cytokine, interleukin 23 (IL-23), plays a role in tumor progression by inducing inflammation in the tumor microenvironment, although there is debate about its role in carcinogenesis. Direct effects of IL-23 on tumor cells have been reported rarely, and contradictory effects have been observed. Here, we studied such effects of IL-23 in lung cancer cells in vitro and in vivo and explored the underlying mechanism. We found IL-23 receptor expression in tissues from lung adenocarcinoma and small cell carcinoma but not in lung squamous cell carcinoma tissue. Interestingly, different concentrations of IL-23 had opposite effects in the same types of cells. We confirmed that the different effects could be explained by differences in binding to the IL-23 receptor (subunits IL-23r and IL-12Rbeta1). Low concentrations of IL-23 promoted  the proliferation of IL-23 receptor-positive A549 and SPCA-1 lung cancer cells by binding to IL-23r, whereas high concentrations of IL-23 inhibited proliferation of these cells by binding to both IL-23r and IL-12Rbeta1. In contrast, IL-23 had  no effect on IL-23 receptor-negative SK-MES-1 cells. IL-23 regulated the growth of human lung cancer cells through its effects on STAT3 expression and phosphorylation in a concentration-dependent way; the Ki-67 gene was involved in  these processes. Our findings demonstrate for the first time that IL-23 affects the proliferation of IL-23 receptor-positive lung cancer cells and that this effect is dependent on the IL-23 concentration. This can explain at least part of the inconsistent reports on the role of IL-23 in the progression of carcinogenesis.

 

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[112]

TÍTULO / TITLE:  - Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Int. 2012 Dec;62(12):785-91. doi: 10.1111/pin.12016.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pin.12016

AUTORES / AUTHORS:  - Woo T; Okudela K; Mitsui H; Tajiri M; Yamamoto T; Rino Y; Ohashi K; Masuda M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Division of Thoracic Surgery, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

RESUMEN / SUMMARY:  - A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the  European Respiratory Society (IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One-hundred-and-seventy-nine cases with pathological stage I ADC were classified  according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One-hundred-and-thirty-seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5-year disease-free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high-histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post-operative recurrence (HR 3.661, 95% CI 1.421-9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.

 

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[113]

TÍTULO / TITLE:  - Leptomeningeal carcinomatosis in non-small-cell lung cancer patients: impact on survival and correlated prognostic factors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):185-91. doi: 10.1097/JTO.0b013e3182773f21.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182773f21

AUTORES / AUTHORS:  - Lee SJ; Lee JI; Nam DH; Ahn YC; Han JH; Sun JM; Ahn JS; Park K; Ahn MJ

INSTITUCIÓN / INSTITUTION:  - *Division of Hematology-Oncology, Department of Medicine; daggerDepartment of Neurosurgery; double daggerDepartment of Radiation Oncology; and section signDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - BACKGROUND: : The incidence of leptomeningeal carcinomatosis (LC) has increased in patients with metastatic non-small-cell lung cancer (NSCLC) because of recent  improvements in survival. The clinical features and prognostic factors of LC in NSCLC patients, however, have not been well identified. The aim of this study was to identify the clinical features and prognostic factors of NSCLC patients with LC. METHODS: : One hundred and forty-nine consecutive NSCLC patients with cytologically proven LC diagnoses between 2001 and 2009 at Samsung Medical Center were retrospectively reviewed. RESULTS: : The median age was 58 years (range, 34-80) with most patients (135, 95%) having histology indicating adenocarcinoma.  Twenty-six patients (17.4%) had LC at the initial presentation of lung cancer. Treatment for LC consisted of intrathecal chemotherapy (ITC) alone in 44 patients, ITC plus systemic therapy in 18 patients, ITC plus radiotherapy in 29 patients, all three treatments in 18 patients, and other treatments without ITC in 20 patients. Twenty patients received only supportive care. The median follow-up duration was 34 months and the median overall survival from diagnosis of LC was 14 weeks (95% confidence interval [CI] 12, 16). In univariate analysis, encephalopathy, Eastern Cooperative Oncology Group (ECOG) performance status, low initial cerebrospinal fluid (CSF) glucose, high initial CSF protein, high initial CSF white blood cell count, treatment with ITC, systemic therapy with epidermal growth factor receptor tyrosine kinase inhibitors or cytotoxic chemotherapy, whole-brain radiotherapy (WBRT), ventriculoperitoneal (VP) shunt operations, and  negative cytologic conversion after ITC were identified as variables that had prognostic influence on survival. In multivariate analysis, poor ECOG performance status (p = 0.026), high protein level of CSF (p = 0.027), and high initial CSF WBC count (p = 0.015) remained significant predictors of poor prognosis for survival, whereas ITC (p < 0.001), EGFR-TKI use (p = 0.018), WBRT (p = 0.009), and VP shunt operation (p = 0.013) remained significant predictors of favorable prognosis for survival. CONCLUSIONS: : Even though the prognosis of LC from NSCLC is poor, small subsets of these patients survive longer. Our results suggest that more active treatment strategies including ITC, WBRT, and EGFR-TKI use might improve clinical outcomes in NSCLC patients with LC and good performance status,  low initial CSF protein and WBC counts.

 

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[114]

TÍTULO / TITLE:  - Positron emission tomography combined with diagnostic chest computed tomography enhances detection of regional recurrence after stereotactic body radiation therapy for early stage non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Cardiovasc Surg. 2013 Jan 12. pii: S0022-5223(12)01568-1. doi: 10.1016/j.jtcvs.2012.12.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2012.12.024

AUTORES / AUTHORS:  - Ebright MI; Russo GA; Gupta A; Subramaniam RM; Fernando HC; Kachnic LA

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Boston Medical Center and Boston University School of Medicine, Boston, Mass. Electronic address: michael.ebright@bmc.org.

RESUMEN / SUMMARY:  - OBJECTIVE(S): Recommendations for surveillance after stereotactic body radiation  therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) are not well defined. Prospective studies evaluating the efficacy of SBRT have used interval posttreatment imaging with computed tomography (CT). We set out to determine whether positron emission tomography (PET) combined with diagnostic chest CT (PET/d-chest) can enhance detection of potentially salvageable recurrence after SBRT. METHODS: We performed a retrospective analysis of posttreatment imaging for 35 patients consecutively treated with SBRT for biopsy-proven early-stage NSCLC.  PET/d-chest was generally performed every 3 months after treatment. A board-certified radiologist who did not have access to the PET results retrospectively interpreted the CT scans. CT results were reported according to response criteria used in Radiation Therapy Oncology Group 0236 and compared with PET/d-chest readings. Local and regional recurrence-free survival was compared using the Mantle-Cox (log-rank) test. RESULTS: Median follow-up was 12.8 months.  Twenty-four patients had stage IA, 7 stage IB, 3 stage IIA, and 1 stage IIB biopsy-proven NSCLC. Two-year overall survival was 62%. CT scans indicated no regional recurrences. PET/d-chest indicated 10 regional recurrences. The 1-year rate of regional recurrence-free survival as evaluated by CT and PET/d-chest was  100% and 69.4%, respectively (P = .0045). Four of 10 patients with a diagnosis of regional recurrence underwent salvage treatment with definitive chemoradiotherapy. CONCLUSIONS: PET/d-chest enhances the detection of regional progression of NSCLC after SBRT over currently recommended practices. In patients who are fit for salvage treatment, where early detection of recurrence can increase the likelihood of successful treatment, PET/d-chest appears critical for follow-up.

 

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[115]

TÍTULO / TITLE:  - Nesfatin-1 in advanced lung cancer patients with weight loss.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Regul Pept. 2012 Dec 23;181C:1-3. doi: 10.1016/j.regpep.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.regpep.2012.11.005

AUTORES / AUTHORS:  - Cetinkaya H; Karagoz B; Bilgi O; Ozgun A; Tuncel T; Emirzeoglu L; Top C; Kandemir EG

INSTITUCIÓN / INSTITUTION:  - Gulhane Military Medical Academy, Department of Nephrology, Turkey.

RESUMEN / SUMMARY:  - The cachexia occurs frequently in lung cancer patients. Among appetite regulatory peptides, alteration of expressions of leptin and ghrelin is demonstrated in cachectic cancer patients, but nesfatin-1 has not been yet studied in cancer. We  investigated serum nesfatin-1 level in advanced lung cancer patients. Forty-one lung cancer patients and 24 healthy subjects were included to the study. Nesfatin-1 serum levels were analyzed by ELISA kit. Serum nesfatin-1 levels were  lower in lung cancer patients than in healthy subjects (0.52+/-0.19ng/ml vs 0.75+/-0.23ng/ml; p<0.001). In lung cancer patients with weight loss, nesfatin-1  levels were decreased compared to the patients without weight loss (0.44+/-0.16ng/ml vs 0.63+/-0.18ng/ml; p<0.001). Whereas, there were no any difference between patients without weight loss and control subjects (0.63+/-0.18ng/ml vs 0.75+/-0.23ng/ml; p:0.129) or between SCLC and NSCLC patients (0.53+/-0.18ng/ml vs 0.52+/-0.20ng/ml; p:0.458). No significant correlation was found between serum nesfatin-1 values and BMI. In conclusion, loss of fat mass may decrease serum nesfatin-1 level in lung cancer patients with weight loss. The future studies which explore biological significance of low serum nesfatin-1 level in cancer are needed.

 

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[116]

TÍTULO / TITLE:  - Feasibility and safety of nonintubated thoracoscopic lobectomy for geriatric lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Feb;95(2):405-11. doi: 10.1016/j.athoracsur.2012.10.082. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.10.082

AUTORES / AUTHORS:  - Wu CY; Chen JS; Lin YS; Tsai TM; Hung MH; Chan KC; Cheng YJ

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology, National Kinmen Hospital, Kinmen, Taiwan.

RESUMEN / SUMMARY:  - BACKGROUND: The feasibility and safety of thoracoscopic lobectomy using anesthesia without tracheal intubation for treatment of geriatric non-small cell  lung cancer patients is unclear, although it has been used with success in younger populations. METHODS: From 2009 through 2011, 84 consecutive patients aged 65 years or older with stage I or II non-small cell lung cancer underwent thoracoscopic lobectomy. Among them, 36 patients were treated without tracheal intubation using epidural anesthesia, intrathoracic vagal blockade, and sedation  (nonintubated group). The other 48 patients were treated with single-lung ventilation under general anesthesia intubated with a double-lumen tube (intubated group). The perioperative profiles and short-term outcomes of the two  groups were compared. RESULTS: The 84 patients were a mean age of 73.0 years (range, 65-87 years). Both groups had comparable preoperative demographic and cancer staging profiles. The anesthetic duration of the nonintubated group was shorter. Both groups had comparable operation duration and blood loss. One patient in the nonintubated group was converted to tracheal intubation due to persistent hypoxemia. Postoperatively, the two groups had comparable hospital stays, complication rates, and dissected lymph nodes. Stridor was noted in 3 patients and delirium in 4 in the intubated group, but none occurred in the nonintubated group. CONCLUSIONS: Nonintubated thoracoscopic lobectomy is technically feasible and was as safe as thoracoscopic lobectomy performed with tracheal intubation in the geriatric lung cancer patients. Thoracoscopic lobectomy without tracheal intubation during anesthesia is a valid alternative for managing selected geriatric patients with non-small cell lung cancer.

 

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[117]

TÍTULO / TITLE:  - Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Gene Ther. 2013 Jan;20(1):25-32. doi: 10.1038/cgt.2012.80. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2012.80

AUTORES / AUTHORS:  - Wunder T; Schmid K; Wicklein D; Groitl P; Dobner T; Lange T; Anders M; Schumacher U

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy and Experimental Morphology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

RESUMEN / SUMMARY:  - Coxsackie adenovirus receptor (CAR) is the primary receptor to which oncolytic adenoviruses have to bind for internalization and viral replication. A total of 171 neuroendocrine lung tumors in form of multitissue arrays have been analyzed resulting in a positivity of 112 cases (65.5%). Immunostaining correlated statistically significant with histopathology and development of recurrence. The  subtype small cell lung cancer (SCLC) showed the highest CAR expression (77.6%),  moreover the CAR level was correlated to the disease-free survival. Further, high CAR expression level in SCLC cell lines was found in vitro and in vivo when cell  lines had been transplanted into immunodeficient mice. A correlation between CAR  expression in the primary tumors and metastases development in the tumor model underlined the clinical relevance. Cell lines with high CAR level showed a high infectivity when infected with a replication-deficient adenovirus. Low levels of  CAR expression in SCLC could be upregulated with Trichostatin A, a histone deacetylase inhibitor. As a result of the unaltered poor prognosis of SCLC and its high CAR expression it seems to be the perfect candidate for oncolytic therapy. With our clinically relevant tumor model, we show that xenograft experiments are warrant to test the efficiency of oncolytic adenoviral therapy.

 

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[118]

TÍTULO / TITLE:  - Postoperative Surveillance for Non-Small Cell Lung Cancer Resected With Curative  Intent: Developing a Patient-Centered Approach.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Jan 23. pii: S0003-4975(12)02165-0. doi: 10.1016/j.athoracsur.2012.09.075.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.09.075

AUTORES / AUTHORS:  - Mollberg NM; Ferguson MK

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, University of Washington, Seattle, Washington. Electronic address: nathan.mollberg@gmail.com.

RESUMEN / SUMMARY:  - Local recurrence or the development of metachronous cancer after surgical therapy for early-stage non-small cell lung cancer (NSCLC) is not uncommon, and these conditions are often amenable to curative therapy. Predictors of recurrence based on surgical, patient, and pathologic factors are well known. A literature search  was performed for articles regarding identification or treatment with curative intent of early local recurrence or metachronous cancer after resection of NSCLC. A patient-centered algorithm for surveillance after resection can be developed based on both risk of recurrence and potential benefit from further treatment to  optimize individual follow-up algorithms.

 

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[119]

TÍTULO / TITLE:  - Fowlpox-based survivin vaccination for malignant mesothelioma therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 21. doi: 10.1002/ijc.28048.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28048

AUTORES / AUTHORS:  - Bertino P; Panigada M; Soprana E; Bianchi V; Bertilaccio S; Sanvito F; Rose AH; Yang H; Gaudino G; Hoffmann PR; Siccardi A; Carbone M

INSTITUCIÓN / INSTITUTION:  - Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai’i, Honolulu, HI. pbertino@hawaii.edu.

RESUMEN / SUMMARY:  - Survivin protein is an attractive candidate for cancer immunotherapy since it is  abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available. In this study, we evaluated the therapeutic efficacy of a novel survivin-based vaccine by subcutaneous or intraperitoneum injection of BALB/c mice with murine fiber-induced MM tumor cells followed by vaccination with recombinant Fowlpox virus replicons encoding survivin. Vaccination generated significant immune responses in both models, leading to delayed tumor growth and  improved animal survival. Flow cytometry and immunofluorescence analyses of tumors from vaccinated mice showed CD8(+) T cell infiltration, and real-time PCR  demonstrated increased mRNA and protein levels of immunostimulatory cytokines. Analyses of survivin peptide-pulsed spleen and lymph node cells from vaccinated mice using ELISPOT and intracellular cytokine staining confirmed antigen-specific, interferon-gamma-producing CD8(+) T cell responses. In addition pentamer-based flow cytometry showed that vaccination generated survivin-specific CD8(+) T cells. Importantly, vaccination did not affect fertility or induce autoimmune abnormalities in mice. Our results demonstrate that vaccination with recombinant Fowlpox expressing survivin improves T cell responses against aggressive MM tumors and may form the basis for promising clinical applications.

 

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[120]

TÍTULO / TITLE:  - Rapid On-Site Cytologic Evaluation During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Nodal Staging in Patients With Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2012 Dec 12. pii: S0003-4975(12)02164-9. doi: 10.1016/j.athoracsur.2012.09.074.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.09.074

AUTORES / AUTHORS:  - Nakajima T; Yasufuku K; Saegusa F; Fujiwara T; Sakairi Y; Hiroshima K; Nakatani Y; Yoshino I

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Thoracic Surgery, Toronto General Hospital, University of Toronto, University Health Network, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - BACKGROUND: The utility of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in lung cancer is still controversial. The aim of this study was to assess the role of ROSE during EBUS-TBNA and the interpretation of its results. METHODS: We performed a retrospective chart review of patients with suspected or  diagnosed lung cancer who underwent EBUS-TBNA for lymph node staging. The slides  were air-dried and Diff-Quik (American Scientific Products, McGaw Park, IL) staining was used for ROSE. Additional smears were prepared for Papanicolaou staining and any remaining sample was placed in 10% formalin for histologic evaluation. The results of ROSE were compared with the results of the final pathologic diagnosis. RESULTS: EBUS-TBNA was performed in 438 patients on 965 lymph nodes. Eighty-four lymph nodes (8.7%) were determined insufficient for definitive diagnosis by final cytologic evaluation. However 45 of the 84 lymph nodes were able to be diagnosed by histologic examination. The non-diagnostic sampling rate was 4.0%. There were no false-positive results on ROSE; however 25  cases (5.7%) were falsely evaluated as negative on ROSE. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3%. The sensitivity, specificity, negative predictive value, and diagnostic accuracy rate of EBUS-TBNA for correct lymph node staging was 96.5%, 100%, 89.8%, and 98.2%, respectively. CONCLUSIONS: ROSE during EBUS-TBNA for material adequacy showed a low rate of non-diagnostic sampling. There was a high agreement between the on-site and final pathologic evaluation during EBUS-TBNA; however immediate diagnosis should be approached with caution.

 

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[121]

TÍTULO / TITLE:  - Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Vaccine. 2012 Nov 20;30 Suppl 5:F34-54. doi: 10.1016/j.vaccine.2012.05.070.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.vaccine.2012.05.070

AUTORES / AUTHORS:  - Gillison ML; Alemany L; Snijders PJ; Chaturvedi A; Steinberg BM; Schwartz S; Castellsague X

INSTITUCIÓN / INSTITUTION:  - Viral Oncology, The Ohio State University Comprehensive Cancer Center, Columbus,  OH, USA. Maura.gillison@osumc.edu

RESUMEN / SUMMARY:  - Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and  oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper  airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression  to be necessary for the initiation and maintenance of the malignant phenotype of  these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as  determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination  has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for  secondary prevention with HPV detection. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

 

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[122]

TÍTULO / TITLE:  - Aberrant expression and association of VEGF and Dll4/Notch pathway molecules under hypoxia in patients with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Feb;28(2):277-84.

AUTORES / AUTHORS:  - Yu S; Sun J; Zhang J; Xu X; Li H; Shan B; Tian T; Wang H; Ma D; Ji C

INSTITUCIÓN / INSTITUTION:  - Department of Hematology, Qilu Hospital, Shandong University, Jinan, PR China.

RESUMEN / SUMMARY:  - Tumor angiogenesis plays important roles in the pathogenesis and prognosis of lung cancer. Both vascular endothelial growth factor (VEGF) and Dll4/Notch pathways are critical for angiogenesis, whereas their relationship under hypoxia  in lung cancer remains unknown. Thus, in the present study, we evaluated the expression of VEGF and Dll4/Notch signaling molecules, and assessed their association with the microvessel density (CD31) and hypoxia (HIF1a) in lung cancer and normal lung tissues using immunohistochemical and Real-time RT-PCR techniques. Then, we investigated the biological function of Dll4 by transfecting Dll4 into HUVECs. In lung cancer tissues, Notch pathway molecules (HES1) and VEGF pathway molecules (VEGFR1 and VEGFR2) were significantly up-regulated, while the  ratio of VEGFR1/VEGFR2 was decreased. CD31 and HIF1a were also found to be elevated in lung cancer. VEGFR1 was negatively correlated with Notch1 while positively correlated with Dll4. CD31 was positively correlated with HIF1a but negatively correlated with VEGFR1. Moreover, HIF1a was nearly positively correlated with HES1 in lung cancer tissues. After transfection, Dll4, Notch1 and VEGFR1 were up-regulated while VEGF and VEGFR2 were down-regulated in Dll4-transfected HUVECs compared with controls. Also, our findings suggest that the expression of VEGF and VEGFR2 increased gradually with the disease progression of lung cancer. In summary, VEGF and Notch signaling pathway molecules were overexpressed in lung cancer, which positively correlates with hypoxia (HIF1a) and angiogenesis (CD31). There might be a negative feedback loop  between VEGF and Dll4/Notch signaling pathway in lung tumor angiogenesis.

 

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[123]

TÍTULO / TITLE:  - When less is better: the safety and efficacy of reduced intensity gemcitabine in  a difficult patient population with advanced non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):370. doi: 10.1007/s12032-012-0370-1. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0370-1

AUTORES / AUTHORS:  - Nacci A; Calvani N; Rizzo P; Fedele P; Orlando L; Schiavone P; Cinefra M; Marino A; Sponziello F; D’Amico M; Cinieri S

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Division and Breast Unit, Sen. Antonio Perrino Hospital, S.S. 7, 72100, Brindisi, Italy.

RESUMEN / SUMMARY:  - Treatment of elderly or poor performance status (PS) patients with advanced non-small-cell lung cancer (NSCLC) is a debated topic. To evaluate the efficacy of a modified schedule of gemcitabine, 59 patients unfit for platinum were enrolled. Mean age was 75.8 years and 41 % of patients had an ECOG PS 2. Gemcitabine was given at 1000 mg/m(2) on days 1, 8 each 28. Most of patients received gemcitabine as first-line chemotherapy, which was continued as maintenance over 6 cycles in responding and stable patients. Median overall survival (OS) and progression-free survival (PFS) were 7.2 and 5 months. In those 45 evaluable patients, treatment resulted in 1 complete remission (CR), 9 partial remissions (PR), and 20 stable diseases (SDs) with a response rate (CR + PR) of 22 % and a clinical benefit (CR + PR + SD) of 68 %. Gemcitabine was continued over 6 cycles in 16 patients (27 %). These patients were treated until progression with a mean of further 8.6 cycles. Median OS and PFS in these selected patients were 19 and 16 months. The toxicity profile was excellent with  only 8 % of overall G3-G4 adverse events. None of the 16 patients under the maintenance phase reported significant toxicity. Gemcitabine given at a lower dose intensity than standard should be considered as valuable therapeutic option  in elderly or poor PS patients with advanced NSCLC unfit for platinum. Extending  the treatment beyond 6 cycles in responding patients is feasible and may prolong  survival.

 

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[124]

TÍTULO / TITLE:  - Causes of death of patients with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec;136(12):1552-7. doi: 10.5858/arpa.2011-0521-OA.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2011-0521-OA

AUTORES / AUTHORS:  - Nichols L; Saunders R; Knollmann FD

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Pittsburgh Medical Center Presbyterian Hospital, Pittsburgh, Pennsylvania, USA. lnichol5@uthsc.edu

RESUMEN / SUMMARY:  - CONTEXT: The causes of death for patients with lung cancer are inadequately described. OBJECTIVE: To categorize the immediate and contributing causes of death for patients with lung cancer. DESIGN: The autopsies from 100 patients who  died of lung cancer between 1990 and February 2011 were analyzed. RESULTS: Tumor  burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20  patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded  as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. CONCLUSIONS: The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

 

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[125]

TÍTULO / TITLE:  - BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone  acetyltransferase p300.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2489

AUTORES / AUTHORS:  - Liu Y; Mayo MW; Nagji AS; Hall EH; Shock LS; Xiao A; Stelow EB; Jones DR

INSTITUCIÓN / INSTITUTION:  - Surgery, University of Virginia.

RESUMEN / SUMMARY:  - The mechanisms through which the metastasis suppressor gene BRMS1 functions are poorly understood. Herein, we report the identification of a previously undescribed E3 ligase function of BRMS1 on the histone acetyltransferase p300. BRMS1 induces polyubiquitination of p300 resulting in its proteasome-mediated degradation. We identify BRMS1 as the first eukaryote structural mimic of the bacterial IpaH E3 ligase family, and establish that the evolutionarily conserved  CXD motif located in in BRMS1 is responsible for its E3 ligase function. Mutation of this E3 ligase motif not only abolishes BRMS1-induced p300 polyubiquitination  and degradation, but importantly, dramatically reduces the metastasis suppressor  function of BRMS1 in both in vitro and in vivo models of lung cancer metastasis.

 

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[126]

TÍTULO / TITLE:  - Imaging and characterization of stretch-induced ATP release from alveolar A549 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Physiol. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1113/jphysiol.2012.244145

AUTORES / AUTHORS:  - Grygorczyk R; Furuya K; Sokabe M

INSTITUCIÓN / INSTITUTION:  - University of Montreal;

RESUMEN / SUMMARY:  - Mechano-transduction at the cellular and tissue levels often involves ATP release and activation of the purinergic signaling cascade. In the lungs, stretch is an important physical stimulus but its impact on ATP release, the underlying release mechanisms and transduction pathways are poorly understood. Here, we investigated the effect of unidirectional stretch on ATP release from human alveolar A549 cells by real-time luciferin-luciferase bioluminescence imaging coupled with simultaneous infrared imaging, to monitor the extent of cell stretch and to identify ATP-releasing cells. In sub-confluent (<90%) cell cultures, single 1-s stretch (10%-40%) induced transient ATP release from a small fraction (</=1.5%) of cells that grew in number dose-dependently with increasing extent of stretch.  ATP concentration in the proximity (</=150mum) of releasing cells often exceeded  10 muM, sufficient for autocrine/paracrine purinoreceptor stimulation of neighboring cells. ATP release responses were insensitive to the putative ATP channel blockers carbenoxolone and 5-nitro-2-(3-phenylpropyl-amino) benzoic acid, but were inhibited by N-ethylmaleimide and bafilomycin. In confluent cell cultures, the maximal fraction of responding cells dropped to <0.2%, but was enhanced several-fold in the wound/scratch area after it was re-populated by new  cells during the healing process. Fluo8 fluorescence experiments revealed 2 types of stretch-induced intracellular Ca(2+) responses, rapid sustained Ca(2+) elevations in a limited number of cells, and delayed secondary responses in neighboring cells, seen as Ca(2+) waves whose propagation was consistent with extracellular diffusion of released ATP. Our experiments revealed that single >10% stretch was sufficient to initiate intercellular purinergic signaling in alveolar cells, which may contribute to the regulation of surfactant secretion and wound healing.

 

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[127]

TÍTULO / TITLE:  - Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Intern Med. 2012 Dec 4;157(11):776-84. doi: 10.7326/0003-4819-157-11-201212040-00005.

            ●● Enlace al texto completo (gratuito o de pago) 7326/0003-4819-157-11-201212040-00005

AUTORES / AUTHORS:  - Veronesi G; Maisonneuve P; Bellomi M; Rampinelli C; Durli I; Bertolotti R; Spaggiari L

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435,  20141 Milan, Italy. giulia.veronesi@ieo.it

RESUMEN / SUMMARY:  - BACKGROUND: Lung cancer screening may detect cancer that will never become symptomatic (overdiagnosis), leading to overtreatment. Changes in size on sequential low-dose computed tomography (LDCT) screening, expressed as volume-doubling time (VDT), may help to distinguish aggressive cancer from cases  that are unlikely to become symptomatic. OBJECTIVE: To assess VDT for screening-detected lung cancer as an indicator of overdiagnosis. DESIGN: Retrospective estimation of the VDT of cancer detected in a prospective LDCT screening cohort. SETTING: Nonrandomized, single-center screening study involving persons at high risk for lung cancer enrolled between 2004 and 2005 who received  LDCT annually for 5 years. PATIENTS: 175 study patients diagnosed with primary lung cancer. MEASUREMENTS: VDT was measured on LDCT and classified as fast-growing (&lt;400 days), slow-growing (between 400 and 599 days), or indolent (>/=600 days). RESULTS: Fifty-five cases of cancer were diagnosed at baseline, and 120 were diagnosed subsequently. Of the latter group, 19 cases (15.8%) were new (not visible on previous scans) and fast-growing (median VDT, 52 days); 101 (84.2%) were progressive, including 70 (58.3%) fast-growing and 31 (25.8%) slow-growing (15.0%) or indolent (10.8%) cases. Lung cancer-specific mortality was significantly higher (9.2% per year) in patients with new compared with slow-growing or indolent (0.9% per year) cancer. Sixty percent of fast-growing progressive cancer and 45% of new cancer were stage I, for which survival was good. LIMITATIONS: This is a retrospective study. Volume-doubling time can only indicate overdiagnosis and was estimated for new cancer from 1 measurement (a diameter of 2 mm assumed the previous year). CONCLUSION: Slow-growing or indolent cancer comprised approximately 25% of incident cases, many of which may have been overdiagnosed. To limit overtreatment in these cases, minimally invasive limited  resection and nonsurgical treatments should be investigated. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research.

 

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[128]

TÍTULO / TITLE:  - Stimulation of the chemosensory TRPA1 cation channel by volatile toxic substances promotes cell survival of small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Feb 1;85(3):426-38. doi: 10.1016/j.bcp.2012.11.019. Epub  2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2012.11.019

AUTORES / AUTHORS:  - Schaefer EA; Stohr S; Meister M; Aigner A; Gudermann T; Buech TR

INSTITUCIÓN / INSTITUTION:  - Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilian University, 80336 Munchen, Germany. Electronic address: eva.schaefer@lrz.uni-muenchen.de.

RESUMEN / SUMMARY:  - TRPA1, a member of the transient receptor potential (TRP) family of cation channels, has mainly been characterized as a chemosensory protein in neuronal cells. TRPA1 is activated by toxic or irritating volatile agents like allyl isothiocyanate (AITC), tear gas, formalin, or cigarette smoke. To date, little is known about a function of TRPA1 in non-neuronal cells in the respiratory system and even less regarding a possible role in cancer biology. Here, we show that TRPA1 is expressed in a panel of human small cell lung cancer (SCLC) cell lines.  Of note, TRPA1 mRNA was also significantly higher expressed in tumor samples of SCLC patients as compared to non-SCLC tumor samples or non-malignant lung tissue. Stimulation of SCLC cells with AITC led to a rise of the intracellular calcium concentration. This calcium response was inhibited by TRPA1 antagonists. Furthermore, AITC or formalin stimulated ERK1/2 in TRPA1-expressing HEK293 cells  and in SCLC cells via a Src- and calcium-dependent mechanism. More importantly, TRPA1 activation in SCLC cells prevented apoptosis induced by serum starvation and thus promoted cell survival, an effect which could be blocked by inhibition of TRPA1 or ERK1/2. Vice versa, down-regulation of TRPA1 severely impaired anchorage-independent growth of SCLC cells. Since TRPA1 appears to play a pivotal role for cell survival in SCLC cells we propose that this channel could represent a promising target for therapeutic interventions. Furthermore, our data suggest that exogenous, inhalable activators of TRPA1 could be able to exert tumor promoting effects in SCLC cells.

 

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[129]

TÍTULO / TITLE:  - Mechanisms of cisplatin-induced cell death in malignant mesothelioma cells: Role  of inhibitor of apoptosis proteins (IAPs) and caspases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):444-52. doi: 10.3892/ijo.2012.1715. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1715

AUTORES / AUTHORS:  - Cregan IL; Dharmarajan AM; Fox SA

INSTITUCIÓN / INSTITUTION:  - School of Anatomy and Human Biology, The University of Western Australia, Crawley, WA, Australia.

RESUMEN / SUMMARY:  - Malignant mesothelioma (MM) is an aggressive and highly chemoresistant tumour. Although cisplatin is used in frontline therapy of this disease treatment remains palliative at best. The biochemical pathways activated by cisplatin and the mechanisms of resistance in mesothelioma cells are poorly understood. Overexpression of inhibitor of apoptosis proteins (IAPs) has been described in clinical mesothelioma tumours and proposed as therapeutic targets. In this study, we examined cisplatin-induced cell death pathways and IAPs in three mesothelioma-derived cell lines. Cisplatin induced cell death in mesothelioma cell lines was characterised by biochemical mechanisms classically associated with apoptosis including: mitochondrial depolarisation, phosphatidylserine translocation and caspase activation. Surprisingly mRNA expression of IAPs in mesothelioma was not upregulated relative to primary mesothelial cells except for survivin which was higher in the most resistant cell line. In contrast, protein expression of both XIAP and survivin was upregulated in all mesothelioma cells, consistent with post-translational regulation. Knockdown of either XIAP or survivin by RNAi did not affect the sensitivity to cisplatin in any of the cell lines. Survivin RNAi did, however, inhibit proliferation in the highest expressing cell line, ONE58. The pan-caspase inhibitor z-VAD and the more selective caspase 3/7 inhibitor z-DEVD had no effect upon the sensitivity of any  of the cell lines to cisplatin indicating that caspase-independent pathways predominate. The findings of the present study provide insights into cisplatin-induced mechanisms in mesothelioma cells and show that alternative pathways are operating which may provide new options for targeting this extremely resistant tumour.

 

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[130]

TÍTULO / TITLE:  - Using socio-demographic and early clinical features in general practice to identify people with lung cancer earlier.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorax. 2013 Jan 15. doi: 10.1136/thoraxjnl-2012-202348.

            ●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2012-202348

AUTORES / AUTHORS:  - Iyen-Omofoman B; Tata LJ; Baldwin DR; Smith CJ; Hubbard RB

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Public Health, University of Nottingham, , Nottingham, UK.

RESUMEN / SUMMARY:  - INTRODUCTION: In the UK, most people with lung cancer are diagnosed at a late stage when curative treatment is not possible. To aid earlier detection, the socio-demographic and early clinical features predictive of lung cancer need to be identified. METHODS: We studied 12 074 cases of lung cancer and 120 731 controls in a large general practice database. Logistic regression analyses were  used to identify the socio-demographic and clinical features associated with cancer up to 2 years before diagnosis. A risk prediction model was developed using variables that were independently associated with lung cancer up to 4 months before diagnosis. The model performance was assessed in an independent dataset of 1 826 293 patients from the same database. Discrimination was assessed by means of a receiver operating characteristic (ROC) curve. RESULTS: Clinical and socio-demographic features that were independently associated with lung cancer were patients’ age, sex, socioeconomic status and smoking history. From 4  to 12 months before diagnosis, the frequency of consultations and symptom records of cough, haemoptysis, dyspnoea, weight loss, lower respiratory tract infections, non-specific chest infections, chest pain, hoarseness, upper respiratory tract infections and chronic obstructive pulmonary disease were also independently predictive of lung cancer. On validation, the model performed well with an area under the ROC curve of 0.88. CONCLUSIONS: This new model performed substantially  better than the current National Institute for Health and Clinical Excellence referral guidelines and all comparable models. It has the potential to predict lung cancer cases sufficiently early to make detection at a curable stage more likely by allowing general practitioners to better risk stratify their patients.  A clinical trial is needed to quantify the absolute benefits to patients and the  cost effectiveness of this model in practice.

 

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[131]

TÍTULO / TITLE:  - Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endoscopy. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1325988

AUTORES / AUTHORS:  - Uemura S; Yasuda I; Kato T; Doi S; Kawaguchi J; Yamauchi T; Kaneko Y; Ohnishi R; Suzuki T; Yasuda S; Sano K; Moriwaki H

INSTITUCIÓN / INSTITUTION:  - First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

RESUMEN / SUMMARY:  - Background and study aims: The aim of the current study was to assess the detection rate of the right adrenal gland and the diagnostic ability of endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) for the diagnosis of adrenal metastasis in potentially resectable lung cancer.Patients and methods: This retrospective cohort study included a consecutive series of 150 patients undergoing EUS/EUS - FNA for staging of lung cancer. The detection rate of the right adrenal gland by EUS and the diagnostic accuracies of computed tomography (CT), positron emission tomography-CT (PET-CT), and EUS/EUS - FNA for the diagnosis of adrenal metastasis were evaluated.Results: The right adrenal gland was visualized by EUS in 131 patients (87.3 %); the left adrenal gland was visualized in all patients. Findings suggestive of metastasis in either one of the adrenal glands or in both were observed in 6 patients (4.0 %) by CT, in 5 patients (3.3 %) by PET-CT, and in 11 patients (7.3 %) by EUS. EUS - FNA was performed simultaneously in the 11 patients, and in 4 patients the diagnosis of metastasis was established. The accuracy for the diagnosis of adrenal metastasis  was 100 % for EUS/EUS - FNA, 96.0 % for CT, and 97.0 % for PET-CT (P = 0.1146). Conclusions: As well as the left adrenal gland, the right adrenal gland was also  usually visible by EUS. EUS/EUS - FNA provided an accurate diagnosis of adrenal metastasis, although the prevalence of adrenal metastasis was relatively low in these patients with potentially resectable lung cancer.

 

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[132]

TÍTULO / TITLE:  - Radiographic assessment and therapeutic decisions at RECIST progression in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 14. pii: S0169-5002(12)00628-9. doi: 10.1016/j.lungcan.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.007

AUTORES / AUTHORS:  - Nishino M; Cardarella S; Dahlberg SE; Jackman DM; Ramaiya NH; Hatabu H; Rabin MS; Janne PA; Johnson BE

INSTITUCIÓN / INSTITUTION:  - Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA; Department of Radiology, Brigham and Women’s Hospital, 75 Francis St. Boston MA, 02215, USA. Electronic address: Mizuki_Nishino@DFCI.HARVARD.EDU.

RESUMEN / SUMMARY:  - PURPOSE: Advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) typically progresses after initial response due to acquired resistance. TKIs are often continued beyond progressive disease by RECIST. We investigated the practice of continuing EGFR-TKIs after RECIST-PD via CT findings. METHODS: Among 101 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line EGFR-TKIs, 70 patients had baseline and at least one follow-up CT for retrospective radiographic assessments using RECIST1.1; 56 patients had experienced PD by the data closure date of June 2011. RESULTS: Among 56 patients experiencing PD, 82% were female, median age was 63 years, 50% were never-smokers, 57% had distant metastasis, 57% had exon 19 deletion, and 89% were treated with erlotinib. 49 patients (88%) continued TKI therapy beyond retrospectively assessed PD. 31/32 (97%) patients who progressed by an increase in their target lesions continued TKI. 13/16 (81%) patients who progressed by appearance of a new lesion remained on TKI. 5/6 (83%) patients with both increase of target lesions and new lesion at PD continued TKI. Two patients with PD in non-target lesions discontinued therapy at PD. In 49 continuing patients, the median time from retrospectively assessed RECIST-PD to termination of TKI was 10.1 months. CONCLUSIONS: 88% of EFGR-mutant  NSCLC patients who progressed on first-line TKI continued therapy beyond RECIST-PD, which is not the single determining factor for terminating TKI in EGFR-mutant NSCLC patients. Additional radiographically defined progression criteria are needed for this population.

 

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[133]

TÍTULO / TITLE:  - Primary lung adenocarcinoma occurring in a PTEN related syndrome (Cowden’s disease): Routine EGFR sequencing also highlights two rare somatic mutations S768I and V769L.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 19. pii: S0169-5002(12)00641-1. doi: 10.1016/j.lungcan.2012.11.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.020

AUTORES / AUTHORS:  - Boespflug A; Couraud S; Bringuier PP; Isaac S; Geriniere L; Perrot E; Edery P; Durieu I; Souquet PJ

INSTITUCIÓN / INSTITUTION:  - Service de pneumologie et oncologie thoracique, Hospices Civils de Lyon, CH Lyon  Sud, 165 chemin du Grand Revoyet, 69495 Pierre Benite Cedex, France; Faculte de medecine et de Maieutique Lyon Sud - Charles Merieux, Universite Claude Bernard Lyon I, 69600 Oullins, France.

RESUMEN / SUMMARY:  - Cowden’s syndrome is a rare autosomal dominant disorder that has been linked to germline mutations in the phosphatase and TENsin homolog (PTEN) gene. PTEN is a tumour suppressor gene that negatively regulates the PI3K-AKT-mTOR pathway. Cowden’s syndrome is a multi-system disease with increased risks for a number of  malignancies but very rarely for lung cancer. A systematic follow-up chest CT scan was performed to a 42 year’s old female, light smoker. It showed a 20mm opacity of the left upper pulmonary lobe. Differential diagnose with benign tumours (such as hamartoma) was carefully searched. Procedures led to the diagnosis of a primitive lung adenocarcinoma. EGFR sequencing shows two rare somatic mutations (S768I and V769L). Lack of expression of PTEN is a non-sufficient condition leads to lung cancer formation alone. Nevertheless, it increases cell oncogenic potential. PTEN lacking in non small cell lung cancer is a frequent issue. It could be an alternative mechanism of non-efficacy of EGFR-TKI in cells with a sensitizing EGFR mutation. This case report, a very rare entity: a patient with a PTEN germline mutation and a lung adenocarcinoma harbouring two concomitant rare somatic mutations of EGFR. This observation comforts PTENs role in lung oncogenesis.

 

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[134]

TÍTULO / TITLE:  - Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 14. pii: S0169-5002(12)00639-3. doi: 10.1016/j.lungcan.2012.11.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.018

AUTORES / AUTHORS:  - Yanagawa N; Wang A; Kohler D; Santos GD; Sykes J; Xu J; Pintilie M; Tsao MS

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University Health Network, Princess Margaret Hospital site and Ontario Cancer Institute, Toronto, Ontario M5G2M9, Canada.

RESUMEN / SUMMARY:  - The reported prevalence for presence of human papillomavirus (HPV) genome in lung cancer varies across the world, and limited data are available for North America. P16 immunostaining is used as a surrogate marker for the presence of HPV in cervical and head and neck cancers. In non-small cell lung carcinoma (NSCLC), the association between P16 protein overexpression and HPV remains unclear. We investigated the presence of HPV genome by in situ hybridization (ISH) and polymerase chain reaction (PCR) and P16 or Rb protein expression by immunohistochemistry (IHC) in 336 surgically resected primary NSCLC: 204 adenocarcinoma (AdC) and 132 squamous cell carcinoma (SqCC). HPV genome was detected in 5 (1.5%) of 336 tumors studied by both ISH and PCR; all of them were  typed as HPV16 and found in SqCC (3.8%). Despite being solitary tumors and clinically considered as primary lung cancers, all 5 patients had past history of HPV associated squamous cell carcinomas of other organ sites, thus highly suggestive of being metastases. P16 immunostaining was found in 137 (40.8%) tumors, with 109 (32.4%) showing high level expression. All HPV positive (+) cases showed P16 high expression. P16 and Rb protein expressions were inversely correlated (P<0.001), suggesting that the high P16 expression is largely driven by non-HPV loss of Rb protein expression. We conclude that HPV is not or rarely associated with NSCLC in Canadian and most likely North American patients, and P16 immunostaining is not a surrogate marker for its presence.

 

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[135]

TÍTULO / TITLE:  - Preoperative platelet count in predicting lymph node metastasis and prognosis in  patients with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasma. 2013;60(2):203-8.

AUTORES / AUTHORS:  - Liu HB; Gu XL; Ma XQ; Lv TF; Wu Y; Xiao YY; Yuan DM; Li YF; Song Y

RESUMEN / SUMMARY:  - Recent studies have shown an indirect link between platelet count and blood vessel metastasis, but this association with lymphatic vessels metastasis has not been established in NSCLC. So we investigated whether an association exists between preoperative platelet count and lymph node metastasis in NSCLC patients.  Between January 2001 and January 2011, platelet counts were obtained from 883 NSCLC patients who were resistant to chemotherapy, radiotherapy, and surgery. The preoperative platelet counts, tumor metastasis, and overall survival of NSCLC patients were analyzed for correlations via statistical analysis. Upon considering patients according to their TNM lymph node metastasis stage (N0-N3),  multiple comparison analyses revealed that the mean preoperative platelet count of the N0 group was significantly lower than that of the N1-N3. Analysis of variance showed that the preoperative platelet count of patients in stage Iwas significantly lower than that of those in stages II, III, and IV, with no significant difference among the latter three stages. According to the Kaplan-Meier survival analysis, the overall survival of patients with platelet counts <214.5 x 109/L was significantly longer than that of those with platelet counts >/=214.5 x 109/L. Cox regression analysis indicated that, besides preoperative platelet count, patient age, gender, and TNM stage were independent  prognostic factors. In conclusion, preoperative platelet count was significantly  associated with metastasis of lymph nodes in NSCLC patients. Preoperative platelet count may be areliable biomarker of lymph node metastasis possibility and an independent prognostic factor of overall survival in patients with NSCLC.  Keywords: non-small cell lung cancer, preoperative platelet count, lymph nodes, metastasis, prognosis.

 

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[136]

TÍTULO / TITLE:  - Predictors for Locoregional Recurrence for Clinical Stage III-N2 Non-small Cell Lung Cancer with Nodal Downstaging After Induction Chemotherapy and Surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2800-x

AUTORES / AUTHORS:  - Amini A; Lou F; Correa AM; Baldassarre R; Rimner A; Huang J; Roth JA; Swisher SG; Vaporciyan AA; Lin SH

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

RESUMEN / SUMMARY:  - PURPOSE: Pathologic downstaging following chemotherapy for stage III-N2 NSCLC is  a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown. METHODS: Between 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All had pathologic N0-1 disease, and none received postoperative radiotherapy. LRR were defined as recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular), or both. RESULTS: Median follow-up was 39.3 months. Pretreatment N2 status was confirmed pathologically (18.2 %) or by PET/CT (81.8 %). Overall, the 5-year LRR rate was 30.8 % (n = 38), with LRR being the first site of failure in 51 % (22/+99877943). Five-year overall survival for patients with LRR compared with those without was  21 versus 60.1 % (p < 0.001). Using multivariate analysis, significant predictors for LRR were pN1 disease at time of surgery (p < 0.001, HR 3.43, 95 % CI 1.80-6.56) and a trend for squamous histology (p = 0.072, HR 1.93, 95 % CI 0.94-3.98). Five-year LRR rate for pN1 versus pN0 disease was 62 versus 20 %. Neither single versus multistation N2 disease (p = 0.291) nor initial staging technique (p = 0.306) were predictors for LRR. N1 status also was predictive for  higher distant recurrence (p = 0.021, HR 1.91, 95 % CI 1.1-3.3) but only trended  for poorer survival (p = 0.123, HR 1.48, 95 % CI 0.9-2.44). CONCLUSIONS: LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease.

 

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[137]

TÍTULO / TITLE:  - The presence of mutations in epidermal growth factor receptor gene is not a prognostic factor for long-term outcome after surgical resection of non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):171-8. doi: 10.1097/JTO.0b013e318277a3bb.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318277a3bb

AUTORES / AUTHORS:  - Kim YT; Seong YW; Jung YJ; Jeon YK; Park IK; Kang CH; Kim JH

INSTITUCIÓN / INSTITUTION:  - *Department of Thoracic and Cardiovascular Surgery, Clinical Research Institute,  Seoul National University Hospital, Seoul, Korea; daggerGenomic Medicine Institute, Medical Research Center and Cancer Research Institute, double daggerDepartment of Pathology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - BACKGROUND: : The presence of mutation in EGFR gene is known as a predictive marker for the response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. However, whether or not these EGFR mutations are prognostic factors for non-small-cell lung cancer (NSCLC) is debatable. METHODS: : We retrospectively collected a series of samples from patients whose EGFR mutation status had been tested, and analyzed their survival. The pathologic cell types of 863 patients (520 men, 343 women) were squamous cell carcinoma in 227, adenocarcinoma in 636 patients. RESULTS: : EGFR mutations were detected in 354 patients and it was frequently observed in adenocarcinoma in younger, early-stage, female never-smokers. In univariate analysis of younger, early-stage, never-smoker women, bronchioloalveolar carcinoma pattern and the presence of EGFR mutation showed better long-term survival. However, in multivariate analysis, age, pathologic stage, and smoking status remained significant prognostic factors, whereas EGFR mutation was not. For recurrence, pathologic stage was the only independent prognostic factor. After recurrence, smoking status was the only significant risk factor that affected postrecurrence  survival. However, when EGFR TKIs were used in EGFR-mutated patients, survival was longer than for those treated with conventional chemotherapy. CONCLUSIONS: :  Although the EGFR mutation is a predictive marker for EGFR TKI response, it is not a prognostic factor in NSCLC. The clinical observation that patients with EGFR mutation seem to survive longer may be because EGFR mutation is more frequently associated with other good prognostic factors. Once there is a recurrence, administration of EGFR TKI for patients with EGFR mutation may increase survival.

 

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[138]

TÍTULO / TITLE:  - Polymorphism of VEGF-460C/T associated with the risk and clinical characteristics of lung cancer in Chinese population.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):410. doi: 10.1007/s12032-012-0410-x. Epub 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0410-x

AUTORES / AUTHORS:  - Sun SF; Huang DB; Cao C; Deng ZC

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Affiliated Hospital, Medical College, Ningbo  University, Ningbo, 315020, China.

RESUMEN / SUMMARY:  - Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. Different VEGF gene polymorphisms have been shown to result in different VEGF protein expression in cancer cells and tumor angiogenic activity. We conducted a case-control study to evaluate the  genetic effects of VEGF-460C/T polymorphism on the development of lung cancer. One hundred and twenty-six lung cancer patients and 160 sex-, age-, and ethnic-matched healthy controls were recruited for this study. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism  (PCR-RFLP). Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated  by logistic regression analysis. Our study showed that the TT genotype was associated with increased lung cancer risk than those with the CC (OR = 1.99, 95  % CI 1.05-3.77) or CT/CC (OR = 1.89, 95 % CI 1.17-3.06) genotype. Moreover, it was observed that the TT genotype associated with the advanced stage among lung cancer patients (TT vs. CC: OR = 3.09, 95 % CI 1.10-8.66). More studies are needed to detect VEGF-460C/T polymorphism and its association with lung cancer in different ethnic populations incorporated with environmental exposures.

 

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[139]

TÍTULO / TITLE:  - Assessment of the impact of adjunctive proactive telephone counseling to promote  smoking cessation among lung cancer patients’ social networks.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Health Promot. 2013 Jan;27(3):181-90. doi: 10.4278/ajhp.101122-QUAN-387.

            ●● Enlace al texto completo (gratuito o de pago) 4278/ajhp.101122-QUAN-387

AUTORES / AUTHORS:  - Bastian LA; Fish LJ; Peterson BL; Biddle AK; Garst J; Lyna P; Molner S; Bepler G; Kelley M; Keefe FJ; McBride CM

RESUMEN / SUMMARY:  - Abstract Purpose. When a patient is diagnosed with lung cancer, members of his/her social network may be more likely to engage in smoking cessation efforts. Proactive telephone counseling combined with a tailored self-directed intervention may be more effective at promoting smoking cessation than a tailored self-directed intervention alone. Design. Randomized controlled trial. Setting. Four clinical sites. Subjects. Current smokers who are family members and close friends of patients with lung cancer. Intervention. Six counselor-initiated counseling calls using motivational interviewing techniques and focusing on teaching adaptive coping skills based on the transactional model of stress and coping along with tailored self-directed materials (including nicotine patches, if not contraindicated) (n = 245) vs. tailored self-directed materials (including nicotine patches, if not contraindicated) (n = 251). Measures. Participants were  surveyed at baseline and at 2 weeks, 6 months, and 12 months postintervention. The outcome was 7-day point prevalent abstinence. Analysis. The objective of this study was to test for arm differences in smoking cessation rates at 2 weeks and 6 months postintervention (primary) and at 12 months postintervention (secondary).  Results. We found no overall effect of the proactive intervention on cessation rates. Among younger participants (age <50), the cessation rate in the intervention group was higher than in the control group at 2 weeks postintervention (16% vs. 4%, p = .046). For older participants (age >50), there  were no group differences. Conclusion. Proactive telephone counseling focusing on adaptive coping skills was difficult to implement among smokers in lung cancer patients’ social network. Although this study did not demonstrate any added benefit to cessation rates, this null finding may be a result of an intervention  that was weaker than intended, owing to difficulties in completing the counseling phone calls. We discuss lessons learned and areas for future research in this special population.

 

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[140]

TÍTULO / TITLE:  - Combined Treatment with Erlotinib and a Transforming Growth Factor-beta Type I Receptor Inhibitor Effectively Suppresses the Enhanced Motility of Erlotinib-Resistant Non-Small-Cell Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318279e942

AUTORES / AUTHORS:  - Serizawa M; Takahashi T; Yamamoto N; Koh Y

INSTITUCIÓN / INSTITUTION:  - *Drug Discovery and Development Division, and daggerDivision of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

RESUMEN / SUMMARY:  - INTRODUCTION:: Despite an initial dramatic response to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, the majority of non-small cell lung cancer (NSCLC) patients with EGFR-activating  mutations develop acquired resistance. Therefore, there is an urgent need to elucidate the unknown mechanisms and biological behaviors of EGFR TKI-resistant lung tumors. We investigated the motility of EGFR TKI-resistant cells, as these characteristics are relevant to cancer metastasis. METHODS:: Erlotinib-resistant  PC-9ER cells were generated from PC-9 NSCLC cells, which harbor an EGFR-activating mutation, and used in this study. We investigated the involvement of the transforming growth factor beta (TGF-beta) pathway in cell motility, and tested the effects of erlotinib and TGF-beta type I receptor (RI) inhibition on cell motility. RESULTS:: PC-9ER cells displayed enhanced motility resulting from  autocrine activation of the TGF-beta pathway. Increased TGF-beta2 secretion resulting from TGF-beta2 up-regulation at the transcriptional level was suggested to be responsible for the phosphorylation of Smad2 and the subsequently elevated  transcriptional regulatory activity in PC-9ER cells. The motility of PC-9ER cells was suppressed by treatment with either the TGF-betaRI inhibitor LY364947 or erlotinib, and greater suppression was observed when used in combination. LY364947 or erlotinib exerted no growth-inhibitory effects, suggesting that motility and growth are driven by different signaling pathways in PC-9ER cells. CONCLUSIONS:: Our results imply that blockade of the TGF-beta signaling pathway combined with continuous EGFR TKI treatment will be beneficial in preventing metastasis in patients with EGFR TKI-resistant NSCLC without the EGFR T790M resistance mutation.

 

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[141]

TÍTULO / TITLE:  - Efficient down-regulation of PKC-alpha gene expression in A549 lung cancer cells  mediated by antisense oligodeoxynucleotides in dendrosomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Pharm. 2013 Jan 30;441(1-2):82-91. doi: 10.1016/j.ijpharm.2012.12.015. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijpharm.2012.12.015

AUTORES / AUTHORS:  - Movassaghian S; Moghimi HR; Shirazi FH; Koshkaryev A; Trivedi MS; Torchilin VP

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Valiasr Ave., Niayesh Junction, PO Box 14155-6153, Tehran, Iran; Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA.

RESUMEN / SUMMARY:  - The completion of human genome project has increased our knowledge of the molecular mechanisms of many diseases, including cancer, thus providing new opportunities for gene therapy. Antisense oligodeoxynucleotides (AsODN) possess great potential as sequence-specific therapeutic agents, which in contrast to classic treatments provide more efficient and target-specific approach to modulate disease-related genes. To be therapeutically effective, sufficient concentrations of intact AsODN must bypass membrane barriers and access the site  of action. In this study, a dendrosome delivery strategy was designed to improve  the encapsulation of AsODN in non-cationic liposomes to target PKC-alpha in lung  cancer cells in vitro. Subcellular trafficking of fluorescently labeled AsODN was visualized using confocal microscopy. Uptake and expression of mRNA and target protein after AsODN delivery was measured by flow cytometry, qRT-PCR and Western  blot analysis, respectively. Dendrosomes showed favorable physicochemical parameters: high encapsulation efficiency and uptake in serum-containing medium with no apparent cytotoxicity. AsODN encapsulated in dendrosome efficiently and specifically suppress the target gene at both mRNA and protein levels. Additional in vivo studies on the application of dendrosome as a delivery system for nucleic acid molecules may lead to improvement of this technology and facilitate the development of therapeutic antisense techniques.

 

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[142]

TÍTULO / TITLE:  - PARP inhibition selectively increases sensitivity to cisplatin in ERCC1-low non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs393

AUTORES / AUTHORS:  - Cheng H; Zhang Z; Borczuk A; Powell CA; Balajee AS; Lieberman HB; Halmos B

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, NY 10032, USA.

RESUMEN / SUMMARY:  - Platinum compounds are the foundation of chemotherapy regimens for non-small cell lung cancer (NSCLC) despite poor response rates and limited response duration. It has been reported that tumor expression of excision repair cross-complementation  group 1 (ERCC1), a key component in nucleotide excision repair, may correlate with clinical response to platinum agents. We found that most primary lung tumor  specimens demonstrated a stronger protein expression of poly (adenosine diphosphate ribose) polymerases 1 (PARP1) than their normal counterparts. Therefore, we hypothesized that combining PARP inhibition with platinum compounds may be an approach to improve platinum-based therapy for NSCLC. Drug combination  experiments revealed that two distinct PARP inhibitors, olaparib and veliparib, not only potentiated the cell killing by cisplatin but also conferred cytotoxicity as a single agent specifically in ERCC1-low HCC827 and PC9 but not in ERCC1-high A549 and H157 lung cancer cells. Moreover, small interfering RNA knockdown of ERCC1 in A549 and H157 cells increased their sensitivities to both cisplatin and olaparib in a synergistic manner in our model. Furthermore, mechanistic studies indicated that combined PARP inhibitor and cisplatin could lead to sustained DNA double-strand breaks, prolonged G(2)/M cell cycle arrest with distinct activation of checkpoint kinase 1 signaling and more pronounced apoptosis preferentially in lung cancer cells with low ERCC1 expression. Collectively, these data suggest that there is a synergistic relationship between PARP inhibition and low ERCC1 expression in NSCLC that could be exploited for novel therapeutic approaches in lung cancer therapy based on tumor ERCC1 expression.

 

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[143]

TÍTULO / TITLE:  - The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):320. doi: 10.1007/s12032-012-0320-y. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0320-y

AUTORES / AUTHORS:  - Holgersson G; Bergqvist M; Nyman J; Hoye E; Helsing M; Friesland S; Holgersson M; Ekberg L; Morth C; Ekman S; Blystad T; Ewers SB; Loden B; Henriksson R; Bergstrom S

INSTITUCIÓN / INSTITUTION:  - Section of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden, georg.h@telia.com.

RESUMEN / SUMMARY:  - The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments  for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected  to curatively intended irradiation (>/=50 Gy) during the years 1990 to 2000. The  included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Patients who did not have a histopathological diagnosis date and/or death date/last follow-up date as well as patients being surgically treated were excluded from the study (n = 592). Thus, 695 patients were included  in the present study. Patients who received hyperfractionated radiotherapy (HR) had a higher local control rate compared with patients receiving conventional fractionation (CF) (38 vs. 49 % local relapse). The difference in survival between the two radiotherapy regimens was statistically significant in a univariate Cox analysis (p = 0.023) in favor of HR. This significance was, however, not retained in a multivariate Cox analysis (p = 0.56). Thus, the possible beneficial effects of hyperfractionation are still unclear and need to be further investigated in well-controlled prospective clinical trials, preferably including systemic treatment with novel drugs.

 

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[144]

TÍTULO / TITLE:  - Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with HER1- and HER2-targeted Radiolabeled Antibodies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12121021

AUTORES / AUTHORS:  - Nayak TK; Bernardo M; Milenic DE; Choyke PL; Brechbiel MW

INSTITUCIÓN / INSTITUTION:  - Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, and Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Building 10, Room B3B69F, Bethesda, MD 20892.

RESUMEN / SUMMARY:  - Purpose:To evaluate the potential of anti-human epidermal growth factor receptor  (HER)1- and anti-HER2-targeted radiolabeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models.Materials and Methods:Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1- and HER2-targeted indium 111 ((111)In)- and iodine 125 ((125)I)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups.Results:Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean (111)In-panitumumab uptake of 29.6% injected dose (ID) per gram +/- 2.2 (standard error of the mean) was significantly greater than the (111)In-trastuzumab uptake of 13.6% ID/g +/- 1.0 and the (125)I-panitumumab uptake of 7.4% ID/g +/- 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about (111)In-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone.Conclusion:This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121021/-/DC1.

 

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[145]

TÍTULO / TITLE:  - The novel PI3K-mTOR inhibitor, BEZ235, circumvents erlotinib- resistance of EGFR  mutant lung cancer cells triggered by HGF.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 15. doi: 10.1002/ijc.28034.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28034

AUTORES / AUTHORS:  - Sano T; Takeuchi S; Nakagawa T; Ishikawa D; Nanjo S; Yamada T; Nakamura T; Matsumoto K; Yano S

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

RESUMEN / SUMMARY:  - Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, is a critical problem in the management of patients with EGFR mutant lung cancer. Several mechanisms have  been reported involved in this acquired resistance, including hepatocyte growth factor (HGF) activation of an alternative pathway. PI3K and mTOR are downstream molecules of receptor tyrosine kinases, such as EGFR and Met, and are thought to  be ideal targets for controlling various tumor types. We assessed whether BEZ235, a dual inhibitor of PI3K and mTOR, could overcome the EGFR-TKI resistance induced by HGF in an EGFR mutant lung cancer model. Exogenous and endogenous HGF triggered resistance to erlotinib in the PC-9 and HCC827, EGFR mutant lung cancer cell lines. BEZ235 alone inhibited the viability of PC-9 and HCC827 cells in vitro, irrespective of the presence or absence of HGF. Using a xenograft model of SCID mice with HGF-gene transfected PC-9 cells (PC-9/HGF), we found that BEZ235 inhibited tumor growth, whereas erlotinib did not. BEZ235 monotherapy also inhibited the phosphorylation of Akt and p70S6K/S6RP, downstream molecules of PI3K and mTOR, respectively, as well as suppressing tumor-cell proliferation and  angiogenesis of PC-9/HGF tumors. These results suggest that BEZ235, even as monotherapy, may be useful in managing HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer. © 2013 Wiley Periodicals, Inc.

 

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[146]

TÍTULO / TITLE:  - Presurgical Planning Using a Three-Dimensional Pulmonary Model of the Actual Anatomy of Patient with Primary Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Cardiovasc Surg. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1328923

AUTORES / AUTHORS:  - Kanzaki M; Kikkawa T; Shimizu T; Maeda H; Wachi N; Isaka T; Murasugi M; Onuki T

INSTITUCIÓN / INSTITUTION:  - Department of Surgery I, School of Medicine, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan.

RESUMEN / SUMMARY:  - Objectives Video-assisted thoracoscopic surgery (VATS) for both lobectomy and segmentectomy has been used widely for early stage nonsmall cell lung cancer (NSCLC). The objective of this study was to investigate the clinical feasibility  of surgical planning using patient’s actual three-dimensional (3D) pulmonary model for the thoracoscopic surgical treatment of early stage NSCLC.Methods We examined 57 patients with stage IA NSCLC </= 2 cm in diameter. Based on patient’s actual 3D pulmonary model created by using a homemade software program called CTTRY (Tokyo Women’s Medical University, Tokyo, Japan), both the location of and  extent of tumor invasion were assessed, and a suitable type of VATS lung resection for an individual was selected.Results By the 3D models, tumors in 47 patients were localized within one segment, and other tumors (10 patients, 18%) were involved in multiple segments. VATS lung resections consisted of a single segmentectomy were performed in 25 patients; upper division resections, 9; lingulectomy, 5; extended segmentectomy, 7; single subsegmentectomy, 6; and multiple subsegmentectomy, 5. All 57 patients underwent successful VATS lung resection without massive bleeding.Conclusion Presurgical planning based on patient’s actual 3D pulmonary model is useful for patients with stage IA NSCLC </= 2 cm in diameter and for selecting an appropriate VATS lung resection for an  individual.

 

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[147]

TÍTULO / TITLE:  - Solitary pulmonary metastasis from lung cancer harboring EML4-ALK after a 15-year disease-free interval.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 29. pii: S0169-5002(12)00678-2. doi: 10.1016/j.lungcan.2012.12.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.011

AUTORES / AUTHORS:  - Tomizawa K; Ito S; Suda K; Fukui T; Usami N; Hatooka S; Kuwano H; Yatabe Y; Mitsudomi T

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.

RESUMEN / SUMMARY:  - It is often difficult to differentiate metachronous primary lung cancers from local pulmonary recurrences when the histopathological findings are similar. A 43-year-old man underwent right upper lobectomy with lymph node dissection for primary lung adenocarcinoma (p-T2aN0M0, stage IB). Fifteen years later, he developed a lung nodule in his right middle lobe. The tumor was preoperatively thought to be a metachronous second primary lung adenocarcinoma, and was surgically resected. Histopathological findings for both tumors were of poorly differentiated adenocarcinoma with mucus production. Both tumors also harbored the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene (variant 3a+b). Based on this molecular finding, the pulmonary nodule was considered to be a recurrence after very long latent period.

 

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[148]

TÍTULO / TITLE:  - Evaluation of methods for selecting the midventilation bin in 4DCT scans of lung  cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.762993

AUTORES / AUTHORS:  - Nygaard DE; Persson GF; Brink C; Specht L; Korreman SS

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Rigshospitalet, University of Copenhagen , Denmark.

RESUMEN / SUMMARY:  - Background. In lung cancer radiotherapy, planning on the midventilation (MidV) bin of a four-dimensional (4D) CT scan can reduce the systematic errors introduced by respiratory tumour motion compared to conventional CT. In this study four different methods for MidV bin selection are evaluated. Material and methods. The study is based on 4DCT scans of 19 patients with a total of 23 peripheral lung tumours having peak-to-peak displacement >/= 5 mm in at least one of the left-right (LR), anterior-posterior (AP) or cranio-caudal (CC) directions. For each tumour, the MidV bin was selected based on: 1) visual evaluation of tumour displacement; 2) rigid registration of tumour position; 3) diaphragm displacement in the CC direction; and 4) carina displacement in the CC direction. Determination of the MidV bin based on the displacement of the manually delineated gross tumour volume (GTV) was used as a reference method. The accuracy of each method was evaluated by the distance between GTV position in the selected MidV bin and the time-weighted mean position of GTV throughout the bins (i.e. the geometric MidV error). Results. Median (range) geometric MidV error was 1.4 (0.4-5.4) mm, 1.4 (0.4-5.4) mm, 1.9 (0.5-6.9) mm, 2.0 (0.5-12.3) mm and 1.1 (0.4-5.4) mm for the visual, rigid registration, diaphragm, carina, and reference method. Median (range) absolute difference between geometric MidV error for the evaluated methods and the reference method was 0.0 (0.0-1.2) mm, 0.0 (0.0-1.7) mm, 0.7 (0.0-3.9) mm and 1.0 (0.0-6.9) mm for the visual, rigid registration, diaphragm and carina method. Conclusion. The visual and semi-automatic rigid registration methods were equivalent in accuracy for selecting the MidV bin of a  4DCT scan. The methods based on diaphragm and carina displacement cannot be recommended without modifications.

 

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[149]

TÍTULO / TITLE:  - 2,3,6-Trisubstituted quinoxaline derivative, a small molecule inhibitor of the Wnt/beta-catenin signaling pathway, suppresses cell proliferation and enhances radiosensitivity in A549/Wnt2 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Jan 21. pii: S0006-291X(13)00100-9. doi: 10.1016/j.bbrc.2013.01.038.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.038

AUTORES / AUTHORS:  - Lee SB; Gong YD; Park YI; Dong MS

INSTITUCIÓN / INSTITUTION:  - School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

RESUMEN / SUMMARY:  - GDK-100017, a 2,3,6-trisubstituted quinoxaline derivative, reduced beta-catenin-T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity and inhibited cell proliferation in a dose-dependent manner with an IC(50) value of about 10muM in A549/Wnt2 cells. GDK-100017 down-regulated the expression of Wnt/beta-catenin pathway target genes such as cyclin D1 and Dkk1 but not c-myc or survivin. GDK-100017 inhibited cell proliferation by arresting the cell cycle in the G1 phase not only in A549/wnt2 cells but also in SW480 colon cancer cells. In addition to its wnt signaling inhibitory properties, GDK-100017 also enhanced the radiosensitivity of the A549  human NSCLC line. These results suggest that GDK-100017 possesses potential anti-cancer activity by inhibiting the Wnt/beta-catenin signal pathway, blocking  the beta-catenin-TCF/LEF interaction, and enhancing radiosensitivity.

 

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[150]

TÍTULO / TITLE:  - Use of the cytokinesis-blocked micronucleus assay to detect gender differences and genetic instability in a lung cancer case-control study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):135-45. doi: 10.1158/1055-9965.EPI-12-0435. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-0435

AUTORES / AUTHORS:  - McHugh MK; Lopez MS; Ho CH; Spitz MR; Etzel CJ; El-Zein RA

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Randa El-Zein, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. relzein@mdanderson.org.

RESUMEN / SUMMARY:  - BACKGROUND: Although tobacco exposure is the predominant risk factor for lung cancer, other environmental agents are established lung carcinogens. Measuring the genotoxic effect of environmental exposures remains equivocal, as increases in morbidity and mortality may be attributed to coexposures such as smoking. METHODS: We evaluated genetic instability and risk of lung cancer associated with exposure to environmental agents (e.g., exhaust) and smoking among 500 lung cancer cases and 500 controls using the cytokinesis-blocked micronucleus (CBMN) assay. Linear regression was applied to estimate the adjusted means of the CBMN endpoints (micronuclei and nucleoplasmic bridges). Logistic regression analyses were used to estimate lung cancer risk and to control for potential confounding by age, gender, and smoking. RESULTS: Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared with controls (mean +/- SEM = 3.54 +/- 0.04 vs. 1.81 +/- 0.04 and mean +/- SEM = 4.26 +/- 0.03 vs. 0.99 +/- 0.03, respectively; P < 0.001) with no differences among participants with or without reported environmental exposure. No differences were observed when stratified by smoking or environmental exposure among cases or controls. A difference in lung cancer risk was observed between nonexposed male and female heavy smokers, although it was not statistically significant (I(2) = 64.9%; P value for Q statistic = 0.09). CONCLUSIONS: Our study confirms that the CBMN assay is an accurate predictor of lung cancer and supports the premise that heavy smoking may have an effect on DNA repair capacity and in turn modulate the risk of lung cancer. Impact: Identifying factors that increase lung cancer risk may lead to more effective prevention measures. Cancer Epidemiol Biomarkers Prev; 22(1); 135-45. ©2012 AACR.

 

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[151]

TÍTULO / TITLE:  - Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):349. doi: 10.1007/s12032-012-0349-y. Epub 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0349-y

AUTORES / AUTHORS:  - Yoshida T; Yamada K; Azuma K; Kawahara A; Abe H; Hattori S; Yamashita F; Zaizen Y; Kage M; Hoshino T

INSTITUCIÓN / INSTITUTION:  - Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.

RESUMEN / SUMMARY:  - Previous studies have demonstrated that both gefitinib and erlotinib are markedly effective for the treatment of non-small-cell lung cancer (NSCLC) with somatic activating mutations of the epidermal growth factor receptor gene (EGFR-mt). These agents are considered to act on EGFR through the same mechanism. However, the efficacy of these agents against EGFR wild-type (-wt) NSCLC remains unclear,  and the frequency of adverse events (AEs) appears to differ between them at each  approved dose. Here, we conducted a retrospective analysis of AEs and drug efficacy in patients with NSCLC whose EGFR mutation status had been confirmed and who all received 250 mg gefitinib or 150 mg erlotinib once daily. The erlotinib group (n = 35) had more AEs, including rash, fatigue, stomatitis, anorexia and constipation. On the other hand, liver dysfunction and nail change were more frequent in the gefitinib group (n = 107). AEs of >/=grade 2, including rash, fatigue and nausea, were more frequent in the erlotinib group. The erlotinib group also showed more of a tendency to require dose reduction due to AEs. With regard to treatment efficacy for patients with EGFR-wt, there was no significant  difference in progression-free survival between the two drug groups. However, this study has several limitations as of the nature of retrospective design; our  data suggest that gefitinib and erlotinib might have almost equal efficacy for patients with EGFR-wt NSCLC, as is the case for patients with EGFR-mt tumors, although erlotinib appears to have higher toxicity than gefitinib at each approved dose.

 

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[152]

TÍTULO / TITLE:  - Association of RASSF1A and p63 with Poor Recurrence-Free Survival in Node-Negative Stage I-II Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2848

AUTORES / AUTHORS:  - Ko E; Lee BB; Kim Y; Lee EJ; Cho EY; Han J; Shim YM; Park J; Kim DH

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, and Departments of Pathology and Thoracic and Cardiovascular  Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: This study was aimed at analyzing the recurrence-related prognostic significance of 12 candidate molecular biomarkers in node-negative stage I-II non-small cell lung cancer (NSCLC).EXPERIMENTAL DESIGN: We retrospectively analyzed promoter methylation of eight genes using methylation-specific PCR in formalin-fixed and paraffin-embedded tissues from 328 node-negative stage I-II NSCLCs. The expression of Bcl-2, E-cadherin, p53, and p63 proteins was also assessed by immunohistochemistry.RESULTS: Recurrence was found in 145 (44%) of 328 node-negative stage I-II NSCLCs with a median follow-up period of 6.2 years.  No association was found between recurrence and alteration of individual biomarker in univariate analysis. We defined recurrently divergent groups on the  basis of recursive partitioning analyses for 12 biomarkers and found a significant association of co-alteration of RASSF1A and p63 with poor recurrence-free survival (RFS). Cox proportional hazards analysis showed that hypermethylation of RASSF1A and negative expression of p63 was associated with poor RFS [HR, 1.93; 95% confidence interval (CI), 1.13-5.47; P = 0.009] compared  with those without co-alteration of RASSF1A and p63, after adjusting for age, adjuvant therapy, histology, and tumor size. Random forest classifier including RASSF1A and p63 showed best performance in the prediction of recurrence in node-negative stage I-II NSCLCs: area under receiver operator characteristic curve for random forest was 0.91 and error rate for the model was 17%.CONCLUSION: The present study suggests that RASSF1A and p63 may be independent prognostic indicators for RFS in node-negative stage I-II NSCLCs. Clin Cancer Res; 1-9. ©2012 AACR.

 

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[153]

TÍTULO / TITLE:  - Derlin-1 Is Overexpressed in Non-Small Cell Lung Cancer and Promotes Cancer Cell  Invasion via EGFR-ERK-Mediated Up-Regulation of MMP-2 and MMP-9.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Pathol. 2013 Jan 7. pii: S0002-9440(12)00885-1. doi: 10.1016/j.ajpath.2012.11.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.11.019

AUTORES / AUTHORS:  - Dong QZ; Wang Y; Tang ZP; Fu L; Li QC; Wang ED; Wang EH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

RESUMEN / SUMMARY:  - Previous studies indicated a role of Derlin-1 in human cancers; however, its expression pattern in non-small cell lung cancer (NSCLC) and the molecular mechanism of Derlin-1 on cancer progression have not been characterized. In the present study, Derlin-1 expression was examined in lung cancer cell lines and human tissues. Derlin-1 overexpression correlated with pTNM stage, lymph node metastasis, and poor overall survival. siRNA knockdown of Derlin-1 impaired anchorage-dependent and anchorage-independent cell growth and invasion in A549 and H1299 cell lines, and its overexpression promoted proliferation and invasion  in HBE and LTE cell lines. Derlin-1 depletion decreased matrix metalloproteinase  (MMP)-2/9 at both protein and mRNA levels, with decreased MAP kinase/extracellular signal-regulated kinase (ERK)/ERK phosphorylation. Derlin-1  overexpression up-regulated MMP-2/9 expression and ERK phosphorylation, which could be reversed by MAP kinase/ERK kinase inhibitor, PD98059. The effect of Derlin-1 on MMP-2/9 up-regulation was abolished in ERK1/2 siRNA-treated cells. Further analysis showed that Derlin-1 overexpression induced EGFR phosphorylation. EGFR inhibitor blocked Derlin-1-mediated up-regulation of EGFR and ERK phosphorylation. MMP-2/9 and p-ERK up-regulation by Derlin-1 was partly blocked in EGFR-depleted cells with siRNA treatment. Immunoprecipitation confirmed the association between Derlin-1 and EGFR. In summary, our results showed that Derlin-1 is overexpressed in NSCLC and promotes invasion by EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Derlin-1 may serve as a therapeutic target for NSCLC.

 

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[154]

TÍTULO / TITLE:  - The presence of merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 25. doi: 10.1002/ijc.28062.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28062

AUTORES / AUTHORS:  - Lasithiotaki I; Antoniou KM; Derdas SP; Sarchianaki E; Symvoulakis EK; Psaraki A; Spandidos DA; Stathopoulos EN; Siafakas NM; Sourvinos G

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Medicine, University Hospital, Medical School, University  of Crete, Heraklion 71110, Crete.

RESUMEN / SUMMARY:  - Polyomaviruses such as BK virus (BKV), JC virus (JCV) and Merkel Cell Polyomavirus (MCPyV) are typically non-oncogenic, although they have been detected in a variety of human neoplasms. The aim of this study was to determine  the frequency of the most common polyomaviruses MCPyV, BKV and JCV as well as the gene expression profile of genes involved in oncogenesis including K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in a cohort of non-small cell lung cancer (NSCLC) patients. Real-Time and nested PCR were employed to assess the presence of polyomaviruses DNA in tissue biopsies from 110 patients with primary NSCLC and 14 tissue specimens from macroscopically healthy sites of their lung. Real Time PCR  was also employed to determine the mRNA expression of K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in selected samples. Results showed that 10 NSCLC specimens were positive for the presence of MCPyV DNA (10/110, 9.1%), whereas no control sample was tested positive for the virus. The MCPyV-positive samples were predominantly obtained from male smokers (9/10). BKV and JCV DNA was not detected either in lung tissues biopsies or the control specimens. Interestingly, gene expression analysis revealed increased mRNA and protein expression of BRAF gene in association with BRAF phosphorylation in the MCPyV-positive samples, whereas Bcl-2 gene expression was downregulated in the same type of samples. The detected MCPyV prevalence in NSCLC in combination with the deregulated expression of BRAF  and Bcl-2 genes suggests that these events are likely to contribute to the pathogenesis of NSCLC.

 

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[155]

TÍTULO / TITLE:  - Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Chromosomes Cancer. 2013 Mar;52(3):305-15. doi: 10.1002/gcc.22030. Epub 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1002/gcc.22030

AUTORES / AUTHORS:  - Liang Y; Liu M; Wang P; Ding X; Cao Y

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

RESUMEN / SUMMARY:  - Chromosomal aberrations at 12q13 are frequent in nonsmall-cell lung cancer (NSCLC). Here, we examined mRNA expression of 20 genes within chromosome band 12q13 by quantitative real-time polymerase chain reaction in NSCLC. Of the 20 genes, nine were upregulated, while two genes were downregulated. Among the nine  upregulated genes, mRNA values of RACGAP1, MCRS1, EIF4B, WNT1, and PTGES3 were significantly higher in NSCLCs compared with normal lung tissues. Subsequently, overexpressions of RACGAP1 and MCRS1 were confirmed at the protein level in tissues and cultured cells of lung cancer by immunostaining and Western blot. RACGAP1 was labeled in the nucleus of tumor cells in 89% of the tumor specimens.  In the cultured cells, RACGAP1 was present principally in the nucleus of nonmitotic cells, but showed a diffuse distribution in the cytoplasm of mitotic cells (metaphase) and at the contractile ring between two separating daughter cells (telophase). Furthermore, RACGAP1 downregulation by RNA interference caused cytokinesis defects, indicating that RACGAP1 is required for cytokinesis. MCRS1 was stained in all tumor specimens and strongly stained in 31% of cases. Interestingly, MCRS1 exhibits different localization in the mitotic cells of cultured immortalized human bronchial epithelial cells and cultured lung cancer cells. In vitro, downregulation of MCRS1 in lung cancer cells inhibited cell proliferation, increased apoptosis, and induced cell cycle arrest at the G1 phase. These findings indicate that RACGAP1 and MCRS1 may be cancer-related genes in NSCLC. © 2012 Wiley Periodicals, Inc.

 

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[156]

TÍTULO / TITLE:  - Ionizing radiation-induced gamma-H2AX activity in whole blood culture and the risk of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-0794

AUTORES / AUTHORS:  - He Y; Gong Y; Lin J; Chang DW; Gu J; Roth JA; Wu X

INSTITUCIÓN / INSTITUTION:  - 1Department of Epidemiology, University of Texas M.D. Anderson Cancer Center.

RESUMEN / SUMMARY:  - BACKGROUND: Phenotypic biomarkers of DNA damage repair may enhance cancer risk prediction. The gamma-H2AX formed at the sites of double strands break (DSB) after ionizing radiation (IR) is a specific marker of DNA damage. METHODS: In an  ongoing case-control study, the baseline and IR-induced gamma-H2AX levels in peripheral blood lymphocytes (PBLs) from frequency-matched 306 untreated lung cancer patients and 306 controls were measured by a laser scanning cytometer-based immunocytochemical method. The ratio of IR-induced gamma-H2AX level to the baseline was used to evaluate inter-individual variation of DSB damage response and to assess the risk of lung cancer by using unconditional multivariable logistic regression with adjustment of age, sex, ethnicity, smoking status, family history of lung cancer, dust exposure and emphysema. RESULTS: The  mean gamma-H2AX ratio was significantly higher in cases than controls (1.46+/-0.14 vs. 1.41+/-0.12, P < 0.001). Dichotomized at the median in controls, high gamma-H2AX ratio was significantly associated with increased risk of lung cancer (OR = 2.43, 95% CI: 1.66-3.56). There was also a significant dose-response relationship between gamma-H2AX ratio and lung cancer risk in quartile analysis.  Analysis of joint effects with other epidemiological risk factors revealed elevated risk with increasing number of risk factors. CONCLUSIONS: gamma-H2AX activity as shown by measuring DSB damage in IR-irradiated PBLs may be a novel phenotypic marker of lung cancer risk. Impact: gamma-H2AX assay is a robust and quantifiable image-based cytometer method that measures mutagen-induced DSB response in PBLs as a potential biomarker in lung cancer risk assessment.

 

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[157]

TÍTULO / TITLE:  - Patterns of failure after stereotactic body radiation therapy or lobar resection  for clinical stage I non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):192-201. doi: 10.1097/JTO.0b013e31827ce361.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ce361

AUTORES / AUTHORS:  - Robinson CG; Dewees TA; El Naqa IM; Creach KM; Olsen JR; Crabtree TD; Meyers BF; Puri V; Bell JM; Parikh PJ; Bradley JD

INSTITUCIÓN / INSTITUTION:  - *Department of Radiation Oncology, Washington University School of Medicine, St.  Louis, Missouri; and daggerDepartment of Oncology, McGill University Health Centre, Montreal, Quebec.

RESUMEN / SUMMARY:  - INTRODUCTION: : The purpose of this study was to compare patterns of failure between lobar resection (lobectomy or pneumonectomy) and stereotactic body radiation therapy (SBRT) for patients with clinical stage I non-small-cell lung cancer (NSCLC). METHODS: : From January 2004 to January 2008, 338 patients underwent definitive treatment for pathologically confirmed clinical stage I NSCLC with lobar resection (n = 260) or SBRT (n = 78). Most surgical patients underwent lobectomy (n = 237). SBRT patients received a biologically effective dose of at least 100 Gy10. Lobar resection patients were younger, healthier, and  had superior pulmonary function, whereas most of the patients in the SBRT group had T1 tumors. Final pathology upstaged 32.7% of surgery patients, and 20.0% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy.  RESULTS: : In an unmatched comparison, 4-year lobar local control (98.7% versus 93.6%, p = 0.015) was greater for lobar resection versus SBRT, respectively, though primary tumor (98.7% versus 95.3%, p = 0.088), regional (82.9% versus 78.1%, p = 0.912), and distant control (76.1% versus 54.0%, p = 0.152) were similar. Overall survival (OS, 63.5% versus 29.6%, p < 0.0001) was greater for lobar resection, though cause-specific survival (CSS, 81.3% versus 75.3%, p = 0.923) was similar. In a T-stage matched comparison of 152 patients, there was no significant difference in patterns of failure or CSS, whereas OS favored surgery. CONCLUSION: : Lobectomy/pneumonectomy or SBRT results in comparable patterns of failure for clinical stage I NSCLC. In this retrospective comparison, OS was superior for surgery, though CSS was similar. Randomized trials are necessary to  control for fundamental differences in comorbidity, which impact interpretation of both tumor control and survival.

 

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[158]

TÍTULO / TITLE:  - Relationship between the Phase Angle and Volume of Tumours in Patients with Lung  Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Nutr Metab. 2013;62(1):68-74. doi: 10.1159/000345588. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345588

AUTORES / AUTHORS:  - Castanho IA; Lopes AJ; Koury JC; Tessarollo B; Silva AC; Nunes RA

INSTITUCIÓN / INSTITUTION:  - University Centre for Cancer Control, State University of Rio de Janeiro, Rio de  Janeiro, Brazil.

RESUMEN / SUMMARY:  - Background/Aims: The phase angle (PA) obtained by bioelectrical impedance has been used as a predictor of nutritional status in cancer. This study aimed to verify the association between the PA and tumour volume in non-small cell lung cancer (NSCLC) patients. Methods: Volumetric determination of the tumour mass was performed using a computerised image analysis system incorporated in helical tomography. Lesion segmentation was performed by a semi-automatic process using a region growth algorithm with voxel aggregation. The PA was measured by bioelectrical impedance. Results: A total of 30 male patients with a mean age of  65.6 years were evaluated. The mean values observed for body mass index, PA and tumour volume were 22.5 +/- 4.19, 5.66 +/- 0.9 degrees and 163.2 +/- 207.5 ml, respectively. The tumour volumes were negatively correlated with the PA (r = -0.55; p < 0.001) and positively correlated with the ratio between the extracellular mass and the body cell mass (ECM/BCM) (r = 0.59; p < 0.001). In multivariate analysis, independent predictors for both PA and ECM/BCM were tumour volume and Karnofsky performance status score. Conclusions: In NSCLC, the PA is closely associated with tumour volume, which may be important in early nutritional intervention.

 

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[159]

TÍTULO / TITLE:  - Chronic exposure of lung alveolar epithelial type II cells to tobacco-specific carcinogen nnk results in malignant transformation: A new in vitro lung carcinogenesis model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Carcinog. 2012 Nov 30. doi: 10.1002/mc.21987.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mc.21987

AUTORES / AUTHORS:  - Mennecier G; Torres LN; Cogliati B; Sanches DS; Mori CM; Latorre AO; Chaible LM; Mackowiak II; Nagamine MK; Da Silva TC; Fukumasu H; Dagli ML

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. This disease is strongly associated with tobacco smoking. The aim of this manuscript was to establish an in vitro model that mimics the chronic exposures of alveolar epithelial type II cells to the tobacco-specific nitrosamine carcinogen, NNK. Immortalized non-neoplastic alveolar epithelial cells type II, (E10 cells), from BALB/c mice were exposed to  low concentration of NNK (100 pM) during 5, 10, 15, and 20 cycles of 48 h. NNK-transformed cells showed an increase of proliferation rate and motility. Moreover, these cells underwent epithelial-to-mesenchymal transition (EMT). Increased migratory capacity and EMT were correlated to the time of exposure to NNK. NNK-transformed cells were tested for their growth and metastatic capacity in vivo. Subcutaneous injection of cells exposed to NNK for 20 cycles (E10-NNK20  clone) into BALB/c mice led to the formation of subcutaneous tumors that arose after 40 +/- 17 d in all animals, which died 95 +/- 18 d after cell inoculation,  with lymph nodes and lung metastasis. The morphological characteristics of tumors were compatible with metastatic undifferentiated carcinoma. Cells exposed to NNK  for 5-10 cycles did not display metastatic capacity, while those exposed for 15 cycles displayed low capacity. Our results show that prolonged exposures to NNK led the cells to increasingly acquire malignant properties. The cellular model presented in this study is suitable for studying the molecular events involved in the different stages of malignant transformation. © 2012 Wiley Periodicals, Inc.

 

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[160]

TÍTULO / TITLE:  - Low-LET Proton Irradiation of A549 Non-small Cell Lung Adenocarcinoma Cells: Dose Response and RBE Determination.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Res. 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1667/RR3008.1

AUTORES / AUTHORS:  - Wera AC; Heuskin AC; Riquier H; Michiels C; Lucas S

INSTITUCIÓN / INSTITUTION:  - a Research Center in Physics of Matter and Radiation and.

RESUMEN / SUMMARY:  - Since 1957, broad proton beam radiotherapy with a spread out Bragg peak has been  used for cancer treatment. More recently, studies on the use of proton therapy in the treatment of non-small cell lung cancer (NSCLC) were performed and although the benefit of using protons for the treatment of NSCLC is recognized, more work  is needed to gather additional data for the understanding of cell response. Human A549 cell survival was evaluated by colony forming assay 11 days after 10 keV/mum proton beam irradiation at 0.1 and 1 Gy/min. The residual energy of the proton beam at the location of the irradiated cells was 3.9 MeV. In parallel, early effects on the cell viability and DNA damage were assessed and DNA synthesis was  measured. The survival curve obtained was fitted with both the linear and the induced-repair models, as a hyper-radiosensitivity was evidenced at very low doses. Above 0.5 Gy, a linear shape was observed with the alpha parameter equal to 0.824 +/- 0.029 Gy(-1). In addition, early cell death and cell proliferation arrest were enhanced. Moreover, a clear correlation between DNA damage and surviving fraction was observed. Finally, comparisons with X and gamma ray results indicate that proton irradiation at 10 keV/mum enhanced the tumor radiosensitivity with a significant dose-dependent decrease in the survival fraction. The RBE value of 1.9 +/- 0.4 obtained for a 10% survival support this observation.

 

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[161]

TÍTULO / TITLE:  - Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onkologie. 2012;35(12):783-6. doi: 10.1159/000345109. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345109

AUTORES / AUTHORS:  - Then C; von Einem JC; Muller D; Flaig MJ; Huber RM; Reincke M

INSTITUCIÓN / INSTITUTION:  - Medizinische Klinik und Poliklinik IV, University Hospital Munich, Germany. cornelia.then@med.uni-muenchen.de

RESUMEN / SUMMARY:  - BACKGROUND: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. CASE REPORT: We present the case of a 58-year-old woman with history of Sharp’s syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. CONCLUSION: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration  are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases.

 

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[162]

TÍTULO / TITLE:  - High NUAK1 expression correlates with poor prognosis and involved in NSCLC cells  migration and invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Lung Res. 2013 Feb;39(1):9-17. doi: 10.3109/01902148.2012.744115. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 3109/01902148.2012.744115

AUTORES / AUTHORS:  - Chen P; Li K; Liang Y; Li L; Zhu X

INSTITUCIÓN / INSTITUTION:  - 1Lung Cancer Medicine Department.

RESUMEN / SUMMARY:  - ABSTRACT Novel (nua) kinase family 1 (NUAK1) is a member of the human adenosine monophosphate (AMP)-activated protein kinase family that has been identified as a key tumor cell survival factor. In the present study, we investigated the role of NUAK1 in the migration and invasion of human nonsmall cell lung cancer (NSCLC) cells. Immunohistochemistry staining showed that the expression of NUAK1 correlated with the differentiation and stage of the carcinoma, as well as with lymph node metastasis. Inhibition of NUAK1 expression by small interference RNA severely impaired migration and invasion in A549 cells. In addition, we found that the knockdown of NUAK1 suppressed the expression of MMP-2 and MMP-9 and the  activation of NF-kB, which can regulate the transcription of MMP-2 and MMP-9. Correspondingly, NUAK1 knockdown reduced lung metastasis in a xenograft mouse model of NSCLC. Taken together, our results suggest that NUAK1 plays an important role in NSCLC cell migration and invasion.

 

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[163]

TÍTULO / TITLE:  - Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):699-711. doi: 10.3892/ijo.2012.1748. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1748

AUTORES / AUTHORS:  - Ouyang W; Yang C; Zhang S; Liu Y; Yang B; Zhang J; Zhou F; Zhou Y; Xie C

INSTITUCIÓN / INSTITUTION:  - Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, P.R. China.

RESUMEN / SUMMARY:  - Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is  a major limitation for its clinical use. The mechanisms of TRAIL resistance have  been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that contribute to the development of acquired resistance during treatment with TRAIL. In this study, we established H460R, an isogenic cell line with acquired TRAIL resistance, from the TRAILsensitive human lung cancer cell line H460 to investigate the mechanisms of acquired resistance. The acquired TRAILresistant H460R cells remained sensitive to cisplatin. The mRNA and protein expression levels of death receptor 4 (DR4) and death receptor 5 (DR5) were not altered in either of the TRAIL-treated cell lines. Nevertheless, tests in which the DR4 or DR5 gene was overexpressed or silenced suggest that death receptor expression is  necessary but not sufficient for TRAILinduced apoptosis. Compared with parental TRAIL-sensitive H460 cells, H460R cells showed a decreased TRAIL-induced translocation of DR4/DR5 into lipid rafts. Further studies showed that nystatin partially prevented lipid raft aggregation and DR4 and DR5 clustering and reduced apoptosis in H460 cells again. Analysis of apoptotic molecules showed that more pro-caspase-8, FADD, caspase-3 and Bid, but less cFLIP in H460 cells than in H460R cells. Our findings suggest that the lack of death receptor redistribution  negatively impacts DISC assembly in lipid rafts, which at least partially leads to the development of acquired resistance to TRAIL in H460R cells.

 

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[164]

TÍTULO / TITLE:  - Ligation of CM1 enhances apoptosis of lung cancer cells through different mechanisms in conformity with EGFR mutation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):469-77. doi: 10.3892/ijo.2012.1731. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1731

AUTORES / AUTHORS:  - Lee HK; Park GB; Kim YS; Song H; Broaddus VC; Hur DY

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.

RESUMEN / SUMMARY:  - Although remarkable developments in lung cancer treatments have been made, lung cancer remains the leading cause of cancer mortality worldwide. Epidermal growth  factor receptor (EGFR) is occasionally mutated in non-small cell lung cancer and  heterogeneity in treatment response results from different EGFR mutations. In the present study, we found that centrocyte/centroblast marker 1 (CM1), previously reported as a possible apoptosis inducer of B lymphoma cells, is expressed on both A549 with wildtype EGFR and HCC827 with mutant EGFR lung cancer cells. Ligation of CM1 with anti-CM1 mAb enhanced apoptosis in both lung cancer cell lines through generation of reactive oxygen species (ROS) and disruption of mitochondrial membrane potential, however, the signaling mechanisms differed from each other. Further studies to investigate the signaling mechanisms identified that ligation of CM1induced apoptosis in A549 cell involved FasL expression, caspase-8, ERK1/2 and Akt kinase, whereas apoptosis of HCC827 cells was induced through caspase-9, JNK and c-jundependent pathways. Taken together, we suggest that CM1 could be developed as a therapeutic target of lung cancer regardless of  EGFR mutation status.

 

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[165]

TÍTULO / TITLE:  - Prognostic factors and the significance of treatment after recurrence in completely resected stage I non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chest. 2013 Jan 24. doi: 10.1378/chest.12-1717.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-1717

AUTORES / AUTHORS:  - Shimada Y; Saji H; Yoshida K; Kakihana M; Honda H; Nomura M; Usuda J; Kajiwara N; Ohira T; Ikeda N

RESUMEN / SUMMARY:  - ABSTRACT INTRODUCTION: The objective of this study was to identify the clinicopathological factors influencing postrecurrence survival (PRS), and the effect of postrecurrence therapy (PRT) on patients with completely resected stage I non-small cell lung cancer (NSCLC). METHODS: We reviewed the data of 919 patients in whom complete resection of stage I NSCLC had been performed. RESULTS: Of the 919 patients, 170 had recurrent disease (18.5%). Initial PRT was performed in 118 (69.4%) patients (surgery 8, chemotherapy 79, radiotherapy 10, chemoradiotherapy 21). On multivariate analyses, PRT (HR0.542; 95%CI0.344-0.853;  p=0.008), female gender (HR0.487; 95%CI0.297-0.801; p=0.005) and differentiation  (HR1.810; 95%CI1.194-2.743; p=0.005) demonstrated a statistically significant association with favorable PRS. Bone metastasis (HR3.288; 95%CI1.783-6.062; p&lt;0.001), liver metastasis (HR4.518; 95%CI1.793-11.379; p=0.001), chemotherapy (HR0.478; 95%CI0.236-0.975; p=0.040), epidermal growth factor receptor-tyrosine kinase inhibitors treatment (EGFR-TKIs; HR0.460; 95%CI0.245-0.862; p=0.015), and  non-adenocarcinoma (HR2.136; 95%CI1.273-3.585; p=0.004) were independently and significantly associated with PRS in the 118 patients who underwent any PRT. Subgroup analysis with a combination of these 5 PRS factors in the patients who underwent any PRT revealed median PRS times of 42.4 months for 20 patients lacking all 5 risk factors and 18.8 months for 98 patients with at least one of these risk factors, respectively (p=0.001). CONCLUSION: PRT, gender and differentiation were independently associated with PRS. In the patients who underwent any PRT, PRS was related to EGFR-TKIs, chemotherapy, histology, and initial recurrence sites. One challenge for the future will be to create systematic treatment strategies for recurrent NSCLC according to the risk factor  status of individual patients.

 

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[166]

TÍTULO / TITLE:  - Fine-mapping of the 5p15.33, 6p22.1-p21.31 and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Epidemiol Biomarkers Prev. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-1007-T

AUTORES / AUTHORS:  - Walsh KM; Gorlov IP; Hansen HM; Wu X; Spitz MR; Zhang H; Lu EY; Wenzlaff AS; Sison JD; Wei C; Lloyd SM; Chen W; Frazier ML; Seldin MF; Bierut LJ; Bracci PM; Wrensch MR; Schwartz AG; Wiencke JK; Amos CI

INSTITUCIÓN / INSTITUTION:  - 1Epi/Biostat, ucsf.

RESUMEN / SUMMARY:  - BACKGROUND: Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31 and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans refined previous association signals by utilizing the reduced linkage disequilibrium observed in African-Americans. METHODS: 1308 African-American cases and 1241 African-American controls from three centers were genotyped for 760 single nucleotide polymorphisms spanning three regions, and additional SNP imputation was performed. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate. RESULTS: The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution (rs16969968: OR = 1.57, 95% CI = 1.25-1.97, P = 1.1 x 10-4) and variants in the 5’-UTR. Associations on 6p22.1-p21.31 were histology-specific and included a missense variant in BAT2 associated with squamous-cell carcinoma (rs2736158: OR = 0.64, 95% CI = 0.48-0.85, P = 1.82 x 10-3). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR = 0.82, 95% CI = 0.73-0.93, P = 1.1 x 10-3). This association was stronger among cases with adenocarcinoma (OR = 0.75, 95% CI = 0.65-0.86, P =  8.1 x 10-5). CONCLUSIONS: Polymorphisms in 5p15.33, 6p22.1-p21.31 and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only  with squamous-cell carcinoma. Impact: Results implicate the BAT2, TERT and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.

 

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[167]

TÍTULO / TITLE:  - A polysaccharide fraction of adlay seed (Coixlachryma-jobi L.) induces apoptosis  in human non-small cell lung cancer A549 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Jan 11;430(2):846-51. doi: 10.1016/j.bbrc.2012.11.058. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.11.058

AUTORES / AUTHORS:  - Lu X; Liu W; Wu J; Li M; Wang J; Wu J; Luo C

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.

RESUMEN / SUMMARY:  - Different seed extracts from Coix lachryma-jobi (adlay seed) have been used for the treatment of various cancers in China, and clinical data support the use of these extracts for cancer therapy; however, their underlying molecular mechanisms have not been well defined. A polysaccharide fraction, designated as CP-1, was extracted from the C.lachryma-jobi L. var. using the ethanol subsiding method. CP-1 induced apoptosis in A549 cells in a dose-dependent manner, as determined by MTT assay. Apoptotic bodies were observed in the cells by scanning electronic microscopy. Apoptosis and DNA accumulation during S-phase of the cell cycle were  determined by annexin V-FITC and PI staining, respectively, and measured by flow  cytometry. CP-1 also extended the comet tail length on single cell gel electrophoresis, and disrupted the mitochondrial membrane potential. Further analysis by western blotting showed that the expression of caspase-3 and caspase-9 proteins was increased. Taken together, our results demonstrate that CP-1 is capable of inhibiting A549 cell proliferation and inducing apoptosis via  a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data suggest that in addition to its nutritional properties, CP-1 is a very promising candidate polysaccharide for the development of anti-cancer medicines.

 

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[168]

TÍTULO / TITLE:  - The relevance of monitoring of antibodies against the Polycyclic aromatic hydrocarbon (PAH) and PAH-DNA adducts in serum in relation to lung cancer and chronic obstructive pulmonary disease (COPD).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasma. 2013;60(2):182-7.

AUTORES / AUTHORS:  - Pauk N; Klimesova S; Kara J; Topinka J; Labaj J

RESUMEN / SUMMARY:  - Certain substances from the polycyclic aromatic hydrocarbons (PAHs) group are major inducers of respiratory tract carcinogenesis. The presented are the results of aserological epidemiological study aimed at monitoring the levels of anti-PAH  antibodies and antibodies to PAH-DNA adducts in serum. The patients studied belonged both to the group of those with known lung disease (COPD and lung cancer), as well as to the healthy population of people who due to the work conditions or those at the place of residence can expect increased exposure to PAHs. In addition to the results proper that confirm increase of the genotoxic exposure risk to PAH in smoke-polluted places of residence and other PAH polluted environments. There has also been proved the relevance of still commonly used markers (DNA adducts), as well as the suitability of new markers, more favourable from the economic and practical viewpoints (anti-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA [anti-BPDE-DNA], anti-Benzo(a)pyrene antibodies of the IgA class). Keywords: polycyclic aromatic hydrocarbons (PAHs), anti-PAH antibodies, DNA adducts, antibodies against PAH-DNA adducts, COPD, lung cancer.

 

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[169]

TÍTULO / TITLE:  - Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Jan 11;430(2):529-34. doi: 10.1016/j.bbrc.2012.12.001. Epub 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.12.001

AUTORES / AUTHORS:  - Zu Y; Ban J; Xia Z; Wang J; Cai Y; Ping W; Sun W

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

RESUMEN / SUMMARY:  - Polymorphisms in 3’ untranslated region (UTR) of cancer-related genes might affect their regulation by microRNAs (miRNAs) and thereby contribute to carcinogenesis. In this study, we screened single nucleotide polymorphisms (SNPs) in 3’ UTR of cancer-related genes and investigated their effects on risk of lung  cancer. First, we genotyped seven SNPs in a Chinese Han population with 600 lung  cancer patients and 600 matched healthy controls and found that compared with the TT genotype of rs2239680 in 3’ UTR of baculoviral IAP repeat containing 5 (BIRC5), C allele was associated with a significantly increased risk of lung cancer and advanced pathologic stage, with the odds ratio for participants carrying the CT or CC genotype being 1.50 [95% confidence interval (CI) 1.20-1.89, P<0.01] and 2.29 (95% CI 1.64-3.18, P<0.01), respectively. These results were further replicated and confirmed in another independent population with 1000 lung cancer cases and 1000 matched healthy controls. In support of the  postulation that the 3’ UTR SNP may directly affect miRNA-binding site, reporter  gene assays indicated BIRC5 was a direct target of miR-335, and the rs2239680 T>C change resulted in altered regulation of BIRC5 expression. Moreover, BIRC5 was over expressed in lung cancer tissues compared with the normal lung tissues, and  the protein levels of BIRC5 correlated with SNP genotypes in normal lung tissues. Our findings defined a 3’ UTR SNP in human BIRC5 oncogene that may increase individual susceptibility to lung cancer probably by attenuating the interaction  between miR-335 and BIRC5.

 

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[170]

TÍTULO / TITLE:  - Vitamin A (retinol) downregulates the receptor for advanced glycation endproducts (RAGE) by oxidant-dependent activation of p38 MAPK and NF-kB in human lung cancer A549 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Signal. 2013 Jan 16. pii: S0898-6568(13)00016-8. doi: 10.1016/j.cellsig.2013.01.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cellsig.2013.01.013

AUTORES / AUTHORS:  - de Bittencourt Pasquali MA; Gelain DP; Zeidan-Chulia F; Pires AS; Gasparotto J; Terra SR; Moreira JC

INSTITUCIÓN / INSTITUTION:  - Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Electronic address: 00124262@ufrgs.br.

RESUMEN / SUMMARY:  - As an essential component of the diet, retinol supplementation is often considered harmless and its application is poorly controlled. However, recent works demonstrated that retinol may induce a wide array of deleterious effects, especially when doses used are elevated. Controlled clinical trials have demonstrated that retinol supplementation increased the incidence of lung cancer  and mortality in smokers. Experimental works in cell cultures and animal models showed that retinol may induce free radical production, oxidative stress and extensive biomolecular damage. Here, we evaluated the effect of retinol on the regulation of the receptor for advanced glycation end-products (RAGE) in the human lung cancer cell line A549. RAGE is constitutively expressed in lungs and was observed to be down-regulated in lung cancer patients. A549 cells were treated with retinol doses reported as physiologic (2muM) or therapeutic (5, 10 or 20muM). Retinol at 10 and 20muM increased free radical production, oxidative damage and antioxidant enzyme activity in A549 cells. These doses also downregulated RAGE expression. Antioxidant co-treatment with Trolox®, a hydrophilic analog of alpha-tocopherol, reversed the effects of retinol on oxidative parameters and RAGE downregulation. The effect of retinol on RAGE was mediated by p38 MAPK activation, as blockade of p38 with PD169316 (10muM), SB203580 (10muM) or siRNA to either p38alpha (MAPK14) or p38beta (MAPK11) reversed the effect of retinol on RAGE. Trolox also inhibited p38 phosphorylation, indicating that retinol induced a redox-dependent activation of  this MAPK. Besides, we observed that NF-kB acted as a downstream effector of p38  in RAGE downregulation by retinol, as NF-kB inhibition by SN50 (100mug/mL) and siRNA to p65 blocked the effect of retinol on RAGE, and p38 inhibitors reversed NF-kB activation. Taken together, our results indicate a pro-oxidant effect of retinol on A549 cells, and suggest that modulation of RAGE expression by retinol  is mediated by the redox-dependent activation of p38/NF-kB signaling pathway.

 

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[171]

TÍTULO / TITLE:  - CHRNA3 Variant for Lung Cancer Is Associated with Chronic Obstructive Pulmonary Disease in Korea.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respiration. 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000342976

AUTORES / AUTHORS:  - Kim WJ; Oh YM; Kim TH; Lee JH; Kim EK; Lee JH; Lee SM; Shin TR; Yoon HI; Lim SY; Lee SD

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Kangwon National University, Chuncheon, South Korea.

RESUMEN / SUMMARY:  - Background: Genome-wide association studies have identified CHRNA3 as a lung cancer and chronic obstructive pulmonary disease (COPD) candidate gene in non-Hispanic Caucasian cohorts. However, there are differences in minor allele frequencies among ethnic groups, and limited data exists for Asian populations. Objectives: The aim of this case-control study was to determine whether there is  an association between COPD and genetic variation in CHRNA3 in the Korean population. In addition, we investigated the association of CHRNA3 with intermediate disease phenotypes including emphysema and lung function in COPD subjects. Methods: Two single-nucleotide polymorphisms (SNPs) in CHRNA3 (rs660652 and rs12910984) were genotyped in 219 COPD subjects registered in the Korean Obstructive Lung Disease cohort study and in 305 control subjects. Volumetric computed tomography was performed in all COPD subjects. Emphysema severity was measured quantitatively by determining the volume fraction of the lung below -950 Hounsfield units. Logistic regression analysis for case-control analysis and linear regression modeling for quantitative analysis were performed using SAS. Results: This case-control analysis of 219 COPD patients and 305 control participants identified a significant association between an SNP of CHRNA3 (rs12910984) and COPD (p = 0.049). Analysis in COPD subjects revealed that genetic variations were not associated with FEV(1). There was no association between SNPs and emphysema severity. However, both SNPs were significantly associated with DLCO. Conclusion: Genetic variations in CHRNA3 are associated with COPD in the Korean population.

 

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[172]

TÍTULO / TITLE:  - Distinct profile of driver mutations and clinical features in immunomarker-defined subsets of pulmonary large-cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mod Pathol. 2012 Nov 30. doi: 10.1038/modpathol.2012.195.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.195

AUTORES / AUTHORS:  - Rekhtman N; Tafe LJ; Chaft JE; Wang L; Arcila ME; Colanta A; Moreira AL; Zakowski MF; Travis WD; Sima CS; Kris MG; Ladanyi M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

RESUMEN / SUMMARY:  - Pulmonary large-cell carcinoma-a diagnostically and clinically controversial entity-is defined as a non-small-cell carcinoma lacking morphologic differentiation of either adenocarcinoma or squamous cell carcinoma, but suspected to represent an end stage of poor differentiation of these tumor types. Given the recent advances in immunohistochemistry to distinguish adenocarcinoma and squamous cell carcinoma, and the recent insights that several therapeutically relevant genetic alterations are distributed differentially in these tumors, we hypothesized that immunophenotyping may stratify large-cell carcinomas into subsets with distinct profiles of targetable driver mutations. We therefore analyzed 102 large-cell carcinomas by immunohistochemistry for TTF-1 and DeltaNp63/p40 as classifiers for adenocarcinoma and squamous cell carcinoma, respectively, and correlated the resulting subtypes with nine therapeutically relevant genetic alterations characteristic of adenocarcinoma (EGFR, KRAS, BRAF,  MAP2K1/MEK1, NRAS, ERBB2/HER2 mutations and ALK rearrangements) or more common in squamous cell carcinoma (PIK3CA and AKT1 mutations). The immunomarkers classified large-cell carcinomas as variants of adenocarcinoma (n=62; 60%), squamous cell carcinoma (n=20; 20%) or marker-null (n=20; 20%). Genetic alterations were found  in 38 cases (37%), including EGFR (n=1), KRAS (n=30), BRAF (n=2), MAP2K1 (n=1), ALK (n=3) and PIK3CA (n=1). All molecular alterations characteristic of adenocarcinoma occurred in tumors with immunoprofiles of adenocarcinoma or marker-null, but not in tumors with squamous immunoprofiles (combined mutation rate 50% vs 30% vs 0%, respectively; P<0.001), whereas the sole PIK3CA mutation occurred in a tumor with squamous profile (5%). Furthermore, marker-null large-cell carcinomas were associated with significantly inferior disease-free (P<0.001) and overall (P=0.001) survival. In conclusion, the majority (80%) of large-cell carcinomas can be classified by immunomarkers as variants of adenocarcinoma or squamous cell carcinoma, which stratifies these tumors into subsets with a distinct distribution of driver mutations and distinct prognoses.  These findings have practical implications for diagnosis, predictive molecular testing and therapy selection.Modern Pathology advance online publication, 30 November 2012; doi:10.1038/modpathol.2012.195.

 

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[173]

TÍTULO / TITLE:  - EMT markers in lung adenocarcinoma pleural effusion spheroid cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Physiol. 2012 Dec 18. doi: 10.1002/jcp.24300.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcp.24300

AUTORES / AUTHORS:  - Giarnieri E; De Vitis C; Noto A; Roscilli G; Salerno G; Mariotta S; Ricci A; Pierdonato B; Russo G; Laurenzi A; Giovagnoli MR; Ciliberto G; Mancini R

INSTITUCIÓN / INSTITUTION:  - Department of Clinical and Molecular Medicine. University of Rome “La Sapienza”.  S Andrea Hospital, Rome, Italy. enrico.giarnieri@uniroma1.it.

RESUMEN / SUMMARY:  - Epithelial-to-Mesenchymal Transition (EMT) is a process in which cells undergo a  developmental switch from epithelial to mesenchymal phenotype. This process has been related to embryologic morphogenesis but also to cancer progression and metastasis. The aim of the current study was to investigate the expression of EMT related markers in adherent and spheroid cell cultures derived from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinoma. On the basis of efficient in vitro propagation, six cases of MPEs were selected and analyzed by immunocytochemistry staining for EMT markers and by RT-PCR for transcription factors known to orchestrate EMT. EMT markers immunostaining showed in spheroids a statistically significant correlation between the loss of E-cadherin immunoreactivity and overexpression of N-cadherin (P < 0.001). Likewise loss of EpCAM epithelial marker was coincident with Vimentin overexpression (P < 0.001). RT-PCR analysis of transcription factors Snail, Slug  and Twist showed a highly variable expression, although a general trend to increase was observed. Importantly in some selected cases it was possible to establish a precise relationship between spheroid formation, EMT switch and increased upregulation of the marker related to cancer stemness such as ALDH positivity. Therefore MPE-derived cell cultures, while recapitulating the heterogeneity of lung cancer, are a suitable system to study the mechanisms at the basis of EMT and to understand its relationship with the generation of cancer stem cells. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.

 

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[174]

TÍTULO / TITLE:  - SLC1A5 Mediates Glutamine Transport Required for Lung Cancer Cell Growth and Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2334

AUTORES / AUTHORS:  - Hassanein M; Hoeksema MD; Shiota M; Qian J; Harris BK; Chen H; Clark JE; Alborn WE; Eisenberg R; Massion PP

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine; Departments of Molecular Physiology and Biophysics, Biostatistics, and Pathology; Jim Ayers Institute of Precancer Detection and Diagnosis, Vanderbilt University School of Medicine; Department of Cancer Biology, Vanderbilt-Ingram Cancer Center; and Veterans Affairs, Tennessee Valley  Healthcare System, Nashville Campus, Nashville, Tennessee.

RESUMEN / SUMMARY:  - PURPOSE: We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival.EXPERIMENTAL DESIGN: To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines  in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines.RESULTS: Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling.CONCLUSIONS: These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells’ metabolism, growth, and survival. Clin Cancer Res; 1-11. ©2012 AACR.

 

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[175]

TÍTULO / TITLE:  - Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Cell Res. 2012 Dec 27. pii: S0014-4827(12)00495-8. doi: 10.1016/j.yexcr.2012.12.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexcr.2012.12.018

AUTORES / AUTHORS:  - Takeda H; Takigawa N; Ohashi K; Minami D; Kataoka I; Ichihara E; Ochi N; Tanimoto M; Kiura K

INSTITUCIÓN / INSTITUTION:  - Department of Hematology, Oncology, and Respiratory Medicine, Okayama University  Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

RESUMEN / SUMMARY:  - The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact PTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The  effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack PTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined.

 

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[176]

TÍTULO / TITLE:  - Genetic Susceptibility to Lung Cancer - Light at the End of the Tunnel?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt016

AUTORES / AUTHORS:  - Marshall AL; Christiani DC

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215,  USA.

RESUMEN / SUMMARY:  - Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer  is cigarette smoking. Additionally, there are multiple genetic factors which may  also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate leans leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies (GWAS) has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and and  patterns of genetic risk may be useful in the earlier detection and treatment of  lung cancer patients.

 

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[177]

TÍTULO / TITLE:  - Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt024

AUTORES / AUTHORS:  - Leng S; Picchi MA; Liu Y; Thomas CL; Willis DG; Bernauer AM; Carr TG; Padilla MT; Han Y; Amos CI; Lin Y; Stidley CA; Gilliland FD; Jacobson MR; Belinsky SA

INSTITUCIÓN / INSTITUTION:  - Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM;

RESUMEN / SUMMARY:  - Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks (DSBs) induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267  SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P=0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (Odds Ratio = 1.69, P = 8.2x10(-5)) and greater survival in SCC cases (Hazard Ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells  and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggested that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners.

 

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[178]

TÍTULO / TITLE:  - Malignant mesothelioma: New insights into a rare disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Treat Rev. 2012 Dec 28. pii: S0305-7372(12)00244-7. doi: 10.1016/j.ctrv.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ctrv.2012.12.005

AUTORES / AUTHORS:  - Remon J; Lianes P; Martinez S; Velasco M; Querol R; Zanui M

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Department, Hospital de Mataro, Carretera de la Cirera, s/n, 08304 Mataro, Barcelona, España. Electronic address: jremon@csdm.cat.

RESUMEN / SUMMARY:  - Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy of the pleura associated with exposure to asbestos. Its incidence is anticipated to increase over the next 10years in both Europe and the developing nations. In advanced disease, chemotherapy is the cornerstone of treatment, especially platinum-containing regimens. Most efforts are directed toward improving standard first-line therapy or developing effective second-line therapy, which is still not yet standardized 10years after the first-line standard of care was established. This review focuses on the systemic management of MPM in patients who are not considered suitable for surgical approaches, and it discusses some questions that remain open such as the benefits of administering a maintenance treatment, whether it is better to give cisplatin or carboplatin as first-line therapy, the role of new drugs as second-line therapy, and the treatment of the elderly population. It also summarizes the results from clinical trials that have evaluated new treatments as first- or second-line therapy, which are based on the understanding of mesothelioma biology, such as antiangiogenic drugs, immunotherapies and growth factors agents.

 

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[179]

TÍTULO / TITLE:  - Smokers have 10 times more genetic damage in lung cancer tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2013 Jan 15;119(2):248-9. doi: 10.1002/cncr.27944.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27944

 

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[180]

TÍTULO / TITLE:  - Serum C-reactive protein and risk of lung cancer: a case-control study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):319. doi: 10.1007/s12032-012-0319-4. Epub 2012 Dec 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0319-4

AUTORES / AUTHORS:  - Xu M; Zhu M; Du Y; Yan B; Wang Q; Wang C; Zhao J

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China.

RESUMEN / SUMMARY:  - Recent advances in lung cancer biology presuppose their inflammatory origin. Thus, CRP is regarded to play a key role in the development of lung cancer. Nevertheless, this interesting hypothesis and the role of inflammation in tumor biology remain complex and incompletely sure. Meanwhile, the association between  CRP and risk of lung cancer was not stable in many published results. This study  was conducted to evaluate the association between serum CRP and SNPs in the aspect of lung cancer risks, in order to assess its possible diagnostic and prognostic importance. We conducted a case-control study of 96 patients newly diagnosed of lung cancer and 124 controls in this research. Controls were individuals matched to lung cancer cases on age, gender and tobacco use. In order to increase the statistical power, never smokers were matched to patients by using a 3:1 ratio, whereas former and current smokers were matched equal to the patients. CRP concentrations were measured using a chemiluminescent immunoassay,  and SNPs were assessed at five loci within the CRP gene (rs1417938, rs1800947, rs1205, rs2808630 and rs3093077) as part of a Golden Gate assay. Logistic regression was used to calculate OR and 95 % CI for lung cancer. CRP concentrations tended to be in positive association with lung cancer risk in our  research (Q4 vs Q1: OR = 2.11, 95 % CI, 1.66-2.91, p trend < 0.01). Although CRP  SNPs were related to CRP levels, they were not associated with lung cancer risk.  In combined analyses, we observed a significant interaction (p (interaction) = 0.02) that positive associations were suggestive in younger (Q4 vs Q1: OR = 1.65, 95 % CI, 1.02-2.67, p trend = 0.18) and older individuals (Q4 vs Q1: OR = 2.66, 95 % CI, 1.45-3.98 p trend = 0.42). The risks of lung cancer were higher with elevated CRP levels among former smokers and current smokers. High levels of CRP  were associated with increasing lung cancer risk, suggesting that CRP could be used as surrogate biomarker of angiogenesis and prognosis in lung cancer.

 

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[181]

TÍTULO / TITLE:  - A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 25. pii: S0169-5002(12)00650-2. doi: 10.1016/j.lungcan.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.005

AUTORES / AUTHORS:  - Akerley W; Boucher K; Rich N; Egbert L; Harker G; Bylund J; Van Duren T; Reddy C

INSTITUCIÓN / INSTITUTION:  - Huntsman Cancer Institute at University of Utah, United States; Department of Medicine, University of Utah, United States; Huntsman-Intermountain Cancer Care Program, United States. Electronic address: wallace.akerley@hci.utah.edu.

RESUMEN / SUMMARY:  - BACKGROUND: Erlotinib alone or bevacizumab in combination with chemotherapy improve survival in patients with advanced non-small cell lung cancer. The current trial of erlotinib and bevacizumab was designed as an alternative to initial conventional chemotherapy for advanced lung cancer and a platform to explore selection factors. METHODS: Eligibility criteria included stage IIIB/IV or recurrent non-squamous, non-small cell lung cancer (NSNSCLC), no prior chemotherapy for metastatic disease, PS=0-1, and no history of brain metastases for the first 40 patients. An expansion cohort of an additional 10 patients allowed treated brain metastases. Patients received erlotinib 150mg/day and bevacizumab 15mg/kg/3 weeks until objective or symptomatic progression. Pretreatment serum was collected for blinded VeriStrat(®) evaluation. RESULTS:  Fifty patients were accrued. The median age was 65 years, 10 were octogenarians,  37 had PS=1, 25 were female and 12 were never-smokers. Histologies were adenocarcinoma in 26 and unspecified in 24. Partial responses were observed in 12 (24%), stable in 30 (60%) and progressive disease in 8 (16%). The median time on  therapy was 15.5 weeks. The median survival was 50.4 weeks with 1 and 2 years survivals of 50% and 21%, respectively. Only 38% of eligible patients received second line therapy, most often due to decline in PS. VeriStrat(®) analysis was performed in 42 subjects (Good 32, Poor 9, and Indeterminate 1). Significant differences based on VeriStrat(®) signature were noted in PFS (Good=18.9 weeks, Poor=6.3 weeks, p=0.0035) and overall survival (Good=71.4 weeks, Poor=19.9 weeks, p=0.0015). CONCLUSIONS: Survival in an unselected population of patients with NSNSCLC treated with bevacizumab and erlotinib approximated that expected with conventional chemotherapy. VeriStrat(®) analyses distinguished patients who were likely or unlikely to benefit from this combination.

 

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[182]

TÍTULO / TITLE:  - Genetic single-nucleotide polymorphisms of inflammation-related factors associated with risk of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):414. doi: 10.1007/s12032-012-0414-6. Epub 2013 Jan 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0414-6

AUTORES / AUTHORS:  - Bai L; Yu H; Wang H; Su H; Zhao J; Zhao Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001, Shenyang, China.

RESUMEN / SUMMARY:  - This study was to investigate the association of inflammation-related factors with the risk of lung cancer. All subjects were unrelated ethnic Han Chinese in Liaoning province. Our study conducted a hospital-based case-control study, the case group consisted of 193 histologically diagnosed lung cancer patients, and 211 controls were selected from cancer-free patients at the same. 5 single-nucleotide polymorphisms (TGFbeta1 +869T/C, IL6 -634C/G, TGFbeta1 -509C/T, IL1beta -511C/T, and IL1alpha -899C/T) in inflammatory genes (IL1, IL6, TGF) were analyzed by Taqman real-time PCR method. All statistical analyses were performed  with statistical product and service solutions v13.0. The genotype distribution frequency of IL6 -634C/G exists significant difference between case and control group. Individuals carrying -634GG and CG genotype had a higher risk of lung cancer. The risk allele was G in IL6 -634C/G.

 

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[183]

TÍTULO / TITLE:  - Knockdown of integrin alpha3beta1 expression induces proliferation and migration  of non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb;29(2):662-8. doi: 10.3892/or.2012.2169. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2169

AUTORES / AUTHORS:  - Yoon HJ; Cho YR; Joo JH; Seo DW

INSTITUCIÓN / INSTITUTION:  - Quality Management Department, Hugel Inc., Chuncheon 200-821, Republic of Korea.

RESUMEN / SUMMARY:  - Integrin alpha3beta1 is expressed on many types of cancer cells and can regulate  tumor growth and progression. In the present study, we examined the roles and molecular mechanism of integrin alpha3beta1 in modulating cell proliferation and  migration of p53-deficient non-small cell lung cancer (NSCLC) cells. Reduced expression of integrin alpha3 by RNA silencing clearly induces cell proliferation and migration in H1299 cells, compared with those in control cells. Enhanced proliferation in integrin alpha3-silenced cells is mediated by upregulation and nuclear localization of cyclin-dependent kinases, and these effects require the activation of Akt and ERK as evidenced by treatment with LY294002 and PD98059, respectively. Furthermore, suppression of integrin alpha3 expression induces the  expression of nuclear factor-kappaB and Bcl-2 as well as epidermal growth factor  receptor, which are positively correlated with cell proliferation and survival. In contrast, increase in cell migration of integrin alpha3-silenced cells is found to be independent of Akt or ERK signaling pathways. Collectively, these findings suggest that integrin alpha3beta1 plays pivotal roles in regulating cell proliferation and migration that enhance the invasive type of p53-deficient NSCLC cells.

 

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[184]

TÍTULO / TITLE:  - Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Immunol. 2013 May;54(1):74-83. doi: 10.1016/j.molimm.2012.10.035. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.molimm.2012.10.035

AUTORES / AUTHORS:  - Zheng Y; Xu M; Li X; Jia J; Fan K; Lai G

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory and Critical Care Medicine, Fuzong Clinical College of  Fujian Medical University, Fuzhou General Hospital, Fuzhou, Fujian 350000, PR China.

RESUMEN / SUMMARY:  - Cimetidine, a histamine type-2 receptor antagonist, is known to inhibit the growth of several tumors in human and animals, however the mechanism of action underlying this effect remains largely unknown. Here, in the mice model of 3LL lung tumor, cimetidine showed significant inhibition of tumor growth. However, an in vitro study demonstrated that cimetidine showed no effect on proliferation, survival, migration and invasion of 3LL cells. We found that cimetidine reduced CD11b(+)Gr-1(+) myeloid derived-suppressive cell (MDSC) accumulation in spleen, blood and tumor tissue of tumor-bearing mice. In vitro coculture assay showed that cimetidine reversed MDSC-mediated T-cell suppression, and improved IFN-gamma production. Further investigation demonstrated that the NO production and arginase I expression of MDSCs were reduced, and MDSCs prone to apoptosis by cimetidine treatment. However, MDSC differentiation was not affect by cimetidine. Importantly, although histamine H2 receptor was expressed in MDSC surface, histamine could not reverse the proapoptosis of cimetidine. Moreover, famotidine  also did not have this capacity. We found that cimetidine could induce Fas and FasL expression in MDSC surface, and sequentially regulate caspase-dependent apoptosis pathway. Thus, these findings revealed a novel mechanism for cimetidine to inhibit tumor via modulation of MDSC apoptosis.

 

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[185]

TÍTULO / TITLE:  - Are Pretreatment 18F-FDG PET Tumor Textural Features in Non-Small Cell Lung Cancer Associated with Response and Survival After Chemoradiotherapy?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nucl Med. 2013 Jan;54(1):19-26. doi: 10.2967/jnumed.112.107375. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.107375

AUTORES / AUTHORS:  - Cook GJ; Yip C; Siddique M; Goh V; Chicklore S; Roy A; Marsden P; Ahmad S; Landau D

INSTITUCIÓN / INSTITUTION:  - Division of Imaging Sciences and Biomedical Engineering, Kings College London, London, United Kingdom.

RESUMEN / SUMMARY:  - There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). METHODS: Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria  in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. RESULTS: Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027;  P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. CONCLUSION: In NSCLC, baseline (18)F-FDG PET scan uptake showing abnormal texture as measured by coarseness, contrast, and busyness is associated with nonresponse to chemoradiotherapy by RECIST and with poorer prognosis. Measurement of tumor metabolic heterogeneity with these parameters may provide indices that can be used to stratify patients in clinical trials for lung cancer chemoradiotherapy.

 

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[186]

TÍTULO / TITLE:  - Anacardic acid induces mitochondrial-mediated apoptosis in the A549 human lung adenocarcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):1045-51. doi: 10.3892/ijo.2013.1763. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1763

AUTORES / AUTHORS:  - Seong YA; Shin PG; Kim GD

INSTITUCIÓN / INSTITUTION:  - Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea.

RESUMEN / SUMMARY:  - Anacardic acid (AA) is a constituent of the cashew nut shell and is known as an inhibitor of nuclear factor-kappaB (NF-kappaB). We investigated the cytotoxicity  of AA on cancer cells and more experiments to reveal the cell death mechanism focused on A549 lung adenocarcinoma cells for our interest in lung cancer. To examine the molecular mechanism of cell death in AA treated A549 cells, we performed experiments such as transmission electron microscopy (TEM), western blot analysis, fluorescence-activated cell sorting (FACS), genomic DNA extraction and staining with 4’,6-diamidino-2-phenylindole (DAPI). For the first time we revealed that AA induces caspaseindependent apoptosis with no inhibition of cytotoxicity by pan-caspase inhibitor, Z-VAD-fmk, in A549 cells. Our results showed the possibility of mitochondrial-mediated apoptosis through the activation of apoptosis-inducing factor (AIF) and an intrinsic pathway executioner such as cytochrome c. This study will be helpful in revealing the cell death mechanisms and in developing potential drugs for lung cancer using AA.

 

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[187]

TÍTULO / TITLE:  - Loss of mesothelin expression by mesothelioma cells grown in vitro determines sensitivity to anti-mesothelin immunotoxin SS1P.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5151-8.

AUTORES / AUTHORS:  - Zhang J; Qiu S; Zhang Y; Merino M; Fetsch P; Avital I; Filie A; Pastan I; Hassan R

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room 5116, Bethesda, MD 20892-4264, USA.

RESUMEN / SUMMARY:  - BACKGROUND/AIM: To determine if early passage tumor cells obtained from patients  with mesothelioma continue to express the tumor differentiation antigen mesothelin and their sensitivity to the anti-mesothelin immunotoxin SS1P. MATERIALS AND METHODS: Cell cultures were established from ascites or pleural effusion of 6 peritoneal and 3 pleural mesothelioma patients, respectively. These cells were evaluated for mesothelin expression by immunohistochemistry and flow cytometry. RESULTS: Although mesothelin was highly expressed in tumor biopsies of all patients, only 3 out of 9 malignant effusions from these patients when grown  in short-term culture showed strong mesothelin positivity by IHC. By flow cytometry, the number of mesothelin sites per cell was variable ranging from 580  to 210,000 sites/cell. Cells with strong mesothelin expression by IHC and increased number of mesothelin sites/cell were sensitive to SS1P. CONCLUSIONS: Most mesothelioma tumors loose mesothelin when grown in vitro and the sensitivity of these cells to SS1P is dependent on the number of mesothelin sites/cell.

 

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[188]

TÍTULO / TITLE:  - Impact of Genetic Markers on Treatment of Non-small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Adv Exp Med Biol. 2013;779:145-64. doi: 10.1007/978-1-4614-6176-0_6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6176-0_6

AUTORES / AUTHORS:  - Lamparella N; Barochia A; Almokadem S

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Penn State Hershey Medical Center, 500 University Dr., Hershey, PA, 17033, USA.

RESUMEN / SUMMARY:  - Non-small cell lung cancer represents a group of heterogeneous diseases. The last decade witnessed significant progress in improving our understanding of the biology of non-small cell lung cancer, which led to the identification of several genetic targets. Those genetic targets were utilized to explain clinical phenomena, such as the occurrence of non-small cell lung cancer in never-smokers, to predict response to conventional chemotherapy and biological agents, and to explain and predict resistance to therapy. The progress in the treatment of non-small cell lung cancer in the last few years was based on a new generation of population-enriched clinical trials that utilized genetic targets such as somatic EGFR mutations and ALK-EML4 mutations. In this review we will discuss the available information about the key genetic markers of non-small cell lung cancer and the pivotal clinical trials that validate the use of those genetic markers in non-small cell lung cancer patients.

 

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[189]

TÍTULO / TITLE:  - Does a more refined assessment of exposure to bitumen fume and confounders alter  risk estimates from a nested case-control study of lung cancer among European asphalt workers?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Occup Environ Med. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1136/oemed-2012-100839

AUTORES / AUTHORS:  - Agostini M; Ferro G; Burstyn I; de Vocht F; Portengen L; Olsson A; Boffetta P; Kromhout H

INSTITUCIÓN / INSTITUTION:  - Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, , Utrecht, The Netherlands.

RESUMEN / SUMMARY:  - OBJECTIVE: To investigate whether a refined assessment of exposure to bitumen fume among workers in the European asphalt industry within a nested case-control  study resulted in a different interpretation pertaining to risk of lung cancer mortality compared with the cohort study. METHODS: Pearson correlation coefficients between refined and original estimates were calculated. Logistic regression and generalised additive models (penalised splines) were fitted to estimate ORs for exposure to bitumen fume using the refined and original exposure estimates, respectively, while adjusting for potential confounding. RESULTS: 1555 subjects included in the nested case-control study had both refined and original  estimates for exposure to bitumen fume. Exposure assessment in the nested case-control study (compared with the cohort phase) increased the number of subjects never-exposed to bitumen fume from 18% to 32%. From the 1282 subjects originally considered exposed in the cohort phase, 309 (24%) became unexposed after the nested case-control exposure assessment. From the 273 subjects originally considered non-exposed in the cohort phase, 87 (32%) became exposed in the nested case-control study. The majority (75%) of subjects however did not change exposure status and changes were similar among cases and controls. Correlation coefficients between refined and original exposure estimates were moderate overall (range 0.42-0.46), but varied considerably among countries. The  ORs and exposure-response curves for exposure to bitumen fume were not meaningfully different between analyses that used refined and original exposure estimates. Adjustment for tobacco smoking and exposure to coal tar did not change these patterns. CONCLUSIONS: Our results showed that more detailed data collection and exposure assessment in the nested case-control study compared with the cohort study did change exposure status of many subjects, but did not alter results of the exposure-response analysis. Adjustment for tobacco smoking did not have a noticeable effect on risk estimates either.

 

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[190]

TÍTULO / TITLE:  - T-cell immunoglobulin- and mucin-domain-containing molecule 3 gene polymorphisms  and prognosis of non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0610-1

AUTORES / AUTHORS:  - Bai J; Li X; Tong D; Shi W; Song H; Li Q

INSTITUCIÓN / INSTITUTION:  - Internal Medicine Division of the Emergency Center, Shanghai East Hospital, Tongji University, 150 Jimo Road, Shanghai, 200120, China.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of death worldwide. Non-small-cell lung cancer (NSCLC) accounts for most of these cases. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. Studies have shown that polymorphisms in TIM-3 gene can be associated with various diseases. The aim of this study was to investigate whether polymorphisms in the TIM-3 gene  were associated with susceptibility to NSCLC. Three polymorphisms in TIM-3 gene (-1516G/T, -574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 432 NSCLC patients and 466 healthy controls. Results showed that frequencies of TIM-3 +4259TG genotype for cases and controls were 10.9 and 4.1 %, respectively; subjects carrying the +4259TG genotype had a 2.81-fold increased risk of NSCLC compared to the wild-type genotype (P < 0.0001). The TIM-3 -1516G/T and -574G/T polymorphisms did not show any correlation with NSCLC. In addition, when analyzing the survival time of NSCLC patients with TIM-3 +4259T/G polymorphism, cases with +4259TG genotype had significantly shorter survival time compared to the wild-type patients (15.2 months vs. 26.7 months, P = 0.007). These results suggested polymorphism in TIM-3 gene is associated with increased susceptibility to NSCLC and could be used as prognostic factor for this malignancy.

 

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[191]

TÍTULO / TITLE:  - Biodegradable cisplatin-eluting Tracheal Stent for malignant airway obstruction:  In vivo and in vitro studies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chest. 2013 Jan 24. doi: 10.1378/chest.12-2282.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-2282

AUTORES / AUTHORS:  - Chao YK; Liu KS; Wang YC; Huang YL; Liu SJ

INSTITUCIÓN / INSTITUTION:  - YK Chao and KS Liu have equal contribution to this study and are co-first authors of this paper.

RESUMEN / SUMMARY:  - ABSTRACT BACKGROUND: Self expandable metallic stents (SEMS) are effective in the  palliation of malignant airway obstruction. Tumor in-growth, however, frequently  occurs because of a shortage of effective local therapy. Additionally, SEMS are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems. METHODS: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, micro-injection molding machine. In vitro mechanical strength of the stents was compared to the strength  of ultraflex SEMS. Polylactide-polyglycolide copolymer and cisplatin were coated  onto the surfaces of the stents. Elution method and high performance liquid chromatography (HPLC) analysis were utilized to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 approximately 5 weeks) before euthanasia. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histological examination was also performed. RESULTS: The biodegradable stent exhibited mechanical strength comparable to the strength of ultraflex SEMS and provided a steady release of cisplatin for more than 4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for more than 5 weeks with a  minimum drug level in blood. Histological examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area. CONCLUSIONS: Our study demonstrated that the biodegradable stents provided  physical properties comparable to the properties of SEMs and a sustained release  of cisplatin for more than 5 weeks, which showed great potential in the treatment of malignant airway obstruction.

 

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[192]

TÍTULO / TITLE:  - Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):429-36. doi: 10.3892/ijo.2012.1755. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1755

AUTORES / AUTHORS:  - Takahashi R; Sato T; Klinman DM; Shimosato T; Kaneko T; Ishigatsubo Y

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 2360004, Japan.

RESUMEN / SUMMARY:  - Immunosuppressive oligodeoxynucleotides (Sup ODNs) containing repetitive TTAGGG motifs reduce inflammation and, thus, may have an impact on inflammationrelated tumor growth. In this study, we found a significant antiproliferative effect of Sup ODNs on the A549 nonsmall cell lung cancer (NSCLC) cell line compared to those treated with control ODNs (p<0.05). Sup-ODN-mediated G1 phase cell cycle arrest was achieved via inhibition of Akt and extracellular signal-regulated kinase ½ phosphorylation and the p15INK4b and p27KIP1/retinoblastoma protein pathway. In addition, Sup ODNs induced apoptosis and enhanced apoptosis when combined with vinorelbine. In a setting similar to clinical use of multidrug chemotherapy for advanced NSCLC, these effects were investigated by using Sup ODNs in combination with conventional anticancer drugs. Sup ODNs had a significant synergistic effect with 5-fluorouracil, vinorelbine, gemcitabine, paclitaxel and irinotecan, with a mean combination index of 0.43-0.78 (<1.0 indicates synergism) in the A549 NSCLC cell line. In conclusion, our results showed that Sup ODNs have an anticancer effect and increase the sensitivity of NSCLC cells to conventional anticancer drugs by modifying Akt and the extracellular signal-regulated kinase ½ pathway. Thus, Sup ODNs may serve as a  novel therapeutic strategy for NSCLC patients.

 

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[193]

TÍTULO / TITLE:  - Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and  hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):238-45. doi: 10.1097/JTO.0b013e31827740f0.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827740f0

AUTORES / AUTHORS:  - Gomez DR; Hong DS; Allen PK; Welsh JS; Mehran RJ; Tsao AS; Liao Z; Bilton SD; Komaki R; Rice DC

INSTITUCIÓN / INSTITUTION:  - Departments of *Radiation Oncology, daggerThoracic & Cardiovascular Surgery, and  double daggerThoracic/Head & Neck Medical Oncology, The University of Texas M.D.  Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - INTRODUCTION: : We investigated safety, efficacy, and recurrence after postoperative hemithoracic intensity-modulated radiation therapy (IMRT) in patients with malignant pleural mesothelioma treated with extrapleural pneumonectomy (EPP), during the past decade at a single institution. METHODS: : In 2001-2011, 136 consecutive patients with malignant pleural mesothelioma underwent EPP with planned adjuvant IMRT. Eighty-six patients (64%) underwent hemithoracic IMRT; the rest were not eligible because of postoperative complications, disease progression, or poor performance status. We assessed toxicity, survival, and patterns of failure in these 86 patients. Toxicity was scored with the Common Terminology Criteria for Adverse Events version 4.0; survival outcomes were estimated with the Kaplan-Meier method; and locoregional patterns of failure were classified as in-field, marginal, or out-of-field. Risk  factors related to survival were identified by univariate and multivariate Cox regression analysis. RESULTS: : Median overall survival time for all 86 patients  receiving IMRT was 14.7 months. Toxicity rates of grade of 3 or more were: skin 17%, lung 12%, heart 2.3%, and gastrointestinal toxicity 16%. Five patients experienced grade 5 pulmonary toxicity. Rates of locoregional recurrence-free survival, distant metastasis-free survival, and overall survival (OS) were 88%, 55%, and 55% at 1 year and 71%, 40%, and 32% at 2 years. On multivariate analysis, pretreatment forced expiratory volume in 1 second, nonepithelioid histology, and nodal status were associated with distant metastasis-free survival and OS. CONCLUSION: : IMRT after EPP is associated with low rates of locoregional recurrence, though some patients experience life-threatening lung toxicity. Tumor histology and nodal status can be helpful in identifying patients for this aggressive treatment.

 

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[194]

TÍTULO / TITLE:  - Radical treatment of non-small cell lung cancer during the last 5 years.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Jan 23. pii: S0959-8049(12)01032-5. doi: 10.1016/j.ejca.2012.12.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.12.023

AUTORES / AUTHORS:  - McCloskey P; Balduyck B; Van Schil PE; Faivre-Finn C; O’Brien M

INSTITUCIÓN / INSTITUTION:  - Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.

RESUMEN / SUMMARY:  - The management of non-small cell lung cancer (NSCLC) has continued to improve over the last 5years due to advances in surgery, radiological staging, combined modality therapies and advances in radiation technology. We have an updated staging classification (7th Edition American Joint Committee on Cancer staging) and now in 2011, a new histology classification introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications as the role of limited resection is reconsidered for early stage lesions. Surgery is curative in early stage disease. The role of surgery in locally advanced NSCLC remains controversial. The principal aim is a complete resection as this will determine long-term prognosis. Intraoperative staging of lung cancer is extremely important to determine the extent of resection according to the tumour and nodal status. Systematic nodal dissection is generally advocated to obtain accurate intraoperative staging and to help decide on adjuvant therapy. Radiotherapy currently plays a major role in  the management of lung cancer as most patients are not surgical candidates due to disease stage, fitness and co-morbidities. In the last 5years we have seen continuing optimisation of chemo-radiotherapy combinations and technological advances including the development of image guided radiotherapy (IGRT), stereotactic ablative body radiotherapy (SABR) and intensity modulated radiotherapy (IMRT). Quality of life evaluation is becoming increasingly important and should be considered when deciding on a specific treatment, especially in a multimodality setting.

 

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[195]

TÍTULO / TITLE:  - Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lancet Oncol. 2013 Jan;14(1):38-47. doi: 10.1016/S1470-2045(12)70489-8. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(12)70489-8

AUTORES / AUTHORS:  - Janne PA; Shaw AT; Pereira JR; Jeannin G; Vansteenkiste J; Barrios C; Franke FA; Grinsted L; Zazulina V; Smith P; Smith I; Crino L

INSTITUCIÓN / INSTITUTION:  - Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: pjanne@partners.org.

RESUMEN / SUMMARY:  - BACKGROUND: No targeted therapies are available for KRAS-mutant non-small-cell lung cancer (NSCLC). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC. METHODS: Eligible patients were older than 18 years of age; had histologically or cytologically confirmed stage IIIB-IV KRAS-mutant NSCLC; had failed first-line therapy for advanced NSCLC; had WHO performance status of 0-1; had not received previous therapy with either a MEK inhibitor or docetaxel;  and had adequate bone marrow, renal, and liver function. Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m(2) on day 1 of a 21 day cycle). Randomisation was done with an interactive voice response system and investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival, analysed for all patients with confirmed KRAS mutations. This study is registered with ClinicalTrials.gov, number NCT00890825. FINDINGS: Between April 20, 2009, and June 30, 2010, we randomly assigned 44 patients to receive selumetinib and docetaxel (selumetinib group) and 43 to receive placebo and docetaxel (placebo group). Of these, one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive. Median overall survival was 9.4 months (6.8-13.6) in the selumetinib group and 5.2 months (95% CI 3.8-non-calculable) in the placebo group (hazard ratio [HR] for death 0.80, 80% CI 0.56-1.14; one-sided  p=0.21). Median progression-free survival was 5.3 months (4.6-6.4) in the selumetinib group and 2.1 months (95% CI 1.4-3.7) in the placebo group (HR for progression 0.58, 80% CI 0.42-0.79; one-sided p=0.014). 16 (37%) patients in the  selumetinib group and none in the placebo group had an objective response (p<0.0001). Adverse events of grade 3 or higher occurred in 36 (82%) patients in  the selumetinib group and 28 (67%) patients in the placebo group. The most common grade 3-4 adverse events were neutropenia (29 [67%] of 43 patients in the selumetinib group vs 23 [55%] of 42 patients in the placebo group), febrile neutropenia (eight [18%] of 44 patients in the selumetinib group vs none in the placebo group), dyspnoea (one [2%] of 44 patients in the selumetinib group vs five [12%] of 42 in the placebo group), and asthenia (four [9%] of 44 patients in the selumetinib group vs none in the placebo group). INTERPRETATION: Selumetinib  plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. These findings warrant further clinical investigation of selumetinib plus  docetaxel in KRAS-mutant NSCLC. FUNDING: AstraZeneca.

 

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[196]

TÍTULO / TITLE:  - Molecular diagnostics of a single multifocal non-small cell lung cancer case using targeted next generation sequencing.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virchows Arch. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00428-012-1346-4

AUTORES / AUTHORS:  - Geurts-Giele WR; Dirkx-van der Velden AW; Bartalits NM; Verhoog LC; Hanselaar WE; Dinjens WN

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands, w.geurts-giele@erasmusmc.nl.

RESUMEN / SUMMARY:  - Histological and molecular subtyping of non-small cell lung cancer (NSCLC) is important for predicting survival and drug response in these patients. Up to 8 %  of NSCLC are multifocal and these tumor foci are often clonally related. Multiple foci can however also represent different primary tumors, with prognostic and therapeutic consequences. We describe a patient with multifocal NSCLC from which  we obtained tissue from two separate lesions. With routine conventional molecular determinations, the clonal relationship between the two lesions was determined. In addition, targeted next generation sequencing with the Ion Torrent Personal Genome Machine (PGM) was performed to explore the accuracy and additional value of this relatively new technique. The two tumors of this patient showed different activating epidermal growth factor receptor (EGFR) mutations, EGFR amplification  status, TP53 mutation status, and loss of heterozygosity patterns. With the PGM,  all conventional detected mutations were confirmed, and an additional variant of  unknown significance in ATM was detected in one of the tumors. The multifocal NSCLC of this patient represents two unrelated primary tumors. Our results suggest that multifocal NSCLC should be considered as potentially multiple primary tumors. As the presence of activating EGFR mutations has important therapeutic consequences, EGFR testing should be performed on all tumor foci present. In the present case, targeted next generation sequencing using the PGM appeared to be accurate and comparable with conventional molecular determinations. However, the application of the PGM in routine pathology molecular diagnostics needs validation in larger series of cases.

 

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[197]

TÍTULO / TITLE:  - Gene expression profile of aquaporin 1 and associated interactors in malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gene. 2013 Jan 9. pii: S0378-1119(12)01634-4. doi: 10.1016/j.gene.2012.12.075.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2012.12.075

AUTORES / AUTHORS:  - Jagirdar R; Solenov EI; Hatzoglou C; Molyvdas PA; Gourgoulianis KI; Zarogiannis SG

INSTITUCIÓN / INSTITUTION:  - GeneClick.org, Hyderabad, India.

RESUMEN / SUMMARY:  - Overexpression of AQP1 has recently been shown to be an independent prognostic factor in pleural mesothelioma favoring survival. This paper presents a data mining and bioinformatics approach towards the evaluation of the gene expression  profile of AQP1 in malignant pleural mesothelioma and of AQP1 associated markers  in the context of mesothelioma disease phenotype, CDKN2A gene deletion, sex and asbestos exposure. The data generated were thus again subjected to differential expression profile analysis. Here we report that AQP1 is overexpressed in epithelioid mesothelioma and identify TRIP6 and EFEMP2 as candidate genes for further investigation in mesothelioma.

 

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[198]

TÍTULO / TITLE:  - Co-operative Effects of Thoracic X-ray Irradiation and N-nitrosobis(2-hydroxypropyl) amine Administration on Lung Tumorigenesis in Neonatal, Juvenile and Adult Wistar Rats.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicol Appl Pharmacol. 2013 Jan 18. pii: S0041-008X(13)00014-8. doi: 10.1016/j.taap.2012.12.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.taap.2012.12.024

AUTORES / AUTHORS:  - Iwata KI; Yamada Y; Nakata A; Oghiso Y; Tani S; Doi K; Morioka T; Blyth BJ; Nishimura M; Kakinuma S; Shimada Y

INSTITUCIÓN / INSTITUTION:  - Radiobiology for Children’s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan. Electronic address: k_iwata@nirs.go.jp.

RESUMEN / SUMMARY:  - Assessment of risks associated with childhood exposure to ionizing radiation when combined with chemical carcinogens is of great importance. We studied the age-dependence of the effect of combined exposure to ionizing radiation (IR) and  a chemical carcinogen on lung carcinogenesis. Female 1-, 5-, and 22-week-old Wistar rats were locally irradiated on the thorax with X-rays (3.18Gy) and/or were injected intraperitoneally with N-nitrosobis(2-hydroxypropyl)amine (BHP) (1g/kg body weight) 1week after X-ray exposure or at 23weeks of age. Rats were sacrificed at 90weeks of age. We found that: (i) the incidence of lung tumors (adenoma and adenocarcinoma) increased slightly as a function of age at X-ray exposure although stastically not significant. On the other hand, the incidence by the BHP decreased with increasing age at the administration; (ii) combined exposure to X-rays at 5 or 22weeks with BHP 1week later enhanced the tumor incidence, and the effect at early-life stage (5weeks irradiation) was more effective than that at late-life stage (22weeks irradiation); (iii) that combined exposure preferentially enhanced malignant transformation; (iv) although a longer interval between the X-ray and BHP treatments reduced the combined effect, risks  of early-life irradiation at 1 or 5weeks of age lasted into adulthood; (v) adenomas and adenocarcinomas induced by X-ray and/or BHP originated from surfactant apoprotein A-positive alveolar type II cells; and (vi), extracellular  signal-regulated kinase pathway activation was observed in half the adenocarcinomas, regardless of the exposure schedule. In conclusion, combined exposure may enhance lung tumorigenesis more synergistically at early-life stage  (5weeks of age) than later-life stage.

 

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[199]

TÍTULO / TITLE:  - Chemoprevention of lung tumorigenesis by intranasally administered diindolylmethane in A/J mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs390

AUTORES / AUTHORS:  - Qian X; Song JM; Melkamu T; Upadhyaya P; Kassie F

INSTITUCIÓN / INSTITUTION:  - Department of Veterinary Clinical Sciences Masonic Cancer Center.

RESUMEN / SUMMARY:  - The main reasons for the failure of most chemopreventive agents during clinical trials are poor in vivo bioavailability and dose-limiting side effects. One potential approach to surmount these problems in lung cancer chemoprevention trials could be direct delivery of agents into the pulmonary tissue. In this study, we assessed the efficacy of intranasally delivered bio-response diindolylmethane (BRD) against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Mice treated with NNK (two doses of 50mg/kg at an interval of a week, intraperitoneal) developed 16.3+/-2.9 lung tumors per mouse. Post-carcinogen administration of BRD, via intranasal instillation, for 24 weeks, twice a week, at a dose of 2mg per mouse (0.6mg pure  diindolylmethane per mouse) reduced the lung tumor multiplicity to 4.6+/-2.2 tumors per mouse (72% reduction). Likewise, large tumors (>1mm) were almost completely abolished and multiplicities of tumors with a size of 0.5-1mm were reduced by 74%. Tumor volume was also reduced by 82%. Further studies using an in vitro model of lung tumorigenesis showed that BRD exhibited pronounced antiproliferative and apoptotic effects in premalignant and malignant bronchial cells but only minimal effects in parental immortalized cells through, at least in part, suppression of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. These results showed the potent lung tumor inhibitory activities of low  doses of BRD given via intranasal instillation and, therefore, intranasal delivery of BRD holds a great promise for lung cancer chemoprevention in subjects at high risk to develop lung cancer.

 

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[200]

TÍTULO / TITLE:  - Long-term exposure to traffic-related air pollution and the risk of death from hemorrhagic stroke and lung cancer in Shizuoka, Japan.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Sci Total Environ. 2013 Jan 15;443:397-402. doi: 10.1016/j.scitotenv.2012.10.088. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.scitotenv.2012.10.088

AUTORES / AUTHORS:  - Yorifuji T; Kashima S; Tsuda T; Ishikawa-Takata K; Ohta T; Tsuruta K; Doi H

INSTITUCIÓN / INSTITUTION:  - Department of Human Ecology, Okayama University Graduate School of Environmental  and Life Science, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: yorichan@md.okayama-u.ac.jp.

RESUMEN / SUMMARY:  - A number of studies have linked exposure to long-term outdoor air pollution with  cardiopulmonary disease; however, the evidence for stroke is limited. Furthermore, evidence with the risk for lung cancer (LC) is still inconsistent. We, therefore, evaluated the association between long-term exposure to traffic-related air pollution and cause-specific mortality. Individual data were  extracted from participants of an ongoing cohort study in Shizuoka, Japan. A total of 14,001 elderly residents completed questionnaires and were followed from December 1999 to January 2009. Annual individual nitrogen dioxide (NO(2)) exposure data, as an index for traffic-related exposure, were modeled using a Land Use Regression model and assigned to the participants. We then estimated the adjusted hazard ratios (HRs) and their confidence intervals (CIs) associated with a 10mug/m(3) elevation in NO(2) for all-cause or cause-specific mortality using time-varying Cox proportional hazards models. We found positive associations of NO(2) levels with all-cause (HR=1.12, 95% CI: 1.07-1.18), cardiopulmonary disease (HR=1.22, 95% CI: 1.15-1.30), and LC mortality (HR=1.20, 95% CI: 1.03-1.40). Among cardiopulmonary disease mortality, not only the risk for ischemic heart disease (HR=1.27, 95% CI: 1.11-1.47) but also the risks for stroke were elevated: intracerebral hemorrhage (HR=1.28, 95% CI: 1.05-1.57) and ischemic stroke (HR=1.20, 95% CI: 1.04-1.39). The present study supports the existing evidence that long-term exposure to traffic-related air pollution increases the risk of cardiopulmonary as well as LC mortality, and provides additional evidence for adverse effects on intracerebral hemorrhage as well as ischemic stroke.

 

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[201]

TÍTULO / TITLE:  - Systemic therapy of advanced non-small cell lung cancer: Major-developments of the last 5-years.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2012 Dec 19. pii: S0959-8049(12)00917-3. doi: 10.1016/j.ejca.2012.11.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.11.021

AUTORES / AUTHORS:  - Cufer T; Ovcaricek T; O’Brien ME

INSTITUCIÓN / INSTITUTION:  - University Clinic Golnik, Medical Oncology Unit, Golnik 36, 4204 Golnik, Slovenia. Electronic address: tanja.cufer@klinika-golnik.si.

RESUMEN / SUMMARY:  - The standard palliative treatment for advanced stage NSCLC remains a platinum doublet but by tailoring chemotherapy according to tumour histology the results can be improved through using pemetrexed-containing schemas in non-squamous-cell  disease. In addition, maintenance chemotherapy appears to be effective in patients achieving clinical benefit by induction therapy. Targeted therapy based  on the presence of activating epidermal growth factor receptor (EGFR) activating  mutations or EML4-ALK gene rearrangement is becoming standard practice with high  median survival rates, up to 30months. There are still numerous other molecular targeted drugs in development. This review presents the most recent relevant progress in systemic anti-cancer therapy of advanced NSCLC in the past 5years and delineates today’s new treatment options.

 

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[202]

TÍTULO / TITLE:  - (-)-Epigallocatechin-3-gallate inhibits human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell lung cancer cells by targeting HIF-1alpha

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2063-z

AUTORES / AUTHORS:  - He L; Zhang E; Shi J; Li X; Zhou K; Zhang Q; Le AD; Tang X

INSTITUCIÓN / INSTITUTION:  - Institute of Biochemistry and Molecular Biology, Guangdong Medical College, 2 Wenming Donglu, Xiashan, Zhanjiang, 524023, Guangdong, People’s Republic of China.

RESUMEN / SUMMARY:  - PURPOSE: To investigate the effects of (-)-epigallocatechin-3-gallate (EGCG) on human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell  lung cancer (NSCLC) cells and the underlying mechanisms. METHODS: NSCLC cells (A549 and NCI-H460) transfected with EGFP plasmids containing HPV-16 E6 or E7 oncogene were treated with different concentrations of EGCG for 16 h. The effects of EGCG on angiogenesis in vitro and in vivo were observed. The expression of HIF-1alpha, p-Akt, and p-ERK1/2 proteins in NSCLC cells was analyzed by Western blot. The levels of HIF-1alpha mRNA in NSCLC cells were detected by real-time RT-PCR. The concentration of VEGF and IL-8 in the conditioned media was determined by ELISA. HIF-1alpha, VEGF, and CD31 expression in A549 xenografted tumors of nude mice was analyzed by immunohistochemistry. RESULTS: HPV-16 E6 and  E7 oncoproteins HIF-1alpha-dependently promoted angiogenesis in vitro and in vivo, which was inhibited by EGCG. Mechanistically, EGCG inhibited HPV-16 oncoprotein-induced HIF-1alpha protein expression but had no effect on HIF-1alpha mRNA expression in NSCLC cells. Additionally, 50 and 100 mumol/L of EGCG significantly reduced the secretion of VEGF and IL-8 proteins induced by HPV-16 E7 oncoprotein in NSCLC A549 cells. Meanwhile, HPV-16 E6 and E7 oncoproteins HIF-1alpha-dependently enhanced Akt activation in A549 cells, which was suppressed by EGCG. Furthermore, EGCG inhibited HPV-16 oncoprotein-induced HIF-1alpha and HIF-1alpha-dependent VEGF and CD31 expression in A549 xenografted  tumors. CONCLUSIONS: EGCG inhibited HPV-16 oncoprotein-induced angiogenesis conferred by NSCLC through the inhibition of HIF-1alpha protein expression and HIF-1alpha-dependent expression of VEGF, IL-8, and CD31 as well as activation of  Akt, suggesting that HIF-1alpha may be a potential target of EGCG against HPV-related NSCLC angiogenesis.

 

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[203]

TÍTULO / TITLE:  - CD44 promotes Kras-dependent lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2012 Dec 3. doi: 10.1038/onc.2012.542.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.542

AUTORES / AUTHORS:  - Zhao P; Damerow MS; Stern P; Liu AH; Sweet-Cordero A; Siziopikou K; Neilson JR; Sharp PA; Cheng C

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

RESUMEN / SUMMARY:  - Kras-induced non-small-cell lung adenocarcinoma is the major subtype of lung cancers and is associated with poor prognosis. Using a lung cancer mouse model that expresses a cre-mediated Kras(G12D) mutant, we identified a critical role for the cell surface molecule CD44 in mediating cell proliferation downstream of  oncogenic Kras signaling. The deletion of CD44 attenuates lung adenocarcinoma formation and prolongs the survival of these mice. Mechanistically, CD44 is required for the activation of Kras-mediated signaling through the mitogen-activated protein kinase (MAPK) pathway and thus promotes tumor cell proliferation. Together, these results reveal an unrecognized role for CD44 in oncogenic Kras-induced lung adenocarcinoma and suggest that targeting CD44 could  be an effective strategy for halting Kras-dependent carcinomas.Oncogene advance online publication, 3 December 2012; doi:10.1038/onc.2012.542.

 

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[204]

TÍTULO / TITLE:  - Identification of proteins expressed differently among surgically resected stage  I lung adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Biochem. 2012 Nov 29. pii: S0009-9120(12)00649-2. doi: 10.1016/j.clinbiochem.2012.11.014.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinbiochem.2012.11.014

AUTORES / AUTHORS:  - Ha ES; Choi S; In KH; Lee SH; Lee EJ; Lee SY; Kim JH; Shin C; Shim JJ; Kang KH; Phark S; Sul D

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.

RESUMEN / SUMMARY:  - RATIONALE: Among patients with surgically resected stage I lung adenocarcinoma, some succumb to early recurrence, while others survive for more than 5years. Few  markers to predict prognoses in these patients have been accepted. Recent advances in proteomic methodologies offer a unique chance to identify new candidate biomarkers. The aim of this study is to find differences in protein expression in resected lung cancer tissue of stage I adenocarcinoma from patients with no recurrence for more than 5years and from those with early recurrence. METHODS: Lung cancer tissues were obtained from 15 patients with pathologically confirmed stage I adenocarcinoma. The patients were divided into two groups, those with recurrence within 36months (early recurrence group, n=9) and those that were disease-free for over 5years (disease free group, n=6). Tissue proteins were separated by a two-dimensional electrophoresis long gel system (30x40cm) with set ranges (3-10NL) and examined by nano-LC-ESI-MS/MS. Western blot assays were performed to validate these proteins. RESULTS: Twelve protein spots were up-regulated and 8 were down-regulated in the disease-free group as compared with the recurrence group. Of the 12 up-regulated proteins, haptoglubin, tau-tubulin kinase-2 (TTBK2), thymidine phosphorylase, annexin-1, PIN1, CAPG, and SEC23 were  validated by Western blot. Among the 8 down-regulated proteins, serpinB6 and trangelin-2 were validated. CONCLUSIONS: A total of 9 differentially expressed proteins were successfully extracted, identified, and confirmed from stage I lung adenocarcinoma tissues. The increased or decreased expression of these proteins according to prognosis may be the basis for further studies of proteomics in developing prognostic biomarkers.

 

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[205]

TÍTULO / TITLE:  - Comparison of Targeted Next-Generation Sequencing (NGS) and Real-Time PCR in the  Detection of EGFR, KRAS, and BRAF Mutations on Formalin-Fixed, Paraffin-Embedded  Tumor Material of Non-Small Cell Lung Carcinoma-Superiority of NGS.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Chromosomes Cancer. 2013 Jan 30. doi: 10.1002/gcc.22047.

            ●● Enlace al texto completo (gratuito o de pago) 1002/gcc.22047

AUTORES / AUTHORS:  - Tuononen K; Maki-Nevala S; Sarhadi VK; Wirtanen A; Ronty M; Salmenkivi K; Andrews JM; Telaranta-Keerie AI; Hannula S; Lagstrom S; Ellonen P; Knuuttila A; Knuutila S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.

RESUMEN / SUMMARY:  - The development of tyrosine kinase inhibitor treatments has made it important to  test cancer patients for clinically significant gene mutations that influence the benefit of treatment. Targeted next-generation sequencing (NGS) provides a promising method for diagnostic purposes by enabling the simultaneous detection of multiple mutations in various genes in a single test. The aim of our study was to screen EGFR, KRAS, and BRAF mutations by targeted NGS and commonly used real-time polymerase chain reaction (PCR) methods to evaluate the feasibility of  targeted NGS for the detection of the mutations. Furthermore, we aimed to identify potential novel mutations by targeted NGS. We analyzed formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens from 81 non-small cell lung carcinoma patients. We observed a significant concordance (from 96.3 to 100%) of  the EGFR, KRAS, and BRAF mutation detection results between targeted NGS and real-time PCR. Moreover, targeted NGS revealed seven nonsynonymous single-nucleotide variations and one insertion-deletion variation in EGFR not detectable by the real-time PCR methods. The potential clinical significance of these variants requires elucidation in future studies. Our results support the use of targeted NGS in the screening of EGFR, KRAS, and BRAF mutations in FFPE tissue material. © 2012 Wiley Periodicals, Inc.

 

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[206]

TÍTULO / TITLE:  - Zebularine-induced apoptosis in Calu-6 lung cancer cells is influenced by ROS and GSH level changes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0656-8

AUTORES / AUTHORS:  - You BR; Park WH

INSTITUCIÓN / INSTITUTION:  - Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju, 561-180, Republic of Korea.

RESUMEN / SUMMARY:  - Zebularine (Zeb) is a DNA methyltransferase (DNMT) inhibitor that has various biological properties including anti-cancer effect. In the present study, we evaluated the effects of Zeb on the growth and death of Calu-6 lung cancer cells  in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Zeb inhibited the growth of Calu-6 cells with an IC(50) of approximately 150 muM at 72 h in a dose-dependent manner. Zeb induced an S phase arrest of the cell cycle  and apoptosis in Calu-6 cells. Pan-caspase inhibitor (Z-VAD) and caspase-8 inhibitor (Z-IETD) significantly rescued some cells from Zeb-induced Calu-6 cell  death. In relation to ROS and GSH levels, O(2) (*-) level was significantly increased in Zeb-treated Calu-6 cells and caspase inhibitors reduced O(2) (*-) level in these cells. Zeb induced GSH depletion in HeLa cells, which was attenuated by caspase inhibitors. L-buthionine sulfoximine (BSO), a GSH synthesis inhibitor, intensified the apoptotic cell death, ROS level, and GSH depletion in  Zeb-treated Calu-6 cells. In addition, BSO increased Bax protein and decreased Bcl-2 protein in Zeb-treated Calu-6 cells. In conclusion, Zeb inhibited the growth of Calu-6 lung cancer cells via cell cycle arrest and caspase-dependent apoptosis and its cell death was influenced by ROS and GSH level changes.

 

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[207]

TÍTULO / TITLE:  - Overexpression of MAC30 is associated with poor clinical outcome in human non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0612-z

AUTORES / AUTHORS:  - Han KY; Gu X; Wang HR; Liu D; Lv FZ; Li JN

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, The Second Affiliated Hospital of Harbin Medical University, No. 148, Baojian Rd, Nangang District, Harbin, 150086, Heilongjiang Province, China.

RESUMEN / SUMMARY:  - The aim of this study was to detect MAC30 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Quantitative real-time RT-PCR was performed to examine the expression of MAC30 mRNA in 20 cases of NSCLC and corresponding non-tumor tissue samples. Immunohistochemistry was performed to detect the expression of MAC30 in 95 NSCLC  tissues. We found that the expression levels of MAC30 mRNA in NSCLC tissues were  significantly higher than those in corresponding non-tumor tissues. High-level MAC30 expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Patients with high expression levels of MAC30 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high MAC30 protein expression was an independent prognostic  factor for NSCLC patients. Our study suggests that over-expression of MAC30 may play an important role in the progression of NSCLC and MAC30 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

 

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[208]

TÍTULO / TITLE:  - Identical Human Papillomavirus (HPV) Genomic Variants Persist in Recurrent Respiratory Papillomatosis for up to 22 Years.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Dis. 2013 Feb;207(4):583-7. doi: 10.1093/infdis/jis733. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1093/infdis/jis733

AUTORES / AUTHORS:  - Kocjan BJ; Gale N; Hocevar Boltezar I; Seme K; Fujs Komlos K; Hosnjak L; Maver PJ; Jelen MM; Zupanic Pajnic I; Balazic J; Poljak M

INSTITUCIÓN / INSTITUTION:  - Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

RESUMEN / SUMMARY:  - Seventy initial and 125 follow-up tissue specimens of laryngeal papillomas, obtained from 70 patients who had had recurrent respiratory papillomatosis for from 1-22 years, were investigated for the presence of human papillomavirus (HPV) DNA and HPV E5a, LCR and/or full-length genomic variants. HPV-6 was found in 130/195, HPV-11 in 63/195, and HPV-6/HPV-11 in 2/195 samples. Within 67/70 (95.7%) patients, all follow-up HPV isolates genetically matched completely initial HPV isolate over the highly variable parts of the genome or over the entire genome. Frequent recurrence of laryngeal papillomas is a consequence of long-term persistence of the identical initial HPV genomic variant.

 

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[209]

TÍTULO / TITLE:  - Imaging the early response to chemotherapy in advanced lung cancer with diffusion-weighted magnetic resonance imaging compared to fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2012 Dec 12. doi: 10.1002/jmri.23959.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.23959

AUTORES / AUTHORS:  - Tsuchida T; Morikawa M; Demura Y; Umeda Y; Okazawa H; Kimura H

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Fukui, Fukui, Japan. tsucchy@u-fukui.ac.jp.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) for assessment of the early response to chemotherapy and outcome in patients with advanced lung cancer through comparison with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT). MATERIALS AND METHODS: Twenty-eight lung cancer patients underwent DW-MRI,  FDG-PET, and CT before and after one course of chemotherapy. Changes in the apparent diffusion coefficient (DeltaADC), the mean standardized uptake value (DeltaSUV), and the maximum diameter (DeltaMD) were measured and compared. According to the response evaluation criteria, patients were divided into two groups, responders and nonresponders, and progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: The relationship between DeltaADC  and DeltaSUV had the highest correlation coefficient. A cutoff value of DeltaADC  between responders and nonresponders was estimated as 21.5%. PFS and OS between responders and nonresponders were significantly different on DW-MRI (PFS, P = 0.012; OS, P = 0.006) and on FDG-PET (PFS, P = 0.017; OS, P = 0.036), but not on  CT (PFS, P = 0.105; OS, P = 0.051). CONCLUSION: DW-MRI can be used to predict prognosis in patients with advanced lung cancer. J. Magn. Reson. Imaging 2012. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2012 Wiley Periodicals, Inc.

 

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[210]

TÍTULO / TITLE:  - Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer. 2012 Dec 20. doi: 10.1002/cncr.27913.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27913

AUTORES / AUTHORS:  - Weickhardt AJ; Aisner DL; Franklin WA; Varella-Garcia M; Doebele RC; Camidge DR

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado. andrew.weickhardt@ucdenver.edu.

RESUMEN / SUMMARY:  - In series dominated by adenocarcinoma histology, approximately 5% of non-small cell lung cancers (NSCLCs) harbor an anaplastic lymphoma kinase (ALK) gene rearrangement. Crizotinib, a tyrosine kinase inhibitor with significant activity  against ALK, has demonstrated high response rates and prolonged progression-free  survival in ALK-positive patients enrolled in phase ½ clinical trials. In 2011, crizotinib received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of proven ALK-positive NSCLC using an FDA-approved diagnostic test. Currently, only break-apart fluorescence in situ hybridization testing is FDA approved as a companion diagnostic for crizotinib; however, many other assays are available or in development. In the current review, the authors  summarize the diagnostic tests available, or likely to become available, that could be used to identify patients with ALK-positive NSCLC, highlighting the pros and cons of each. Cancer 2012. © 2012 American Cancer Society.

 

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[211]

TÍTULO / TITLE:  - Effect of PF-02341066 and radiation on non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):1094-100. doi: 10.3892/or.2012.2198. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2198

AUTORES / AUTHORS:  - Tumati V; Kumar S; Yu L; Chen B; Choy H; Saha D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

RESUMEN / SUMMARY:  - Recently, a fusion protein of echinoderm microtubule associated protein like-4 (EML4) and anaplastic lymphoma kinase (ALK) has been found in non-small cell lung cancer (NSCLC) patients. In addition, endogenous expression of phosphorylated c-Met was found to be increased in many invasive NSCLC cases. PF-02341066 (crizotinib) is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown that treatment with ALK inhibitors leads to drastic tumor regression in xenograft models. A phase I trial of PF-02341066 yielded a 53% response rate and a disease control rate of 79%. We evaluated crizotinib as a potential radiation-sensitizing agent in multiple established NSCLC cell lines with varying expression levels of c-Met and EML4-ALK. The combined effect of ionizing radiation (IR) and PF-02341066 was determined by the surviving cell fraction, cell cycle distribution, apoptosis, DNA double-strand break repair in 5 NSCLC cell lines (A549, H460, H3122, H2228 and H1993) and in in vivo xenograft studies. Treatment of NSCLC cells with either PF-02341066 alone or PF-02341066 +  IR did not significantly alter cellular radiosensitivity, DNA repair kinetics and cell cycle distribution; no significant enhancement of tumor growth delay was noted in response to the combined treatment of PF-02341066 + IR. EML4-ALK and c-Met inhibition leads to activation of parallel pathways that converge on Akt signaling which abrogates any radiation-sensitizing effect. Although PF-02341066  is an effective therapy able to suppress tumor growth in tumors that exhibit positivity for either EML4-ALK or c-Met, it did not affect the intrinsic radiation response of tumor cell lines. In the present study, we demonstrated that PF-02341066 did not enhance radiation sensitivity in a panel of NSCLC cell lines.

 

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[212]

TÍTULO / TITLE:  - Intronic Boundary Mutation rs430397 Cannot Affect Alternate Splicing and Is an Indecisive Risk Factor for Non-small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chest. 2012 Dec;142(6):1691-2. doi: 10.1378/chest.12-1513.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-1513

AUTORES / AUTHORS:  - Zhu X; Fan W; Li D

 

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[213]

TÍTULO / TITLE:  - Is survivin expression prognostic or predictive in malignant pleural mesothelioma?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virchows Arch. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00428-013-1373-9

AUTORES / AUTHORS:  - Hmeljak J; Erculj N; Dolzan V; Pizem J; Kern I; Kovac V; Cemazar M; Cor A

INSTITUCIÓN / INSTITUTION:  - Faculty of Health Sciences, University of Primorska, Polje 42, 6310, Izola, Slovenia, julija.hmeljak@fvz.upr.si.

RESUMEN / SUMMARY:  - Malignant pleural mesothelioma is an incurable cancer strongly associated with asbestos exposure and characterised by poor response to treatment. The inhibitor-of-apoptosis protein family member survivin is involved in apoptosis and proliferation and is expressed in cancer cells only. The aims of the present  study were to elucidate whether survivin expression is associated with tumour cell apoptosis and proliferation and to assess the prognostic and predictive value of survivin expression in malignant pleural mesothelioma. Archival pleural  mesothelioma tissue samples from 101 patients were immunohistochemically analysed for nuclear expression of survivin, for proliferation with the use of Ki-67 as marker and for apoptosis using active caspase-3 as a marker. Staining results and clinical data were included in a survival analysis. Survivin was highly expressed in tumour cell nuclei in all samples and this correlated positively with both apoptosis and proliferation, but did not have a significant prognostic value. We  found significantly higher survivin expression in patients who responded to chemotherapy compared to patients with progressive disease. Survivin expression might contribute to treatment response prediction, but survivin expression in malignant pleural mesothelioma did not have prognostic significance.

 

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[214]

TÍTULO / TITLE:  - Meat consumption and risk of lung cancer: evidence from observational studies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan;24(1):266-7. doi: 10.1093/annonc/mds595.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds595

AUTORES / AUTHORS:  - Wang F; Sun GP; Zou YF

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei.

 

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[215]

TÍTULO / TITLE:  - Survivin expression impacts prognostically on NSCLC but not SCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb;79(2):180-6. doi: 10.1016/j.lungcan.2012.11.004. Epub 2012  Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.004

AUTORES / AUTHORS:  - Rosato A; Menin C; Boldrin D; Santa SD; Bonaldi L; Scaini MC; Del Bianco P; Zardo D; Fassan M; Cappellesso R; Fassina A

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Istituto Oncologico Veneto IRCCS, Padua, Italy. Electronic address: antonio.rosato@unipd.it.

RESUMEN / SUMMARY:  - Survivin is expressed in lung cancer and in most cancer tissues and has a significant impact on prognosis. This work aimed to comparatively assess survivin expression and significance in Non-Small (NSCLC) and Small Cell Lung Cancers (SCLC). Sixty-five NSCLC and 35 SCLC samples were analyzed by semi-quantitative real-time RT-PCR. Survivin mRNA levels were significantly higher in tumors than in normal tissue, and in SCLC than in NSCLC samples. Immunohistochemistry and FISH analyses were performed in 59 and 26 tumor specimens, respectively. In SCLC  survivin was only present in cytoplasm, while in some NSCLC cases it also showed  nuclear or mixed patterns. FISH analysis did not disclose survivin gene amplification, except for one NSCLC case. Finally, 90 samples were genotyped for  the -31G/C SNP of survivin promoter by direct sequencing; the -31G/C SNP genotype status showed a significant association only with nodal NSCLC metastasis, but not with survivin expression in any tumor group. A better prognosis was correlated to higher levels of survivin mRNA and to the presence of at least one G allele at -31 SNP in NSCLC, while these parameters did not correlate with overall survival  in SCLC. Moreover, this SNP would appear to have no effect on the risk of lung cancer in our samples. The different prognostic role played by survivin in NSCLC  and SCLC highlights the biological differences between these lung tumor histotypes and stresses the need to clarify the molecular pathways leading to their neoplastic transformation.

 

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[216]

TÍTULO / TITLE:  - Expression of miR-150 and miR-3940-5p is reduced in non-small cell lung carcinoma and correlates with clinicopathological features.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb;29(2):704-12. doi: 10.3892/or.2012.2152. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2152

AUTORES / AUTHORS:  - Sun Y; Su B; Zhang P; Xie H; Zheng H; Xu Y; Du Q; Zeng H; Zhou X; Chen C; Gao W

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, PR China.

RESUMEN / SUMMARY:  - The present study investigated the expression of miR-150 and miR-3940-5p in non-small cell lung carcinoma (NSCLC) and its relationship with clinicopathologic features. Samples included tumor, tumor-adjacent and normal lung parenchyma tissues from 90 NSCLC patients and 17 cases of embryonic lung cDNA. The expression levels of miR-150, miR-18b-5p, miR-643 and miR-3940-5p were detected by realtime PCR; p53, EGFR, Kras and Ki-67 expression in tumor tissues was determined by immunohistochemistry. p53 mRNA expression levels in NSCLC were examined by SYBR-Green real-time PCR. The relationship between the four miRNAs and clinicopathologic features of 90 cases was analyzed. The expression of miR-150 and miR-3940-5p was significantly downregulated in tumor tissues and embryonic lung tissues compared to normal lung tissues. The expression of miR-150 and miR-3940-5p in tumor tissues was also lower than that in the matched tumor-adjacent tissues. miR-150 was downregulated preferentially in subgroups of  patients with a tumor diameter more than or equal to 3 cm, in smokers and in stage III and IV tumors. Specifically, miR-150 and miR-3940-5p expression was decreased in nuclear cell proliferation antigen Ki-67-positive NSCLC cases. miR-150 and miR-3940-5p were found to be significantly downregulated in p53 IHC-positive NSCLC cases and were negatively correlated with p53 mRNA. Reduced miR-150 and miR-3940-5p expression in tumor tissues and embryonic lung tissues suggests that these miRs may be involved in the tumorigenesis or de-differentiation of NSCLC. Due to this associaton with the Ki-67 proliferation  index in NSCLC, downregulation of miR-150 and miR-3940-5p may contribute to tumor growth and proliferation. miR-150 and miR-3940-5p may affect p53 expression through a direct or indirect pathway.

 

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[217]

TÍTULO / TITLE:  - Neuroendocrine small cell carcinoma of the breast—a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Coll Antropol. 2012 Sep;36(3):1053-5.

AUTORES / AUTHORS:  - Zadro Z; Fuduric J; Frketic I; Stifter S; Bujas T; Zadro AS; Veir Z; Doko I

INSTITUCIÓN / INSTITUTION:  - Karlovac General Hospital, Department of Surgery, Karlovac, Croatia. zvonko.zadro@zg.htnet.hr

RESUMEN / SUMMARY:  - Neuroendocrine tumors are very rare tumors that occur most commonly in the gastrointestinal tract. The occurrence of neuroendocrine tumors outside gastrointestinal tract is very rare but not unknown. Thus, neuroendocrine tumors  and their primary seat can be found in the bronchi and lungs, as well as in the testicles, ovaries, prostate, etc. The occurrence of neuroendocrine tumors as a primary seat in the breast is extremely rare phenomenon that is described in literature. We present the case of 55-year old female in where routine mammographic examination found suspicious lesions that we recommended for further processing. The patient made a breast ultrasound examination in which tumor formation was found in size 27 x 19 mm and cytological puncture found breast adenocarcinoma. Further pathohystologic and immunohistochemical analysis set the  diagnosis of neuroendocrine carcinoma, small cell type, second grade. Tumor formation by ultrasound initially sized 27 x 19 mm and pathohistologic diagnosis  showed tumor size 26 x 20 x 20 mm. The axillary lymph node biopsy did not found distant metastases in lymph nodes as well as gatherings in other organs. Neuroendocrine small cell carcinomas are exceedingly rare phenomena in the literature. By the year 2009 in the USA there were described only 50 cases of this extremely rare tumor of the breast.

 

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[218]

TÍTULO / TITLE:  - Telomere shortening and cell senescence induced by perylene derivatives in A549 human lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Bioorg Med Chem. 2012 Dec 23. pii: S0968-0896(12)00991-1. doi: 10.1016/j.bmc.2012.12.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bmc.2012.12.020

AUTORES / AUTHORS:  - Taka T; Huang L; Wongnoppavich A; Tam-Chang SW; Lee TR; Tuntiwechapikul W

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

RESUMEN / SUMMARY:  - Cancer cells evade replicative senescence by re-expressing telomerase, which maintains telomere length and hence chromosomal integrity. Telomerase inhibition  would lead cancer cells to senesce and therefore prevent cancer cells from growing indefinitely. G-quadruplex ligands can attenuate telomerase activity by inducing G-quadruplex formation at the 3’-overhang of telomere and at the human telomerase reverse transcriptase (hTERT) promoter; the former prevents telomerase from accessing the telomere, and the latter acts as a transcriptional silencer. The present investigation found that perylene derivatives PM2 and PIPER induced G-quadruplex formation from both telomeric DNA and the hTERT promoter region in vitro. Further, TRAP assay showed that these compounds inhibited telomerase in a  dose-dependent manner. When A549 human lung cancer cells were treated with these  compounds, hTERT expression was down-regulated. Moreover, the crude protein extract from these treated cells exhibited less telomerase activity. In the long-term treatment of A549 lung cancer cells with sub-cytotoxic dose of these perylenes, telomere shortening, reduction of cell proliferation and tumorigenicity, and cell senescence were observed. The results of this study indicate that perylene derivatives warrant further consideration as effective agents for cancer therapy.

 

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[219]

TÍTULO / TITLE:  - Indoor air pollution and risk of lung cancer among Chinese female non-smokers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Causes Control. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10552-012-0130-8

AUTORES / AUTHORS:  - Mu L; Liu L; Niu R; Zhao B; Shi J; Li Y; Swanson M; Scheider W; Su J; Chang SC; Yu S; Zhang ZF

INSTITUCIÓN / INSTITUTION:  - Department of Social and Preventive Medicine, School of Public Health and Health  Professions, University at Buffalo, SUNY, 270 Farber Hall, Buffalo, NY, 14214, USA, ln_mu2000@yahoo.com.

RESUMEN / SUMMARY:  - PURPOSE: To investigate indoor particulate matter (PM) level and various indoor air pollution exposure, and to examine their relationships with risk of lung cancer in an urban Chinese population, with a focus on non-smoking women. METHODS: We conducted a case-control study in Taiyuan, China, consisting of 399 lung cancer cases and 466 controls, of which 164 cases and 218 controls were female non-smokers. Indoor PM concentrations, including PM(1), PM(2.5), PM(7), PM(10), and TSP, were measured using a particle mass monitor. Unconditional logistic regression models were used to calculate odds ratios (ORs) and 95 % confidence intervals after adjusting for age, education, annual income, and smoking. RESULTS: Among non-smoking women, lung cancer was strongly associated with multiple sources of indoor air pollution 10 years ago, including heavy exposure to environmental tobacco smoke at work (aOR = 3.65), high frequency of cooking (aOR = 3.30), and solid fuel usage for cooking (aOR = 4.08) and heating (aOR(coal stove) = 2.00). Housing characteristics related to poor ventilation, including single-story, less window area, no separate kitchen, no ventilator, and rarely having windows open, are associated with lung cancer. Indoor medium PM(2.5) concentration was 68 mug/m(3), and PM(10) was 230 mug/m(3). PM levels in  winter are strongly correlated with solid fuel usage for cooking, heating, and ventilators. PM(1) levels in cases are more than 3 times higher than that in controls. Every 10 mug/m(3) increase in PM(1) is associated with 45 % increased risk of lung cancer. CONCLUSIONS: Indoor air pollution plays an important role in the development of lung cancer among non-smoking Chinese women.

 

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[220]

TÍTULO / TITLE:  - Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lab Invest. 2013 Jan 28. doi: 10.1038/labinvest.2013.2.

            ●● Enlace al texto completo (gratuito o de pago) 1038/labinvest.2013.2

AUTORES / AUTHORS:  - Sakaeda M; Sato H; Ishii J; Miyata C; Kamma H; Shishido-Hara Y; Shimoyamada H; Fujiwara M; Endo T; Tanaka R; Kondo H; Goya T; Aoki I; Yazawa T

INSTITUCIÓN / INSTITUTION:  - 1] Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan [2] Department of Pathology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

RESUMEN / SUMMARY:  - Thyroid transcription factor 1 (TTF1) plays crucial roles in thyroid, lung, and developing brain morphogenesis. Because TTF1-expressing neoplasms are generated from organs and tissues that normally express TTF1, such as the thyroid follicular epithelium and peripheral lung airway epithelium, TTF1 is widely used  as a cell lineage-specific and diagnostic marker for thyroid carcinomas and for lung adenocarcinomas with terminal respiratory unit (TRU) differentiation. However, among lung neuroendocrine tumors, small-cell carcinomas (small-cell lung cancers (SCLCs)), most of which are generated from the central airway, also frequently express TTF1 at high levels. To clarify how SCLCs express TTF1, we investigated the molecular mechanisms of its expression using cultivated lung cancer cells and focusing upon neural cell-specific transcription factors. Both SCLC cells and lung adenocarcinoma cells predominantly expressed isoform 2 of TTF1, and TTF1 promoter assays in SCLC cells revealed that the crucial region for activation of the promoter, which is adjacent to the transcription start site of  TTF1 isoform 2, has potent FOX-, LHX-, and BRN2-binding sites. Transfection experiments using expression vectors for FOXA1, FOXA2, LHX2, LHX6, and BRN2 showed that BRN2 substantially upregulated TTF1 expression, whereas FOXA1/2 weakly upregulated TTF1 expression. BRN2 and FOXA1/2 binding to the TTF1 promoter was confirmed through chromatin immunoprecipitation experiments, and TTF1 expression in SCLC cells was considerably downregulated after BRN2 knockdown. Furthermore, the TTF1 promoter in SCLC cells was scarcely methylated, and immunohistochemical examinations using a series of primary lung tumors indicated  that TTF1 and BRN2 were coexpressed only in SCLC cells. These findings suggest that TTF1 expression in SCLC is a cell lineage-specific phenomenon that involves  the developing neural cell-specific homeoprotein BRN2.Laboratory Investigation advance online publication, 28 January 2013; doi:10.1038/labinvest.2013.2.

 

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[221]

TÍTULO / TITLE:  - Mesenchymal stem cells in non-small cell lung cancer-Different from others? Insights from comparative molecular and functional analyses.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 4. pii: S0169-5002(12)00684-8. doi: 10.1016/j.lungcan.2012.12.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.015

AUTORES / AUTHORS:  - Gottschling S; Granzow M; Kuner R; Jauch A; Herpel E; Xu EC; Muley T; Schnabel PA; Herth FJ; Meister M

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Oncology, Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. Electronic address: sandra.gottschling@thoraxklinik-heidelberg.de.

RESUMEN / SUMMARY:  - BACKGROUND: Cancer-associated fibroblasts (CAF) play a vital role in lung cancer  initiation and progression. Although mesenchymal stem cells (MSC) are considered  progenitor cells of fibroblasts and show cancer modulating abilities themselves,  analyses on their presence and properties in lung cancer are lacking so far. METHODS: We performed a comparative molecular and functional analysis of MSC derived from non-small cell lung cancer (NSCLC) and corresponding normal lung tissue (NLT) of a total of 15 patients. MSC were identified and selected according to their mesenchymal multilineage differentiation capability and surface marker profile. RESULTS: Compared to NLT-MSC, NSCLC-MSC showed accelerated growth kinetics and reduced sensitivity to cisplatin. Karyotyping, comparative genomic hybridization and multiplex fluorescence in situ hybridization revealed no chromosomal aberrations. However, gene expression profiling of NSCLC- and NLT-MSC indicated variable expression of 62 genes involved in proliferation, DNA repair, apoptosis, extracellular matrix synthesis, tissue remodeling and angiogenesis. Differential expression of the selected candidate genes butyrylcholinesterase, clusterin and quiescin Q6 sulfhydryl oxidase 1 was validated by quantitative real-time PCR and, on protein level, by immunohistochemical analyses of original tumor tissue. Upon exposure to tumor cell-conditioned medium or transforming growth factor-beta, both, NSCLC-MSC and NLT-MSC acquired expression of alpha-smooth muscle actin (alpha-SMA), a major characteristics of CAF. CONCLUSIONS: This study indicates that NSCLC tissue contains MSC with specific molecular and functional properties. These cells might represent a progenitor reservoir for CAF and thus crucially contribute to lung cancer progression.

 

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[222]

TÍTULO / TITLE:  - RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Gene Ther. 2013 Jan 18. doi: 10.1038/cgt.2012.91.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2012.91

AUTORES / AUTHORS:  - Li C; Zhang X; Cheng L; Dai L; Xu F; Zhang J; Tian H; Chen X; Shi G; Li Y; Du T; Zhang S; Wei Y; Deng H

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China.

RESUMEN / SUMMARY:  - Transfection of plasmid vectors coexpressing short hairpin RNA (shRNA) for focal  adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) significantly inhibited protein level of FAK and EGFR. Knockdown of FAK and EGFR expression significantly inhibited cell proliferation and induced cell apoptosis of A549 lung cancer cells in vitro. In A549 subcutaneous xenograft model, mice treated for 3 weeks with plasmid that coexpresses FAK and EGFR shRNA had significantly smaller tumors than those in control mice (P<0.01). FAK and EGFR dual silencing also significantly decreased microvessel density, tumor cell proliferation and increased the level of apoptosis in tumor cells. Moreover, administration with plasmid that coexpresses FAK and EGFR shRNA significantly inhibited the A549 experimental lung metastases. Collectively, our data suggest that the dual inhibition of FAK and EGFR by using plasmid vector-based RNA interference might be a novel therapeutic approach to the treatment of human NSCLC.Cancer Gene Therapy advance online publication, 18 January 2013; doi:10.1038/cgt.2012.91.

 

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[223]

TÍTULO / TITLE:  - Molecular mechanism depressing PMA-induced invasive behaviors in human lung adenocarcinoma cells by cis- and trans-cinnamic acid.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Pharm Sci. 2012 Dec 7;48(3):494-501. doi: 10.1016/j.ejps.2012.11.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejps.2012.11.013

AUTORES / AUTHORS:  - Tsai CM; Sun FM; Chen YL; Hsu CL; Yen GC; Weng CJ

INSTITUCIÓN / INSTITUTION:  - Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo North Rd., Taichung 40256, Taiwan; Tainan Hospital, Department of Health, Executive Yuan, No. 125, Zhongshan Rd., Tainan City 70043, Taiwan; Hualien Hospital, Department of Health, Executive Yuan, No. 600, Chungjen Rd., Hualien City, Hualien County 97061, Taiwan.

RESUMEN / SUMMARY:  - Dietary polyphenols have been reported as an effective phytochemical for health protection and cinnamic acid (CA) is one of the polyphenols that has been demonstrated having chemopreventive potential. It was known that the early and distal metastasis might lead to the high mortality of patients with lung adenocarcinoma. We previously compared and verified the inhibitory effect of cis-CA and trans-CA on phorbol-12-myristate-13-acetate (PMA)-induced invasion of  human lung adenocarcinoma A549 cells. The aim of this study was to explore the underlying molecular mechanism. By gelatin zymography and semi-quantitative RT-PCR, the activities and mRNA of MMP-9/MMP-2 exerted a significantly (p<.05) dose-dependent reduction by treating with cis-CA and trans-CA. Western blots further showed that the cis-CA- and trans-CA-inhibited MMPs might partly through  modulating TIMP-1 and the PAI-2-regulated uPA activity. In molecular level, the AP-1 and NF-kappaB as well as the downstream of the MAPK pathway might be involved in cis-CA- and trans-CA-inhibited MMPs expression. This study disclosed  the molecular mechanism underlying the anti-invasive activity of cis-CA and trans-CA and concluded the cis- and trans-form of CA should be a safe and potential agent to prevent lung tumor cells from metastasizing.

 

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[224]

TÍTULO / TITLE:  - Midkine mRNA level in peripheral blood mononuclear cells is a novel biomarker for primary non-small cell lung cancer: a prospective study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Clin Oncol. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00432-012-1357-1

AUTORES / AUTHORS:  - Ma Z; Li H; Wang B; Shen Q; Cui E; Min L; Qian F; Ping J; Dai L

INSTITUCIÓN / INSTITUTION:  - Huzhou Central Hospital, Huzhou, China.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: Midkine (MK) mRNA was highly expressed in various human cancer tissues and cells. The present study aimed to investigate whether MK mRNA level in peripheral blood mononuclear cells (PBMC) could serve as a diagnostic biomarker for patients having primary non-small cell lung cancer (NSCLC). METHODS: MK mRNA level in PBMC from 87 patients with primary NSCLC, 35 patients with lung benign lesion (LEL), and 30 healthy volunteers was analyzed by real-time quantitative RT-PCR. The levels of serum carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase were detected by chemiluminescent microparticle enzyme immunoassay. RESULTS: PBMC MK mRNA level was significantly higher in patients with primary NSCLC than that in other groups (P < 0.001), while there was no significant difference between LEL patients and healthy volunteers (P > 0.05). Higher MK mRNA level was correlated with clinical  stages (P = 0.026), differentiation (P = 0.025), and lymph node metastasis (P = 0.022) of NSCLC. Using a cutoff of 0.0063, the sensitivity and specificity of MK  mRNA levels to differentiate between patients with NSCLC and patients with LEL were 57.47 and 93.33 %,and it were 56.32 and 93.33 % for patients with NSCLC and  healthy volunteers, respectively. Furthermore, multivariate analysis indicated that PBMC MK mRNA level above the cutoff value presented a chance of 11-fold higher for NSCLC occurrence. CONCLUSIONS: MK mRNA level in PBMC may be a potential non-invasive molecular marker for the diagnosis of primary NSCLC.

 

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[225]

TÍTULO / TITLE:  - Use of CT to Evaluate Pleural Invasion in Non-Small Cell Lung Cancer: Measurement of the Ratio of the Interface between Tumor and Neighboring Structures to Maximum Tumor Diameter.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12120864

AUTORES / AUTHORS:  - Imai K; Minamiya Y; Ishiyama K; Hashimoto M; Saito H; Motoyama S; Sato Y; Ogawa JI

INSTITUCIÓN / INSTITUTION:  - Department of Chest, Breast and Endocrinologic Surgery and Department of Integrated Medicine, Division of Radiology and Radiation Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo Akita City 010-8543, Japan.

RESUMEN / SUMMARY:  - Purpose:To develop a simple noninvasive technique for evaluating pleural invasion by using routine preoperative computed tomography (CT).Materials and Methods:The  institutional review board approved this retrospective study, and written informed consent was obtained for performing the initial and follow-up CT studies. Preoperative CT findings (169 patients with possible pleural invasion) and pathologic diagnoses after surgical resection were evaluated. The length of the interface between the primary tumor and neighboring structures (arch distance) and the maximum tumor diameter were measured on CT images, after which  arch distance-to-maximum tumor diameter ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the ratios.Results:Median arch distance-to-maximum tumor diameter ratios for pleural  invasion categories (pl1, pl2, pl3) assessed by using the Union Internationale Contre le Cancer TNM staging system were as follows: pl1, 0.206 (25th-75th percentile, 0-0.486); pl2, 0.638 (25th-75th percentile, 0.385-0.830); and pl3, 1.092 (25th-75th percentile, 1.045-1.214) (P < .001 between groups). On the basis of the ROC curves, the cut-off value for invasion was an arch distance-to-maximum tumor diameter ratio of 0.9. When the ratio was greater than 0.9, the sensitivity and specificity for thoracic invasion and area under the ROC curve were 89.7%, 96.0%, and 0.976, respectively, which represents an improvement over values obtained by using conventional criteria (radiologists A and B: 46.7% and 74.2% and 91.3% and 84.8%, respectively).Conclusion:When diagnosing T3 or T4 lung cancer based on arch distance-to-maximum tumor diameter ratios, a higher performance level was achieved than that with use of conventional criteria. Measurement of the ratios is a simple noninvasive technique for evaluating pleural invasion at CT.© RSNA, 2013.

 

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[226]

TÍTULO / TITLE:  - PTEN protein expression in malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2012 Dec 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0615-9

AUTORES / AUTHORS:  - Agarwal V; Campbell A; Beaumont KL; Cawkwell L; Lind MJ

INSTITUCIÓN / INSTITUTION:  - Cancer Biology Proteomics Group, Postgraduate Medical Institute of the University of Hull, Hull, UK.

RESUMEN / SUMMARY:  - Malignant pleural mesothelioma is associated with poor prognosis and despite recent advances in chemotherapy, the median survival is still approximately 12 months. Loss of phosphatase and tensin homolog (PTEN) protein expression may lead to constitutive activation of AKT resulting in cell survival and proliferation. Small studies reported that PTEN protein expression is rarely lost in mesothelioma whilst a larger study demonstrated prognostic significance of PTEN protein expression status with absence in 62 % of cases. We aimed to analyse PTEN protein expression in mesothelioma. Immunohistochemical analysis was performed in 86 archival mesothelioma samples to determine the PTEN protein expression status  and statistical analysis was performed to identify any prognostic significance. Mesothelial cells in normal pleura demonstrated positive staining for PTEN protein and served as a positive reference. For mesothelioma samples, the expression of PTEN protein was scored as 0 (negative), 1 (intensity less than that of positive normal pleura reference slide) and 2 (intensity equal to or greater than positive normal pleura reference slide). A total of 23/86 (26.7 %) scored 0, 23/86 (26.7 %) scored 1 and 40/86 (46.5 %) scored 2 for PTEN expression. Univariate analysis demonstrated that lack of PTEN expression was not associated with survival. PTEN protein expression was undetectable in 26.7 % of mesothelioma samples; however, no prognostic significance was identified. Absence of PTEN protein may result in activation of the PI3K/AKT/MTOR pathway. Targeting  this pathway with inhibitors further downstream of PTEN may provide a potential therapeutic target in selected patients.

 

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[227]

TÍTULO / TITLE:  - Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0675-5

AUTORES / AUTHORS:  - Shi MM; Xiong YL; Jia XS; Li X; Zhang L; Li XL; Wang EH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang, China, shimumu2009@139.com.

RESUMEN / SUMMARY:  - Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive  potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.

 

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[228]

TÍTULO / TITLE:  - Rib Fractures after Percutaneous Radiofrequency and Microwave Ablation of Lung Tumors: Incidence and Relevance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12120933

AUTORES / AUTHORS:  - Alexander ES; Hankins CA; Machan JT; Healey TT; Dupuy DE

INSTITUCIÓN / INSTITUTION:  - Warren Alpert Medical School of Brown University, Rhode Island Hospital, Department of Diagnostic Imaging, 593 Eddy St, Providence, RI 02903.

RESUMEN / SUMMARY:  - Purpose:To retrospectively identify the incidence and probable risk factors for rib fractures after percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) of neoplasms in the lung and to identify complications related to  these fractures.Materials and Methods:Institutional review board approval was obtained for this HIPAA-compliant retrospective study. Study population was 163 patients treated with MWA and/or RFA for 195 lung neoplasms between February 2004 and April 2010. Follow-up computed tomographic images of at least 3 months were retrospectively reviewed by board-certified radiologists to determine the presence of rib fractures. Generalized estimating equations were performed to assess the effect that patient demographics, tumor characteristics, treatment parameters, and ablation zone characteristics had on development of rib fractures. Kaplan-Meier curve was used to estimate patients’ probability of rib fracture after ablation as a function of time. Clinical parameters (ie, pain in ribs or chest, organ damage caused by fractured rib) were evaluated for patients  with confirmed fracture.Results:Rib fractures in proximity to the ablation zone were found in 13.5% (22 of 163) of patients. Estimated probability of fracture was 9% at 1 year and 22% at 3 years. Women were more likely than were men to develop fracture after ablation (P = .041). Patients with tumors closer to the chest wall were more likely to develop fracture (P = .0009), as were patients with ablation zones that involved visceral pleura (P = .039). No patients with rib fractures that were apparently induced by RFA and MWA had organ injury or damage related to fracture, and 9.1% (2 of 22) of patients reported mild pain.Conclusion:Rib fractures were present in 13.5% of patients after percutaneous RFA and MWA of lung neoplasms. Patients who had ablations performed  close to the chest wall should be monitored for rib fractures.© RSNA, 2013.

 

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[229]

TÍTULO / TITLE:  - A Novel Nomogram for Peritoneal Mesothelioma Predicts Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2651-5

AUTORES / AUTHORS:  - Schaub NP; Alimchandani M; Quezado M; Kalina P; Eberhardt JS; Hughes MS; Beresnev T; Hassan R; Bartlett DL; Libutti SK; Pingpank JF; Royal RE; Kammula US; Pandalai P; Phan GQ; Stojadinovic A; Rudloff U; Alexander HR; Avital I

INSTITUCIÓN / INSTITUTION:  - GI and Hepatobiliary Malignancies Section, Surgery Branch, National Cancer Institute/NIH, Bethesda, MD, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Estimation of personalized survival times can potentially guide treatment and surveillance. METHODS: We analyzed 104 patients who underwent CRS and cisplatin-based HIPEC for MPM. By means of 25 demographic, laboratory, operative, and histopathological variables, we developed a novel nomogram using machine-learned Bayesian belief networks with stepwise training, testing, and cross-validation. RESULTS: The mean peritoneal carcinomatosis index (PCI) was 15, and 66 % of patients had a completeness of cytoreduction (CC) score of 0 or 1. Eighty-seven percent of patients had epithelioid histology. The median follow-up  time was 49 (1-195) months. The 3- and 5-year overall survivals (OS) were 58 and  46 %, respectively. The histological subtype, pre-CRS PCI, and preoperative serum CA-125 had the greatest impact on OS and were included in the nomogram. The mean  areas under the receiver operating characteristic curve for the 10-fold cross-validation of the 3- and 5-year models were 0.77 and 0.74, respectively. The graphical calculator or nomogram uses color coding to assist the clinician in quickly estimating individualized patient-specific survival before surgery. CONCLUSIONS: Machine-learned Bayesian belief network analysis generated a novel nomogram predicting 3- and 5-year OS in patients treated with CRS and HIPEC for MPM. Pre-CRS estimation of survival times may potentially individualize patient care by influencing the use of systemic therapy and frequency of diagnostic imaging, and might prevent CRS in patients unlikely to achieve favorable outcomes despite surgical intervention.

 

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[230]

TÍTULO / TITLE:  - Straight to the heart: pulmonary vein leiomyosarcoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Med. 2013 Feb;126(2):117-9. doi: 10.1016/j.amjmed.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.amjmed.2012.11.002

AUTORES / AUTHORS:  - Patel SM; Kadakia KC; Maleszewski JJ; Marks RS

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Mayo Clinic, Rochester, Minn.

 

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[231]

TÍTULO / TITLE:  - Role of TGF-beta signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Clin Oncol. 2012 Nov 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00432-012-1352-6

AUTORES / AUTHORS:  - Datta R; Halder SK; Zhang B

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

RESUMEN / SUMMARY:  - PURPOSE: Curcumin has been shown to have potent anticancer activities like inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis. Transforming growth factor-beta (TGF-beta) signaling plays a complex role in tumor suppression and promotion depending on the tumor type and stage. However, the effect of curcumin on TGF-beta signaling in cancer cells and  the role of TGF-beta signaling in curcumin-induced anticancer activities have not been determined. Here, we investigate the role of curcumin on TGF-beta signaling, and whether TGF-beta signaling is involved in the antitumor activities of curcumin. METHODS: Human non-small cell lung cancer (NSCLC) cell lines, ACC-LC-176 (without TGF-beta signaling), H358, and A549 (with TGF-beta signaling) were treated with curcumin to determine cell growth, apoptosis, and tumorigenicity. Antitumor activities of curcumin were determined using these cell lines and an in vivo mouse model. We also tested the effect of curcumin on TGF-beta/Smad signaling by western blotting and by luciferase assays. RESULTS: Curcumin inhibited cell growth and induced apoptosis of all three NSCLC cell lines in vitro and in vivo. It significantly reduced subcutaneous tumor growth by these three cell lines irrespective of TGF-beta signaling status. Curcumin inhibited TGF-beta-induced Smad2/3 phosphorylation and transcription in H358 and  A549 cells, but not in ACC-LC-176 cells. CONCLUSIONS: Curcumin reduces tumorigenicity of human lung cancer cells in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. These results suggest that TGF-beta signaling is not directly involved in curcumin-mediated growth inhibition, induction of apoptosis, and inhibition of tumorigenicity.

 

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[232]

TÍTULO / TITLE:  - Overexpression of Smac Promotes Cisplatin-Induced Apoptosis by Activating Caspase-3 and Caspase-9 in Lung Cancer A549 Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1261

AUTORES / AUTHORS:  - Qin S; Yang C; Wang X; Xu C; Li S; Zhang B; Ren H

INSTITUCIÓN / INSTITUTION:  - 1 Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine,  Xi’an Jiaotong University , Xi’an, P.R. China.

RESUMEN / SUMMARY:  - Abstract Second mitochondrial-derived activator of caspase (Smac) plays crucial roles in mitochondrial apoptosis pathways and promotes chemotherapy-induced apoptosis. In this study, Smac levels were examined in various lung cancer cell lines, and the effects of overexpressed Smac in the nonsmall-cell lung cancer cell line A549 were assayed by stable transfection of Smac. Subsequently, MTT assays, cell counting, and flow cytometry were applied to show that overexpression of Smac inhibits cell viability and cell growth and enhances apoptosis after cisplatin treatment. Western blotting was performed before and after cisplatin treatment to demonstrate that drug treatment could release Smac from mitochondria into the cytosol and promote apoptosis by activating caspase-3  and caspase-9. Promotion of apoptosis by cytosolic Smac could be blocked by pretreating cells with the caspase-9 inhibitor z-LEHD-FMK. Our findings indicate  that overexpressed Smac significantly inhibited A549 cell growth and promoted apoptosis following cisplatin treatment due to the release of Smac from mitochondria into the cytosol, which increased the activities of caspase-3 and caspase-9.

 

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[233]

TÍTULO / TITLE:  - The Tumor Suppressor, p53, Contributes to Radiosensitivity of Lung Cancer Cells by Regulating Autophagy and Apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1297

AUTORES / AUTHORS:  - Guanghui C; Dejuan K; Xue H; Bing L; Mengzi H; Nan L; Shumei M; Xiaodong L

INSTITUCIÓN / INSTITUTION:  - 1 Department of Radiation Oncology, China-Japan Union Hospital, Jilin University  , Changchun, China .

RESUMEN / SUMMARY:  - Abstract Purpose: Cell death is one of the most important endpoints of radiosensitivity. The tumor suppressor p53 participates not only in regulation of apoptosis, but also in autophagy mechanism. In this study, H1299-P53 (with wild-type p53) and H1299-175H (with mutant 175H) were used, and the effects of p53 on radiosensitivity were analyzed. Methods: Cell models with different p53 status were established by gene engineering, and cell viability was examined by colony formation assay, and cell counting kit-8 (CCK-8), 3-Methyladenine, and Z-VAD were used to block autophagy and apoptosis, respectively. Western blot was  used to detect protein expression; monodansylcadaverine (MDC) staining was used to analyze autophagy rate; DAPI/Propidium Iodide (PI) staining and flow cytometry were used to assess apoptosis and necrosis. Results: In parental H1299, H1299-P53, and H1299-175H cells, radiosensitivity exhibited different by colony formation and CCK-8 assay (D0: 1.764 Gy, 1.407 Gy and 1.695 Gy; Dq: 2.977 Gy, 1.199 Gy and 2.312 Gy in turn). The radiosensitization of p53 was associated with the increase of MDM2 and P21 expression. The ionizing radiation (IR)-induced apoptosis was significant in H1299-P53 compared with in H1299 and H199-175H (p<0.05) by flow cytometry, and the expression of cleaved-caspase3 was increased  in H1299-P53 cells. While the IR-induced autophagy was significant in H1299 cells (p<0.01) and decreased in H1299-P53 and H1299-175H cells (p<0.01) by MDC staining, the expression of MAPLC3II and Beclin-1 increased in H1299, but not in  H1299-p53 and H199-175H cells. The IR-induced cell survival was significantly increased by Z-VAD-FMK and decreased by 3MA in H1299-P53 cells; IR- induced autophagy was significantly increased by Z-VAD-FMK in H1299-P53 cells (p<0.01), but not changed in H1299 cells. Conclusion: p53 could regulate radiosensitivity by inhibiting autophagy and activating apoptosis; autophagy provides a prosurvival mechanism, and p53 potently abrogated the IR-induced autophagy, while mutant 175H shown no effect on radiosensitivity, suggesting that individual treatment strategies should be based on p53 status in patients.

 

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[234]

TÍTULO / TITLE:  - Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low doses of arsenic.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Carcinog. 2012 Dec 19. doi: 10.1002/mc.21989.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mc.21989

AUTORES / AUTHORS:  - Liu Y; Hock JM; Van Beneden RJ; Li X

INSTITUCIÓN / INSTITUTION:  - Maine Institute for Human Genetics and Health, EMHS, Brewer, Maine; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.

RESUMEN / SUMMARY:  - Environmental or occupational exposure to low doses of arsenic induces a series of health problems including cancer. The molecular events in arsenic-induced carcinogenicity remain to be defined. In the NuLi-1 immortalized human lung epithelial cell line with p53 and pRb deficiency, exposure to low doses of arsenic trioxide for 72 h promoted cell proliferation and upregulated the gene transcription levels of FOXM1, CDC6, CDC25A, and cyclin D1, which are both critical cell cycle regulatory genes and proto-oncogenes. Continuous in vitro exposure to 1 microM arsenic trioxide for 34 wks induced malignant cell transformation, as evidenced by enhanced anchorage-independent cell growth. The expression of FOXM1, CDC6, CDC25A, and Cyclin D1 was dynamically elevated at the  gene transcription and protein levels in the process of cell transformation. The  carcinogenic ability of transformed cell colonies coincides with the expression levels of FOXM1 in in vitro anchorage-independent growth assays and in vivo tumor xenograft formation assays. In reverse, the knockdown of FOXM1 in lung adenocarcinoma A549 cells or arsenic-transformed NuLi-1 cells significantly decreased anchorage-independent cell growth and tumor xenograft formation. The transformed NuLi-1 cells showed genomic instability in the form of copy number variation (CNV) at chromosome 1, 5, 6, 18, and 20, but not loss of heterozygosity (LOH). These results showed for the first time that chronic exposure to low doses of arsenic trioxide promoted lung carcinogenicity, in part by aberrantly upregulating FOXM1 and its associated oncogenes, when the tumor suppressor genes  p53 and pRb were inactivated. © 2012 Wiley Periodicals, Inc.

 

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[235]

TÍTULO / TITLE:  - Methylenetetrahydrofolate reductase 677TT genotype might be associated with an increased lung cancer risk in Asians.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gene. 2013 Feb 15;515(1):214-9. doi: 10.1016/j.gene.2012.11.036. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2012.11.036

AUTORES / AUTHORS:  - Liu ZB; Wang LP; Shu J; Jin C; Lou ZX

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Geriatrics, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Division of Pulmonary and Critical Care Medicine, Department for Scientific Research and Medical Education, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

RESUMEN / SUMMARY:  - BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and lung cancer risk has been studied in various populations  with conflicting results. The aim of this study was to assess the association strength by a meta-analysis of published studies. METHODS: We searched PubMed and Chinese Biomedical (CBM) databases for relevant literatures published by July 18, 2012. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to  assess the strength of the association. RESULTS: A total of 20 studies comprising 11,653 cases and 12,032 controls were included in the final meta-analysis. Using  the random effect model, we found that MTHFR 677TT variant genotype was associated with an increased lung cancer risk (OR=1.26, 95% CI=1.05-1.50, P=0.011 for TT vs. CC; OR=1.19, 95% CI=1.03-1.37, P<0.001 for TT vs. CC+CT; OR=1.11, 95%  CI=1.02-1.22, P=0.017 for T allele vs. C allele). In the further stratified analyses, the increased lung cancer risk was found in Asian subjects (OR=1.31, 95% CI=1.01-1.71, P=0.045 for TT vs. CC; OR=1.17, 95% CI=1.00-1.38, P=0.048 for TT vs. CC+CT). There were no evidences for obvious publication bias in the overall meta-analysis and Asian subjects. CONCLUSIONS: MTHFR 677TT genotype might increase the susceptibility of lung cancer, especially in Asians.

 

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[236]

TÍTULO / TITLE:  - Sparse-data bias accompanying overly fine stratification in an analysis of beryllium exposure and lung cancer risk.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Epidemiol. 2013 Feb;23(2):43-8. doi: 10.1016/j.annepidem.2012.11.005. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.annepidem.2012.11.005

AUTORES / AUTHORS:  - Rothman KJ; Mosquin PL

INSTITUCIÓN / INSTITUTION:  - RTI Health Solutions, Research Triangle Institute, 200 Park Offices Drive, Research Triangle Park, NC. Electronic address: KRothman@rti.org.

RESUMEN / SUMMARY:  - PURPOSE: Beryllium’s classification as a carcinogen is based on limited human data that show inconsistent associations with lung cancer. Therefore, a thorough  examination of those data is warranted. We reanalyzed data from the largest study of occupational beryllium exposure, conducted by the National Institute of Occupational Safety and Health (NIOSH). METHODS: Data had been analyzed using stratification and standardization. We reviewed the strata in the original analysis, and reanalyzed using fewer strata. We also fit a Poisson regression, and analyzed simulated datasets that generated lung cancer cases randomly without regard to exposure. RESULTS: The strongest association reported in the NIOSH study, a standardized rate ratio for death from lung cancer of 3.68 for the highest versus lowest category of time since first employment, is affected by sparse-data bias, stemming from stratifying 545 lung cancer cases and their associated person-time into 1792 categories. For time since first employment, the measure of beryllium exposure with the strongest reported association with lung cancer, there were no strata without zeroes in at least one of the two contrasting exposure categories. Reanalysis using fewer strata or with regression models gave substantially smaller effect estimates. Simulations confirmed that the original stratified analysis was upwardly biased. Other metrics used in the NIOSH study found weaker associations and were less affected by sparse-data bias. CONCLUSIONS: The strongest association reported in the NIOSH study seems to be biased as a result of non-overlap of data across the numerous strata. Simulation  results indicate that most of the effect reported in the NIOSH paper for time since first employment is attributable to sparse-data bias.

 

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[237]

TÍTULO / TITLE:  - Lactate Dehydrogenase B Is Required for the Growth of KRAS-Dependent Lung Adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2638

AUTORES / AUTHORS:  - McCleland ML; Adler AS; Deming L; Cosino E; Lee L; Blackwood EM; Solon M; Tao J; Li L; Shames D; Jackson E; Forrest WF; Firestein R

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Pathology, Translational Oncology, Bioinformatics & Computational Biology, Molecular Diagnostics & Cancer Cell Biology, Research Oncology, and Biostatistics, Genentech, Inc., South San Francisco, California.

RESUMEN / SUMMARY:  - PURPOSE: This study is aimed to identify genes within the KRAS genomic amplicon that are both coupregulated and essential for cell proliferation when KRAS is amplified in lung cancer.EXPERIMENTAL DESIGN: We used an integrated genomic approach to identify genes that are coamplified with KRAS in lung adenocarcinomas and subsequently preformed an RNA interference (RNAi) screen to uncover functionally relevant genes. The role of lactate dehydrogenase B (LDHB) was subsequently investigated both in vitro and in vivo by siRNA and short hairpin RNA (shRNA)-mediated knockdown in a panel of lung adenocarcinoma cells lines. LDHB expression was also investigated in patient tumors using microarray and immunohistochemistry analyses.RESULTS: RNAi-mediated depletion of LDHB abrogated  cell proliferation both in vitro and in xenografted tumors in vivo. We find that  LDHB expression correlates to both KRAS genomic copy number gain and KRAS mutation in lung cancer cell lines and adenocarcinomas. This correlation between  LDHB expression and KRAS status is specific for lung cancers and not other tumor  types that harbor KRAS mutations. Consistent with a role for LDHB in glycolysis and tumor metabolism, KRAS-mutant lung tumors exhibit elevated expression of a glycolysis gene signature and are more dependent on glycolysis for proliferation  compared with KRAS wild-type lung tumors. Finally, high LDHB expression was a significant predictor of shorter survival in patients with lung adenocarcinomas.CONCLUSION: This study identifies LDHB as a regulator of cell proliferation in a subset of lung adenocarcinoma and may provide a novel therapeutic approach for treating lung cancer. Clin Cancer Res; 19(4); 1-12. ©2012 AACR.

 

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[238]

TÍTULO / TITLE:  - TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 8. pii: S0169-5002(12)00649-6. doi: 10.1016/j.lungcan.2012.12.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.004

AUTORES / AUTHORS:  - Odate S; Nakamura K; Onishi H; Kojima M; Uchiyama A; Nakano K; Kato M; Tanaka M; Katano M

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression  in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand  brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice,  although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

 

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[239]

TÍTULO / TITLE:  - Clinicopathologic significance of beta-catenin and matrix metalloproteinase-2 expression in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):437. doi: 10.1007/s12032-012-0437-z. Epub 2013 Jan 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0437-z

AUTORES / AUTHORS:  - Li GH; Cui YS; Wu QY; Zhang XJ; Gao YF

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, First Bethune Hospital of Jilin University, Changchun, Jilin, People’s Republic of China.

RESUMEN / SUMMARY:  - The purpose of this study was to analyze beta-catenin and matrix metalloproteinase-2 (MMP-2) expression in non-small cell lung cancer (NSCLC) and  to investigate the association between their expression and clinicopathologic characteristics of NSCLC patients. Immunohistochemistry was performed to examine  beta-catenin and MMP-2 protein expression in 39 resected NSCLC samples and 8 adjacent normal lung tissues. Statistical analysis with SPSS13.0 software was performed to investigate the association between beta-catenin and MMP-2 expression and clinicopathologic features of the patients. Expression of cytosolic beta-catenin in NSCLC tissue was significantly higher than that in normal tissues (P < 0.001). In addition, cytosolic protein expression of beta-catenin in lung squamous cell carcinoma was significantly elevated compared  to that in lung adenocarcinoma (P = 0.02). However, cell membrane protein expression of beta-catenin in squamous cell carcinoma was lower than that in adenocarcinoma (P = 0.041). Cytosolic MMP-2 protein expression in NSCLC samples was significantly higher than that in normal tissues (P = 0.002). MMP-2 expression in N (1-2) NSCLC patients was significantly increased relative to N (0) patients (P = 0.019). However, statistical analysis showed no correlation between beta-catenin and MMP-2 expression in NSCLC samples. Collectively, our results show that cytosolic protein expression of beta-catenin in NSCLC samples is increased relative to normal lung tissues. Also, expression of beta-catenin is significantly elevated in squamous cell carcinoma compared to that in lung adenocarcinoma subtypes. Additionally, MMP-2 expression in N (1-2) NSCLC tissues  is higher than that in N (0) lung tissue. There is no correlation between beta-catenin and MMP-2 expression in NSCLC, and our study suggests that evaluation of beta-catenin and MMP-2 expression may have potential in diagnosis and progression in patients with NSCLC.

 

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[240]

TÍTULO / TITLE:  - Oxidative stress and inflammatory response to printer toner particles in human epithelial A549 lung cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicol Lett. 2013 Feb 4;216(2-3):171-80. doi: 10.1016/j.toxlet.2012.11.018. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.toxlet.2012.11.018

AUTORES / AUTHORS:  - Konczol M; Weiss A; Gminski R; Merfort I; Mersch-Sundermann V

INSTITUCIÓN / INSTITUTION:  - Department of Environmental Health Sciences, University Medical Center Freiburg,  Freiburg, Germany; Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany. Electronic address: mathias.koenczoel@pharmazie.uni-freiburg.de.

RESUMEN / SUMMARY:  - Reports on adverse health effects related to occupational exposure to toner powder are still inconclusive. Therefore, we have previously conducted an in vitro-study to characterize the genotoxic potential of three commercially available black printer toner powders in A549 lung cells. In these cell-based assays it was clearly demonstrated that the tested toner powders damage DNA and induce micronucleus (MN) formation. Here, we have studied the cytotoxic and proinflammatory potential of these three types of printer toner particles and the influence of ROS and NF-kappaB induction in order to unravel the underlying mechanisms. A549 cells were exposed to various concentrations of printer toner particle suspensions for 24h. The toner particles were observed to exert significant cytotoxic effects in the WST-1 and neutral red (NR)-assays, although  to a varying extent. Caspase 3/7 activity increased, while the mitochondrial membrane potential (MMP) was not affected. Particles of all three printer toner powders induced concentration-dependent formation of reactive oxygen species (ROS), as measured in the DCFH-DA assay. Furthermore, toner particle exposure enhanced interleukin-6 and interleukin-8 production, which is in agreement with activation of the transcription factor NF-kappaB in A549 cells shown by the electrophoretic mobility shift assay (EMSA). Therefore, it can be concluded that  exposure of A549 lung cells to three selected printer toner powders caused oxidative stress through induction of ROS. Increased ROS formation may trigger genotoxic effects and activate proinflammatory pathways.

 

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[241]

TÍTULO / TITLE:  - Decreased expression of microRNA-375 in nonsmall cell lung cancer and its clinical significance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Int Med Res. 2012;40(5):1662-9.

AUTORES / AUTHORS:  - Li Y; Jiang Q; Xia N; Yang H; Hu C

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Emerging evidence has shown the association of aberrant microRNA-375 (miR-375) expression with tumourigenesis in many types of human malignancy. This  prospective study characterized the contribution of miR-375 to the initiation and progression of nonsmall cell lung cancer (NSCLC). METHODS: The real-time reverse  transcription-polymerase chain reaction was used to examine miR-375 levels prospectively in 96 pairs of samples of NSCLC tissue and adjacent noncancerous tissue (> 2 cm from cancer tissue). The relationship between miR-375 levels and clinico pathological features was also explored. RESULTS: MiR-375 was downregulated in 89% (85/96) of NSCLC samples compared with matched noncancerous  tissue samples. Decreased miR-375 correlated significantly with advanced disease  stage and lymphatic metastasis. Univariate and multivariate Cox proportional hazard regression analyses revealed that underexpression of miR-375 was an unfavourable prognostic factor for overall survival in NSCLC. CONCLUSIONS: This study suggested that miR-375 is a novel prognostic indicator in NSCLC and might be a potential target for diagnosis and gene therapy.

 

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[242]

TÍTULO / TITLE:  - Clinical and prognostic significance of coagulation assays in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respir Med. 2012 Nov 29. pii: S0954-6111(12)00418-0. doi: 10.1016/j.rmed.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.rmed.2012.11.007

AUTORES / AUTHORS:  - Tas F; Kilic L; Serilmez M; Keskin S; Sen F; Duranyildiz D

INSTITUCIÓN / INSTITUTION:  - Institute of Oncology, University of Istanbul, Istanbul, Turkey. Electronic address: faruktas2002@yahoo.com.

RESUMEN / SUMMARY:  - Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the  prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05  and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer  was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In  conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

 

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[243]

TÍTULO / TITLE:  - Naked Eye Detection of Lung Cancer Associated miRNA by Paper Based Biosensing Platform.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anal Chem. 2013 Jan 15;85(2):820-4. doi: 10.1021/ac3034008. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 1021/ac3034008

AUTORES / AUTHORS:  - Yildiz UH; Alagappan P; Liedberg B

INSTITUCIÓN / INSTITUTION:  - Center for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive, Singapore 637553.

RESUMEN / SUMMARY:  - This letter demonstrates a biosensing platform for naked eye detection of miRNA,  fabricated using a poly(vinylidene fluoride) thin paper impregnated with positively charged poly(3-alkoxy-4-methylthiophene) as luminescent reporters. The miRNA assay is based on the formation of a duplex and a triplex species between the “reporter and miRNA” and “reporter and miRNA-peptide nucleic acid (PNA) hybrid”, which yields two significantly different optical signals, thereby facilitating naked eye detection. This letter illustrates the successful validation of the proposed methodology via a mir21 assay (miRNA sequence associated with lung cancer). Furthermore, this facile platform enables rapid, sensitive, and selective detection of miRNA, at clinically relevant concentration levels as well as single base pair mismatch, without requiring complex and expensive instrumentation.

 

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[244]

TÍTULO / TITLE:  - Downregulation of cell-free miR-198 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 25. doi: 10.1002/ijc.28054.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28054

AUTORES / AUTHORS:  - Han HS; Yun J; Lim SN; Han JH; Lee KH; Kim ST; Kang MH; Son SM; Lee YM; Choi SY; Yun SJ; Kim WJ; Lee OJ

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju.

RESUMEN / SUMMARY:  - Circulating cell-free microRNAs (miRNAs) are potential cancer biomarkers. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE). The expression level of cell-free miRNA was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (10 BPEs and  10 LA-MPEs). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA-MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs and other common tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1. Microarray profiling showed that miR-198 was significantly downregulated in LA-MPE compared with BPE (P = 0.002). The miRNA microarray analysis results were confirmed by qRT-PCR (P < 0.001) using the validation set.  The AUCs for miR-198, CEA, and CYFRA 21-1 in the validation set were 0.887, 0.898, and 0.836, respectively. The diagnostic performance of miR-198 was comparable with that of CEA, but better than that of CYFRA 21-1. The AUC for all  three markers combined was 0.926 (95% confidence interval, 0.843-0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study suggests that  cell-free miR-198 from patients with pleural effusion might have diagnostic potential for differentiating LA-MPE from BPE.

 

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[245]

TÍTULO / TITLE:  - PIM1 kinase inhibitors induce radiosensitization in non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pharmacol Res. 2013 Jan 23. pii: S1043-6618(13)00015-7. doi: 10.1016/j.phrs.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.phrs.2013.01.005

AUTORES / AUTHORS:  - Kim W; Youn H; Kwon T; Kang J; Kim E; Son B; Yang HJ; Jung Y; Youn B

INSTITUCIÓN / INSTITUTION:  - Department of Biological Sciences, Pusan National University, Busandaehak-ro 63,  Geumjeong-gu, Busan, 609-735, South Korea. Electronic address: kkhjjang01@pusan.ac.kr.

RESUMEN / SUMMARY:  - Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC). However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC. To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, PRAS40, FOXO3a, 14-3-3, and protein phosphatases. Among these proteins, PIM1 functioned as an oncogene and was found to act as a crucial mediator in radioresistant NSCLC cells. Therefore, we investigated the use of PIM1-specific inhibitors as novel therapeutic drugs to regulate radiosensitivity in NSCLC. After structure-based drug selection, SGI-1776, ETP-45299, and tryptanthrin were  selected as candidates of PIM1 inhibitors that act as radiosensitizers. With irradiation, these drugs inhibited only PIM1 kinase activity without affecting PIM1 mRNA/protein levels or cellular localization. When PIM1 kinase activity was  suppressed by these inhibitors, PRAS40 was not phosphorylated. Consequently, unphosphorylated PRAS40 did not form trimeric complexes with 14-3-3 and FOXO3a, leading to increased nuclear localization of FOXO3a. Nuclear FOXO3a promoted the  expression of pro-apoptotic proteins such as Bim and FasL, resulting in a radiosensitizing effect on radioresistant NSCLC cells. Moreover, an in vivo xenograft mouse model confirmed this radiosensitizing effect induced by PIM1 inhibitors. In these model systems, tumor volume was significantly reduced by a combinational treatment with irradiation and PIM1 inhibitors compared to irradiation alone. Taken together, our findings provided evidence that PIM1-specific inhibitors, SGI-1776, ETP-45299, and tryptanthrin, can act as novel radiosensitizers to enhance the efficacy of radiotherapy by inhibiting irradiation-induced signaling pathway associated with radioresistance.

 

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[246]

TÍTULO / TITLE:  - Pleurodesis outcome in malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorax. 2013 Jan 7. doi: 10.1136/thoraxjnl-2012-203043.

            ●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2012-203043

AUTORES / AUTHORS:  - Fysh ET; Tan SK; Read CA; Lee F; McKenzie K; Olsen N; Weerasena I; Threlfall T; de Klerk N; Musk AW; Lee YC

INSTITUCIÓN / INSTITUTION:  - Respiratory Department, Sir Charles Gairdner Hospital, , Perth, Australia.

RESUMEN / SUMMARY:  - Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients  (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

 

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[247]

TÍTULO / TITLE:  - Circulating tumor cells in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):655-60. doi: 10.1159/000345182. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345182

AUTORES / AUTHORS:  - Young R; Pailler E; Billiot F; Drusch F; Barthelemy A; Oulhen M; Besse B; Soria JC; Farace F; Vielh P

INSTITUCIÓN / INSTITUTION:  - Biology of Circulating Cells Unit, Institut de Cancerologie Gustave Roussy, Villejuif, France.

RESUMEN / SUMMARY:  - Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS  abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a ‘liquid biopsy’ is therefore an exciting possibility providing information on patient prognosis and treatment  efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment.

 

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[248]

TÍTULO / TITLE:  - Advantages of Diffusion-Weighted Imaging Over Positron Emission Tomography-Computed Tomography in Assessment of Hilar and Mediastinal Lymph Node  in Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2799-z

AUTORES / AUTHORS:  - Usuda K; Sagawa M; Motono N; Ueno M; Tanaka M; Machida Y; Matoba M; Kuginuki Y; Taniguchi M; Ueda Y; Sakuma T

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa,  Japan, usuda@kanazawa-med.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: The significance of diffusion-weighted imaging (DWI) is uncertain for the diagnosis of nodal involvement. The purpose of this study was to examine diagnostic capability of DWI compared with PET-CT for nodal involvement of lung cancer. METHODS: A total of 160 lung cancers (114 adenocarcinomas, 36 squamous cell carcinomas, and 10 other cell types) were analyzed in this study. DWI and PET-CT were performed preoperatively. RESULTS: The optimal cutoff values to diagnose metastatic lymph nodes were 1.70 x 10(-3) mm(2)/s for ADC value and 4.45 for SUVmax. DWI correctly diagnosed N staging in 144 carcinomas (90 %) but incorrectly diagnosed N staging in 16 (10 %) [3 (1.9 %) had overstaging, 13 (8.1  %) had understaging]. PET-CT correctly diagnosed N staging in 133 carcinomas (83.1 %) but incorrectly diagnosed N staging in 27 (16.8 %) [4 (2.5 %) had overstaging, 23 (14.4 %) had understaging]. Sensitivity, accuracy, and negative predictive value for N staging by DWI were significantly higher than those by PET-CT. Of the 705 lymph node stations examined, 61 had metastases, and 644 did not. The maximum diameter of metastatic lesions in lymph nodes were 3.0 +/- 0.9 mm in 21 lymph node stations not detected by either DWI or PET-CT: 7.2 +/- 4.1 mm in 39 detected by DWI, and 11.9 +/- 4.1 mm in 24 detected by PET-CT. There were significant differences among them. The sensitivity (63.9 %) for metastatic lymph node stations by DWI was significantly higher than that (39.3 %) by PET-CT. The accuracy (96.2 %) for all lymph node stations by DWI was significantly higher than that (94.3 %) by PET-CT. CONCLUSIONS: DWI has advantages over PET-CT in diagnosing malignant from benign lymph nodes of lung cancers.

 

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[249]

TÍTULO / TITLE:  - Comparison of EGFR and KRAS mutations in primary and unpaired metastatic lung adenocarcinoma with potential chemotherapy effect.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 18. pii: S0046-8177(12)00397-8. doi: 10.1016/j.humpath.2012.10.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.10.016

AUTORES / AUTHORS:  - Munfus-McCray D; Cui M; Zhang Z; Gabrielson E; Askin F; Li QK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287.

RESUMEN / SUMMARY:  - Several recent studies have suggested that EGFR and KRAS mutations may be different in primary and metastatic tumors. It is also not well studied whether or not conventional chemotherapy has any effect on EGFR or KRAS mutations. In this study, we compared EGFR and KRAS mutations in primary and unrelated metastatic lung adenocarcinomas from retrospectively collected clinical cases. We also examined the potential effect of chemotherapy on EGFR and KRAS mutations in  these 2 groups based on available clinical information. Using Johns Hopkins Hospital archives, 379 lung adenocarcinomas with EGFR and KRAS mutational analyses were included. Mutational status was determined by sequencing exons 18 to 21 of EGFR and codons 12 and 13 of KRAS. Clinical information was correlated.  The overall mutational rates in primary and metastatic tumors were comparable. In 213 primary tumors, there was no significant difference of EGFR and KRAS mutational rates in the prechemotherapy and postchemotherapy groups (P > .05), whereas in 166 metastatic tumors, EGFR and KRAS mutations were 12.8% and 36.1% in the prechemotherapy group and 27.3% and 18.2% in the postchemotherapy group (P <  .05). Although our study is an unpaired study, it suggests that mutational status in metastatic tumors may need to be tested, especially if the patient had chemotherapy before the test. Additional studies are needed to further investigate the mechanism and clinical significance of the findings.

 

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[250]

TÍTULO / TITLE:  - The maximum standardized uptake value of fluorodeoxyglucose positron emission tomography of the primary tumour is a good predictor of pathological nodal involvement in clinical N0 non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs604

AUTORES / AUTHORS:  - Miyasaka Y; Suzuki K; Takamochi K; Matsunaga T; Oh S

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in the evaluation of resectable non-small-cell lung cancer (NSCLC). However, this modality cannot be used to detect histological nodal involvement, which can result in stage-migration for resectable lung cancer. In this study, we tried to evaluate the possibility of predicting histological nodal involvement in patients with NSCLC using the maximum standardized uptake value (SUVmax) of FDG-PET of the primary tumour instead of that of the lymph nodes. METHODS: Between February 2008 and September 2011, 898 patients underwent lung cancer surgery at our institute. Among them, we retrospectively analysed 265 patients with clinical N0 NSCLC, who underwent preoperative FDG-PET. The relationships between clinicopathological features, including the findings of FDG-PET and pathological nodal involvement, were investigated. The factors investigated were age, gender, preoperative carcinoembryonic antigen titre, maximum tumour dimension, consolidation/tumour dimension ratio (C/T ratio), SUVmax in the primary tumour and smoking history. RESULTS: Of the 265 clinical N0 NSCLC patients, 214 (80.8%) had pathological N0 status and 27 (10.2%) and 24 (9.0%) had pathological N1 and N2 disease. In a multivariate analysis, the C/T ratio (P = 0.046) and SUVmax of the primary tumour (P = 0.016) were significant predictors of pathological nodal involvement. With regard to pathological N1-2 disease, the sensitivity, specificity, accuracy and positive and negative predictive values of mediastinal node involvement in patients with NSCLC with an  SUVmax for FDG-PET of 10 or more were 49.0, 83.2, 76.6, 41.0 and 87.3%, respectively. Of the 61 patients with NSCLC with an SUVmax for FDG-PET of 10 or more, 25 (41.0%) had pathological N1-2 disease, while only 26 (12.7%) of the remaining 204 patients with an SUVmax for FDG-PET of <10 had nodal disease (P < 0.0001). CONCLUSIONS: Postoperative nodal status was significantly predicted by the SUVmax of FDG-PET of the primary tumour instead of the lymph nodes themselves. The patients with NSCLC in particular who show strong uptake values of SUVmax in the primary tumour could have occult nodal metastases, and may be indicated for a further preoperative modality for an accurate staging.

 

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[251]

TÍTULO / TITLE:  - Artonin E mediates MCL1 down-regulation and sensitizes lung cancer cells to anoikis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5343-51.

AUTORES / AUTHORS:  - Wongpankam E; Chunhacha P; Pongrakhananon V; Sritularak B; Chanvorachote P

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulakongkorn University, Phatumwan, Bangkok, 10330 Thailand.

RESUMEN / SUMMARY:  - BACKGROUND: Anoikis, or detachment-induced apoptosis, is recognized as a key inhibitory process of cancer metastasis. Since lung cancer cells possess an ability to resist anoikis, resulting in a high rate of metastasis and death, the  present study aimed to investigate the possible anoikis-sensitizing effect of artonin E (AE). MATERIALS AND METHODS: AE was extracted from bark of Artocarpus gomezianus. Anoikis sensitization of AE was investigated in H460, A549 and H292 human lung cancer cells. The level of anoikis-related proteins was determined by  western blot analysis and viable cells were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method. RESULTS: AE was shown to enhance anoikis of H460 cells in a dose-dependent manner. We investigated the underlying mechanisms of AE on anoikis sensitization and found that AE sensitized the cells by down-regulating the anti-apoptotic myeloid leukemia cell sequence-1 (MCL1) protein but had no significant effect on other proteins of the B-cell lymphoma-2 (BCL2) family, including BCL2 and BCL2-associated X protein (BAX). Anoikis sensitization of AE was consistently observed in A549 and H292 lung cancer cells. CONCLUSION: The present study demonstrates a novel activity of AE on lung cancer cell anoikis for the first time which might lead to the development of a new strategy for lung cancer therapy.

 

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[252]

TÍTULO / TITLE:  - Peripheral lymphadenopathy as the initial manifestation of malignant mesothelioma in a child.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 10. pii: S0046-8177(12)00352-8. doi: 10.1016/j.humpath.2012.09.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.09.011

AUTORES / AUTHORS:  - Gong YS; Rong YT; Han WC; Zhang YC

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Xuzhou Medical College, Xuzhou, 221002, China; Department of Pathology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.

RESUMEN / SUMMARY:  - Peripheral lymphadenopathy is a rare presentation in malignant mesothelioma. We describe a unique case of malignant mesothelioma arising in an 11-year-old boy, for whom peripheral lymphadenopathy was the initial manifestation of the disease. The final diagnosis was confirmed by a broad panel of immunohistochemical markers. Literature review disclosed only 2 cases in childhood that initially presented with peripheral lymphadenopathy. Pathologists should be aware of this rare biologic behavior of malignant mesothelioma to reach the correct and prompt  diagnosis.

 

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[253]

TÍTULO / TITLE:  - Biopsy-site Changes in Lung Adenocarcinoma With Prior Core Needle Biopsy: A Potential Pitfall in the Assessment of Stromal Invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e3182744a25

AUTORES / AUTHORS:  - Doxtader EE; Mukhopadhyay S; Katzenstein AL

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, State University of New York Upstate Medical University, Syracuse, NY.

RESUMEN / SUMMARY:  - Although biopsy-site changes are known to cause diagnostic difficulties in thyroid and breast specimens, especially when assessing invasion, such changes have not been described in the lung. Assessment of invasion is important in lung  cancers to distinguish bronchioloalveolar carcinoma [adenocarcinoma in situ (AIS)] from invasive adenocarcinoma. The aim of this study was to determine whether biopsy-site changes occur in the lung and whether they may impact this differential diagnosis. Lobectomy specimens were examined from patients whose previous core needle biopsies showed well-differentiated adenocarcinoma with a lepidic pattern. There were 26 adenocarcinomas, including 14 minimally invasive adenocarcinomas, 2 invasive well-differentiated adenocarcinomas, and 10 AISs. Biopsy-site changes were identified in 9 of 26 (35%), including 4 minimally invasive adenocarcinomas, 3 AISs, and 2 well-differentiated adenocarcinomas. The  interval between biopsy and resection ranged from 12 to 45 days (mean, 26.1 d). The biopsy sites consisted of a linear scar composed of collagen and plump fibroblasts, ranging from 2.0 to 13.1 mm in length and 0.5 to 1.6 mm in width. Scattered lymphocytes and plasma cells were present in 8 cases, pigment-laden macrophages in 4, and foreign body giant cells in 3. Benign entrapped lung epithelium was present within the scar in all 9 and entrapped malignant epithelium in 4. Biopsy-site changes can be identified in a significant proportion of lung tumors after core needle biopsy. They need to be distinguished from tumor-related stromal reactions that are considered an indication of invasion and are important in the differentiation of AIS and invasive adenocarcinoma.

 

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[254]

TÍTULO / TITLE:  - Effects of voltage-gated K+ channel blockers in gefitinib-resistant H460 non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5279-84.

AUTORES / AUTHORS:  - Jeon WI; Ryu PD; Lee SY

INSTITUCIÓN / INSTITUTION:  - DVM, Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea.

RESUMEN / SUMMARY:  - Voltage-gated K(+) (Kv) channels are known to be associated with the proliferation of several types of cancer cells, including lung adenocarcinoma cells, and certain Kv channel blockers inhibit cancer cell proliferation. In the  present study, we investigated the effects of Kv channel blockers in gefitinib-resistant H460 non-small cell lung cancer (NSCLC) cells. Treatment with dendrotoxin-kappa (DTX-kappa), which is a Kv1.1-specific blocker, reduced H460 cell viability and arrested cells in G(1)/S transition during cell-cycle progression. We administered DTX-kappa in a xenograft model using nude mice. The  tumor volume was reduced by the injection of DTX-kappa into the tumor tissues compared to the control group. These results indicate that DTX-kappa has antitumor effects in gefitinib-resistant H460 cells through the pathway governing the G(1)/S transition both in vitro and in vivo. These findings suggest that Kv1.1 could serve as a novel therapeutic target for gefitinib-resistant NSCLC.

 

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[255]

TÍTULO / TITLE:  - Second line treatment in advanced non-small cell lung cancer (NSCLC): Comparison  of efficacy of Erlotinib and chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasma. 2013;60(2):129-34.

AUTORES / AUTHORS:  - Fiala O; Pesek M; Finek J; Krejci J; Bortlicek Z; Benesova L; Minarik M

RESUMEN / SUMMARY:  - Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of novel options for management of NSCLC. Erlotinib is EGFR tyrosine kinase inhibitor used for treatment of the advanced NSCLC. This presented study is focused on comparison of erlotinib and chemotherapy efficacy in the second line treatment of the advanced NSCLC. DCR and PFS became the primary endpoints.Total number of patients was 290. Agroup treated with chemotherapy in the second line consisted of 150 patients and agroup treated with erlotinib in the second line consisted of 140 patients. Comparison of DCR was performed using Fisher’s exact test, visualization of PFS was performed using Kaplan-Meier survival curves and differences were tested using the log-rank test. Genetic testing was performed using PCR direct sequencing. In the group treated with chemotherapy 2 CR, 23 PR and 51 SD were achieved vs. 5 CR, 10 PR and 55 SD in the group treated with erlotinib in the second line. DCR in patients treated with chemotherapy was 54.0% vs. 51.3% in patients without EGFR mutation treated with erlotinib (p=0.707); in patients harboring EGFR mutation, treated with erlotinib (n=9) outstanding results were achieved: 4 CR, 2 PR and 3 SD (not tested). Median of PFS in patients treated with chemotherapy was 2.1 months vs. 1.9 months in patients without EGFR mutation (p=0.879) vs. 8.4 months in patients harboring EGFR mutation treated with erlotinib (p=0.017). Results of analysis show that even patients without EGFR mutation are able to benefit from erlotinib  treatment in the second line. The efficacy (DCR, PFS) of erlotinib in patients without EGFR mutation was comparable with chemotherapy. The treatment efficacy in asubgroup of patients harbouring EGFR mutation treated with erlotinib was significantly better than in patients without EGFR mutation. Keywords: EGFR-TKI,  NSCLC, erlotinib, targeted treatment of NSCLC.

 

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[256]

TÍTULO / TITLE:  - Radon, Smoking, and Lung Cancer: The Need to Refocus Radon Control Policy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Public Health. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 2105/AJPH.2012.300926

AUTORES / AUTHORS:  - Lantz PM; Mendez D; Philbert MA

INSTITUCIÓN / INSTITUTION:  - Paula M. Lantz is with the Department of Health Policy, School of Public Health and Health Services, George Washington University, Washington, DC. David Mendez is with the Department of Health Management and Policy, School of Public Health,  University of Michigan, Ann Arbor. Martin A. Philbert is with the School of Public Health and the Department of Environmental Health Sciences, University of  Michigan.

RESUMEN / SUMMARY:  - Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy. (Am J Public  Health. Published online ahead of print January 17, 2013: e1-e5. doi:10.2105/AJPH.2012.300926).

 

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[257]

TÍTULO / TITLE:  - The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt005

AUTORES / AUTHORS:  - Lai YH; Yu SL; Chen HY; Wang CC; Chen HW; Chen JJ

INSTITUCIÓN / INSTITUTION:  - Institutes of Biomedical Sciences and Molecular Biology, National Chung Hsing University, Taichung, Taiwan, Republic of China.

RESUMEN / SUMMARY:  - HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance  HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2 binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic  analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, FDR < 0.05) that are dominantly involved in the cell cycle, apoptosis and adhesion-related biological signalling, including mitogen-activated protein kinase, focal adhesion and tight junction pathways, indicating the diverse effects of andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

 

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[258]

TÍTULO / TITLE:  - Targeting receptor activator of nuclear factor-kappa B as a new therapy for bone  metastasis in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Opin Oncol. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CCO.0b013e32835d720b

AUTORES / AUTHORS:  - Peters S; Meylan E

INSTITUCIÓN / INSTITUTION:  - aMultidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois bSwiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: The review aims at comprehensively discussing our current knowledge on bone metastases incidence in non-small cell lung cancer (NSCLC), their related complications as well as clinical impact in patients suffering from advanced disease. RECENT FINDINGS: After evoking the use of zoledronic acid as the established standard of care until recently, the new class of drugs available to prevent skeletal related events and targeting receptor activator of nuclear factor-kappa B (RANK) will be emphasized, reporting on denosumab clinical trials, a RANK-ligand (RANKL) targeting monoclonal antibody. Biological hypothesis regarding their mechanisms of action as well a potential direct impact on tumor cells are described according to the most recent laboratory as well as hypothesis-generating clinical data. SUMMARY: Targeting the RANK pathway is an efficient way to prevent complications of bone metastases in NSCLC. Interesting additional direct effects on tumor biology and evolution are being analyzed and prospectively assessed in clinical trials.

 

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[259]

TÍTULO / TITLE:  - The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb;79(2):151-5. doi: 10.1016/j.lungcan.2012.11.003. Epub 2012  Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.003

AUTORES / AUTHORS:  - Uzunoglu FG; Heumann A; Musici S; Kutup A; Koenig A; Roch N; Thomssen A; Dohrmann T; Tsui TY; Mann O; Izbicki JR; Vashist YK

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral and Thoracic Surgery, University Medical Centre of Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

RESUMEN / SUMMARY:  - INTRODUCTION: The GNAS1 T393C single nucleotide polymorphism (T393C-SNP) correlates with Galphas mRNA stability and protein expression and augmented apoptosis. Genetic germ line variations as stable and reproducible markers potentially serve as prognostic marker in oncology. The aim of this study was to  evaluate the potential prognostic value of T393C-SNP in complete resected non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In total 163 Caucasian  patients, who had been surgically treated for NSCLC between 1998 and 2010, were included in this study. Genotyping of peripheral blood cells was performed by polymerase chain reaction and digestion using the restriction enzyme FokI. The T393C-SNP was correlated with clinic-pathological parameters and survival. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of the T393C-SNP. RESULTS: C-allele carriers had a higher recurrence rate (p=0.018) and a shorter disease-free survival compared to  homozygous T-allele carriers (12.26 months vs. 44.65 months, p=0.009). The overall survival in homozygous C allele carriers was shorter (19.10 months vs. 53.95 months, p=0.019). Multivariate Cox regression identified the CC genotype as a negative independent prognostic factor for recurrence (hazard ratio 2.36, p=0.007) and survival (hazard ratio 2.51, p=0.008). CONCLUSION: Determination of  T393C-SNP preoperatively potentially allows allocation of NSCLC patients into different risk profiles and may influence the therapeutic strategy.

 

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[260]

TÍTULO / TITLE:  - Expression of the coxsackie and adenovirus receptor in human lung cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Feb;34(1):17-24. doi: 10.1007/s13277-012-0342-2. Epub 2013 Jan  11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0342-2

AUTORES / AUTHORS:  - Chen Z; Wang Q; Sun J; Gu A; Jin M; Shen Z; Qiu Z; Wang J; Wang X; Zhan Z; Li JW

INSTITUCIÓN / INSTITUTION:  - Department of Health and Environment, Institute of Health and Environmental Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food  Safety, No. 1, Dali Road, Tianjin, 300050, People’s Republic of China.

RESUMEN / SUMMARY:  - The aim of this study is to elucidate the relation between expression of coxsackie and adenovirus receptor (CAR) and formation of lung cancer. We investigated the expression of CAR by immunohistochemistry, Western blot and real-time RT-PCR in 120 lung cancers. We found that CAR expression in tumor tissues was significantly higher than that in normal lung tissues. CAR expression had a correlation with the histological grade of lung squamous cell carcinoma; however, there was no relationship between the CAR expression and the other clinical pathological features. In vitro, silencing or overexpression of CAR could significantly inhibit or promote colony formation, cell adhesion, and invasion in A549 cells. Our findings demonstrated that CAR may play an essential  role in the formation of lung cancer.

 

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[261]

TÍTULO / TITLE:  - Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5393-9.

AUTORES / AUTHORS:  - Pasello G; Marulli G; Polo V; Breda C; Bonanno L; Loreggian L; Rea F; Favaretto A

INSTITUCIÓN / INSTITUTION:  - Via Gattamelata 64, 35128, Padua, Italy. giulia.pasello@ioveneto.it

RESUMEN / SUMMARY:  - AIM: The objective of this study was the retrospective evaluation of tolerability and activity of pemetrexed with carboplatin (AC) or cisplatin (AP) as neoadjuvant chemotherapy in a consecutive series of patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with operable MPM received three cycles of AC or AP followed by surgery and radiotherapy. RESULTS: Since 2005, 51 patients have been treated with AC (27) and AP (24). We observed higher  incidence of grade 3 anaemia, cumulative grade 2-3 asthenia and worsening of performance status in the AP group. Response to AC and AP were; complete: 4% vs.  0%, partial: 18% vs. 17%, stable disease: 74% vs. 79%, progressive disease: 4%; the resection rate was 81% vs. 79%. CONCLUSION: AC and AP are active and feasible neoadjuvant regimens. Progression-free survival, response, disease control and resection rate were similar in the two treatment groups. The lower tolerability to AP treatment could impair the clinical condition of patients undergoing surgery.

 

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[262]

TÍTULO / TITLE:  - Root cause analysis of problems in the frozen section diagnosis of in situ, minimally invasive, and invasive adenocarcinoma of the lung.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec;136(12):1515-21. doi: 10.5858/arpa.2012-0042-OA.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0042-OA

AUTORES / AUTHORS:  - Walts AE; Marchevsky AM

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA. walts@cshs.org

RESUMEN / SUMMARY:  - CONTEXT: Frozen sections can help determine the extent of surgery by distinguishing in situ, minimally invasive, and invasive adenocarcinoma of the lung. OBJECTIVE: To evaluate our experience with the frozen section diagnosis of  these lesions using root-cause analysis. DESIGN: Frozen sections from 224 consecutive primary pulmonary adenocarcinomas (in situ, 27 [12.1%]; minimally invasive, 46 [20.5%]; invasive, 151 [67.4%]) were reviewed. Features that could have contributed to frozen section errors and deferrals were evaluated. RESULTS:  There were no false-positive diagnoses of malignancy. Frozen section errors and deferrals were identified in 12.1% (27 of 224) and 6.3% (14 of 224) of the cases, respectively. Significantly more errors occurred in the diagnosis of in situ and  minimally invasive adenocarcinoma than in the diagnosis of invasive adenocarcinoma (P < .001). Frozen section errors and deferrals were twice as frequent in lesions smaller than 1.0 cm (P = .09). Features significantly associated with errors and deferrals included intraoperative consultation by more than one pathologist (P = .003) and more than one sample of frozen lung section (P = .001). Inflammation with reactive atypia, fibrosis/scar, sampling problems,  and suboptimal quality sections were identified in 51.2% (21 of 41), 36.6% (15 of 41), 26.8% (11 of 41), and 9.8% (4 of 41) of the errors and deferrals, respectively (more than one of these factors was identified in some cases). Frozen section errors and deferrals had significant clinical impact in only 4 patients (1.8%); each had to undergo completion video-assisted thoracoscopic lobectomy less than 90 days after the initial surgery. CONCLUSIONS: The distinction of in situ from minimally invasive adenocarcinoma is difficult in both frozen and permanent sections. We identified several technical and interpretive features that likely contributed to frozen section errors and deferrals and suggest practice modifications that are likely to improve diagnostic accuracy.

 

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[263]

TÍTULO / TITLE:  - Variations of Lung Cancer Risk from Asbestos Exposure: Impact on Estimation of Population Attributable Fraction.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ind Health. 2012 Dec 25.

AUTORES / AUTHORS:  - Moon EK; Son M; Jin YW; Park S; Lee WJ

INSTITUCIÓN / INSTITUTION:  - Department of Preventive Medicine, College of Medicine, Korea University.

RESUMEN / SUMMARY:  - The purpose of this study is to investigate the potential impact of differing lung cancer risks in study populations on estimating population attributable fraction (PAF) from asbestos exposure. Studies were identified via a MEDLINE search up to September 2009 and from the reference lists of publications about asbestos exposure and lung cancer risk. Relative risk estimates were extracted from 160 studies and meta-relative risks were calculated according to random-effect models. Hypothetical PAFs were calculated based on the meta results and on the difference exposure scenarios. The risks for lung cancer from asbestos exposure were extremely variable according to the region as well as other study characteristics. The risk estimates proved higher in Asian countries (RR=3.53), in studies with 500 or fewer subjects (RR=2.26), and papers published in the 1990s or earlier (RR=1.91), than did those for European or North American countries, studies with more than 500 subjects, and papers published in the 2000s, respectively. The differences in PAFs between Asian and North American studies were 15.5%, 30.3%, and 36.2% when the exposure prevalence was 10%, 30%, and 50%, respectively. This study suggested that it is important to apply appropriate lung cancer estimates to each study population when calculating PAF from asbestos exposure.

 

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[264]

TÍTULO / TITLE:  - Toward prevention or cure for recurrent respiratory papillomatosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Laryngoscope. 2012 Dec;122 Suppl 4:S63-4. doi: 10.1002/lary.23805.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23805

AUTORES / AUTHORS:  - Hughes OR

INSTITUCIÓN / INSTITUTION:  - Great Ormond Street Hospital, London, United Kingdom. owainrhyshughes@gmail.com.

 

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[265]

TÍTULO / TITLE:  - Native Soluble Carcinoembryonic Antigen Is Not Involved in the Impaired Activity  of CD56 Natural Killer Cells in Malignant Pleural Effusion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respiration. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345214

AUTORES / AUTHORS:  - Qi J; Li D; Feng J; Yang S; Su Y; Fang M; Tan Z; Shi H; Yan X; Gong F; Zheng F

INSTITUCIÓN / INSTITUTION:  - Department of Immunology, Tongji Medical College, Huazhong University of Science  and Technology, Wuhan, China.

RESUMEN / SUMMARY:  - Background: Natural killer (NK) cells are lymphocytes of the innate immune system that play a crucial role in tumor immune surveillance. Accumulated data indicated that NK cells in the tumor microenvironment often display a suppressed function.  However, the mechanism is not clear. Objective: In this study, the effects and relative mechanisms of malignant pleural effusion (MPE) from patients with lung cancer on NK cells were researched. Methods: MPE and peripheral blood (PB) samples were collected from patients with lung cancer. The cytotoxic activity of  CD56(dim) NK cells in PB and MPE mononuclear cells was analyzed by fl ow cytometry. Results: It was observed that the percentages of total NK cells and a  CD56(dim) NK subset in MPE reduced accompanying impaired cytotoxic activity compared with that in paired PB. Cell-free MPE treatment reduced both the proportion and cytotoxic activity of CD56(dim) NK cells in PB from healthy donors. The suppression effects were not based on soluble carcinoembryonic antigen and the inhibitory cytokines interleukin-10 and transforming growth factor-beta(1), but were dependent on the factor with a molecular weight >100 kDa. Conclusions: These results demonstrated that native soluble carcinoembryonic antigen does not suppress the activity of NK cells, and an unknown factor with a  molecular weight >100 kDa plays a critical role in the impairment of CD56(dim) NK cells in MPE, which might lead to tumor progression.

 

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[266]

TÍTULO / TITLE:  - Photodynamic therapy for bronchial carcinoid tumours: complete response over a 10-year follow-up.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs660

AUTORES / AUTHORS:  - Moghissi K; Dixon K; Gibbins S

INSTITUCIÓN / INSTITUTION:  - The Yorkshire Laser Centre, Goole, UK.

RESUMEN / SUMMARY:  - A 63-year old woman diagnosed in September 2001 with a typical bronchial carcinoid of the left upper lobe bronchus extending into the left main stem bronchus is presented. The patient was unsuitable for standard surgical treatment, and the topography was not amenable for a parenchyma-saving bronchoplastic procedure. Two cycles of bronchoscopic photodynamic therapy (PDT)  were undertaken at 6 monthly intervals. The patient has now been followed up regularly for over 10 years without signs of recurrence bronchoscopically or radiologically. To our knowledge, this is the first case of a carcinoid tumour treated solely by PDT.

 

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[267]

TÍTULO / TITLE:  - Gene expression profiling of endobronchial ultrasound (EBUS)-derived cytological  fine needle aspirates from hilar and mediastinal lymph nodes in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cytopathology. 2012 Dec 10. doi: 10.1111/cyt.12034.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cyt.12034

AUTORES / AUTHORS:  - Lee R; Cousins DJ; Ortiz-Zapater E; Breen R; McLean E; Santis G

INSTITUCIÓN / INSTITUTION:  - Department of Asthma Allergy and Respiratory Science, King’s College London Division of Asthma, Allergy & Lung Biology, King’s College London, London, UK MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK Department of Respiratory Medicine Department of Cellular Pathology, Guy’s & St Thomas’ NHS Foundation Trust, London, UK.

RESUMEN / SUMMARY:  - R. Lee, D. J. Cousins, E. Ortiz-Zapater, R. Breen, E. McLean and G. Santis Gene expression profiling of endobronchial ultrasound (EBUS)-derived cytological fine  needle aspirates from hilar and mediastinal lymph nodes in non-small cell lung cancer Objective: Endobronchial ultrasound (EBUS) allows minimally invasive sampling of hilar and mediastinal lymph nodes and has an established role in non-small cell lung cancer (NSCLC) diagnosis and staging. Molecular biomarkers are being explored increasingly in lung cancer research. Gene expression profiling (GEP) is a microarray-based technology that comprehensively assesses genome-wide changes in gene expression that can provide tumour-specific molecular signatures with the potential to predict prognosis and treatment responsiveness.  We assessed the feasibility of using EBUS-derived aspirates from benign and tumour-infiltrated lymph nodes for GEP. Methods: RNA was extracted from EBUS-directed transbronchial fine needle aspiration samples in routine clinical practice. GEP was subsequently performed in six patients with NSCLC, three of whom had tumour-infiltrated nodes and three who had benign lymph nodes; the differences in gene expression were then compared. Results: RNA was successfully  extracted in 29 of 32 patients, 12 of whom were diagnosed with NSCLC. RNA yield (median, 12.1 mug) and RNA integrity (median, 6.3) were sufficient after amplification for GEP. Benign and malignant nodes in adenocarcinoma were discriminated by principal component analysis and hierarchical clustering with different expression patterns between malignant and benign nodes. Conclusion: We  have demonstrated the feasibility of RNA extraction and GEP on EBUS-derived transbronchial fine needle aspirates from benign and tumour-infiltrated lymph nodes in patients with known NSCLC in routine clinical practice. Further studies  on larger patient cohorts are required to identify expression profiles that robustly differentiate benign from malignant lymph nodes in NSCLC.

 

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[268]

TÍTULO / TITLE:  - Small cell carcinoma of the uterine cervix: clinical outcome of concurrent chemoradiotherapy with a multidrug regimen.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tohoku J Exp Med. 2013;229(1):75-81.

AUTORES / AUTHORS:  - Tokunaga H; Nagase S; Yoshinaga K; Tanaka S; Nagai T; Kurosawa H; Kaiho-Sakuma M; Toyoshima M; Otsuki T; Utsunomiya H; Takano T; Niikura H; Ito K; Yaegashi N

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.

RESUMEN / SUMMARY:  - Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established  due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with  advanced stage disease, the response rate was 75% (complete response, 1; partial  response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

 

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[269]

TÍTULO / TITLE:  - Reproducibility of Immunohistochemical Scoring for Epidermal Growth Factor Receptor Expression in Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0605-OA

AUTORES / AUTHORS:  - Ruschoff J; Kerr KM; Grote HJ; Middel P; von Heydebreck A; Alves VA; Baldus SE; Buttner R; Carvalho L; Fink L; Jochum W; Lo AW; Lopez-Rios F; Marx A; Molina TJ; Olszewski WT; Rieker RJ; Volante M; Thunnissen E; Wrba F; Celik I; Storkel S

INSTITUCIÓN / INSTITUTION:  - From the Department of Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs Ruschoff and Middel); Targos Advance AG, Kassel, Germany (Drs Ruschoff and Middel); the Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); Histopathology Biomarker Technologies, Merck  KGaA, Darmstadt, Germany (Dr Grote); Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology, LIM14-University of Sao Paulo School of Medicine & CICAP-Pathology, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil (Dr Alves); the Institute of Pathology, University Hospital Dusseldorf, Dusseldorf, Germany (Dr Baldus); the Institute of Pathology, University Hospital Cologne, Cologne, Germany (Dr Buttner); the Department of Pathology, Hospitais da Universidade de Coimbra, Coimbra, Portugal (Dr Carvalho); the Institute of Pathology and Cytology, Interregional Group Practice, Wetzlar, Germany (Dr Fink); the Institute of Pathology, Kantonsspital St Gallen, St Gallen, Switzerland (Dr Jochum); the Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China (Dr Lo); the Laboratory of Therapeutic Targets, Hospital Universitario Madrid Sanchinarro, Madrid, España (Dr Lopez-Rios); the Department of Pathology, University Hospital of Mannheim, Mannheim, Germany (Dr Marx); the Department of Anatomy and Cytology, Universite Paris Descartes, Paris, France (Dr Molina); the Department of Pathology, Institute of Oncology, Warsaw, Poland (Dr Olszewski); Institute for Pathology, University Hospital, Erlangen, Germany (Dr Rieker); the Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Turin, Italy (Mr Volante); the Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands (Dr Thunnissen); the Department of Pathology, Clinical Institute of Pathology, Vienna, Austria (Dr Wrba); the Global Clinical Development Unit Oncology, Merck KGaA, Darmstadt, Germany (Dr Celik); and the Institute of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal, Germany (Dr Storkel).

RESUMEN / SUMMARY:  - Context.-The addition of cetuximab to first-line chemotherapy substantially prolonged survival in patients with advanced non-small cell lung cancer whose tumors expressed high levels of epidermal growth factor receptor (EGFR; immunohistochemistry score of >/=200 on a scale of 0-300). Objective.-To evaluate the interobserver reproducibility of this EGFR immunohistochemistry scoring system, based on both the tumor cell membrane staining intensity (graded 0-3+) and the percentage of cells staining at each intensity. Design.-In parts 1 (initial feasibility study) and 2 of this 2-part round robin test, sections of different non-small cell lung cancer tissue microarrays were stained in a central reference laboratory. Following reference evaluation, EGFR expression in 30 selected tumor cores was characterized in serial sections by lung cancer pathology specialists. The reproducibility of scoring by different raters was assessed. Analysis of between-rater agreement was based on the allocation of EGFR immunohistochemistry scores into low- (<200) and high- (>/=200) EGFR expression groups. Results.-After discussion with raters of the issues impacting reproducibility identified in part 1 and following adjustment of processes, part  2 of the round robin test showed a high interobserver agreement in EGFR immunohistochemistry scoring, with an overall concordance rate of 90.9% and a mean kappa coefficient of 0.812. Specimens with a reference EGFR immunohistochemistry score of lower than 200 and of 200 or higher showed mean concordance rates of 94.7% and 85.6%, respectively. Conclusions.-After appropriate training, assessing EGFR expression by this immunohistochemistry-based method allowed a highly reproducible allocation of non-small cell lung cancers into clinically relevant high- or low-EGFR expression groups.

 

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[270]

TÍTULO / TITLE:  - Genotoxic and inflammatory effects of organic extracts from traffic-related particulate matter in human lung epithelial A549 cells: The role of quinones.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicol In Vitro. 2013 Jan 16. pii: S0887-2333(13)00009-X. doi: 10.1016/j.tiv.2013.01.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.tiv.2013.01.008

AUTORES / AUTHORS:  - Shang Y; Fan L; Feng J; Lv S; Wu M; Li B; Zang YS

INSTITUCIÓN / INSTITUTION:  - Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200444, PR  China. Electronic address: yushang@shu.edu.cn.

RESUMEN / SUMMARY:  - Traffic-related particulate matter (PM) is associated with adverse health effects. Quinones present in the traffic-related PM are hypothesized to contribute to these harmful effects through reactive oxygen species (ROS) generation. However, the impact of the traffic-related PM and quinones on inflammatory processes and genotoxic damage are less well known. In present study we aimed to examine the genotoxic and inflammatory impacts of organic extracts from traffic-related PM (oTRP) in human lung epithelial A549 cells, and reveal the contributions from quinones. Significant cytotoxicity and DNA damage was caused by oTRP. The pro-inflammatory genes, interleukin-6 (Il-6), interleukin-8 (Il-8) and tumor necrosis factor (Tnf), and two aromatic hydrocarbon receptor-regulated genes, Cyp1a1 and 1b1, were significantly up-regulated by oTRP. A concomitant increase in ROS was observed, suggesting that oTRP may mediate genotoxic and inflammatory effects through oxidative stress pathway. Second, the effects from two typical airborne quinones, 9,10-anthraquinone (AQ) and 1,4-naphthroquinone (NQ) were compared. NQ, but not AQ, induced significant DNA damage in A549 cells. NQ up-regulated Il-8, Tnf, and Mcp-1 genes, while AQ induced the expression of Rantes gene. These results suggest that the NQ and AQ may participate in the pro-inflammatory responses through releasing different types of cytokines/chemokines.

 

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[271]

TÍTULO / TITLE:  - Pollution level, inhalation exposure and lung cancer risk of ambient atmospheric  polycyclic aromatic hydrocarbons (PAHs) in Taiyuan, China.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Environ Pollut. 2013 Feb;173:150-6. doi: 10.1016/j.envpol.2012.10.009. Epub 2012  Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.envpol.2012.10.009

AUTORES / AUTHORS:  - Xia Z; Duan X; Tao S; Qiu W; Liu D; Wang Y; Wei S; Wang B; Jiang Q; Lu B; Song Y; Hu X

INSTITUCIÓN / INSTITUTION:  - Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. baotazunnan@gmail.com

RESUMEN / SUMMARY:  - Passive air samplers were deployed to collect both gas and particulate phase polycyclic aromatic hydrocarbons in Taiyuan between 2009 and 2010. Annual average concentrations of BaP equivalent concentration (B[a]P(eq)) in background, rural and urban areas were 2.90 +/- 0.29, 23.2 +/- 30.8 and 27.4 +/- 28.1 ng/m(3), respectively, with higher concentration in the winter than in other seasons. The  median B[a]P(eq) concentrations of annual inhalation exposure were estimated to be in the range of 103-347 ng/d for all population groups in rural as well as in  urban areas. The median values of incremental lifetime cancer risk (ILCR) induced by whole year inhalation exposure for all groups were basically larger than 10(-6), with higher values in winter than in other seasons and in urban than in rural area. In the same season and area, the ILCR of adults was larger than other age groups and that of females was a little higher than males.

 

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[272]

TÍTULO / TITLE:  - Understanding diagnosis of lung cancer in primary care: qualitative synthesis of  significant event audit reports.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Gen Pract. 2013 Jan;63(606):37-46. doi: 10.3399/bjgp13X660760.

            ●● Enlace al texto completo (gratuito o de pago) 3399/bjgp13X660760

AUTORES / AUTHORS:  - Mitchell ED; Rubin G; Macleod U

INSTITUCIÓN / INSTITUTION:  - Social Dimensions of Health Institute, Universities of Dundee and St Andrews, Dundee, UK.

RESUMEN / SUMMARY:  - BACKGROUND: Most lung cancers present symptomatically, but the pathway to diagnosis in primary care can be complex and is poorly understood. Significant event audit (SEA) is a quality improvement technique widely used in UK general practice. AIM: To gain insights into the diagnostic process for lung cancer, drawn from analysis of SEA documents. DESIGN AND SETTING: Qualitative analysis of SEAs from 92 general practices in the North of England Cancer Network. METHOD: Participating practices were provided with a standardised electronic template and asked to undertake a significant event audit related to the most recent diagnosis of lung cancer in the practice, even if that patient had since died. Reported accounts for 132 diagnoses were analysed using a modified framework approach. RESULTS: Most SEAs demonstrated timely recognition and referral. Where this had taken longer, there were often reasonable explanations, including: chest X-rays reported as normal or with benign findings; patient-mediated factors, such as delay in re-presenting or declining earlier referral; and presentation complicated by comorbidity. Some opportunities for earlier referral were also found. Lessons drawn from these events included limitations of chest X-ray as a diagnostic tool, the need for vigilance in patients with existing morbidity, and  the importance of ‘safety-netting’. CONCLUSION: Qualitative synthesis of SEAs offered considerable value in understanding circumstances surrounding the diagnostic process for lung cancer in primary care. The most common presentation  was with cough or other symptoms indicative of infection, and it is by understanding more about these patients in particular that most can be gained.

 

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[273]

TÍTULO / TITLE:  - Cost-effectiveness of continuation maintenance pemetrexed after Cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the chinese health care system.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Ther. 2013 Jan;35(1):54-65. doi: 10.1016/j.clinthera.2012.12.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinthera.2012.12.013

AUTORES / AUTHORS:  - Zeng X; Peng L; Li J; Chen G; Tan C; Wang S; Wan X; Ouyang L; Zhao Z

INSTITUCIÓN / INSTITUTION:  - School of Pharmaceutical Sciences, Central South University, Changsha Hunan, People’s Republic of China; Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha Hunan, People’s Republic of China.

RESUMEN / SUMMARY:  - BACKGROUND: Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. OBJECTIVE: We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. METHODS: A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. RESULTS: The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. CONCLUSIONS: Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent  clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option for meeting the treatment demands of Chinese patients ClinicalTrials.gov identifier: NCT00789373.

 

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[274]

TÍTULO / TITLE:  - Role of 14-3-3sigma in resistance to cisplatin in non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Biol Int. 2013 Jan;37(1):78-86. doi: 10.1002/cbin.10006. Epub 2012 Nov 14.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10006

AUTORES / AUTHORS:  - Cetintas VB; Tetik A; Cok G; Kucukaslan AS; Kosova B; Gunduz C; Veral A; Eroglu Z

INSTITUCIÓN / INSTITUTION:  - Department of Medical Biology, Ege University School of Medicine, Bornova 35100 Izmir, Turkey. vildan.bozok.cetintas@ege.edu.tr.

RESUMEN / SUMMARY:  - The efficacies of chemotherapeutic agents are often limited by side effects and acquired drug resistance. We have investigated whether the differential expression pattern of 14-3-3sigma affects cisplatin response in non-small cell lung cancer cell lines. Two pairs of parental/cisplatin resistant cell lines (A549/CRA549 and Calu1/CR-Calu1) and clinical lung cancer biopsy samples were analysed for 14-3-3sigma expression. Cell viability was assessed by WST assay; and 14-3-3sigma expression was suppressed by siRNA transfection. 14-3-3sigma mRNA expression increased in CR-A549 and CR-Calu1 compared with their cisplatin-sensitive parental A549 and Calu1 cell lines. But when 14-3-3sigma expression was suppressed, elevated cisplatin response was seen in A549 and CR-Calu1 cell lines. Increased 14-3-3sigma expression might also account for reduced cisplatin response in vivo, since, 14-3-3sigma expression in clinical biopsy samples obtained from lung cancer patients undergoing cisplatin-based chemotherapy significantly higher in the non-responder compared with the responder group. We therefore propose that increased 14-3-3sigma expression is correlated with cisplatin response in non-small cell lung cancer cells; monitoring its expression might become useful in the future in predicting poor outcome to cisplatin treatment and/or the verification of acquired cisplatin resistance in lung cancer patients.

 

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[275]

TÍTULO / TITLE:  - Phase I/II study of amrubicin in combination with S-1 as second-line chemotherapy for non-small-cell lung cancer without EGFR mutation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2061-1

AUTORES / AUTHORS:  - Murakami S; Oshita F; Sugiura M; Kondo T; Saito H; Yamada K

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Oncology, Kanagawa Cancer Center, Nakao 1-1-2, Asahi-ku, Yokohama, 241-0815, Japan.

RESUMEN / SUMMARY:  - INTRODUCTION: Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth. METHODS: We conducted a phase I/II study of  Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks. RESULTS: Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1  administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this  dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were  observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0 %. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60 %. CONCLUSION: Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.

 

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[276]

TÍTULO / TITLE:  - Factors predicting poor survival after lung-sparing radical pleurectomy of IMIG stage III malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs648

AUTORES / AUTHORS:  - Bolukbas S; Eberlein M; Kudelin N; Demes M; Stallmann S; Fisseler-Eckhoff A; Schirren J

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Dr.-Horst-Schmidt-Klinik (Teaching Hospital of Johannes Gutenberg University, Mainz), Wiesbaden, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: The role of radical pleurectomy (RP) in the management of IMIG stage  III in malignant pleural mesothelioma (MPM) remains controversial. The aim of the study was to investigate the feasibility and outcome as well as to determine factors predicting poor survival. METHODS: Patients having IMIG stage III MPM were identified within a prospective multimodality treatment study (RP followed by chemoradiation) between 2002 and 2010 at a single institution. Kaplan-Meier analyses, log-rank test and Cox regression analyses were used to estimate survival and to determine predictors of survival. RESULTS: A total of 78 patients (66.3 +/- 2.5 years, 65 males) underwent RP followed by chemoradiation. A total of 42 (54%) had IMIG stage III. Mortality and morbidity were 4.8 and 31%, respectively. Median survival and 5-year survival were 21 months and 28%, respectively, for stage III patients. Progression-free survival was 11 months. The sites of failure were predominantly locoregional (20/42, 47.6%). Pathological detection of tumour spread at the resected thoracoscopy incisions (median survival 12 vs 35 months, P < 0.001), incomplete resections (median survival 13 vs 35 months, P = 0.01) and male gender (median survival 18 vs 68 months, P < 0.039) were associated with inferior survival in the univariate analyses. Histology, lymph node metastases, laterality and age had no significant impact on survival. The tumour spread at the resected previous incisions remained the only  significant prognostic factor (hazard ratio (HR) = 4.3; P = 0.027) in the multivariate analysis. Patients having tumour spread had survival comparable to that of patients at stage IV in the complete patient cohort (median survival 12 vs 8 months; P = 0.39). CONCLUSIONS: Lung-sparing RP for IMIG stage III MPM is feasible and offers promising long-term survival. The tumour spread at the resected previous incisions is associated with more incomplete resections and was a negative prognosticator for long-term survival. The tumour spread at the resected previous incisions or chest tube sites should be considered as T4 or stage IV according to the IMIG staging system.

 

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[277]

TÍTULO / TITLE:  - Assessment of lung cancer mortality reduction after chest X-ray screening in smokers: A population-based cohort study in Varese, Italy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 4. pii: S0169-5002(12)00683-6. doi: 10.1016/j.lungcan.2012.12.014.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.014

AUTORES / AUTHORS:  - Dominioni L; Poli A; Mantovani W; Pisani S; Rotolo N; Paolucci M; Sessa F; Conti V; D’Ambrosio V; Paddeu A; Imperatori A

INSTITUCIÓN / INSTITUTION:  - Center for Thoracic Surgery, University of Insubria, Ospedale di Circolo, Varese, Italy. Electronic address: lorenzo.dominioni@uninsubria.it.

RESUMEN / SUMMARY:  - BACKGROUND: The effectiveness of screening for lung cancer (LC) in smokers on a population level, as distinct from the special circumstances that may apply in a  randomized trial of selected volunteers, has not been thoroughly investigated. Here we evaluate by the standardized mortality ratio (SMR) indicator the impact of a chest X-ray (CXR) screening programme carried out at community level on LC mortality in smokers. METHODS: All smokers of >10 pack-years, of both genders, ages 45-75 years, resident in 50 communities of the Province of Varese, Italy, screening-eligible, in 1997 were invited by their National Health Service (NHS) general practitioner physicians to a nonrandomized programme of five annual CXR screenings. The entire invitation-to-screen cohort (n=5815 subjects) received NHS usual care, with the addition of CXR exams in volunteer participants (21% of invitees), and was observed through December 2006. To overcome participants’ selection bias of LC mortality assessment, for the entire invitation-to-screen cohort we estimated the LC-specific SMR, based on the local reference population  receiving the NHS usual care. RESULTS: Over the 8-year period 1999-2006, a total  of 172 cumulative LC deaths were observed in the invitation-to-screen cohort; 210 were expected based on the reference population. Each year in the invited cohort  the observed LC deaths were fewer than expected. The cumulative LC SMR was 0.82 (95%CI, 0.67-0.99; p=0.048), suggesting that LC mortality was reduced by 18% with CXR screening. CONCLUSION: Implementation of a CXR screening programme at community level was associated with a significant reduction of LC mortality in smokers.

 

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[278]

TÍTULO / TITLE:  - PRR11 is a novel gene implicated in cell cycle progression and lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Biochem Cell Biol. 2012 Dec 12;45(3):645-656. doi: 10.1016/j.biocel.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biocel.2012.12.002

AUTORES / AUTHORS:  - Ji Y; Xie M; Lan H; Zhang Y; Long Y; Weng H; Li D; Cai W; Zhu H; Niu Y; Yang Z; Zhang C; Song F; Bu Y

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China; Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.

RESUMEN / SUMMARY:  - Identification and functional analysis of novel potential cancer-associated genes is of great importance for developing diagnostic, preventive and therapeutic strategies for cancer treatment and management. In the present study, we isolated and identified a novel gene, proline-rich protein 11 (PRR11), implicated in both  cell cycle progression and lung cancer. Our results showed that PRR11 was periodically expressed in a cell cycle-dependent manner, and RNAi-mediated silencing of PRR11 caused significant S phase arrest as well as growth retardation in HeLa cells. Moreover, PRR11 was overexpressed at both mRNA and protein levels in lung cancer tissues as compared with normal lung tissues. Large scale in silico analysis of clinical microarray datasets also indicated that high expression of PRR11 was significantly associated with poor prognosis in lung cancer patients. RNAi-mediated silencing of PRR11 caused S phase arrest, suppressed cellular proliferation, colony formation ability in lung cancer cells  and inhibited tumorigenic potential in nude mice. Knockdown of PRR11 also inhibited cell migration and invasion ability in lung cancer cells. Furthermore,  microarray analysis revealed that PRR11 knockdown caused the dysregulation of multiple critical pathways and various important genes involved in cell cycle, tumorigenesis and metastasis (e.g. CCNA1, RRM1, MAP4K4 and EPB41L3). Taken together, our results strongly demonstrated that this newly identified gene, PRR11, had a critical role in both cell cycle progression and tumorigenesis, and  might serve as a novel potential target in the diagnosis and/or treatment of human lung cancer.

 

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[279]

TÍTULO / TITLE:  - Diagnostic Usefulness of p16/CDKN2A FISH in Distinguishing Between Sarcomatoid Mesothelioma and Fibrous Pleuritis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Pathol. 2013 Jan;139(1):39-46. doi: 10.1309/AJCPT94JVWIHBKRD.

            ●● Enlace al texto completo (gratuito o de pago) 1309/AJCPT94JVWIHBKRD

AUTORES / AUTHORS:  - Wu D; Hiroshima K; Matsumoto S; Nabeshima K; Yusa T; Ozaki D; Fujino M; Yamakawa H; Nakatani Y; Tada Y; Shimada H; Tagawa M

INSTITUCIÓN / INSTITUTION:  - Dept of Pathology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba 276-8524, Japan.

RESUMEN / SUMMARY:  - The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis  and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.

 

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[280]

TÍTULO / TITLE:  - Effect of siRNAs targeting T790M mutation and wild type EGFR in non-small cell lung cancer cell line resistant to gefitinib or erlotinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2012 Dec 22. pii: S0006-291X(12)02418-7. doi: 10.1016/j.bbrc.2012.12.070.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.12.070

AUTORES / AUTHORS:  - Chen G; Kronenberger P; Teugels E; Umelo IA; De Greve J

INSTITUCIÓN / INSTITUTION:  - Laboratory of Medical and Molecular Oncology, Department of Medical Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium; Department of Pathology, First Affiliated Hospital, Guangxi Medical University, Shuangyong Road 6, 530021 Nanning, Guangxi, PR China.

RESUMEN / SUMMARY:  - The epidermal growth factor receptor (EGFR) is a validated therapeutic target in  non-small cell lung cancer (NSCLC). However, some mutations confer resistance to  current available agents, especially the T790M mutation. In the current study, we have examined in a NSCLC cell line H1975 containing both L858R and T790M mutations, the effect of T790M-specific-siRNAs. T790M-specific-siRNAs were able to inhibit T790M and EGFR mRNA, to reduce EGFR protein expression, as well as to  reduce the cell growth and induce cell caspase activity in H1975 cells. However,  this effect showed less potency compared to the EGFR-specific-siRNAs. EGFR-specific-siRNAs offered strong activity to inhibit cell growth and induce apoptosis in H358, H1650, H292, HCC827 and also H1975 cells, which showed weak response to tyrosine kinase inhibitors (TKIs) or cetuximab. The addition of T790M-specific-siRNAs could rescue the sensitivity of T790M mutant H1975 cells to TKIs. The combination of T790M-specific-siRNAs and cetuximab also additively enhanced cell growth regression and induction of apoptosis in H1975 cells. Among  the anti-EGFR agents tested, the strongest biological effect was observed when afatinib combined with T790M-specific-siRNAs. Afatinib also offered extra effect  when combined with cetuximab in H1975 cells. In a conclusion, knock-down of T790M transcript by siRNAs further decreases the cell growth of T790M mutant lung cancer cells that are treated with TKIs or cetuximab alone. The combination of a  potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation.

 

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[281]

TÍTULO / TITLE:  - Expression of Adiponectin Receptor 1 Is Indicative of Favorable Prognosis in Non-small Cell Lung Carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tohoku J Exp Med. 2013;229(2):153-62.

AUTORES / AUTHORS:  - Abdul-Ghafar J; Soo Oh S; Park SM; Wairagu P; Nyung Lee S; Jeong Y; Eom M; Yong SJ; Jung SH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Yonsei University Wonju College of Medicine.

RESUMEN / SUMMARY:  - Lung cancer is a major cause of cancer-related death worldwide. It is believed that obesity-related malignancies such as breast, endometrial, colorectal, and kidney carcinomas have lower plasma level and/or tissue expression of adiponectin receptors. However, the association between adiponectin receptors and lung cancer, a non obesity-related malignancy, is still unknown. We evaluated the tissue expression of adiponectin receptor (AdipoR) 1 and AdipoR2 in 83 cases of non-small cell lung carcinoma (NSCLC) and matched non-neoplastic lung tissues by  immunohistochemistry and real-time polymerase chain reaction (PCR). Clinicopathological data, including smoking history, smoker’s bronchiolitis, emphysema, lymph node metastasis, and T-stage were collected and evaluated. Expression of immunohistochemically stained AdipoR1 and AdipoR2 was observed in all samples of non-neoplastic lung tissues. Both receptors showed higher mRNA expression in non-neoplastic than neoplastic tissues (p < 0.05). In NSCLC tissues, AdipoR1 immunohistochemical expression was not observed in most of patients with squamous cell carcinoma and current smoking history (31/42, p = 0.04 and 25/29, p = 0.003, respectively). Additionally, AdipoR1 mRNA expression was significantly lower in patients with lymph node metastasis (p = 0.05). Meanwhile, AdipoR2 immunohistochemical stain expression was inversely correlated  with T-stage (p = 0.05) and AdipoR2 mRNA expression was significantly lower in patients with smoker’s bronchiolitis (p = 0.01) and emphysema (p = 0.03). Patients with expression of AdipoR1 had longer overall survival. AdipoR2 expression was not correlated with patients’ survival. In conclusion, we suggest  that expression of AdipoR1 is indicative of favorable prognosis and may be used as prognostic marker in NSCLC.

 

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[282]

TÍTULO / TITLE:  - Verifying the Role of Surgical Pathologists in the Precision Medicine of Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0659-ED

AUTORES / AUTHORS:  - Cagle PT; Olsen RJ

 

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[283]

TÍTULO / TITLE:  - Non-Small-Cell Lung Cancer with HER2 Exon 20 Mutation: Regression with Dual HER2  Inhibition and Anti-VEGF Combination Treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):e19-20. doi: 10.1097/JTO.0b013e31827ce38e.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ce38e

AUTORES / AUTHORS:  - Falchook GS; Janku F; Tsao AS; Bastida CC; Stewart DJ; Kurzrock R

INSTITUCIÓN / INSTITUTION:  - Departments of *Investigational Cancer Therapeutics (phase I Clinical Trials Program), daggerThoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; double daggerDepartment of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ontario, Canada; and section signMoores Cancer Center, University of California, San Diego, San Diego, California.

 

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[284]

TÍTULO / TITLE:  - Ly6/uPAR-Related Protein C4.4A as a Marker of Solid Growth Pattern and Poor Prognosis in Lung Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):152-160.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318279d503

AUTORES / AUTHORS:  - Jacobsen B; Muley T; Meister M; Dienemann H; Christensen IJ; Santoni-Rugiu E; Laerum OD; Ploug M

INSTITUCIÓN / INSTITUTION:  - *The Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark; daggerBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark; double daggerTranslational Research Unit, section signDepartment of Surgery, Thoraxklinik-Heidelberg gGmbH, University of Heidelberg, Heidelberg, Germany; ||Department of Pathology, Rigshospitalet, Copenhagen, Denmark; paragraph signThe Gade Institute, University of Bergen/Department of Pathology, Haukeland University Hospital, Bergen, Norway; #Danish-Chinese Centre for Proteases and Cancer **Translational Lung Reseach Center Heidelberg (TLRC-H), Member of the German Centre of Lung Research (DZL).

RESUMEN / SUMMARY:  - INTRODUCTION:: We have recently shown that the protein C4.4A is induced in early  precursor lesions of pulmonary adenocarcinomas and squamous cell carcinomas. In the present study, we aimed at analyzing the impact of C4.4A on the survival of non-small cell lung cancer patients and determining whether its unexpected expression in adenocarcinomas could be attributed to a specific growth type (lepidic, acinar, papillary, micropapillary, solid). METHODS:: Sections from the  center and periphery of the primary tumor, as well as N2-positive lymph node metastases, were stained by immunohistochemistry for C4.4A and scored semi-quantitatively for intensity and frequency of positive tumor cells. RESULTS:: C4.4A score (intensity x frequency) in the tumor center was a highly significant prognostic factor in adenocarcinomas (n = 88), both in univariate (p  = 0.004; hazard ratio [95% confidence interval] = 1.44 [1.12-1.85]) and multivariate statistical analysis (p = 0.0005; hazard ratio = 1.65 [1.24-2.19]),  demonstrating decreasing survival with increasing score. In contrast, C4.4A did not provide prognostic information in squamous cell carcinomas (n = 104). Pathological stage was significant in both groups. In the adenocarcinomas, C4.4A  expression was clearly associated with, but a stronger prognostic factor than, solid growth. CONCLUSIONS:: The present results substantiate the potential value  of C4.4A as a prognostic marker in pulmonary adenocarcinomas seen earlier in a smaller, independent patient cohort. Importantly, we also show that C4.4A is a surrogate marker for adenocarcinoma solid growth. Recent data suggest that C4.4A  is negatively regulated by the tumor suppressor liver kinase B1, which is inactivated in some adenocarcinomas, providing a possible link to the impact of C4.4A on the survival of these patients.

 

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[285]

TÍTULO / TITLE:  - Heterogeneity of Clinical N1 Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Cardiovasc Surg. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1333067

AUTORES / AUTHORS:  - Kim D; Choi YS; Kim HK; Kim K; Kim J; Shim YM

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Introduction There have been many reports of N1 node metastasis on computed tomography (CT) scan, but not on positron emission tomography (PET)-CT in nonsmall cell lung cancer. The aim of this study was to analyze the clinicopathologic correlation and survival of N1 disease on preoperative PET-CT.Methods From January 2003 to December 2007, 1,748 curative lung resections were performed at a single institute. We enrolled 91 patients with clinical N1 on PET-CT. All the enrolled patients had undergone pulmonary resection with mediastinal lymph node dissection. According to the preoperative PET-CT, we classified the patients into two groups: those with single N1 metastasis (cN1a, n = 91) and those with multiple N1 metastases (cN1b, n = 8). Clinicopathologic N staging was compared and survival analysis was performed.Results Pathologic N2 was found in 19 (19%) patients and was more common in cN1b (4 of 8) than in cN1a  group (15 of 91) (p = 0.042). Overall or disease-free survival rate was not different between cN1a and cN1b in the pathologic non-N2 (p = 0.723, 0.905) or in pathologic N2 (p = 0.954, 0.607) subgroups.Conclusion Clinical N1 on PET-CT is heterogeneous in its pathologic staging and multiple clinical N1 is more related  to pathologic N2 than single clinical N1. More cases are needed to show the prognostic significance of multiple clinical N1-pathologic N2.

 

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[286]

TÍTULO / TITLE:  - Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15. doi: 10.1038/bjc.2012.567.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.567

AUTORES / AUTHORS:  - Hashida Y; Imajoh M; Nemoto Y; Kamioka M; Taniguchi A; Taguchi T; Kume M; Orihashi K; Daibata M

INSTITUCIÓN / INSTITUTION:  - Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.

RESUMEN / SUMMARY:  - Background:We searched for a viral aetiology for non-small cell lung cancer (NSCLC), focusing on Merkel cell polyomavirus (MCPyV).Methods:We analysed 112 Japanese cases of NSCLC for the presence of the MCPyV genome and the expressions  of RNA transcripts and MCPyV-encoded antigen. We also conducted the first analysis of the molecular features of MCPyV in lung cancers.Results:PCR revealed  that 9 out of 32 squamous cell carcinomas (SCCs), 9 out of 45 adenocarcinomas (ACs), 1 out of 32 large-cell carcinomas, and 1 out of 3 pleomorphic carcinomas were positive for MCPyV DNA. Some MCPyV DNA-positive cancers expressed large T antigen (LT) RNA transcripts. Immunohistochemistry showed that MCPyV LT antigen was expressed in the tumour cells. The viral integration sites were identified in one SCC and one AC. One had both episomal and integrated/truncated forms. The other carried an integrated MCPyV genome with frameshift mutations in the LT gene.Conclusion:We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastoma tumour-suppressor protein-binding domain in NSCLCs. Although the viral prevalence was low, the tumour-specific molecular signatures support the possibility that MCPyV is partly associated with the pathogenesis of NSCLC in a subset of patients.British Journal of Cancer advance online publication, 15 January 2013; doi:10.1038/bjc.2012.567 www.bjcancer.com.

 

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[287]

TÍTULO / TITLE:  - Molecular Profiling of Thin-Prep FNA Samples in Assisting Clinical Management of  Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Biotechnol. 2013 Jan 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12033-012-9640-6

AUTORES / AUTHORS:  - Petriella D; Galetta D; Rubini V; Savino E; Paradiso A; Simone G; Tommasi S

INSTITUCIÓN / INSTITUTION:  - National Cancer Research Centre, Istituto Tumori “Giovanni Paolo II”, v. Orazio Flacco 65, 70124, Bari, Italy.

RESUMEN / SUMMARY:  - The discovery of new target treatments for NSCLC has led to a search for new genetic and epigenetic markers able to selectively predict response to these new  drugs. Somatic mutations in EGFR and KRAS genes are routinely analyzed to predict response to tyrosine kinase inhibitors (TKIs), used in the treatment of NSCLC patients, whose efficacy depend on the presence or the absence of specific mutations. MicroRNA (miRNA) expression evaluation has been recently analyzed because of the involvement of these molecules in lung cancer pathogenesis and in  drug resistance. Only 30 % of NSCLC patients present a resectable stage at time of diagnosis so tissue samples cannot be the only starting material for genetic and epigenetic analysis. Therefore, the possibility to use cytological sampling already used for diagnosis also for molecular testing is emerging. The aim of this study was to evaluate for the first time in lung cancer the use of liquid-based cytology both for EGFR and KRAS mutational testing and for the expression trend of some miRNAs involved in lung cancer pathogenesis: miR-21, miR-155, miR-7, and let7a. We enrolled 20 fine-needle aspirate (FNA) samples diagnosed as NSCLC, 10 FNAs without neoplastic cells, and tissue samples coming from 5 of the 20 patients who underwent surgery after FNA NSCLC diagnosis. All Thin-Prep processed FNA samples were evaluable for DNA and RNA analysis and results were compared with those of the small group of patients whose matched tumor histology was available. The mutational status of the EGFR and KRAS genes and the expression profile of the selected miRNA showed comparable results between FNA samples and histological tissues. Our results underline that cytological samples could give the same genetic information as that obtained from histological specimens and so could be collected to create a nucleic acids bank.

 

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[288]

TÍTULO / TITLE:  - Surgical treatment for non-small cell lung cancer with ipsilateral pulmonary metastases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Today. 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00595-012-0452-x

AUTORES / AUTHORS:  - Okamoto T; Iwata T; Mizobuchi T; Hoshino H; Moriya Y; Yoshida S; Yoshino I

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan, tatsuro@surg2.med.kyushu-u.ac.jp.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this retrospective study was to evaluate the relevance of surgery in non-small cell lung cancer (NSCLC) patients with ipsilateral pulmonary metastases. METHODS: The clinical records of 1,623 consecutive NSCLC patients who underwent surgery between 1990 and 2007 were retrospectively reviewed. Overall, 161 (9.9 %) and 21 (1.3 %) patients had additional nodules in the same lobe as the primary lesion (PM1) and additional nodules in the ipsilateral different lobe (PM2), respectively. RESULTS: The 5-year survival rate was 54.4 % in the PM1 patients and 19.3 % in the PM2 patients (log-rank test: p = 0.001). Tumor size </=3 cm, N0-1 status and surgical procedures less extensive than bilobectomy were identified as favorable prognostic factors in the PM1 patients. The 5-year survival rate in the PM1-N0-1 patients was 68.7 %, while that in the PM1-N2-3 patients was 29.1 % (p < 0.0001). Compared to the non-PM1 stage IIIA patients, the stage IIIA patients with PM1 disease (PM1-N1) tended to experience longer survival times (p = 0.06). Squamous cell types and bilobectomy or more extensive  procedures were found to be unfavorable factors in the PM2 patients. The survival of the PM2 patients was significantly worse than that of the other T4 patients (p = 0.007). CONCLUSIONS: PM1 patients with N0-1 disease are good candidates for surgery, whereas PM2 patients do not appear to benefit from surgery.

 

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[289]

TÍTULO / TITLE:  - Blood plasma metabolites and the risk of developing lung cancer in Russia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer Prev. 2012 Dec 2.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CEJ.0b013e32835b3898

AUTORES / AUTHORS:  - Lokhov PG; Trifonova OP; Maslov DL; Archakov AI

INSTITUCIÓN / INSTITUTION:  - Department of Proteomics, Institute of Biomedical Chemistry RAMS, Pogodinskaya, Moscow, Russia.

RESUMEN / SUMMARY:  - Lung cancer is one of the most common types of cancer in men, and is a leading cause of cancer-related deaths. Therefore, the identification of specific markers associated with a risk of lung cancer development, particularly metabolites that  are more easily assayed, would be very valuable. To this end, small a, Cyrillic comparative metabolomics study of blood plasma samples collected from patients with lung cancer (n=100) and controls (n=100) recruited in Moscow was carried out. After the extraction of blood plasma proteins with methanol, the remaining plasma metabolite fractions were analyzed directly using mass spectrometry. Hundreds of cancer-associated metabolites were detected, and at least 70 metabolite ions with odds ratio values of 10-288 were found to be associated with the presence of cancer. Although these metabolites were present at higher levels  in cancer patients, particularly in the early stages of disease, they did not correlate positively with cancer progression. On the basis of these findings, this metabolomics study of blood plasma samples from cancer patients shows that numerous cancer-associated metabolites were present in the studied population, and these could be used as factors for calculating the risk of lung cancer development in addition to currently used risk factors.

 

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[290]

TÍTULO / TITLE:  - The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 10. pii: S0169-5002(12)00637-X. doi: 10.1016/j.lungcan.2012.11.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.016

AUTORES / AUTHORS:  - Nygaard AD; Garm Spindler KL; Pallisgaard N; Andersen RF; Jakobsen A

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: anneli.nygaard@slb.regionsyddanmark.dk.

RESUMEN / SUMMARY:  - BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cfDNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study  was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS)  in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible for chemotherapy were enrolled in a prospective biomarker trial. A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed. The patients received carboplatin (AUC5) i.v. day 1 and vinorelbine (30mg/m(2) i.v. day 1 and 60mg/m(2) p.o. day 8) for a maximum of six cycles. Response to chemotherapy was evaluated according to RECIST v.1.0 by CT scans of the chest and upper abdomen. The presence of pmKRAS at baseline was assessed by an in-house qPCR method. The primary endpoint was overall survival (OS). Secondary end-points were progression free survival (PFS) and overall response rate. RESULTS: The study included 246 patients receiving a minimum of 1 treatment cycle, and all but four were evaluable for response according to RECIST. Forty-three patients (17.5%) presented with a KRAS mutation. OS was 8.9 months and PFS by intention to treat 5.4 months. Patients with a detectable plasma-KRAS mutation had a significantly shorter OS and PFS compared to the wild type (WT) patients (median OS 4.8 months  versus 9.5 months, HR 1.87, 95% CI 1.23-2.84, p=0.0002 and median PFS 3.0 months  versus 5.6 months, HR 1.60, 95% CI 1.09-2.37, p=0.0043). A multivariate Cox regression analysis confirmed the independent prognostic value of pmKRAS in OS but not in PFS. The response rate to chemotherapy was significantly lower in the  group of patients with a mutation compared to WT (p<0.0001). CONCLUSION: The presence of KRAS mutations in plasma may be a marker of poor prognosis and may also hold predictive value. Further validation in an independent cohort is highly needed.

 

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[291]

TÍTULO / TITLE:  - Asymptomatic pulmonary embolism in lung cancer: prevalence and analysis of clinical and radiological characteristics in 141 outpatients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumori. 2012 Sep-Oct;98(5):594-600. doi: 10.1700/1190.13200.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1190.13200

AUTORES / AUTHORS:  - Tiseo M; Bersanelli M; Pesenti Barili M; Bartolotti M; De Luca G; Gelsomino F; Camisa R; Cademartiri F; Ardizzoni A

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, Parma, Italy. mtiseo@ao.pr.it

RESUMEN / SUMMARY:  - Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unknown and strictly related to the imaging used for tumor assessment. Recent findings suggest a similar clinical outcome of asymptomatic pulmonary embolism events compared to symptomatic events with a significant impact on survival. The aim of the present study was to determine the prevalence  of asymptomatic pulmonary embolism in a population of lung cancer outpatients and to investigate its clinical features. Methods. Outpatients with a diagnosis of lung carcinoma undergoing chemotherapy were selected from October 2006 to June 2009. Disease and patient characteristics, risk factors and treatment modalities  were collected. All the computed tomography images performed for each patient during the study period were retrospectively reviewed to identify pulmonary embolism. Results. A total of 141 consecutive patients were included and 657 computed tomography scans were completely reviewed (from two to six consecutive scans for each patient). Asymptomatic pulmonary embolism in the study population  had a prevalence of 14.9% (21 patients). Most of the events occurred in patients  with adenocarcinoma, advanced stage and poor performance status, during the early phases of first-line chemotherapy or at the same time of the cancer diagnosis. Compared with the symptomatic pulmonary embolism events (5 patients), asymptomatic events occurred earlier (time from cancer diagnosis to pulmonary embolism of 3.5 [95% CI, 2.0-4.9] versus 12.1 months [95% CI, 6.3-17.9; P = 0.02]) and had a better prognosis (survival from PE of 7.5 [95% CI, 3.4-11.6] versus 1.9 months [95% CI, 0-3.9; P = 0.04]). Conclusions. Our findings indicate  an underestimation of embolic events among lung cancer outpatients due to their frequent asymptomatic natur. Such a high prevalence suggests the importance to pay more attention to pulmonary embolism prevention in this population.

 

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[292]

TÍTULO / TITLE:  - Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 10. pii: S0169-5002(12)00630-7. doi: 10.1016/j.lungcan.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.009

AUTORES / AUTHORS:  - Grob TJ; Hoenig T; Clauditz TS; Atanackovic D; Koenig AM; Vashist YK; Klose H; Simon R; Pantel K; Izbicki JR; Bokemeyer C; Sauter G; Wilczak W

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: t.grob@uke.de.

RESUMEN / SUMMARY:  - Next to EGFR mutation, EGFR gene copy number evaluated by fluorescence in situ hybridization (FISH) emerged as a potential predictive marker for sensitivity to  EGFR tyrosine kinase inhibitors, although controversial data exist. As the diagnostic accuracy of predictive biomarkers can be substantially limited by regional differences within tumors, heterogeneity of EGFR gene copy gain in NSCLC was assessed in this study. For this purpose, a novel tissue microarray (TMA) based analysis platform was developed. TMAs were constructed containing 8 different tissue cylinders from 144 primary NSCLCs. From 62 of these patients additional nodal metastases were sampled. EGFR gene copy number and EGFR expression was analyzed by FISH and immunohistochemistry according to the suggested guidelines. 13 (9.0%) of the 144 evaluated tumors showed EGFR amplification and 37 (25.7%) tumors high polysomy in at least one tumor area. In  7 (53.8%) of 13 amplified cases the analysis of different tumor areas revealed subclones without EGFR gene copy gain next to subclones with amplification. All of the 36 evaluable tumors with high polysomy showed heterogeneity of EGFR gene copy number with areas negative for gene copy gain within the individual tumors.  Heterogeneity of EGFR gene copy gain in lung cancer challenges the concept of using small biopsies for the analysis of EGFR FISH status. EGFR gene copy number  is highly heterogeneous within individual NSCLCs and this finding might well be a reason for the controversial clinical data existing regarding responsiveness to anti-EGFR therapy.

 

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[293]

TÍTULO / TITLE:  - Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung  cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 26. pii: S0169-5002(12)00640-X. doi: 10.1016/j.lungcan.2012.11.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.019

AUTORES / AUTHORS:  - Park JY; Kim D; Yang M; Park HY; Lee SH; Rincon M; Kreahling J; Plass C; Smiraglia DJ; Tockman MS; Kim SJ

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States.

RESUMEN / SUMMARY:  - BACKGROUND: Aberrant DNA hypermethylation has been implicated as a component of an epigenetic mechanism that silences genes in cancers. METHODS: We performed a genome-wide search to identify differentially methylated loci between 26 tumor and adjacent non-tumor paired tissues from same lung cancer patients using restriction landmark genomic scanning (RLGS) analysis. Among 229 loci which were  hypermethylated in lung tumors as compared to adjacent non-tumor tissues, solute  carrier family 5, member 8 (SLC5A8) was one of the hypermethylated genes, and known as a tumor suppressor gene which is silenced by epigenetic changes in various tumors. We investigated the significance of DNA methylation in SLC5A8 expression in lung cancer cell lines, and 23 paired tumor and adjacent non-tumor  lung tissues by reverse transcription-PCR (RT-PCR), quantitative methylation specific PCR (QMSP) and bisulfite modified DNA sequencing analyses. RESULTS: Reduced or lost expression of SLC5A8 was observed in 39.1% (9/23) of the tumor tissues as compared with paired adjacent non-tumor tissues. Bisulfite sequencing  results of lung cancer cell lines and tissues which did not express SLC5A8 showed a densely methylated promoter region of SLC5A8. SLC5A8 was reactivated by treatment with DNA methyltransferase inhibitor, 5-Aza and/or HDAC inhibitor, trichostatin A (TSA) in lung cancer cell lines, which did not express SLC5A8. Hypermethylation was detected at the promoter region of SLC5A8 in primary lung tumor tissues as compared with adjacent non-tumor tissues (14/23, 60.9%). CONCLUSION: These results suggest that DNA methylation in the SLC5A8 promoter region may suppress the expression of SLC5A8 in lung tumor.

 

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[294]

TÍTULO / TITLE:  - Occupational exposure to lead and lung cancer: results from two case-control studies in Montreal, Canada.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Occup Environ Med. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1136/oemed-2012-100931

AUTORES / AUTHORS:  - Wynant W; Siemiatycki J; Parent ME; Rousseau MC

INSTITUCIÓN / INSTITUTION:  - Research Centre of the CHUM, , Montreal, Quebec, Canada.

RESUMEN / SUMMARY:  - OBJECTIVES: We investigated the association between workplace lead exposure and lung cancer risk, separately for organic lead and for inorganic lead, from either engine emissions or from other sources. METHODS: Two population-based case-control studies were carried out in Montreal (1979-1986 and 1996-2002) to investigate occupational factors in relation to lung cancer among 1593 men with histologically confirmed incident lung cancer, and 1426 controls from the general population. Interviews elicited information on sociodemographic characteristics,  lifetime smoking and occupational history. Chemists translated each job into potential chemical exposures. Cumulative indices of exposure were derived and classified into non-substantial and substantial exposure. ORs adjusted for several potential confounders including smoking, and 95% CIs were estimated by logistic regression. RESULTS: Lifetime prevalences of exposure in Study I were 3% for organic lead, 40% for inorganic lead from engine emissions and 17% for inorganic lead from other sources; corresponding prevalences in Study II were 4%, 19% and 16%, respectively. No associations were observed when comparing ever to never exposed subjects in pooled analyses (organic lead, OR=1.39, 95% CI 0.77 to  2.52; inorganic lead from engine emissions: OR=0.89, 95% CI 0.72 to 1.09; inorganic lead from other sources: OR=0.99, 95% CI 0.76 to 1.29). Nor were these  exposures associated with lung cancer in subjects with substantial cumulative exposure. CONCLUSIONS: In this large study, using a blinded expert-based assessment of lifetime occupational exposure and adjustment for several potential confounders, we observed no increased risk of lung cancer with exposure to lead compounds.

 

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[295]

TÍTULO / TITLE:  - Robotic surgery for the treatment of early-stage lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Opin Oncol. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CCO.0b013e32835daf4f

AUTORES / AUTHORS:  - Veronesi G

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery-European Institute of Oncology, Milan, Italy.

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: Video-assisted thoracic surgery (VATS) is a minimally invasive approach with several advantages over open thoracotomy for resectable lung cancer. However, VATS use is limited mainly because of rigid instruments and limited vision. Robot technology appears to overcome these limitations. This review examines the recent literature on the only commercially available robotic  system (da Vinci) and comparatively assesses its advantages and disadvantages for the treatment of lung cancer. RECENT FINDINGS: Retrospective studies demonstrate  that robot-assisted lobotomy is feasible and safe. Limited long-term results indicate oncological radicality similar to that of open and VATS approaches. Several different robotic techniques are currently employed. Indications for robotic lung resection may be more extensive than those for VATS. SUMMARY: Randomized controlled trials are not available. Robot-assisted approaches to lung cancer resection and lymph node dissection appear to offer comparable radicality  and safety to VATS and open surgery. More intuitive movements, greater flexibility and high-definition, three-dimensional vision render surgery easier for the surgeon, with shorter learning curve than VATS. High capital and running  costs, limited instrument availability and long operating times are important disadvantages. Entry of competitor companies should drive down costs. Studies are required to assess quality of life, morbidity, oncological radicality and cost-effectiveness.

 

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[296]

TÍTULO / TITLE:  - Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiother Oncol. 2012 Dec 6. pii: S0167-8140(12)00490-2. doi: 10.1016/j.radonc.2012.09.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2012.09.024

AUTORES / AUTHORS:  - Nijkamp J; Rossi M; Lebesque J; Belderbos J; van den Heuvel M; Kwint M; Uyterlinde W; Vogel W; Sonke JJ

INSTITUCIÓN / INSTITUTION:  - The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

RESUMEN / SUMMARY:  - PURPOSE: To correlate radiotherapy (RT) dose to acute esophagitis (AE) by means of FDG-PET scans acquired after concurrent chemo-radiotherapy (cCRT) for locally  advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients treated with 24x2.75Gy were selected on presence of a post-RT PET (PET(post)) scan acquired within 3months after cCRT. The value of PET(post) in relation to AE was evaluated by comparing the mean esophageal SUV of the highest 50% (SUV(50%))  between gr<2 and gr2AE. The local dose on the esophagus wall was correlated to the SUV and modeled using a power-law fit. The Lyman-Kutcher-Burman (LKB) model was used to predict gr2AE. The local dose-response relation was used in the LKB model to calculate the EUD. Resulting prediction accuracy was compared to D(mean), V(35), V(55) and V(60). RESULTS: Eighty-two patients were included (gr<2=25, gr2=57). The SUV(50%) was significantly higher for gr2AE (2.2 vs. 2.6,  p<0.01). The LKB parameters (95% CI) were n=0.130 (0.120-0.141), m=0.25 (0.13-0.85) and TD(50)=50.4Gy (37.5-55.4), which resulted in improved predictability of AE compared to other predictors. CONCLUSION: Esophageal uptake  of FDG post-cCRT reflects AE severity. Predictability of grade 2AE was improved by using the local dose-SUV response model, with narrow confidence intervals for  the optimized LKB parameters.

 

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[297]

TÍTULO / TITLE:  - Elevated Expression of BIRC6 Protein in Non-Small-Cell Lung Cancers is Associated with Cancer Recurrence and Chemoresistance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):161-70. doi: 10.1097/JTO.0b013e31827d5237.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827d5237

AUTORES / AUTHORS:  - Dong X; Lin D; Low C; Vucic EA; English JC; Yee J; Murray N; Lam WL; Ling V; Lam S; Gout PW; Wang Y

INSTITUCIÓN / INSTITUTION:  - Departments of *Experimental Therapeutics and daggerIntegrative Oncology, BC Cancer Agency, Cancer Research Centre, Vancouver, BC, Canada; Departments of double daggerPathology, section signSurgery, vertical lineMedical Oncology, and paragraph signUrologic Sciences, University of British Columbia, Vancouver, BC, Canada; and #The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada.

RESUMEN / SUMMARY:  - INTRODUCTION: : Non-small-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Reliable prognostic assays and more effective treatments  are critically required. BIRC6 (baculoviral inhibitors of apoptosis proteins repeat-containing 6) protein is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. In this study, we investigated whether BIRC6 expression can be used as a prognostic marker or potential therapeutic target for NSCLC. METHODS: : In a retrospective analysis, BIRC6 protein expression was determined for 78 resected primary NSCLCs and nine benign lung tissues. Twenty-nine chemoresistant or chemosensitive subrenal capsule NSCLC tissue xenografts were assessed for BIRC6 expression, using immunohistochemistry, and 13 of them for BIRC6 gene copy number, using array comparative genomic hybridization analysis. The effect of small interfering RNA-induced BIRC6 knockdown on the growth of human NSCLC cell cultures and apoptosis (in combination with cisplatin) was investigated. RESULTS: : Elevated BIRC6 protein expression in NSCLC tissues was associated with poor 3-year relapse-free patient survival, lymph node involvement, and advanced pathological tumor, node, metastasis stage. In patient-derived lung squamous cell carcinoma xenografts, chemoresistance was associated with elevated BIRC6 expression and increased gene copy number. Small interfering RNA-induced BIRC6 down-regulation inhibited growth of the NSCLC cells and sensitized the cells to cisplatin. CONCLUSIONS: : BIRC6 may play an important role in the malignant progression and chemoresistance of NSCLC. Elevated BIRC6 protein expression may serve as a predictive marker for chemoresistance of NSCLCs and a poor prognostic  factor for NSCLC patients. Down-regulation of the BIRC6 gene as a therapeutic approach may be effective, especially in combination with conventional chemotherapeutics.

 

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[298]

TÍTULO / TITLE:  - Spheroid Culture of Primary Lung Cancer Cells with Neuregulin 1/HER3 Pathway Activation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):131-9. doi: 10.1097/JTO.0b013e3182779ccf.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182779ccf

AUTORES / AUTHORS:  - Endo H; Okami J; Okuyama H; Kumagai T; Uchida J; Kondo J; Takehara T; Nishizawa Y; Imamura F; Higashiyama M; Inoue M

INSTITUCIÓN / INSTITUTION:  - Departments of *Biochemistry, daggerThoracic Surgery, double daggerThoracic Oncology, and section signPathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; ||Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan; and paragraph signDepartment of Clinical and Experimental Pathophysiology, Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan.

RESUMEN / SUMMARY:  - INTRODUCTION: : Primary culture of cancer cells is expected to be useful for investigating the biology of cancer and predicting chemosensitivity for individual patients, yet has been hampered by technical difficulties. We recently developed the cancer tissue-originated spheroid (CTOS) method for the primary culture of colorectal cancer cells. In the present study, we applied this system  to the primary culture of non-small-cell lung cancer. METHODS: : We used 125 surgical specimens and 18 pleural effusions for CTOS preparation. Partially digested tumor fragments were cultured in a medium for embryonic stem cells. CTOSs were subjected to sensitivity assay and signal transduction assay for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib. We also investigated the effects of growth factors in culturing lung cancer CTOS. RESULTS: : The success rate of CTOS preparation from surgical specimens was 80.0%. The CTOS method was also suitable for culturing tumor spheroids from pleural effusions. CTOSs from lung cancer consisted mostly of pure cancer cells. CTOSs and CTOS-derived xenografts retained the characteristics of the original tumors. In vitro assay results showed that EGFR mutation status and  expression levels corresponded with erlotinib sensitivity, confirming previous clinical findings. Furthermore, we found that neuregulin 1, a ligand of HER3, potently induced CTOS growth. CONCLUSIONS: : The CTOS method enables us to obtain primary lung tumor cells of high viability and purity. CTOS could be a new platform for studying lung cancer biology.

 

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[299]

TÍTULO / TITLE:  - Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing  peritoneal epithelioid mesotheliomas from serous carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mod Pathol. 2012 Nov 30. doi: 10.1038/modpathol.2012.200.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.200

AUTORES / AUTHORS:  - Ordonez NG

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Texas MD Anderson Cancer Center, Houston,  TX, USA.

RESUMEN / SUMMARY:  - Distinguishing between peritoneal epithelioid mesotheliomas and papillary serous  carcinomas involving the peritoneum can be difficult on routine histological preparations, but this differential diagnosis can be facilitated by the use of immunohistochemistry. Recent investigations have indicated that PAX8, PAX2, claudin-4, and h-caldesmon are immunohistochemical markers that can assist in distinguishing between these two malignancies; however, much of the information published on the value of these markers is either insufficient or contradictory.  The purpose of this study is to resolve some of the existing controversies and to fully determine the practical value of these markers for assisting in the differential diagnosis between peritoneal mesotheliomas and serous carcinomas. In order to do so, a total of 40 peritoneal epithelioid mesotheliomas and 45 serous  carcinomas (15 primary, 30 metastatic to the peritoneum) were investigated. PAX8  and PAX2 nuclear positivity was demonstrated in 42 (93%) and 25 (56%) of the serous carcinomas, respectively, whereas none of the mesotheliomas expressed either marker. Forty-four (98%) of the serous carcinomas exhibited claudin-4 reactivity along the cell membrane, whereas none of the mesotheliomas were positive for this marker. All of the serous carcinomas and mesotheliomas were negative for h-caldesmon. Based on these results, it is concluded that PAX8 and claudin-4 have a higher sensitivity and specificity for assisting in discriminating between peritoneal epithelioid mesotheliomas and serous carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though it is highly specific, PAX2 has little practical value in the diagnosis of peritoneal epithelioid mesotheliomas as its sensitivity is low. The h-caldesmon is not useful.Modern Pathology advance online publication, 30 November 2012; doi:10.1038/modpathol.2012.200.

 

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[300]

TÍTULO / TITLE:  - Expression of the potential cancer stem cell markers, CD133, CD44, ALDH1, and beta-catenin, in primary lung adenocarcinoma-their prognostic significance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Int. 2012 Dec;62(12):792-801. doi: 10.1111/pin.12019.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pin.12019

AUTORES / AUTHORS:  - Okudela K; Woo T; Mitsui H; Tajiri M; Masuda M; Ohashi K

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Division of Pathology, Kanagawa Cardiovascular and Respiratory Center Hospital, Yokohama, Japan.

RESUMEN / SUMMARY:  - The present study investigated expression profiles of the potential CSC markers including CD133, CD44, ALDH1, and beta-catenin, and evaluated their prognostic value in lung adenocarcinomas. One-hundred-and-seventy-seven tumors (stage I) were immunohistochemically examined for the expression of these markers, and thresholds to subdivide expression levels were determined using receiver operating characteristics curves. Tumors with high levels of CD133 (adjusted hazard ratio (HR) 4.55 (95% confidence interval (CI) 1.26-16.40, P = 0.021), CD44 (HR 3.73, 95% CI 1.20-11.58, P = 0.023) or ALDH1 (HR 3.61, 95% CI 1.09-12.3, P =  0.036), but not beta-catenin (HR 2.43, 95% CI 0.59-10.8, P = 0.220), showed a significantly higher risk of recurrence than the corresponding low expressers. In conclusion, levels of CD133, CD44, and ALDH1 had independent prognostic value to  predict the recurrence of lung adenocarcinoma.

 

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[301]

TÍTULO / TITLE:  - Factors associated with smoking abstinence after diagnosis of early stage lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 3. pii: S0169-5002(12)00682-4. doi: 10.1016/j.lungcan.2012.12.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.013

AUTORES / AUTHORS:  - Hopenhayn C; Christian WJ; Christian A; Studts J; Mullet T

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology, College of Public Health, University of Kentucky, 111 Washington Avenue, Suite 211, Lexington, KY 40536-0003, USA. Electronic address:  claudia.hopenhayn@uky.edu.

RESUMEN / SUMMARY:  - Smoking cessation after a diagnosis of lung cancer is associated with improved outcomes, including quality of life and survival. The research presented here is  based on data obtained from sequential interviews with early stage lung cancer patients in Kentucky, on their smoking patterns at four time points: (1) six months before enrollment in the study, before diagnosis, (2) at enrollment (shortly after surgical resection), (3) three months post-enrollment, and (4) six months post-enrollment. A number of covariates were considered to examine the factors associated with smoking abstinence and rebound trajectories. The results  indicate that, while about 75% of patients who were smoking at six months before  enrollment had quit by the first post-surgery interview, almost 50% of them had returned to smoking six months later. Multivariate analysis to evaluate the relative contribution of covariates indicated that low household income, exposure to environmental tobacco smoke at home and evidence of depression were positively associated with returning to smoking. Furthermore, even after controlling for these factors, patients from the Appalachian region of Kentucky, an area with substantially high smoking prevalence and very high lung cancer incidence rates,  were less likely to abstain from smoking throughout the study than subjects in the rest of the state. Future research is suggested to investigate in more detail the tobacco-related behaviors and cessation attempts of patients and their families, which can lead to more targeted, successful smoking cessation interventions for lung cancer patients.

 

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[302]

TÍTULO / TITLE:  - Authors’ response to: Qualitative Job-Exposure Matrix—a tool for the quantification of population attributable fractions for occupational lung carcinogens?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Epidemiol. 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ije/dys193

AUTORES / AUTHORS:  - De Matteis S; Consonni D; Lubin JH; Tucker M; Peters S; Vermeulen RC; Kromhout H; Bertazzi PA; Caporaso NE; Pesatori AC; Wacholder S; Landi MT

INSTITUCIÓN / INSTITUTION:  - Unit of Epidemiology, Department of Preventive Medicine, Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico and Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, Milan, Italy, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA, Institute for Risk Assessment Sciences, Environmental Epidemiology Division, Utrecht University, Utrecht, The Netherlands and Western Australian Institute for Medical Research, University of Western Australia, Nedlands WA, Australia.

 

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[303]

TÍTULO / TITLE:  - Lungs don’t forget: Comparison of the KRAS and EGFR mutation profile and survival of collegiate smokers and never smokers with advanced lung cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):123-5. doi: 10.1097/JTO.0b013e31827914ea.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827914ea

AUTORES / AUTHORS:  - Varghese AM; Sima CS; Chaft JE; Johnson ML; Riely GJ; Ladanyi M; Kris MG

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

RESUMEN / SUMMARY:  - BACKGROUND: We hypothesize that among patients with lung cancers the KRAS/EGFR mutation profile and overall survival of collegiate smokers (former smokers who smoked between 101 lifetime cigarettes and 5 pack-years) are distinct from those  of never smokers and former smokers with 15 pack-years or more. METHODS: We collected age, sex, stage, survival, and smoking history for patients evaluated from 2004 to 2009 with advanced stage lung cancers and known KRAS/EGFR status. Mutation profile and overall survival were compared using Fisher’s exact test and log-rank test, respectively. RESULTS: Data were available for 852 patients with advanced-stage lung cancers with known KRAS/EGFR status, of which 6% were collegiate smokers, 36% were never smokers, and 30% were former smokers with 15 pack-years or more. The mutation profile of collegiate smokers (15% KRAS mutations, 27% EGFR mutations) was distinct from those of never smokers (p < 0.001) and former smokers with 15 pack-years or more (p < 0.001) and not significantly different from those of former smokers with 5 to 15 pack-years (p = 0.9). Median overall survival for collegiate smokers was 25 months, compared with 32 months for never smokers (p = 0.4), 33 months for former smokers with 5 to 15  pack-years (p = 0.48), and 21 months for former smokers with 15 pack-years or more (p = 0.63). CONCLUSIONS: Collegiate smokers with advanced-stage lung cancers represent a distinct subgroup of patients with a higher frequency of KRAS mutations and lower frequency of EGFR mutations compared with never smokers. These observations reinforce the recommendation for routine mutation testing for  all patients with lung cancers and that no degree of tobacco exposure is safe.

 

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[304]

TÍTULO / TITLE:  - Predictive Factors of Lymph Node Status in Small Peripheral Non-small Cell Lung Cancers: Tumor Histology is More Reliable.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2829-x

AUTORES / AUTHORS:  - Zhang Y; Sun Y; Shen L; Li Y; Xiang J; Zhang Y; Hu H; Chen H

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

RESUMEN / SUMMARY:  - BACKGROUND: During the past two decades, many studies have sought to find reliable predictors of N0 status in small-sized lung cancers. However, the way of tumor size measurement was usually not clearly stated, and controversy remains as to whether systematic lymph node dissection should be performed in patients with  subcentimeter tumors. METHODS: We reviewed correlations between lymph node involvement and clinicopathological variables in 243 small peripheral non-small cell lung cancers with their size measured in fresh specimens before formalin fixation. Histologic subtypes of adenocarcinomas were classified in line with the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) lung adenocarcinoma classification. RESULTS: Incidence of N1 and N2 nodal involvement was 5.3 and 6.6 %, respectively. N2 disease was present in a proportion of subcentimeter tumors (2/53, 3.8 %). No lymph node metastasis was revealed in squamous cell carcinomas, adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma. Collectively, the five cell  types accounted for 34.6 % of all the small peripheral cases. CONCLUSIONS: Precise measurement of tumor size in fresh tissues revealed that tumor size was not a reliable predictor of N0 status. However, through histologic classification, systematic lymph node dissection might be avoided in more than one third of small peripheral NSCLC.

 

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[305]

TÍTULO / TITLE:  - Small-cell lung cancer: an update on targeted therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Adv Exp Med Biol. 2013;779:385-404. doi: 10.1007/978-1-4614-6176-0_18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6176-0_18

AUTORES / AUTHORS:  - Joshi M; Ayoola A; Belani CP

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Penn State Hershey Medical Center, 500 University Drive,  CH72, Hershey, PA, 17033, USA, mjoshi@hmc.psu.edu.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer-related deaths world-wide and small-cell lung cancer (SCLC) accounts for up to 25% of lung cancer deaths. There has been a considerable amount of research in the understanding of the depth of biology of SCLC and utilizing this knowledge to develop targeted approaches. The  treatment of SCLC remains a challenge, despite remarkable initial efficacy to combination chemotherapy and radiation therapy. The response is usually short-lived and the prognosis of SCLC has not changed over the past few decades,  necessitating the critical need for evaluating novel agents/therapies. Several signaling pathways have been found to be activated in SCLC tumor cells, forming a rationale for blocking some of the drugable targets. Molecular changes and biological markers have been identified but remain to be validated. Novel and targeted agents have been evaluated but without much success. Increasing understanding of the biology and potential clinical evaluation of biomarkers will pave the way for more effective treatments.

 

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[306]

TÍTULO / TITLE:  - Interim Data from the Medical Research Council QUARTZ Trial: Does Whole Brain Radiotherapy Affect the Survival and Quality of Life of Patients with Brain Metastases from Non-small Cell Lung Cancer?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Oncol (R Coll Radiol). 2012 Dec 1. pii: S0936-6555(12)00356-1. doi: 10.1016/j.clon.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clon.2012.11.002

AUTORES / AUTHORS:  - Langley RE; Stephens RJ; Nankivell M; Pugh C; Moore B; Navani N; Wilson P; Faivre-Finn C; Barton R; Parmar MK; Mulvenna PM

INSTITUCIÓN / INSTITUTION:  - MRC Clinical Trials Unit, London, UK. Electronic address: rel@ctu.mrc.ac.uk.

RESUMEN / SUMMARY:  - AIMS: Over 30% of patients with non-small cell lung cancer (NSCLC) develop brain  metastases. If inoperable, optimal supportive care (OSC), including steroids, and whole brain radiotherapy (WBRT) are generally considered to be standard care, although there is no randomised evidence demonstrating that the addition of WBRT  to OSC improves survival or quality of life. MATERIALS AND METHODS: QUARTZ is a randomised, non-inferiority, phase III trial comparing OSC + WBRT versus OSC in patients with inoperable brain metastases from NSCLC. The primary outcome measure is quality-adjusted life years (QALYs). QUARTZ was threatened with both loss of funding and early closure due to poor accrual. A lack of preliminary randomised data supporting the trial’s hypotheses was thought to underlie the poor accrual,  so, with no knowledge of the data, the independent trial steering committee agreed to the unusual step of releasing interim data. RESULTS: Between March 2007 and April 2010, 151 (of the planned 534) patients were randomised (75 OSC + WBRT, 76 OSC). Participants’ baseline demographics included median age 67 years (interquartile range 62-73), 60% male, 50% with a Karnofsky performance status <70; steroid usage was similar in the two groups; 64/75 (85%) received WBRT (20 Gy in five fractions). Median survival was: OSC + WBRT 49 days (95% confidence interval 39-61), OSC 51 days (95% confidence interval 27-57) - hazard ratio 1.11  (95% confidence interval 0.80-1.53) in favour of WBRT. Quality of life assessed using EQ-5D showed no evidence of a difference. The estimated mean QALYs was: OSC + WBRT 31 days and OSC 30 days, difference -1 day (95% confidence interval -12.0  to +13.2 days). CONCLUSION: These interim data indicate no early evidence of detriment to quality of life, overall survival or QALYs for patients allocated to OSC alone. They provide key information for discussing the trial with patients and strengthen the argument for continuing QUARTZ to definitively answer this important clinical question.

 

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[307]

TÍTULO / TITLE:  - Qualitative job-exposure-matrix—a tool for the quantification of population-attributable fractions for occupational lung carcinogens?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Epidemiol. 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ije/dys192

AUTORES / AUTHORS:  - Taeger D; Pallapies D; Behrens T

INSTITUCIÓN / INSTITUTION:  - Institute for Prevention and Occupational Medicine of the German Social Accident  Insurance, Institute of the Ruhr-Universitat Bochum (IPA), Burkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.

 

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[308]

TÍTULO / TITLE:  - Dietary selenium fails to influence cigarette smoke-induced lung tumorigenesis in A/J mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2012 Dec 5. pii: S0304-3835(12)00709-4. doi: 10.1016/j.canlet.2012.11.047.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.047

AUTORES / AUTHORS:  - Glauert HP; Martin JB; Li J; Tharappel JC; Han SG; Gillespie HD; Cantor AH; Lee EY; Gary Gairola C

INSTITUCIÓN / INSTITUTION:  - Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506, United States; Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, United States. Electronic address: hglauert@uky.edu.

RESUMEN / SUMMARY:  - The goal of the study was to determine if dietary selenium inhibited the induction of lung tumorigenesis by cigarette smoke in A/J mice. Purified diets containing 0.15, 0.5, or 2.0mg/kg selenium in the form of sodium selenite were fed to female A/J mice. Half of the mice in each dietary group were exposed to cigarette smoke 6h/day, 5days/week for five months followed by a four month recovery period in ambient air, while the other half were used as controls. After the recovery period, the mice were euthanized, and their lungs were removed for further analysis. Mice exposed to smoke had a higher tumor incidence and a higher tumor multiplicity, whereas dietary Se did not affect either the tumor incidence  or tumor multiplicity. An increase in dietary selenium led to increased levels of selenium in the lung as well as GPx protein levels, but dietary Se did not affect lung SOD protein levels. In conclusion, these data confirm the carcinogenic activity of cigarette smoke in mice but show that dietary Se provided as sodium selenite does not affect smoke-induced carcinogenesis in this model.

 

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[309]

TÍTULO / TITLE:  - MicroRNA Profiling in Lung Cancer Reveals New Molecular Markers for Diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):645-54. doi: 10.1159/000343473. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000343473

AUTORES / AUTHORS:  - Solomides CC; Evans BJ; Navenot JM; Vadigepalli R; Peiper SC; Wang ZX

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pa., USA.

RESUMEN / SUMMARY:  - Objective: To identify new molecular diagnostic markers for non-small cell lung carcinoma (NSCLC) by analyzing microRNA (miRNA) expression profile differences in samples from NSCLC patients and adults with nonneoplastic diseases. Study Design: miRNA expression was studied in archival formalin-fixed, paraffin-embedded tissues by microarray and confirmed by real-time PCR analysis of NSCLC and normal lung tissues. An algorithm for discriminating normal, squamous cell carcinoma (SQCC), and adenocarcinoma (ADC) tissue was derived from miRNA expression studies and applied towards characterization of poorly differentiated NSCLC samples. Results: Microarray data from a genome-wide scan revealed 34 differentially expressed miRNAs, 5 of which enabled algorithmic discrimination of normal tissue  from carcinoma (SQCC or ADC), as well as SQCC from ADC. Expression of miR-21 was  significantly increased in both tumor types, whereas levels of miR-451 and miR-486-5p were reduced. SQCC was distinguished from normal tissue and ADC by high-level miR-205 expression and decreased miR-26b. Comparison of miRNA profiles to histological and immunohistochemical findings in 19 poorly differentiated specimens demonstrated the potential clinical utility of miRNA profiling to provide important insights into the classification of SQCC and ADC. Conclusion: This study presents a novel algorithm for specimen classification in cases of poorly differentiated NSCLC.

 

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[310]

TÍTULO / TITLE:  - High-dose pemetrexed in combination with high-dose crizotinib for the treatment of refractory CNS metastases in ALK-rearranged non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):e3-5. doi: 10.1097/JTO.0b013e3182762d20.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182762d20

AUTORES / AUTHORS:  - Gandhi L; Drappatz J; Ramaiya NH; Otterson GA

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Leena_Gandhi@dfci.harvard.edu

 

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[311]

TÍTULO / TITLE:  - Temporal trends in outcomes following sublobar and lobar resections for small (</=2 cm) non-small cell lung cancers-a Surveillance Epidemiology End Results database analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Surg Res. 2012 Dec 19. pii: S0022-4804(12)01920-8. doi: 10.1016/j.jss.2012.11.052.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jss.2012.11.052

AUTORES / AUTHORS:  - Yendamuri S; Sharma R; Demmy M; Groman A; Hennon M; Dexter E; Nwogu C; Miller A; Demmy T

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York; Department of Surgery, State University of New York, Buffalo, New York. Electronic address: sai.yendamuri@roswellpark.org.

RESUMEN / SUMMARY:  - BACKGROUND: Since the randomized, controlled study that favored lobectomy for resection of stage I non-small cell lung cancers (NSCLCs) by the Lung Cancer Study Group, there have been improvements in staging. The liberal use of computed tomography also may have altered the types of early lung cancer diagnosed. Studies published since then have drawn contradictory conclusions on the benefit  of lobectomy over sublobar resections for early-stage NSCLC. We examined the Surveillance Epidemiology End Results database to test our hypothesis that the relationship between extent of resection and outcome has changed since the Lung Cancer Study Group study was published. METHODS: We examined stage I NSCLCs </=2  cm in size over three periods: 1988-1998 (Early), 1999-2004 (Intermediate), and 2005-2008 (Late). For each period, we assessed overall and disease-specific survivals and their associations with the extents of resection, by univariate and multivariate analyses. Sublobar resections in the Early group could not be categorized into segmentectomies and wedge resections because these were not coded separately. RESULTS: The proportion of NSCLCs </=2 cm increased from 0.98%  in 1988 to 2.2% in 2008. Multivariate analyses showed that sublobar resection was inferior to lobectomy in the Early period (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.21-1.65). This effect decreased in the Intermediate period, in which segmentectomies but not wedge resections were equivalent to lobectomies (wedge versus lobectomy HR, 1.19; 95% CI, 1.01-1.41; segmentectomy versus lobectomy HR, 1.04; 95% CI, 0.8-1.36). The difference disappeared in the Late period, when both wedge resections and segmentectomies were equivalent to lobectomy (wedge versus lobectomy HR, 1.09; 95% CI, 0.79-1.5; segmentectomy versus lobectomy HR, 0.83; 95% CI, 0.47-1.45). Trends for both overall survival and disease-specific survival were identical. CONCLUSIONS: The survival benefit of lobectomy over sublobar resection decreased over the past 2 decades with no discernible difference in the most contemporary cases. These results support reevaluation of lobectomy as the standard of care for small (</=2-cm) NSCLCs.

 

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[312]

TÍTULO / TITLE:  - Socioeconomic position and surgery for early-stage non-small-cell lung cancer: A  population-based study in Denmark.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 28. pii: S0169-5002(12)00644-7. doi: 10.1016/j.lungcan.2012.11.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.023

AUTORES / AUTHORS:  - Starr LK; Osler M; Steding-Jessen M; Frederiksen BL; Jakobsen E; Osterlind K; Schuz J; Johansen C; Dalton SO

INSTITUCIÓN / INSTITUTION:  - Danish Cancer Society Research Center, Danish Cancer Society, 49 Strandboulevarden, DK-2100 Copenhagen, Denmark; International Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France.

RESUMEN / SUMMARY:  - AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall and separately for stages I, II and IIIa. RESULTS: Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher  odds for not receiving surgery. Low disposable income was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain the association with income or living alone for early-stage NSCLC patients. CONCLUSION: Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer.

 

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[313]

TÍTULO / TITLE:  - Value of Computed Tomography-guided Core Needle Biopsy in Diagnosis of Primary Pulmonary Lymphomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Vasc Interv Radiol. 2013 Jan;24(1):97-102. doi: 10.1016/j.jvir.2012.09.028. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jvir.2012.09.028

AUTORES / AUTHORS:  - Wang Z; Li X; Chen J; Jin Z; Shi H; Zhang X; Pan J; Liu W; Yang N; Chen J

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology, Peking Union Medical College Hospital, Beijing, 100730, China.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the value of computed tomography (CT)-guided core needle biopsy in diagnosis of primary pulmonary lymphoma and its subtypes. MATERIALS AND METHODS: A retrospective analysis of the records of all patients with primary pulmonary lymphoma between January 2005 and August 2011 was performed. There were 25 patients referred to the radiology department for CT-guided core needle biopsy. The success rate and complications were assessed. RESULTS: A definitive diagnosis and accurate histologic subtype were obtained in 21 patients with a success rate of 84.0%. Diagnosis was made in the other four patients with bronchoscopy and surgery. Non-Hodgkin lymphoma (NHL) was the diagnosis in all patients. Most subtypes were mucosa-associated lymphoid tissue (MALT) lymphomas (n = 19). The remaining subtypes included three diffuse large B-cell NHLs, two peripheral T-cell lymphomas not otherwise specified, and one anaplastic large cell NHL. The success rate of core needle biopsy was 95% (18 of 19) for MALT lymphomas, 67% (2 of 3) for diffuse large B cell NHLs, and 33% (1 of 3) for other NHLs. The success rate for MALT lymphomas was significantly higher than that of non-MALT lymphomas according to Fisher exact t test (P = .031). No serious complications occurred in any patients. CONCLUSIONS: CT-guided core needle biopsy is a reliable procedure to assist in diagnosis and classification of primary pulmonary lymphomas, especially MALT lymphomas.

 

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[314]

TÍTULO / TITLE:  - Thyroid transcription factor 1 and napsin a double stain: utilizing different vendor antibodies for diagnosing lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):596-602. doi: 10.1159/000339793. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000339793

AUTORES / AUTHORS:  - Johnson H; Cohen C; Fatima N; Duncan D; Siddiqui MT

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Emory University Hospital, Atlanta, Ga., USA.

RESUMEN / SUMMARY:  - Objective: A combined thyroid transcription factor 1 (TTF-1) and Napsin A double  stain has been shown to be useful in the diagnosis of adenocarcinoma (ADC). This  study compares differences in double staining patterns among vendor antibodies (Leica, Dako, and Biocare). Study Design: The cohorts included 35 FNA cell blocks of lung ADC and 24 cell blocks of lung squamous cell carcinoma (SqCCA). Double-staining immunohistochemistry was performed with TTF-1 as a brown nuclear  stain and Napsin A as a red cytoplasmic stain, using three sets of double stains. Additionally, FISH expression was performed on SqCCAs with aberrant TTF-1 expression. Results: The sensitivity for the double stains ranged from 40 to 74%, while the specificity ranged from 88 to 96%. Two Leica TTF-1-positive SqCCAs also showed low-level amplification by FISH assay not seen in the TTF-1-negative control SqCCAs. Conclusion: The use of Dako TTF-1 antibody paired with Leica Napsin A antibody as a double stain yielded the best results for diagnosing ADC;  additionally, the Leica Napsin A-only staining results had the highest positive predictive value at 97%. Both Dako and Biocare antibodies expressed less staining of SqCCAs than Leica staining.

 

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[315]

TÍTULO / TITLE:  - Evaluation of Soluble Mesothelin-related Peptide as a Diagnostic Marker of Malignant Pleural Mesothelioma Effusions: Its Contribution to Cytology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Invest. 2013 Jan;31(1):48-55. doi: 10.3109/07357907.2012.749265. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2012.749265

AUTORES / AUTHORS:  - Canessa PA; Franceschini MC; Ferro P; Battolla E; Dessanti P; Manta C; Sivori M; Pezzi R; Fontana V; Fedeli F; Pistillo MP; Roncella S

INSTITUCIÓN / INSTITUTION:  - >Division of Pneumology , La Spezia , Italy,1.

RESUMEN / SUMMARY:  - Soluble mesothelin-related peptide (SMRP) is regarded as an FDA approved biomarker for the diagnosis and monitoring of pleural malignant mesothelioma (MPM). We detected the SMRP levels in pleural effusions (PE) by means of an ELISA and analyzed their diagnostic relevance to differentiate MPM from benign pathology and from non-MPM pleural metastasis. Comparison with cytology in MPM-PE was also performed. We found that SMRP detection in MPM-PE can help the diagnosis of MPM and provide additional diagnostic value to cytology. We concluded that SMRP test may be incorporated into clinical practice of PE from patients suspicious for MPM.

 

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[316]

TÍTULO / TITLE:  - Inhibition of ZEB1 reverses the phenotype of epithelial-mesenchymal transition and chemoresistance in docetaxel-resistant human lung adenocarcinoma cell line SPC-A1/DTX.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Biochem. 2012 Dec 17. doi: 10.1002/jcb.24481.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24481

AUTORES / AUTHORS:  - Ren J; Chen Y; Song H; Chen L; Wang R

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.

RESUMEN / SUMMARY:  - Docetaxel has been used as one of the first-line chemotherapies in solid tumors including advanced non-small cell lung cancer (NSCLC). However, limited responses to chemotherapy are observed in clinic and the molecular mechanisms have not been fully understood. Emerging evidence suggests that epithelial-mesenchymal transition (EMT) plays an important role in the processes of tumor metastasis as  well as resistance towards anticancer agents. In this study, it was observed that docetaxel-resistant human lung adenocarcinoma cell line (SPC-A1/DTX) was typical  of mesenchymal phenotype. SPC-A1/DTX cell line has increased migratory and invasive capacity both in vitro and in vivo. Among the master EMT-inducing transcriptional factors, ZEB1 was found to be significantly increased in SPC-A1/DTX cell line. ZEB1 knockdown with RNA interference could reverse the EMT  phenotype and inhibit the migratory ability of SPC-A1/DTX cells. Furthermore, inhibition of ZEB1 significantly enhanced the chemosensitivity of SPC-A1/DTX cells to docetaxel in vitro and in vivo and ectopic expression of ZEB1 increased  the chemoresistance of SPC-A1 cells to docetaxel. All these results provide experimental evidence that ZEB1 might be an attractive target for the treatment of human NSCLC. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.

 

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[317]

TÍTULO / TITLE:  - Alteration of serum miR-206 and miR-133b is associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicol Appl Pharmacol. 2013 Jan 18. pii: S0041-008X(13)00015-X. doi: 10.1016/j.taap.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.taap.2013.01.002

AUTORES / AUTHORS:  - Wu J; Yang T; Li X; Yang Q; Liu R; Huang J; Li Y; Yang C; Jiang Y

INSTITUCIÓN / INSTITUTION:  - Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, People’s Republic of China.

RESUMEN / SUMMARY:  - The alteration of microRNA (miRNA) expression plays an important role in chemical carcinogenesis. Presently, few reports have been published that concern the significance of circulating miRNAs in lung carcinogenesis induced by environmental carcinogens. The purpose of this study was to identify serum miRNAs that could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Male F344 rats were systemically administered with NNK. The rat serum differential expression profiles of miRNAs were analyzed by small RNA solexa sequencing. Using quantitative real-time PCR, the differentially expressed serum miRNAs were identified in each individual rat. Serum miR-206 and miR-133b were selected for further identification in rat serum at different stages of lung carcinogenesis; we detected the levels of serum miR-206 and miR-133b in lung cancer tissues induced by NNK. NNK causes significant alteration of serum miRNA expression. Compared to the control group, serum miR-206 and miR-133b were significantly up-regulated in the early stage of NNK-induced lung carcinogenesis. miR-206 and miR-133b exhibited low-expression in lung cancer tissues. Our results demonstrate that lung carcinogen NNK exposure changes the expression of serum miRNAs. Serum miR-206 and miR-133b could be associated with lung carcinogenesis induced by NNK.

 

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[318]

TÍTULO / TITLE:  - Expression of NDRG2 in human lung cancer and its correlation with prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):421. doi: 10.1007/s12032-012-0421-7. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0421-7

AUTORES / AUTHORS:  - Li SJ; Wang WY; Li B; Chen B; Zhang B; Wang X; Chen CS; Zhao QC; Shi H; Yao L

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi’an, 710032, Shanxi, People’s Republic of China.

RESUMEN / SUMMARY:  - We had reported that N-myc downstream-regulated gene (NDRG2) regulates colorectal cancer, breast cancer, clear cell renal cell carcinoma, pancreatic cancer, thyroid cancer and esophageal squamous cell proliferation, development, and apoptosis. The goal of this study was to determine the expression pattern of NDRG2 in human lung cancer and its correlation with prognosis. Immunohistochemistry, RT-PCR and western blot were used to explore the expression of NDRG2 in 185 human lung cancer patients. The correlation of NDRG2 expression with patients’ survival rate was assessed by Kaplan-Meier and Cox regression. Results showed that the expression level of NDRG2 was decreased in human lung cancer tissues, and NDRG2 was positively correlated with depth of invasion (P = 0.038), vascular invasion (P = 0.036), tumor grade (P = 0.039), and tumor size (P = 0.026). Both RT-PCR and Western blots demonstrated that NDRG2 mRNA and protein  levels were lower in lung cancer compared to the adjacent normal tissue from the  same individual, and NDRG2 level was negatively correlated with UICC stage. Additionally, survival time of lung cancer patients with high expression of NDRG2 was longer than those with low expression during the 5-year follow-up period (P = 0.001). Meanwhile, COX regression analysis indicated that low expression of NDRG2, >/=pT(3), pM(1), >/=pN(1) and vascular invasion were independent, poor prognostic factors of lung cancer patients. These data showed that NDRG2 may play an important role in human lung cancer tumourigenesis, and NDRG2 might serve as a novel prognostic marker in human lung cancer.

 

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[319]

TÍTULO / TITLE:  - Development of a metastatic fluorescent Lewis Lung carcinoma mouse model: Identification of mRNAs and microRNAs involved in tumor invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gene. 2013 Jan 4. pii: S0378-1119(12)01642-3. doi: 10.1016/j.gene.2012.12.083.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2012.12.083

AUTORES / AUTHORS:  - Rask L; Fregil M; Hogdall E; Mitchelmore C; Eriksen J

INSTITUCIÓN / INSTITUTION:  - Department of Oncology 54O5, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark; Faculty of Health Sciences, University of Copenhagen, Denmark. Electronic address: rasklene@gmail.com.

RESUMEN / SUMMARY:  - Cancer metastasis is the foremost cause of death in cancer patients. A series of  observable pathological changes takes place during progression and metastasis of  cancer, but the underlying genetic changes remain unclear. Therefore, new approaches are required, including insights from cancer mouse models. To examine  the mechanisms involved in tumor metastasis, we first generated a stably transfected Lewis Lung carcinoma cell line expressing a far-red fluorescent protein, called Katushka. After in vivo growth in syngeneic mice, two fluorescent Lewis Lung cancer subpopulations were isolated from primary tumors and lung metastases. The metastasis-derived cells exhibited a significant improvement in in vitro invasive activity compared to the primary tumor-derived cells, using a quantitative invasion chamber assay. Moreover, expression levels of 84 tumor metastasis-related mRNAs, 88 cancer-related microRNAs as well as Dicer and Drosha were determined using RT-qPCR. Compared to the primary Lewis Lung carcinoma subculture, the metastasis-derived cells exhibited statistically significantly increased mRNA levels for several matrix metalloproteinases as well as hepatocyte growth factor (HGF) and spleen tyrosine kinase (SYK). A modest decrease in Drosha and Dicer mRNA levels was accompanied by significant downregulation of ten microRNAs, including miR-9 and miR-203, in the lung metastatic Lewis Lung carcinoma cell culture. Thus, a tool for cancer metastasis studies has been established and the model is well suited for the identification of novel microRNAs and mRNAs involved in malignant progression. Our results suggest that increases in metalloproteinase expression and impairment of miRNA processing are  involved in the acquirement of metastatic ability.

 

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[320]

TÍTULO / TITLE:  - Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 23. pii: S0169-5002(13)00008-1. doi: 10.1016/j.lungcan.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.002

AUTORES / AUTHORS:  - Okamura K; Takayama K; Izumi M; Harada T; Furuyama K; Nakanishi Y

INSTITUCIÓN / INSTITUTION:  - Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Japan.

RESUMEN / SUMMARY:  - Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin  19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2ng/mL CEA and 3.5ng/mL CYFRA 21-1 and twice these respective levels (6.4ng/mL and 7.0ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes’ theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%],  and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1,  or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should therefore be taken into account when these serum tumor markers are used as diagnostic tools for lung cancer.

 

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[321]

TÍTULO / TITLE:  - Screening for lung cancer: Who should be screened?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec;136(12):1511-4. doi: 10.5858/arpa.2012-0259-RA.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0259-RA

AUTORES / AUTHORS:  - Jett J

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, National Jewish Health, Denver, Colorado, USA. jettj@njhealth.org

RESUMEN / SUMMARY:  - Lung cancer is the most common cause of death from cancer in the United States. Previous studies of screening with chest radiographs and sputum cytology have not been shown to decrease lung cancer mortality. For the first time, a randomized screening trial with low-dose computed tomography scans has demonstrated a 20% lung cancer mortality reduction compared with screenings with a chest x-ray. Investigation is underway on many breath, sputum, and blood biomarkers to determine markers of high risk. The hope is that some (or one) of them will add to the early detection of lung cancer observed with low-dose computed tomography.

 

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[322]

TÍTULO / TITLE:  - Effect of Sampling Frequency on Perfusion Values in Perfusion CT of Lung Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Feb;200(2):W155-62. doi: 10.2214/AJR.12.8664.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8664

AUTORES / AUTHORS:  - Ng CS; Chandler AG; Wei W; Anderson EF; Herron DH; Kurzrock R; Charnsangavej C

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Unit 1473, 1400 Pressler St, Houston, TX 77030-4009.

RESUMEN / SUMMARY:  - OBJECTIVE: The purpose of this study was to assess as a potential means of limiting radiation exposure the effect on perfusion CT values of increasing sampling intervals in lung perfusion CT acquisition. SUBJECTS AND METHODS: Lung perfusion CT datasets in patients with lung tumors (> 2.5 cm diameter) were analyzed by distributed parameter modeling to yield tumor blood flow, blood volume, mean transit time, and permeability values. Scans were obtained 2-7 days  apart with a 16-MDCT scanner without intervening therapy. Linear mixed-model analyses were used to compare perfusion CT values for the reference standard sampling interval of 0.5 second with those of datasets obtained at sampling intervals of 1, 2, and 3 seconds, which included relative shifts to account for uncertainty in preenhancement set points. Scan-rescan reproducibility was assessed by between-visit coefficient of variation. RESULTS: Twenty-four lung perfusion CT datasets in 12 patients were analyzed. With increasing sampling interval, mean and 95% CI blood flow and blood volume values were increasingly overestimated by up to 14% (95% CI, 11-18%) and 8% (95% CI, 5-11%) at the 3-second sampling interval, and mean transit time and permeability values were underestimated by up to 11% (95% CI, 9-13%) and 3% (95% CI, 1-6%) compared with the results in the standard sampling interval of 0.5 second. The differences were significant for blood flow, blood volume, and mean transit time for sampling intervals of 2 and 3 seconds (p </= 0.0002) but not for the 1-second sampling interval. The between-visit coefficient of variation increased with subsampling for blood flow (32.9-34.2%), blood volume (27.1-33.5%), and permeability (39.0-42.4%) compared with the values in the 0.5-second sampling interval (21.3%, 23.6%, and 32.2%). CONCLUSION: Increasing sampling intervals beyond 1 second yields significantly different perfusion CT parameter values compared with the reference standard (up to 18% for 3 seconds of sampling). Scan-rescan reproducibility is also adversely affected.

 

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[323]

TÍTULO / TITLE:  - Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biosens Bioelectron. 2012 Nov 27;43C:50-55. doi: 10.1016/j.bios.2012.11.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bios.2012.11.012

AUTORES / AUTHORS:  - Chakravarty S; Lai WC; Zou Y; Drabkin HA; Gemmill RM; Simon GR; Chin SH; Chen RT

INSTITUCIÓN / INSTITUTION:  - Omega Optics Inc., 10306 Sausalito Drive, Austin, TX 78759, USA. Electronic address: swapnajit.chakravarty@omegaoptics.com.

RESUMEN / SUMMARY:  - We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of approximately 11mum(2). Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

 

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[324]

TÍTULO / TITLE:  - Validation of the 7th TNM classification for non-small cell lung cancer: A retrospective analysis on prognostic implications for operated node-negative cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.742960

AUTORES / AUTHORS:  - Bergman P; Brodin D; Lewensohn R; de Petris L

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital Solna, Stockholm, Sweden and Department of Molecular Medicine and Surgery, Karolinska Institute , Stockholm , Sweden.

RESUMEN / SUMMARY:  - Background. The 7th TNM staging system for non-small cell lung cancer (NSCLC) developed by the International Association for the study of Lung Cancer (IASLC) has been applied in Sweden since the beginning of the year 2010. The aim of this  retrospective study was to evaluate the prognostic role of the 7th TNM staging system in a surgical Swedish patient cohort with node-negative NSCLC. Material and methods. We collected data from stage I patients (pT1-2 pN0, 6th TNM system)  who underwent surgery for NSCLC at Karolinska University Hospital from 1987 to 2002. Tumors were restaged according to the 7th TNM version. Cox multivariate survival analysis was implemented in order to determine the prognostic impact of  pathological stage when classified according to either the 6th or the 7th TNM systems. Results. The patient population consisted of 452 subjects. Tumor size was </= 3 cm in 51% of cases. The predominant histology was adenocarcinoma (53%)  and lobectomy was the most common surgical procedure (82% of patients). The five-year survival rate in patients with stage IA vs. IB (6th TNM) was 62% vs. 51%, respectively (log-rank p = 0.036). Corresponding figures for the 7th TNM system were 70% in stage IA-T1a, 51% in stage IA-T1b, 54% in stage IB, 51% in stage IIA and 35% in stage IIB (log-rank p = 0.002). On multivariate analysis, adjusted by age, gender, histology, kind of surgery, grade of differentiation and smoking status, pathological stage was an independent prognostic factor if classified according to the 7th TNM version (p = 0.001), but not if scored according to the 6th TNM edition (p = 0.090). Conclusion. The 7th TNM classification system is a more accurate predictor of prognosis in stage I operated patients than the old classification. The new system should be implemented even on retrospective cohorts especially when investigating the prognostic implication of the expression of molecular biomarkers.

 

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[325]

TÍTULO / TITLE:  - Nasal Tip Cutaneous Metastases Secondary to Lung Carcinoma: Three Case Reports and a Review of the Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Derm Venereol. 2013 Jan 10. doi: 10.2340/00015555-1529.

            ●● Enlace al texto completo (gratuito o de pago) 2340/00015555-1529

AUTORES / AUTHORS:  - Chun SM; Kim YC; Lee JB; Kim SJ; Lee SC; Won YH; Yun SJ

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Chonnam National University Medical School, 5 Hak-Dong, Dong-Gu, Gwangju, 501-746, Korea.

RESUMEN / SUMMARY:  - Cutaneous metastatic carcinoma of the nose is a rare presentation associated with lung cancer. We report here 3 cases of cutaneous metastatic carcinoma of the nose that originated from lung cancer. Two men, age 61 and 76 years, with lung cancers were referred for evaluation of a tumour on the tip of the nose. The third patient, a 57-year-old man, had developed a rosacea-like tumour on the tip of the nose; although he had no history of internal cancer, whole-body positron-emission tomography-computed tomography revealed a primary lung cancer. Skin biopsies of all 3 cases showed metastatic squamous cell carcinoma, and all primary lung cancers were squamous cell carcinomas. Only 3 patients are described here, and further reports are needed to substantiate this interesting phenomenon. When an elderly patient presents to dermatology with a tumour on the nose with or without known internal cancer, it is necessary to approach the diagnosis with caution.

 

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[326]

TÍTULO / TITLE:  - Joint Analysis of Three European Nested Case-control Studies of Lung Cancer among Radon Exposed Miners: Exposure Restricted to Below 300 WLM.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Health Phys. 2013 Mar;104(3):282-292.

            ●● Enlace al texto completo (gratuito o de pago) 1097/HP.0b013e3182765857

AUTORES / AUTHORS:  - Hunter N; Muirhead CR; Tomasek L; Kreuzer M; Laurier D; Leuraud K; Schnelzer M; Grosche B; Placek V; Heribanova A; Timarche M

INSTITUCIÓN / INSTITUTION:  - *Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon OX11 0RQ, UK; daggerNewcastle University, Institute of Health and Society, Newcastle upon Tyne, NE2 4AX, UK; double daggerNational Radiation Protection Institute, Bartoskova 28, CZ-140 00 Prague, Czech Republic; section signFederal Office for Radiation Protection, Department Radiation Protection and Health, D-85764 Oberschleissheim, Germany; **Laboratory  of Epidemiology , Institute for Radiological Protection and Nuclear Safety, B.P.  17, F-92262 Fontenay-aux-Roses Cedex, France; daggerdaggerDepartement des Maladies Chroniques et Traumatismes, Institut de Veille Sanitaire, 94415 Saint-Maurice Cedex, France.

RESUMEN / SUMMARY:  - ABSTRACT: Analyses of lung cancer risk were carried out using restrictions to nested case-control data on uranium miners in the Czech Republic, France, and Germany. With the data restricted to cumulative exposures below 300 working-level-months (WLM) and adjustment for smoking status, the excess relative risk (ERR) per WLM was 0.0174 (95% CI: 0.009-0.035), compared to the estimate of  0.008 (95% CI: 0.004-0.014) using the unrestricted data. Analysis of both the restricted and unrestricted data showed that time since exposure windows had a major effect; the ERR/WLM was six times higher for more recent exposures (5-24 y) than for more distant exposures (25 y or more). Based on a linear model fitted to data on exposures <300 WLM, the ERR WLM of lung cancer at 30 y after exposure was estimated to be 0.021 (95% CI: 0.011-0.040), and the risks decreased by 47% per decade increase in time since exposure. The results from analyzing the joint effects of radon and smoking were consistent with a sub-multiplicative interaction; the ERR WLM was greater for non-smokers compared with current or ex-smokers, although there was no statistically significant variation in the ERR  WLM by smoking status. The patterns of risk with radon exposure from the combined European nested case-control miner analysis were generally consistent with those  based on the BEIR VI Exposure-Age-Concentration model. Based on conversions from  WLM to time weighted averaged radon concentration (expressed per 100 Bq m), the results from this analysis of miner data were in agreement with those from the joint analysis of the European residential radon studies.

 

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[327]

TÍTULO / TITLE:  - Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear beta-catenin in cerebral metastasis of lung adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Metastasis. 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10585-012-9552-7

AUTORES / AUTHORS:  - Bleckmann A; Siam L; Klemm F; Rietkotter E; Wegner C; Kramer F; Beissbarth T; Binder C; Stadelmann C; Pukrop T

INSTITUCIÓN / INSTITUTION:  - Department of Hematology/Oncology, University Medical Center Gottingen, 37099, Gottingen, Germany.

RESUMEN / SUMMARY:  - An essential function of the transcription factors LEF1/TCF4 in cerebral metastases of lung adenocarcinomas has been described in mouse models, suggesting a WNT/beta-catenin effect as potential mechanism. Their role in humans is still unclear, thus we analyzed LEF1, TCF4, beta-catenin, and early stage prognostic markers in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). IHC revealed nuclear TCF4 in all adenocarcinoma samples, whereas only 36 % depicted nuclear LEF1 and nuclear beta-catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p = 0.01, HR = 6.68), while nuclear beta-catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. High proliferation index Ki67 was associated with shorter survival in late-stage disease (p = 0.03, HR 3.27). Additionally, we generated a LEF1/TCF4 as well as an AXIN2 signature, the latter as representative of WNT/beta-catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma. To analyze the prognostic relevance in primary lung adenocarcinomas, we applied both signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p = 0.01, HR = 0.32). These clusters displayed  diverging enrichment patterns of the cell cycle pathway. In conclusion, our data  show that LEF1/TCF4, but not beta-catenin, have prognostic relevance in primary and cerebrally metastasized human lung adenocarcinomas. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of beta-catenin in this setting.

 

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[328]

TÍTULO / TITLE:  - Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 26. pii: S0169-5002(12)00647-2. doi: 10.1016/j.lungcan.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.002

AUTORES / AUTHORS:  - Gaughan EM; Cryer SK; Yeap BY; Jackman DM; Costa DB

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

RESUMEN / SUMMARY:  - INTRODUCTION: Inherited susceptibility to lung cancer is understudied. Never smokers are an important subgroup of patients enriched for tumors harboring oncogene aberrations in the EGFR and ALK genes. We aimed to better characterize the incidence of family history of lung cancer among never smokers with NSCLC. METHODS: Clinicopathologic data, tumor genotype, family history of cancer, and specifically family history of lung cancer from 230 consecutive never smokers was retrospectively compiled and analyzed. RESULTS: In our cohort, the median age was 56 years, 67% were women, 75% were white, 59% had advanced NSCLC and 87% had adenocarcinoma histology. In these tumors, 98/230 (42%) had an EGFR mutation, 17/155 (11%) had KRAS mutations and 27/127 (21%) had an ALK translocation. Family history of any cancer was common (57%) and specific family history of lung cancer was present in 42/230 cases (18%). The percentage of cases with family history of lung cancer was higher in the EGFR mutated versus EGFR wild-type NSCLCs. Out of the cases with a family history of any cancer, 22/53 (41.5%) EGFR mutated, 1/5 (20%) KRAS mutated and 3/19 (15.5%) ALK translocated cohorts had a family history of lung cancer. The ratio of family history of lung cancer to family history of cancer was significantly higher in the EGFR mutated cohort when compared to the ALK translocated plus KRAS mutated cohorts (p=0.039). CONCLUSIONS: Family history of lung cancer is common in never smokers with NSCLC, and there seems to be a particular link in families in which the proband has an EGFR mutated tumor when compared to ALK translocated or KRAS mutated tumors. Further study of families with EGFR-mutated NSCLC may yield insights into the pathogenesis of this tumor type.

 

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[329]

TÍTULO / TITLE:  - AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):383. doi: 10.1007/s12032-012-0383-9. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0383-9

AUTORES / AUTHORS:  - Ke ZF; Mao X; Zeng C; He S; Li S; Wang LT

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road 58, Guangzhou, 510080, Province Guangdong, People’s Republic of China.

RESUMEN / SUMMARY:  - Expression of astrocyte-elevated gene-1 (AEG-1), a novel oncoprotein, has been shown to promote cell growth and inhibit apoptosis, but the underlying molecular  mechanisms and its functional significance in non-small cell lung cancer (NSCLC)  remain to be elucidated. In the present study, statistical analysis displayed a significant correlation of AEG-1 expression with clinical staging (P = 0.048), differentiation (P = 0.019) and lymph node metastasis (P = 0.032). Simultaneously, the overall survival time in patients with higher AEG-1 expression was obviously shorter than that in patients with lower expression of AEG-1 (P < 0.001). Furthermore, we found that AEG-1 could inhibit apoptotic cell  death in L-78 cells, as assessed by MTT, TUNEL and flow cytometry assay. After treating L-78 cells with AEG-1 siRNA, caspase-3 protein was significantly up-regulated and Bcl-2 protein was markedly decreased in L-78 cells, which was verified by the immunohistochemistry results about AEG-1, caspase-3 and Bcl-2. Furthermore, PI3K p110 protein and phosphorylated Akt were also largely attenuated by the treatment of AEG-1 siRNA. In conclusion, our results indicated  that AEG-1 played a crucial role in the carcinogenesis of NSCLC and could inhibit apoptosis via activating cell survival signaling (enhancing the level of anti-apoptotic protein Bcl-2 and the activation of PI3K/Akt pathway).

 

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[330]

TÍTULO / TITLE:  - Efficacy of Aerosolized Celecoxib Encapsulated Nanostructured Lipid Carrier in Non-small Cell Lung Cancer in Combination with Docetaxel.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pharm Res. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11095-013-0984-9

AUTORES / AUTHORS:  - Patel AR; Chougule MB; I T; Patlolla R; Wang G; Singh M

INSTITUCIÓN / INSTITUTION:  - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University,, Tallahassee, Florida, 32307, USA.

RESUMEN / SUMMARY:  - PURPOSE: Evaluation of in-vivo anticancer activity of aerosolized Celecoxib encapsulated Nanolipidcarriers (Cxb-NLC) as a single therapeutic agent and combined with intravenously administered Docetaxel (Doc) against non-small cell lung cancer. METHODS: Cxb-NLC were prepared by high-pressure homogenization and were characterized for its physicochemical characteristics. Metastatic A549 tumor model in Nu/Nu mice was used to evaluate response of aerosolized Cxb-NLC & Doc. Isolated lung tumor samples were analyzed for: a) DNA fragmentation and cleaved caspase-3 by immunohistochemistry, b) apoptotic and angiogenic protein markers by western blot, c) global proteomic alterations by an isobaric labeling quantitative proteomic method and d) toxicity studies of NLC. RESULTS: The particle size of Cxb-NLC was 217 +/- 20 nm, while entrapment efficiency was more  than 90%. Cxb-NLC and Doc alone and in combination showed 25 +/- 4%, 37 +/- 5%, and 67 +/- 4% reduction in tumor size respectively compared to control. Proteomic analysis with combination treatment further revealed significantly decreased expression of multiple pro-survival and pro-metastasis proteins as well as tumor  invasion markers and the expression of S100 family proteins, such as S100A6 and S100P were decreased by 2.5 and 1.6 fold. CONCLUSIONS: Combination therapy with Cxb-NLC and Doc showed significant reduction in tumor growth which was further confirmed by proteomic analysis.

 

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[331]

TÍTULO / TITLE:  - Totally Thoracoscopic Surgery and Troubleshooting for Bleeding in Non-Small Cell  Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Jan 4. pii: S0003-4975(12)02490-3. doi: 10.1016/j.athoracsur.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.11.005

AUTORES / AUTHORS:  - Yamashita SI; Tokuishi K; Moroga T; Abe S; Yamamoto K; Miyahara S; Yoshida Y; Yanagisawa J; Hamatake D; Hiratsuka M; Yoshinaga Y; Yamamoto S; Shiraishi T; Kawahara K; Iwasakai A

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic, Breast and Pediatric Surgery, Fukuoka University  School of Medicine, Fukuoka, Japan. Electronic address: yamashi1@fukuoka-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Although accumulating data support the feasibility and efficacy of video-assisted thoracic surgery anatomic resection, few studies have reported on  intraoperative complications, such as vessel injury. The purpose of this study was to evaluate intraoperative vessel injury and to analyze troubleshooting. METHODS: Twenty-six of 557 patients with non-small cell lung cancer who underwent thoracoscopic anatomic lung resection were identified as having intraoperative vessel injury between January 2004 and December 2011. The injured portion, devices used, recovery approach, and hemostatic procedure were analyzed. The perioperative outcomes in patients with and without vessel injury were compared.  RESULTS: The most commonly used devices were ultrasonic coagulation shears in 9 cases, followed by scissors in 5 and an endostapler in 4. Seventeen of the 26 cases were injured at the branches of the pulmonary artery, and the others were at major vessels. Half of the patients were converted to thoracotomy, and 6 were  treated by minithoracotomy. Hemostatic procedures were primary closure in 17 and  sealant in 7. The perioperative outcomes, including operative time and blood loss, were significantly different between the two groups, but duration of chest  tube drainage, length of hospital stay, and morbidity rate were not. No mortality was identified in the patients with vessel injury. CONCLUSIONS: Video-assisted thoracic surgery anatomic resection was feasible and safe, regardless of the intraoperative vessel injury. Although surgeons should pay attention to avoid unexpected bleeding, the magnitude of injury and effectual step-by-step management should lead to a safe operation.

 

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[332]

TÍTULO / TITLE:  - Changes in pulmonary function tests predict radiological response to chemotherapy in malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs624

AUTORES / AUTHORS:  - Marulli G; Di Chiara F; Braccioni F; Perissinotto E; Pasello G; Gino Favaretto A; Breda C; Rea F

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES: Response to chemotherapy in malignant pleural mesothelioma (MPM) is usually evaluated by radiological criteria, but no common agreement exists on their validity, yet. The cytoreductive effect of chemotherapy on pleural thickening may make the lung more expansible, reducing the restrictive ventilatory impairment. The aim of this study was to evaluate the changes in pulmonary function following chemotherapy in patients with MPM and to correlate these findings with radiological changes. METHODS: Between 2004 and 2011, 62 consecutive patients (74% males, median age 63 years) were prospectively investigated. Modified RECIST criteria were used for radiological evaluation of response to chemotherapy. All patients underwent pulmonary function tests before  and after three cycles of platinum-based chemotherapy. Changes between baseline and post-chemotherapy pulmonary function values (Delta) and their differences were assessed by means of Student’s paired and unpaired t-test, respectively. Receiver operating characteristic (ROC) curve analysis was performed on spirometric parameters significantly associated with response. RESULTS: Thirty (48.4%) patients had a radiological stable disease (S), 23 (37.1%) a partial response ® and 9 (14.5%) a progressive disease (P). DeltaFEV1%pred (R: 18.1 +/- 18.5%; S: 0.5 +/- 9.3%; P: -11 +/- 13.5%; P < 0.0001), DeltaFVC%pred (R: 16.1 +/- 11.8%; S: 0.4 +/- 11.2%; P: -9.2 +/- 14.6%; P < 0.0001) and DeltaVC%pred (R: 12.9 +/- 15.7%; S: 1.5 +/- 12.1%; P: -6.1 +/- 13.2%; P = 0.001) were significantly associated with radiological response. A significant correlation was observed between DeltaFEV1%pred (r = 0.46, P = 0.01), DeltaFVC%pred (r = 0.43, P = 0.02) and % change in linear tumour measurement. ROC curve analysis using dichotomized  radiological response (P/S vs R) as classification variables showed AUC = 0.88 (95%CI: 0.77-0.95) for DeltaFEV1%pred (optimal cut-off value: +7%, sensitivity: 83%, specificity: 82%, PPV: 73%, NPV: 89%) and AUC = 0.86 (95%CI: 0.75-0.94) for  DeltaFVC%pred (optimal cut-off value: +6%, sensitivity: 82%, specificity: 74%, PPV: 64%, NPV: 88%). CONCLUSIONS: Dynamic lung volumes and radiological changes after chemotherapy seem directly related. Lung function changes could be an additional tool to better evaluate the response to chemotherapy in MPM.

 

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[333]

TÍTULO / TITLE:  - p40: A p63 Isoform Useful for Lung Cancer Diagnosis - A Review of the Physiological and Pathological Role of p63.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2013;57(1):1-8. doi: 10.1159/000345245. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345245

AUTORES / AUTHORS:  - Nobre AR; Albergaria A; Schmitt F

INSTITUCIÓN / INSTITUTION:  - Cancer Genetics Group, Institute of Molecular Pathology and Immunology of Porto University (IPATIMUP), Porto, Portugal.

RESUMEN / SUMMARY:  - At present, p63, TTF-1, and Napsin-A are the main immunochemical markers used to  distinguish squamous cell carcinoma (SCC) from lung adenocarcinoma (ADC). However, studies using antibodies against p63 have demonstrated false-positive results with positivity in some ADC. In contrast, the expression of one of the p63 isoforms (DeltaNp63), detected by the antibody p40, is highly specific for SCC. Since most cases of lung cancer are diagnosed in small specimens (cytology/biopsies) and saving material for molecular analysis is mandatory, we recommended the use of p40 (in adjunct with TTF-1 and/or Napsin-A) as the best approach to discriminate SCC and lung ADC. In this paper, we review the physiological and pathological role of p63 isoforms as well as their use as diagnostic markers in lung SCC.

 

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[334]

TÍTULO / TITLE:  - Surgical adhesive may cause false positives in integrated positron emission tomography and computed tomography after lung cancer resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs643

AUTORES / AUTHORS:  - Ruiz-Zafra J; Rodriguez-Fernandez A; Sanchez-Palencia A; Cueto A

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Hospital Universitario Virgen de las Nieves, Granada, España.

RESUMEN / SUMMARY:  - Surgical adhesives are frequently used after pulmonary resection to prevent or reduce pulmonary air leakages, since leakages may cause complications delaying the removal of chest drainage tubes and prolonging in-hospital stay. In this paper, we present 2 patients who underwent curative-intent pulmonary resection for non-small-cell lung carcinoma, in which the biological adhesive BioGlue(®)  was used. Follow-up fluoro-2-deoxy-d-glucose positron emission tomography/computed tomographic (FDG-PET/CT) imaging revealed hypermetabolic pulmonary nodular lesions. Subsequent surgical exploration showed that the lesions were foreign body reactions to the bioadhesive. To our knowledge, this is the first study to examine false-positive follow-up FDG-PET/CT scans caused by the use of BioGlue(®) in pulmonary resection procedures.

 

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[335]

TÍTULO / TITLE:  - Feasibility of a Multdisciplinary Lung Cancer Videoconference between a Peripheral Hospital and a Comprehensive Cancer Centre.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncology. 2013;84(3):186-90. doi: 10.1159/000345314. Epub 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345314

AUTORES / AUTHORS:  - Seeber A; Mitterer M; Gunsilius E; Mazzoleni G; Giovannetti R; Farsad M; Eisterer W; Gastl G; Pall G; Wieser A; Lukas P; Wimmer M; Spizzo G

INSTITUCIÓN / INSTITUTION:  - Haemato-Oncological Day Hospital ‘Franz Tappeiner’ Hospital, Merano, Italy.

RESUMEN / SUMMARY:  - Objective: Treatment of lung cancer patients is changing rapidly and new treatment options have emerged in recent years. In 2007, to guarantee the best treatment procedure for lung cancer patients being treated in our peripheral hospital, we decided to introduce an interdisciplinary tumour videoconference between the Haemato-Oncological Day Hospital in Merano and the Comprehensive Cancer Centre Innsbruck. This retrospective analysis aims to describe the feasibility of such a conference. Patients and Methods: Two hundred and three patients with lung cancer treated at the peripheral hospital of Merano between May 2003 until May 2011 were retrospectively analysed. After introduction of the  tumour videoconference in 2007, 54% (n = 110) of the patients in this cohort were discussed in the conference. Results: One hundred and four videoconferences were  performed. Videoconference was feasible for 110 patients. Radiotherapeutic treatments were prescribed more frequently in patients from the conference group. Overall, major and minor treatment changes were undertaken in 7% (n = 8) and 18%  (n = 20), respectively. Conclusion: Interdisciplinary tumour videoconference is feasible between a peripheral hospital and a comprehensive cancer centre. Radiotherapeutic treatment was prescribed more frequently, suggesting that such a conference facilitates the access to cancer-centre-specific treatment modalities. Accordingly, tumour videoconference between a peripheral hospital and a cancer centre is to be recommend.

 

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[336]

TÍTULO / TITLE:  - Liver herniation after extrapleural pneumonectomy due to a mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cir Esp. 2012 Dec 12. pii: S0009-739X(12)00266-7. doi: 10.1016/j.ciresp.2012.05.026.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ciresp.2012.05.026

AUTORES / AUTHORS:  - Pena E; Blanco M; Rivas-Polo JI; Duran JC

INSTITUCIÓN / INSTITUTION:  - Servicio de Cirugia Toracica, Complejo Hospitalario Universitario de Vigo, Vigo,  España.

 

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[337]

TÍTULO / TITLE:  - Increase in fluorodeoxyglucose positron emission tomography activity following complete radiofrequency ablation of lung tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Comput Assist Tomogr. 2013 Jan;37(1):9-14. doi: 10.1097/RCT.0b013e3182732341.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RCT.0b013e3182732341

AUTORES / AUTHORS:  - Sharma A; Lanuti M; He W; Palmer EL; Shepard JA; Digumarthy SR

INSTITUCIÓN / INSTITUTION:  - From the *Departments of Radiology and daggerThoracic Surgery, Massachusetts General Hospital, Boston, MA.

RESUMEN / SUMMARY:  - OBJECTIVE: The objective of this study was to evaluate the F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) findings following complete radiofrequency ablation (RFA) treatment of malignant lung tumors. METHODS: Follow-up PET and computed tomography examinations in 18 patients (mean age, 67 +/- 16 years [range, 30-91 years]; 10 males, 8 females) who underwent 19 RFA sessions for the treatment of primary (n = 14) and metastatic (n = 5) lung tumors with mean follow-up of 18 months (range, 12-24 months) were retrospectively reviewed by 2 thoracic radiologists. All tumors were completely ablated. The maximum standardized uptake value (SUV) of the tumor and surrounding lung at baseline and at 1, 6, 12 and 24 months after RFA was measured. In addition, the size, histology, location of the tumor, presence of underlying emphysema, electrode type, and complications from RFA were recorded. Data were analyzed using Fisher exact test. RESULTS: Baseline tumor SUV was variable (mean, 1.8 +/-  1.5 [range, 0.7-7]). The post-RFA F-FDG-PET appearances could be divided into 2 groups. A ring of peripheral activity and central photopenia was seen following 13 (68%) of 19 of ablations, and no ring was noted following 6 (32%) of 19 of ablations. The ring of F-FDG-PET activity was present at 1 month in 62%, at 6 months in 69% and at both 1 and 6 months in 31%. In all cases, central photopenia at 1 or 6 months was replaced by increased activity as the ring resolved at 6 or  12 months, mimicking local tumor progression. The presence of a ring of activity  was associated with the use of a cluster electrode (P = 0.01). Lesion size, histology, location, baseline SUV, electrode type, or development of cavitation following RFA were not significantly associated with a post-RFA ring (P > 0.05) on PET scans. At 12 or 24 months, the SUV in the center of the lesion was equal to or greater than the SUV at baseline in 9 (47%) of 19 cases. CONCLUSIONS: Recognition of the normal FDG-PET appearances after RFA is important to prevent misdiagnosis of local tumor progression.

 

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[338]

TÍTULO / TITLE:  - Aurora-B overexpression is correlated with aneuploidy and poor prognosis in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 10. pii: S0169-5002(12)00711-8. doi: 10.1016/j.lungcan.2012.12.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.018

AUTORES / AUTHORS:  - Takeshita M; Koga T; Takayama K; Ijichi K; Yano T; Maehara Y; Nakanishi Y; Sueishi K

INSTITUCIÓN / INSTITUTION:  - Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Aurora-B is a key regulator of mitosis, and the overexpression has been detected  in a variety of solid tumors. The Aurora-B overexpression has been suggested to correlate with clinical aggressiveness and aneuploidy in vitro, however, the frequency of overexpression of Aurora-B protein, the association with clinicopathologic parameters and aneuploidy remain poorly defined in non-small-cell lung cancer (NSCLC). Using 157 surgical specimens of human NSCLC,  we here show that overexpression of Aurora-B proteins are significantly correlated with aneuploidy and poor outcomes in NSCLC. We examined immunohistochemical protein expression of Aurora-B, and DNA ploidy by laser scanning cytometry in 157 NSCLC cases. Aurora-B overexpression was found in 83 cases (53%) of NSCLC, and was significantly correlated with vascular invasion (p=0.012), poor differentiation (p<0.001), larger tumor size (p=0.010) and lymph  node metastasis (p=0.05) and poor prognosis (p=0.011). Aneuploidy was found in 87 cases (57%), and was significantly correlated with Aurora-B overexpression (p=0.0065). Logistic multivariate analysis revealed overexpression of Aurora-B protein to be significant risk factors for aneuploidy compared with other factors. These results indicate that Aurora-B overexpression may contribute to malignant potential and increased aneuploidy in NSCLC. Thus, Aurora-B may serve as a new therapeutic target in against patients with NSCLC, although further studies will be necessary.

 

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[339]

TÍTULO / TITLE:  - Induction of apoptosis in non-small cell lung cancer by downregulation of MDM2 using pH-responsive PMPC-b-PDPA/siRNA complex nanoparticles.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomaterials. 2013 Jan 24. pii: S0142-9612(13)00007-0. doi: 10.1016/j.biomaterials.2012.12.042.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2012.12.042

AUTORES / AUTHORS:  - Yu H; Zou Y; Jiang L; Yin Q; He X; Chen L; Zhang Z; Gu W; Li Y

INSTITUCIÓN / INSTITUTION:  - Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.

RESUMEN / SUMMARY:  - Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer caused human death. In this work, we selected oncogene mouse double minute 2 (MDM2) as a therapeutic target for NSCLC treatment and proposed that sufficient MDM2 knockdown could inhibit tumor growth via induction of cell cycle arrest and  cancer cell apoptosis. On this regard, a new pH-responsive diblock copolymer of poly(methacryloyloxy ethyl phosphorylcholine)-block-poly(diisopropanolamine ethyl methacrylate) (PMPC-b-PDPA)/siRNA-MDM2 complex nanoparticle with minimized surface charge and suitable particle size was designed and developed for siRNA-MDM2 delivery in vitro and in vivo. The experimental results showed that the nanoparticles were spherical with particle size around 50 nm. MDM2 knockdown  in p53 mutant NSCLC H2009 cells induced significant cell cycle arrest, apoptosis  and growth inhibition through upregulation of p21 and activation of caspase-3. Furthermore, the growth of H2009 xenograft tumor in nude mice was inhibited via repeated injection of PMPC-b-PDPA/siRNA-MDM2 complex nanoparticles. These results suggested that PMPC-b-PDPA/siRNA complex nanoparticles targeting a unique set of  oncogenes could be developed into a new therapeutic approach for NSCLC treatment.

 

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[340]

TÍTULO / TITLE:  - Management of recurrent malignant pleural effusions: an ever-recurring issue?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chest. 2012 Dec;142(6):1696. doi: 10.1378/chest.12-2038.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-2038

AUTORES / AUTHORS:  - Maldonado F; Astoul P

 

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[341]

TÍTULO / TITLE:  - Zosteriform skin metastasis of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chest. 2012 Dec;142(6):1652-4. doi: 10.1378/chest.11-2898.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.11-2898

AUTORES / AUTHORS:  - Li WH; Tu CY; Hsieh TC; Wu PY

RESUMEN / SUMMARY:  - Skin metastasis from internal organ malignancy has a 5% to about 10% incidence, and zosteriform metastasis is much rarer. We present the case of a 51-year-old male smoker initially given a diagnosis of right lower lung adenocarcinoma T2N3M0 who developed new-onset zosteriform skin metastasis over the right-side T3 approximately T5 dermatomes documented by skin biopsy specimen. The probable mechanism for this band-distributed skin metastasis is the retrograde flow of lymph after obstruction by cancer cells. Such a phenomenon may be demonstrated by lymphoscintigraphy.

 

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[342]

TÍTULO / TITLE:  - The pathological confirmation rate of lung cancer in England using the NLCA database.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb;79(2):125-31. doi: 10.1016/j.lungcan.2012.11.005. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.005

AUTORES / AUTHORS:  - Khakwani A; Rich AL; Tata LJ; Powell HA; Stanley RA; Baldwin DR; Hubbard RB

INSTITUCIÓN / INSTITUTION:  - Division of Epidemiology and Public Health, University of Nottingham, Nottingham  NG5 1PB, UK. Electronic address: mcxak14@nottingham.ac.uk.

RESUMEN / SUMMARY:  - BACKGROUND: The National Lung Cancer Audit (NLCA) recommends that trusts obtain pathology (histology or cytology) for 75% of their lung cancer patients, however  this figure was arbitrarily chosen and the optimal pathological confirmation rate is unknown, and many countries report somewhat higher rates. The aims of this study were to provide a simple means of benchmarking appropriate pathological confirmation rates by stratifying patients into groups, and whether obtaining pathology based on those groups is associated with a survival benefit. METHODS: We calculated the proportion of patients with non-small cell or small cell lung cancer in the NLCA database, first seen between 1st January 2004 and 31st December 2010, who had pathological confirmation of their diagnosis. Using logistic we assessed the independent influence of patient factors on the likelihood of having histology or cytology, and the overall effect on survival. We also used bivariate analysis to identify the features which were most strongly associated with having pathology and performed Cox regression to identify any survival advantage. FINDINGS: We analysed data on 136,993 individuals. Age and performance status (PS) were the strongest predictors of pathological confirmation: age>/=85 odds ratio (OR) 0.20 (95% confidence interval (CI) 0.19-0.22) compared with age<55; PS 4 OR 0.11 (95%CI 0.10-0.12) compared with PS  0. Pathological confirmation of diagnosis was associated with a small early survival advantage for groups 1 & 2 which represented younger patients with good  PS, even after adjusting for other patient features: hazard ratio (HR) 0.93 & 0.89 respectively. CONCLUSION: Stratifying patients by age and performance status is useful and appropriate when benchmarking standards for pathological confirmation of the diagnosis of lung cancer. We have shown better survival at six months and one year for younger patients with better PS, even after adjusting for confounders. Much of the survival advantage was accounted for by adjusting for the use of chemotherapy.

 

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[343]

TÍTULO / TITLE:  - Gefitinib-Resistance Is Related to BIM Expression in Non-Small Cell Lung Cancer Cell Lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1268

AUTORES / AUTHORS:  - Li H; Zhou S; Li X; Wang D; Wang Y; Zhou C; Schmid-Bindert G

INSTITUCIÓN / INSTITUTION:  - 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University  School of Medicine , Shanghai, China .

RESUMEN / SUMMARY:  - Abstract Recent evidence indicates that both the phosphatidylinositol 3-kinase (PI3K)/AKT and the MEK/ERK pathways are strictly regulated by epidermal growth factor receptor in non-small cell lung cancer (NSCLC) that responds to Gefitinib. Gefitinib resistance is partly owing to the activation of two major downstream signaling pathways PI3K/AKT or MEK/ERK. In this study, we found that in Gefitinib-sensitive cell lines, Gefitinib could induce tumor cell apoptosis via upregulation of a proapoptotic protein BIM. Small interfering RNA results showed  that silencing of BIM could alleviate apoptosis induced by Gefitinib. We adopted  a combination of PI3K inhibitor (LY294002) and MEK inhibitor (U0126) against Gefitinib resistance in cell lines. As expected, the combination substantially induced apoptosis and restored the sensitivity to Gefitinib by increasing the expression of BIM. Our studies provided a theoretical basis for overcoming drug resistance in NSCLC via combination therapy.

 

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[344]

TÍTULO / TITLE:  - A non-surgical method for induction of lung cancer in Wistar rats using a combination of NNK and high dietary fats.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Protoplasma. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00709-012-0478-3

AUTORES / AUTHORS:  - Bhatnagar S; Chaudhary N; Katare DP; Jain SK

INSTITUCIÓN / INSTITUTION:  - Department of Biotechnology, Hamdard University, Hamdard Nagar, New Delhi, 110062, India.

RESUMEN / SUMMARY:  - Lung cancer is one of the most common malignant neoplasms all over the world. Smoking and a number of constituents of tobacco are responsible for development of lung tumours; however, the deleterious effects of tobacco-derived carcinogen,  nitrosamine 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone (NNK)) remain unmatched. We report the development of a novel  rodent model by administering multiple doses of NNK to male Wistar rats and feeding them with high-fat and low-protein diet. Tumour cells in lungs were observed in approximately 98 % rats after 8 months of NNK treatment, as evident by histopathological analysis. This rodent model showed slow progression of lung  tumours which has helped us to assess early indicators of oxidative damage in lungs by studying the levels of lipid peroxidation and antioxidant parameters. LPO was elevated by 46.94 %, SOD, CAT, GSH and GR activity was decreased by 48.67 %, 22.04 %, 21.46 % and 20.85 %, respectively in serum of NNK treated rats when compared with control. These findings suggest that increased oxidative stress can represent a risk factor for the development of chronic disease in early future. This new animal model is an attempt to greatly facilitate studies of the pathophysiology, biochemistry and therapy of lung cancer.

 

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[345]

TÍTULO / TITLE:  - True Negative Predictive Value of Endobronchial Ultrasound in Lung Cancer: Are We Being Conservative Enough?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2012 Dec 12. pii: S0003-4975(12)02147-9. doi: 10.1016/j.athoracsur.2012.09.057.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.09.057

AUTORES / AUTHORS:  - Whitson BA; Groth SS; Odell DD; Briones EP; Maddaus MA; D’Cunha J; Andrade RS

INSTITUCIÓN / INSTITUTION:  - Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.

RESUMEN / SUMMARY:  - BACKGROUND: Mediastinal staging in patients with non-small cell lung cancer (NSCLC) with endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) requires a high negative predictive value (NPV) (ie, low false negative rate). We provide a conservative calculation of NPV that calls for caution in the interpretation of EBUS results. METHODS: We retrospectively analyzed our prospectively gathered database (January 2007 to November 2011) to include NSCLC  patients who underwent EBUS-FNA for mediastinal staging. We excluded patients with metastatic NSCLC and other malignancies. We assessed FNAs with rapid on-site evaluation (ROSE). The calculation of NPV is NPV = true negatives/true negatives  + false negatives. However, this definition ignores nondiagnostic samples. Nondiagnostic samples should be added to the NPV denominator because decisions based on nondiagnostic samples could be flawed. We conservatively calculated NPV  for EBUS-FNA as NPV = true negatives/true negatives + false negatives + nondiagnostic. We defined false negatives as negative FNAs but NSCLC-positive surgical biopsy of the same site. Nondiagnostic FNAs were nonrepresentative of lymphoid tissue. We compared diagnostic performance with the inclusion and exclusion of nondiagnostic procedures. RESULTS: We studied 120 patients with NSCLC who underwent EBUS-FNA; 5 patients had false negative findings and 10 additional patients had nondiagnostic results. The NPV with and without inclusion of nondiagnostic samples was 65.9% and 85.3%, respectively. CONCLUSIONS: The inclusion of nondiagnostic specimens into the conservative, worst-case-scenario calculation of NPV for EBUS-FNA in NSCLC lowers the NPV from 85.3% to 65.9%. The  true NPV is likely higher than 65.9% as few nondiagnostic specimens are false negatives. Caution is imperative for the safe application of EBUS-FNA in NSCLC staging.

 

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[346]

TÍTULO / TITLE:  - Reliability of EGFR and KRAS mutation analysis on fine-needle aspiration washing  in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 22. pii: S0169-5002(13)00014-7. doi: 10.1016/j.lungcan.2013.01.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.007

AUTORES / AUTHORS:  - Bozzetti C; Naldi N; Nizzoli R; Azzoni C; Bortesi B; Zobbi V; Bottarelli L; Tiseo M; Gasparro D; Majori M; De Filippo M; Ardizzoni A

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Unit, University Hospital of Parma, Parma, Italy. Electronic address: cbozzetti@ao.pr.it.

RESUMEN / SUMMARY:  - INTRODUCTION: Molecular profiling of advanced non-small cell lung cancer (NSCLC)  has become essential for predicting customized medical treatment decision. In light of recent advances in non-invasive diagnostic procedures in NSCLC, we aimed to demonstrate the reliability of assessing molecular tests for epidermal growth  factor receptor (EGFR) and KRAS genes on cytological samples by comparing the molecular profile obtained on cells from scraped smears with that on paired needle washing in a series of NSCLC cases. METHODS: Thirty-two cytological specimens obtained by fine-needle aspiration biopsy procedures from primary or metastatic lesions of NSCLCs were Giemsa stained for a rapid on-site evaluation and, in case of an adequate sampling, the cellular material obtained from needle  washing was collected into a saline solution. Scraped smears and needle washings  were tested for EGFR and KRAS by polymerase chain reaction followed by direct sequencing. RESULTS: The concordance between EGFR and KRAS mutational status in 29 paired scraped smears and needle washing was 100%, with 7 paired samples showing the same EGFR mutation (4 L858R mutation, 2 E746_A750 deletion and 1 A767_V769 duplication) and 8 paired samples showing the same KRAS mutations (4 G12D, 1 G12A, 1 G12V and 2 G12C). Three scraped smears, uninformative for poor DNA quality, resulted EGFR mutated on paired needle washings. CONCLUSIONS: Needle washing obtained in the course of NSCLC non-invasive fine needle diagnostic procedures allows reliable mutation testing and can be regarded as an additional  important source of biological material for molecular profiling of advanced NSCLC.

 

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[347]

TÍTULO / TITLE:  - Assessment of Tumor Vascularity in Lung Cancer Using Volume Perfusion CT (VPCT) With Histopathologic Comparison: A Further Step Toward an Individualized Tumor Characterization.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Comput Assist Tomogr. 2013 Jan;37(1):15-21. doi: 10.1097/RCT.0b013e318277c84f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RCT.0b013e318277c84f

AUTORES / AUTHORS:  - Spira D; Neumeister H; Spira SM; Hetzel J; Spengler W; von Weyhern CH; Horger M

INSTITUCIÓN / INSTITUTION:  - From the *Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Tubingen, Germany; daggerFinance Department, HEC Paris, Jouy en Josas, France; double daggerDepartment of Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Eberhard-Karls University, Tubingen, Germany; and section signInstitute of Pathology, Eberhard-Karls-University, Tubingen, Germany.

RESUMEN / SUMMARY:  - OBJECTIVE: To measure perfusion in different lung cancer subtypes and compare results with histopathological/immunohistochemical results. METHODS: Seventy-two  consecutive untreated patients with lung cancer (40 adenocarcinomas, 20 squamous  cell, and 12 small cell lung cancers) were enrolled. A 40-second volume perfusion computed tomography of the tumor bulk was obtained. Blood flow (BF), blood volume (BV), and transit constant were determined. Tumor volume and tumor necrosis were  determined on contrast-enhanced computed tomography. Pathologic specimens were assessed for microvessel density (MVD), hypoxia-induced transcription (hif-1/-2), and proliferation (Ki-67). RESULTS: Higher MVD is associated with higher BF and BV. Higher tumor grade leads to lower BF but increased necrosis and tumor volume. Markers of hypoxia were independent from perfusion parameters, extent of necrosis or MVD. Blood flow, BV, and MVD were not significantly different among lung cancer subtypes. Transit constant was significantly reduced in small cell lung cancer versus adenocarcinoma. CONCLUSIONS: Perfusion values are related to MVD and tumor grade but vary considerably among lung cancer subtypes.

 

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[348]

TÍTULO / TITLE:  - Riboflavin at High Doses Enhances Lung Cancer Cell Proliferation, Invasion, and Migration.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Food Sci. 2013 Jan 11. doi: 10.1111/1750-3841.12012.

            ●● Enlace al texto completo (gratuito o de pago) 1111/1750-3841.12012

AUTORES / AUTHORS:  - Yang HT; Chao PC; Yin MC

INSTITUCIÓN / INSTITUTION:  - Authors Yang and Yin are with Dept. of Nutrition, China Medical Univ., Taichung City, Taiwan. Author Chao is with Dept. of Nutrition, Chung Shan Medical Univ. Hospital, Taichung City, Taiwan. Author Yin is also with Dept. of Health and Nutrition Biotechnology, Asia Univ., Taichung City, Taiwan. Direct inquiries to author Yin (E-mail: mcyin@mail.cmu.edu.tw).

RESUMEN / SUMMARY:  - The influence of riboflavin (vitamin B(2) ) upon growth, invasion, and migration  in non-small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25,  50, 100, 200, or 400 mumol/L was added into A549, H3255, or Calu-6 cells. The effects of this compound upon level and/or expression of reactive oxygen species  (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)-1, fibronectin, matrix metalloproteinase (MMP)-9, MMP-2, focal adhesion kinase (FAK), nuclear factor kappa B (NF-kappaB), and mitogen-activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 mumol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 mumol/L significantly increased the release of interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. This agent at 200 and 400 mumol/L also upregulated protein production of ICAM-1, fibronectin, MMP-9, MMP-2, NF-kappaB p50, p-p38 MAPK, and FAK; and at 400 mumol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression.

 

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[349]

TÍTULO / TITLE:  - Prognostic significance of microvascular invasion and microlymphatic permeation in non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs632

AUTORES / AUTHORS:  - Wang J; Wang B; Bi J; Li K

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, General Hospital, Jinan Command of the People’s Liberation Army, Jinan, China.

 

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[350]

TÍTULO / TITLE:  - Evaluation for local failure by (18)F-FDG PET/CT in comparison with CT findings after stereotactic body radiotherapy (SBRT) for localized non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 11. pii: S0169-5002(12)00629-0. doi: 10.1016/j.lungcan.2012.11.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.008

AUTORES / AUTHORS:  - Takeda A; Kunieda E; Fujii H; Yokosuka N; Aoki Y; Oooka Y; Oku Y; Ohashi T; Sanuki N; Mizuno T; Ozawa Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Ofuna Chuo Hospital, Japan.

RESUMEN / SUMMARY:  - PURPOSE: Stereotactic body radiotherapy (SBRT) is the standard care for medically inoperable early non-small-cell lung cancer (NSCLC). However, it can be difficult to differentiate local recurrence from non-recurrence radiation-induced lung opacity. We retrospectively assessed (18)F-FDG PET/CT to detect local recurrence  after SBRT for NSCLC. METHODS: Between 2005 and 2011, 273 NSCLCs in 257 patients  were treated with SBRT. Prescribed doses were 50Gy and 40Gy per 5 fractions for peripheral and central lesions, respectively. Tri-monthly follow-up CT scans were acquired. (18)F-FDG PET/CT scans were scheduled for screening at one year after SBRT or when recurrence was highly suspected. The dual-time-point maximum standardized uptake values (SUVmaxs) and their retention indexes (RIs) were obtained. RESULTS: A total of 214 (18)F-FDG PET/CT scans were obtained for 164 localized NSCLC tumors in 154 patients. The median follow-up period was 24.9 months (range: 6.3-72.1). Among these, 21 scans of 17 tumors were diagnosed as local recurrence. The median SUVmaxs on early and late images of recurrence and their RI were 5.0 (range: 3.2-10.7), 6.3 (range: 4.2-13.4), and 0.20 (range; 0-0.41), respectively. These were significantly higher than the respective values of non-recurrence images of 1.8 (range: 0.5-4.6), 1.7 (range: 0.5-6.1), and 0.00  (range: -0.37-0.41) (all p<0.05). For SUVmaxs on early and late images, optimal thresholds were identified as 3.2 and 4.2. Using each threshold, the sensitivity  and specificity were 100% and 96-98%, respectively. CT findings were classified into ground-glass opacity (N=9), scar or fibrotic change (N=96), consolidation with air-bronchogram (N=34), consolidation only (N=22), and nodule (N=17); the respective numbers of recurrence were 0, 0, 1, 3, and 17. CONCLUSION: SUVmaxs of  (18)F-FDG PET/CT could detect local recurrence after SBRT for localized NSCLC. In contrast, CT scan results had a limited ability to diagnose local recurrence.

 

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[351]

TÍTULO / TITLE:  - Does CA125 binding to mesothelin impact the detection of malignant mesothelioma?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 25. pii: S0169-5002(12)00653-8. doi: 10.1016/j.lungcan.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.008

AUTORES / AUTHORS:  - Creaney J; Dick IM; Dare H; Demelker Y; Nowak AK; Musk AW; Robinson BW

INSTITUCIÓN / INSTITUTION:  - National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Perth, Western Australia 6009, Australia. Electronic address: jenette.creaney@uwa.edu.au.

RESUMEN / SUMMARY:  - The biomarker mesothelin is a useful diagnostic tool in malignant mesothelioma (MM) patients. It has high specificity but a sensitivity of only 50%. As mesothelin binds CA125, and as CA125 is often elevated in MM, we asked whether this binding affected measurable mesothelin levels in a relevant clinical setting. Mesothelin and CA125 concentrations were measured in the serum of 41 patients with MM. An assay was developed to detect mesothelin bound to CA125. Mesothelin was demonstrated to be bound by CA125 in 9 of 41 MM patients. This binding could be broken by the addition of sodium dodecyl sulphate and diethylenetriaminepenta acetic acid (DTPA) to the samples, however this did not lead to any change in the mesothelin level measured. We therefore conclude that binding of mesothelin to CA125 does not alter the measurement of mesothelin for the detection of MM.

 

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[352]

TÍTULO / TITLE:  - Heterogeneity of Genetic Changes Associated with Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318283dcc0

AUTORES / AUTHORS:  - Kim S; Kim TM; Kim DW; Go H; Keam B; Lee SH; Ku JL; Chung DH; Heo DS

INSTITUCIÓN / INSTITUTION:  - *Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; daggerDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; and double daggerDepartment of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND:: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib. However, acquired resistance to crizotinib is inevitable through several mechanisms. Therefore, this study was conducted to identify genetic alterations associated with crizotinib resistance. METHODS:: Tumor samples were derived from seven ALK-positive NSCLC patients who showed acquired resistance to crizotinib, and these patients were analyzed for ALK, EGFR, and KRAS mutations and ALK and EGFR gene amplifications. In vitro cytotoxicity of crizotinib and ALK downstream signals were compared between crizotinib-naive and -resistant NSCLC cells. RESULTS:: After a median duration of 6 months (range, 4-12 months), seven ALK-positive NSCLC patients developed acquired resistance to crizotinib. Three patients harbored secondary ALK mutations, including one patient with both mutations: L1196M (n = 2) and G1269A (n = 2). Of note, one patient displayed ALK  gene copy number gain (4.1-fold increase compared with the pre-crizotinib specimen) and EGFR L858R mutation with high polysomy. The amphiregulin concentration was high in the supernatant fluid from five patients with malignant pleural effusion (116.4-18934.0 pg/ml). SNU-2535 cells derived from a patient who harbored the G1269 mutation were resistant to crizotinib treatment similar to H3122 CR1 cells. L1196M and G1269A mutant clones were less sensitive to crizotinib and ALK downstream signals were ineffectively suppressed in these clones. CONCLUSIONS:: Genetic changes associated with crizotinib resistance are heterogeneous in ALK-rearranged NSCLC patients who respond to crizotinib and subsequently develop resistance.

 

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[353]

TÍTULO / TITLE:  - Towards the validation of a lung tumorigenesis model with mainstream cigarette smoke inhalation using the A/J mouse.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicology. 2013 Jan 24. pii: S0300-483X(13)00010-3. doi: 10.1016/j.tox.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.tox.2013.01.005

AUTORES / AUTHORS:  - Stinn W; Berges A; Meurrens K; Buettner A; Gebel S; Lichtner RB; Janssens K; Veljkovic E; Xiang Y; Roemer E; Haussmann HJ

INSTITUCIÓN / INSTITUTION:  - Philip Morris Research Laboratories GmbH, 51149 Cologne, Germany.

RESUMEN / SUMMARY:  - A generally accepted and validated laboratory model for smoking-associated pulmonary tumorigenesis would be useful for both basic and applied research applications, such as the development of early diagnostic endpoints or the evaluation of modified risk tobacco products, respectively. The A/J mouse is susceptible for developing both spontaneous and induced lung adenomas and adenocarcinomas, and increased lung tumor multiplicities were also observed in previous cigarette smoke inhalation studies. The present study was designed to collect data useful towards the validation of an 18-month mainstream smoke (MS) inhalation model. Male and female A/J mice were exposed whole-body at three MS concentration levels for 6h/day, and the results were compared to a previous study in the same laboratory and with a similar design. A linear MS concentration-dependent increase in lung tumorigenesis was observed with similar  slopes for both sexes and both studies and a maximal 5-fold increase in multiplicity beyond sham control. The minimal detectable difference in lung tumor multiplicity for the current study was 37%. In the larynx, papillomas were detectable in all MS-exposed groups in a non-concentration dependent manner. No other extra-pulmonary MS-dependent neoplastic lesions were found. Gene expression signatures of lung tumor tissues allowed a clear differentiation of sham- and high dose MS-exposed mice. In combination with data from previous smoke inhalation studies with A/J mice, the current data suggest that this model for MS inhalation-induced pulmonary tumorigenesis is reliable and relevant, two crucial  requirements towards validation of such a model.

 

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[354]

TÍTULO / TITLE:  - Triple plasty of bronchus, pulmonary artery, and superior vena cava for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Feb;95(2):420-4. doi: 10.1016/j.athoracsur.2012.10.036. Epub 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.10.036

AUTORES / AUTHORS:  - Sun Y; Zheng H; Chen Q; Bao M; Jiang G; Chen C; Gao W

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - BACKGROUND: It has been technically challenging to perform simultaneous triple plasty on the superior vena cava (SVC), pulmonary artery (PA), and main bronchus  for central-type lung cancers. In the present study, the authors describe a corresponding technique and clinical outcomes of this surgical manipulation. METHODS: Clinical data from 4 patients with non-small cell lung cancer (NSCLC) who underwent triple plastic resections and reconstructions were retrospectively  reviewed. Three patients received neoadjuvant chemotherapy for pathologically proven locally advanced disease. For pulmonary arteries, sleeve resection with end-to-end anastomosis was performed in 2 patients; tangential resection was used in the other 2 patients. SVC resection with ringed polytetrafluoroethylene (PTFE) graft interposition was performed in 1 patient; the other 3 patients underwent tangential SVC resection. Sleeve resection of the bronchus was performed in all 4 patients. Systemic lymphadenectomy was accomplished in all patients. RESULTS: There was histologic confirmation of large cell carcinoma, adenocarcinoma, squamous cancer, and adenosquamous cancer, respectively, in these 4 patients. Stage pT4N2M0-IIIB was confirmed in 2 patients, and stage T4N1M0-IIIA and stage T2aN2M0-IIIA were confirmed in the other 2 patients. There were no perioperative  deaths. Postoperative atrial fibrillation and prolonged air leakage occurred in 2 patients, respectively. Four patients underwent postoperative chemotherapy and 2  patients were administered radiotherapy. Patients were followed for 21 to 38 months: Two patients had disease-free survival at their 32-month and 38-month follow-ups, and the other 2 patients died 21 and 22 months, respectively, after operation because of remote metastasis. CONCLUSIONS: Triple plasty of bronchus, PA, and SVC is both practical and safe for patients with locally advanced NSCLC.  For patients with strict indications, the long-term survival is favorable.

 

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[355]

TÍTULO / TITLE:  - Primary pericardial mesothelioma in a 19 year old presenting as pericarditis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Surg. 2013 Jan 23. pii: S0003-4975(13)00150-1. doi: 10.1016/j.athoracsur.2013.01.035.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2013.01.035

AUTORES / AUTHORS:  - Kayatta MO; Dineen SP; Sica G; Puskas JD; Pickens A

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Cardiothoracic Surgery, Emory University, 1365 Clifton Road NE, Atlanta GA 30322.

RESUMEN / SUMMARY:  - Primary pericardial mesothelioma is a rare clinical entity. The association between asbestos and pericardial mesothelioma has not been well established, in part due to the small number of reported cases. Treatment options are limited for this very aggressive cancer. Surgical resection in the form of pericardiectomy can be curative, but due to frequently late presentation surgery is usually palliative. Chemotherapy and radiation treatment have overall poor results. We present the case of a 19 year-old male patient who initially presented with symptoms of pericarditis. He died one year after initial presentation.

 

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[356]

TÍTULO / TITLE:  - Reirradiation for Locoregionally Recurrent Lung Cancer: Outcomes in Small Cell and Non-Small Cell Lung Carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31826b9950

AUTORES / AUTHORS:  - Kruser TJ; McCabe BP; Mehta MP; Khuntia D; Campbell TC; Geye HM; Cannon GM

INSTITUCIÓN / INSTITUTION:  - Departments of *Human Oncology daggerMedical Physics, University of Wisconsin Carbone Cancer Center parallelDepartment of Medicine, Division of Hematology and  Oncology, University of Wisconsin Carbone Cancer Center, Madison, WI double daggerDepartment of Radiation Oncology, Northwestern Memorial Hospital, Chicago,  IL section signWestern Radiation Oncology, Mountain View, CA.

RESUMEN / SUMMARY:  - OBJECTIVES:: To our knowledge this is the largest report analyzing outcomes for reirradiation (reRT) for locoregionally recurrent lung cancer, and the first to assess thoracic reRT outcomes in patients with small cell lung cancer (SCLC). METHODS:: Forty-eight patients [11 SCLC, 37 non-small cell lung cancer (NSCLC)] receiving reRT to the thorax were identified; 44 (92%) received reRT by intensity-modulated radiotherapy. Palliative responses, survival outcomes, and prognostic factors were analyzed. RESULTS:: NSCLC patients received a median of 30 Gy in a median of 10 fractions, whereas SCLC patients received a median of 37.5 Gy in a median of 15 fractions. Median survival for the entire cohort from reRT was 4.2 months. Median survival for NSCLC patients was 5.1 months, versus 3.1 months for the SCLC patients (P=0.15). In NSCLC patients, multivariate analysis demonstrated that Karnofsky performance status>/=80 and higher radiation dose were associated with improved survival following reRT, and 75% of patients with symptoms experienced palliative benefit. In SCLC, 4 patients treated with the intent of life prolongation for radiographic recurrence had a median survival of 11.7 months. However, acute toxicities and new disease symptoms limited the duration of palliative benefit in the 7 symptomatic SCLC patients to 0.5 months.  CONCLUSIONS:: ReRT to the thorax for locoregionally recurrent NSCLC can provide palliative benefit, and a small subset of patients may experience long-term survival. Select SCLC patients may experience meaningful survival prolongation after reRT, but reRT for patients with symptomatic recurrence and/or extrathoracic disease did not offer meaningful survival or durable symptom benefit.

 

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[357]

TÍTULO / TITLE:  - Phase II study of induction cisplatin and irinotecan followed by concurrent carboplatin, etoposide, and thoracic radiotherapy for limited-stage small-cell lung cancer, CALGB 30206.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):102-8. doi: 10.1097/JTO.0b013e31827628e1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827628e1

AUTORES / AUTHORS:  - Kelley MJ; Bogart JA; Hodgson LD; Ansari RH; Atkins JN; Pang H; Green MR; Vokes EE

INSTITUCIÓN / INSTITUTION:  - Medical Service, Durham Veterans Affairs Medical Center, Durham, North Carolina,  USA. kelleym@duke.edu

RESUMEN / SUMMARY:  - INTRODUCTION: We sought to determine the efficacy of using both irinotecan- and etoposide-containing regimens sequentially for patients with untreated limited-stage small-cell lung cancer. METHODS: Patients with untreated, measurable, limited-stage small-cell lung cancer with performance status 0 to 2,  and adequate organ function were eligible. Treatment consisted of induction with  cisplatin 30 mg/m and irinotecan 65 mg/m intravenously on day 1 and 8, every 21 days for two cycles. Beginning day 43, daily chest irradiation to 70 Gy was administered concurrently with carboplatin area under curve 5 on day 1, and etoposide 100 mg/m on days 1 to 3, every 21 days for three cycles. The primary objective was to differentiate between 45% and 60% 2-year survival. RESULTS: Two  induction cycles were delivered to 72 of 75 eligible patients (96%) and all planned treatment was delivered to 59 patients (79%). Cisplatin and irinotecan induction chemotherapy resulted in complete responses in 7% and partial responses in 64% (response rate 71%, 95% confidence interval [CI], 59%-81%). The best response to all therapy included 88% complete or partial responses (95% CI, 78%-94%). With median follow-up of 57 months, the median progression-free survival and overall survival are 12.6 (95% CI, 9.4-14.7) and 18.1 months (15.8-22.9), respectively. The 1- and 2-year survival was 69% and 31%, respectively. Frequent (>20%) grade 3 and 4 toxicities were neutropenia in 84%, hemoglobin in 36%, platelets in 51%, esophagitis in 22%, and dehydration in 24%.  There were no fatal toxicities. CONCLUSIONS: This treatment regimen of irinotecan-cisplatin induction chemotherapy followed by 70 Gy concurrent radiation and etoposide-carboplatin had tolerable toxicity but did not meet the preplanned 2-year survival target for further development.

 

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[358]

TÍTULO / TITLE:  - Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Feb;79(2):111-7. doi: 10.1016/j.lungcan.2012.11.001. Epub 2012  Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.001

AUTORES / AUTHORS:  - Lin BQ; Zeng ZY; Yang SS; Zhuang CW

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, Fuzhou General Hospital of Nanjing Command, Fuzhou 350025, China.

RESUMEN / SUMMARY:  - Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. The aim of present study was to elucidate the therapeutic effect of dietary restriction in human NSCLC xenografts. Adult female nude mice were injected subcutaneously in the right dorsal flank with NSCLC cell line A549 cells. 5 days after tumor implantation, animals were randomly divided into ad libitum-fed group (AL, 95% of average diary intake) or dietary-restriction-fed group (DR, 70% average diary intake). 24 days after implantation, it was found that DR inhibited tumor growth  marked by lower tumor volume and weight. DR suppressed tumor proliferation marked by reduced proliferating cell nuclear antigen (PCNA) expression and activated mitochondria-mediated apoptosis. DR decreased microvessel density marked by decreased CD31 immunostaining and promoted vessel maturation marked by increased  alpha-smooth muscle actin (alpha-SMA) and reduced Factor VIII expression. DR reduced intratumoral interstitial fluid pressure and attenuated tumor hypoxia detected by EF5 immunostaining. In addition, DR suppressed NFkappaB signaling pathway and downregulated its downstream proteins expression including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). DR suppressed phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In conclusion, dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Dietary restriction could thus be envisaged as a nutritional countermeasure against non-small-cell lung cancer.

 

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[359]

TÍTULO / TITLE:  - Diagnostic and predictive role of cell-free midkine in malignant pleural effusions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Clin Oncol. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00432-012-1359-z

AUTORES / AUTHORS:  - Lv M; Mou Y; Wang P; Chen Y; Wang T; Hou Y

INSTITUCIÓN / INSTITUTION:  - Immunology and Reproduction Biology Lab, Medical School and State Key Laboratory  of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.

RESUMEN / SUMMARY:  - PURPOSE: The detection of circulating nucleic acids has long been explored for the diagnosis and prognosis of a variety of clinical conditions. The aim of this  study was to detect the cell-free mRNA expression of midkine (MK) in patients with effusions and its potential diagnostic and predictive value. METHODS: Effusions were collected prospectively from 168 patients. The cell-free RNA was extracted from effusions, and the mRNA expression of MK was detected using real-time PCR. The expression of carcinoembryonic antigen (CEA) and biochemical markers in effusions were also assayed. Primary cancer cells were isolated from the malignant effusions (n = 46). Compared with culture cell lines, the response  of these cancer cells to chemotherapeutic agents was determined by CCK-8 assay. RESULTS: The expression of cell-free MK mRNA was significantly higher in the malignant group than in the benign group (0.13 vs 0.01, P < 0.001). The sensitivity and diagnostic accuracy of MK were 77.5 and 81.5 %, while a combination of CEA and MK reached 86.9 % sensitivity and 88.7 % accuracy. In addition, cell-free MK mRNA expression was significantly correlated with inhibitory rate of cisplatin (R = -0.72, P < 0.01). CONCLUSIONS: Measurement of cell-free MK mRNA levels in effusion supernatant yields a high diagnostic accuracy and a potential predictive value.

 

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[360]

TÍTULO / TITLE:  - Transformation to “high grade” neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 9. pii: S0169-5002(12)00712-X. doi: 10.1016/j.lungcan.2012.12.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.019

AUTORES / AUTHORS:  - Popat S; Wotherspoon A; Nutting CM; Gonzalez D; Nicholson AG; O’Brien M

INSTITUCIÓN / INSTITUTION:  - Royal Marsden Hospital NHS Foundation Trust, London, and Surrey, UK; National Heart and Lung Institute, Imperial College London, UK. Electronic address: sanjay.popat@rmh.nhs.uk.

RESUMEN / SUMMARY:  - Several different acquired resistance mechanisms of EGFR mutant lung adenocarcinoma to EGFR-tyrosine kinase inhibitor (TKI) therapy have been described, most recently transformation to small cell lung carcinoma (SCLC). We describe the case of a 46-year-old female with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with erlotinib, and on resistance, cisplatin-pemetrexed. Liver rebiopsy identified an afatinib-resistant combined SCLC and non-small cell carcinoma with neuroendocrine morphology, retaining the EGFR exon 19 deletion. This case highlights acquired EGFR-TKI resistance through  transformation to the high-grade neuroendocrine carcinoma spectrum and that that  such transformation may not be evident at time of progression on TKI therapy.

 

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[361]

TÍTULO / TITLE:  - Molecular characterization by immunocytochemistry of lung adenocarcinoma on cytology specimens.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):603-10. doi: 10.1159/000339794. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000339794

AUTORES / AUTHORS:  - Moreira AL; Hasanovic A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, N.Y.,  USA.

RESUMEN / SUMMARY:  - The discovery of targetable driver mutations in pulmonary adenocarcinoma has revolutionized the field of thoracic oncology by the introduction of oral small molecule tyrosine kinase inhibitors that target specific EGFR mutations and EML-4/ALK rearrangement. Therefore, testing for EGFR gene mutations and ALK rearrangements has become part of everyday clinical practice. The majority of lung cancer patients present at an advanced stage, where small biopsy and cytology specimens are often the only available material for diagnostic workup and molecular characterization. Mutation testing has become the standard of care. Nonetheless, the technical complexity and relative high cost of the test have challenged the widespread use of molecular techniques in everyday clinical settings. Recently, antibodies to specific molecular alterations have become available and have the potential to become instruments for the molecular characterization of tumors. In this review article we will discuss practical issues in molecular characterization of lung adenocarcinoma on cytology material  and the use of immunocytochemical stains for the detection of mutant protein as an alternative or adjunct to molecular techniques.

 

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[362]

TÍTULO / TITLE:  - Hyaluronan synthesis inhibitor supplements the inhibitory effects of zoledronic acid on bone metastasis of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Metastasis. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10585-012-9563-4

AUTORES / AUTHORS:  - Futamura N; Urakawa H; Arai E; Kozawa E; Ishiguro N; Nishida Y

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65-Tsuruma, Showa, Nagoya, 466-8550, Japan.

RESUMEN / SUMMARY:  - Hyaluronan is known to have pivotal roles in the growth, migration and invasion of malignant tumors. Bone metastases are critical lesions greatly impairing the quality of patients with malignancies. We investigated whether hyaluronan synthesis inhibitor supplements the inhibitory effects of zoledronic acid, which  is a conventional therapeutic agent for bone metastasis. We examined the effects  of methylumbelliferone, an inhibitor of hyaluronan synthesis and/or ZA on the tumorigenicity of one murine lung carcinoma and two human (A549, SK-MES-1) lung cancer cell lines in vitro. The interaction between methylumbelliferone and zoledronic acid was analyzed using Calcucyn software. With a murine bone metastasis model of lung cancer in vivo, we investigated the inhibitory effects and interaction of the two drugs on the progression of metastatic bone lesions. Methylumbelliferone or zoledronic acid treatment individually suppressed proliferation, migration and invasion of 3 cell lines, and combination treatment  showed synergistic effects. Although methylumbelliferone as a single agent did not enhance apoptotic activity, it showed additive effects on apoptotic activity  to those of zoledronic acid. Co-localization of CD44 and ezrin, which might be a  pathway of hyaluronan signaling, was abrogated by methylumbelliferone treatment.  Combination therapy showed additive inhibitory effects on metastatic bone lesions in vivo, which paralleled the inhibition of hyaluronan accumulation by methylumbelliferone, and inhibition of osteoclastogenesis. Although the detailed  mechanisms underlying the synergistic or additive inhibitory effects of these two drugs should be further analyzed, inhibition of hyaluronan synthesis by methylumbelliferone is a promising novel therapeutic candidate for bone metastasis of lung cancer in addition to zoledronic acid.

 

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[363]

TÍTULO / TITLE:  - Effect of ARHI on lung cancer cell proliferation, apoptosis and invasion in vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Biol Rep. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11033-012-2353-x

AUTORES / AUTHORS:  - Wu X; Liang L; Dong L; Yu Z; Fu X

INSTITUCIÓN / INSTITUTION:  - Pulmonary Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

RESUMEN / SUMMARY:  - The purposes of this study were to elucidate the effects of ARHI (aplysia ras homolog I) on several biological features of lung cancer cells, including growth, proliferation and invasion, to collect experimental evidence for the future biological treatment of human lung cancer. The eukaryotic expression vector, pcDNA3.1-ARHI, was constructed and transfected into the human lung cancer cell line SK-MES-1. The biological properties of the resulting ARHI-expressing lung cancer cell line were evaluated using methyl thiazolyl tetrazolium assay, flow cytometry, and a Transwell invasion assay. Additionally, the influence of ARHI on the gene expression levels of cyclin D1, p27(KIP1), death-associated protein kinase 1 (DAPK1), and matrix metalloproteinases1/2 (MMP-1/2) was determined. Compared to the non-transfected SK-MES-1 cells and the cells transfected with the empty pcDNA3.1 plasmid, the ARHI-transfected cells displayed significantly reduced growth rates and decreased viability (P < 0.05). The ARHI-transfected cells also displayed a significantly higher percentage of cells in G1 phase (P <  0.05) and a lower percentage of cells in S phase (P < 0.05); a higher percentage  of apoptosis (P < 0.05); and finally, a notable reduction in the basement membrane-penetration rate in the Transwell invasion assay (P < 0.05). Furthermore, it was determined that ARHI is capable of inhibiting the expression  of cyclin D1, MMP-1, and MMP-2; however, ARHI promotes the expression of both p27(KIP1) and DAPK1 in SK-MES-1 cells. In conclusion, overexpression of ARHI gene might be associated with the inhibition of lung cancer cell growth, proliferation and invasion, and the promotion of apoptosis.

 

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[364]

TÍTULO / TITLE:  - Tissue-Preserving Antibody Cocktails to Differentiate Primary Squamous Cell Carcinoma, Adenocarcinoma, and Small Cell Carcinoma of Lung.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0635-OA

AUTORES / AUTHORS:  - Brown AF; Sirohi D; Fukuoka J; Cagle P; Policarpio-Nicolas M; Tacha D; Jagirdar J

INSTITUCIÓN / INSTITUTION:  - From the Department of Pathology, University of Texas Health Science Center at San Antonio (Drs Brown, Sirohi, Policarpio-Nicolas, and Jagirdar); the Department of Surgical Pathology, Toyama University Hospital, Toyama Prefecture, Japan (Dr Fukuoka); the Department of Pathology, Weill College of Medicine, Cornell University, and the Department of Pathology & Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Cagle); and Biocare Medical LLC, Concord, California (Dr Tacha).

RESUMEN / SUMMARY:  - Context.-With the availability of cell type-specific therapies, differentiating primary lung squamous cell carcinomas (SCCs) and adenocarcinomas (ACAs) has become important. The limitations of small sample size and the need to conserve tissue for additional molecular studies necessitate the use of sensitive and specific marker panels on a single slide. Objective.-To distinguish SCC from ACA  and small cell carcinoma (SmCC) of lung using 2 novel tissue-conserving cocktails. Design.-We compared two antibody cocktails, desmoglein 3 + cytokeratin 5/napsin A and p40/thyroid transcription factor 1 (Biocare Medical, Concord, California) in diagnosing SCC and ACA of the lung on tissue microarray, cytology, and surgical specimens. Both lung and nonlung tissue were evaluated on an 1150-core tissue microarray that contained 200 lung cancers. A microarray of 35 SmCCs and 5 small cell SCCs was also evaluated. Results.-A cocktail of desmoglein 3 + cytokeratin 5/napsin A provided diagnostic accuracy in lung cancers with a sensitivity and specificity of 100% in SCCs and a sensitivity of 86% and a specificity of 100% in ACAs. A p40/thyroid transcription factor 1 cocktail showed p40 to have a specificity of 92% and a sensitivity of 93% in SCCs, whereas thyroid transcription factor 1 had a specificity of 100% and a sensitivity of 77% in ACAs. Cell blocks of fine-needle aspiration cytology compared with corresponding surgical (n = 20) specimens displayed similar findings. The p40 was useful in differentiating bladder from prostate carcinoma with 88% sensitivity. Isolated carcinomas from nonlung tissues were desmoglein 3 + cytokeratin 5 positive. Napsin A was positive in 22% of renal tumors as previously observed. Both cocktails were excellent in differentiating SmCCs and small cell SCCs because none of the SmCCs stained with p40. Conclusions.-Both antibody cocktails  are excellent in differentiating primary lung ACA from SCC, as well as excluding  SmCC and ACAs from all other sites on small specimens. A cocktail of desmoglein 3 + cytokeratin 5/napsin A is slightly superior compared with p40/thyroid transcription factor 1 cocktail.

 

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[365]

TÍTULO / TITLE:  - Lung cancer and pregnancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 14. pii: S0169-5002(12)00635-6. doi: 10.1016/j.lungcan.2012.11.014.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.014

AUTORES / AUTHORS:  - Sariman N; Levent E; Yener NA; Orki A; Saygi A

INSTITUCIÓN / INSTITUTION:  - Pulmonology Department, Maltepe University Hospital, Istanbul, Turkey. Electronic address: nessariman@yahoo.com.

RESUMEN / SUMMARY:  - Lung cancer in the pregnant woman is a very rare and dramatic coincidence with poor prognosis. Treatment depends on the gestational week of the pregnancy, patient’s medical status, social, personal, familial, and even religious beliefs. We present a case of adenocarcinoma of the lung in a 34-year-old pregnant patient whose initial complaints were cough, dyspnea, fever and fatigue. She was diagnosed with pneumonia at another hospital, and antibiotic therapy was administered. Meanwhile, at 28 weeks she delivered a preterm low-birth-weight baby. Chest X-ray and thorax CT revealed a mass lesion in the upper left lung lobe. After admission to our clinic, needle aspiration of left supraclavicular lymph node and bronchoscopic biopsy from upper lobe bronchus showed a non-small lung cancer; adenocarcinoma. Brain MRI was normal. PET CT revealed multiple bone  metastases. Multidisciplinary Tumor Committee at our hospital referred her to the Oncology Department as an advanced stage IV disease. Chemotherapy was administered with paclitaxel and carboplatin for a total of 12 weeks. Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations. The treatment was well tolerated. During a follow up period of 6 months her clinical  condition was stable and no adverse events were encountered.

 

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[366]

TÍTULO / TITLE:  - Is video-assisted lobectomy for non-small-cell lung cancer oncologically equivalent to open lobectomy?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs623

AUTORES / AUTHORS:  - Hanna WC; de Valence M; Atenafu EG; Cypel M; Waddell TK; Yasufuku K; Pierre A; De Perrot M; Keshavjee S; Darling GE

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, University of Toronto, Toronto, ON, Canada.

RESUMEN / SUMMARY:  - OBJECTIVES: The purpose of this study was to compare overall and disease-free survival after VATS and open lobectomy for clinical Stage I and II non-small-cell lung cancer (NSCLC). METHODS: A retrospective review of a prospective database of all patients undergoing VATS or open lobectomy for clinical Stage I or II NSCLC between 2002 and 2010 was performed. Postoperative outcomes, disease-free survival and overall survival were compared between the two groups after optimum  1:1 propensity matching for age, gender, tumour histology and pathological stage. RESULTS: Over an 8-year period, 608 patients underwent lobectomy for NCSLC by VATS (n = 196, 32%) or open technique (n = 412, 68%). After matching, there were  190 patients in each group. Adenocarcinoma was found in 80% (open: 149, VATS: 152) and 55% of tumours were T1 (open: 108, VATS: 105). Pathological N1 disease was found in 21 and 19 patients in the open and VATS group, respectively. Disease-free 5-year survival was 69.1% for the open group vs 69.7% for VATS (P =  0.94). Cancer-specific 5-year survival was 82.9% for the open group vs 76.7% for  VATS (P = 0.170). Five-year overall survival was 73% in the open group vs 64% in  the VATS group (P = 0.17). Operative mortality and postoperative complications were not significantly different between groups. CONCLUSIONS: Overall survival and disease-free survival are not significantly different when compared between VATS lobectomy and open lobectomy. VATS resection appears to provide an adequate  oncological operation for patients with operable clinical Stage I and II NSCLC.

 

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[367]

TÍTULO / TITLE:  - T1aN0M0 and T1bN0M0 Non-Small Cell Lung Cancer: A Retrospective Study of the Prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Cardiovasc Surg. 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1329191

AUTORES / AUTHORS:  - Zhang Z; Wang A; Zhan Z; Sun L; Chen K; Wang C

INSTITUCIÓN / INSTITUTION:  - Department of Lung Cancer, Lung Cancer Center, Tian Jin Medical University Cancer Institute and Hospital, Tian Jin, People’s Republic of China.

RESUMEN / SUMMARY:  - Background Stage IA of non-small cell lung cancer (NSCLC) is divided into two subgroups, T1aN0M0 (d </= 2 cm) and T1bN0M0 (2 < d </= 3 cm), in the International Association for the Study of Lung Cancer, seventh edition of TNM Classification of Malignant Tumors. Objective The purpose of this study was the identification of independent clinicopathological predictors of prognosis of these two subgroups of NSCLC.Methods Between 1986 and 2005, a cohort of 1,929 cases of stage IA NSCLC in Tian Jin Medical University Cancer Institute and Hospital were retrospectively analyzed. The impact of clinicopathological characteristics on patients’ survival was investigated.Results The overall 5-year survival rate was 71.07%. Patients with T1aN0M0 NSCLC had a better 5-year survival than those with T1bN0M0 (73.98 vs. 68.18%, p = 0.0135). The Cox proportional hazard model revealed that the prognostic factors of T1aN0M0 were intratumoral vessel invasion (p = 0.035) and histologic differentiation (p = 0.004). In patients with T1bN0M0 NSCLC, the prognostic factors were histologic differentiation (p < 0.01), intratumoral vessel invasion (p < 0.01), removal of 6 or more lymph node stations (p < 0.01), and removal of lymph node station 7 (p <  0.01).Conclusion Prognostic factors of T1aN0M0 and T1bN0M0 NSCLC are different. In patients with T1bN0M0 NSCLC, 6 or more lymph node stations and lymph node station 7 should be removed.

 

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[368]

TÍTULO / TITLE:  - Adequacy of endobronchial ultrasound transbronchial needle aspiration samples in  the subtyping of non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 9. pii: S0169-5002(12)00690-3. doi: 10.1016/j.lungcan.2012.12.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.017

AUTORES / AUTHORS:  - Esterbrook G; Anathhanam S; Plant PK

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Level 7, Gledhow Wing, St James’s University  Hospital, Leeds, LS9 7TF, United Kingdom. Electronic address: georginaesterbrook@hotmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: The histological subtyping of non small cell lung cancer (NSCLC) is important in the selection of the optimal treatment for patients with advanced disease. There are now important differences in the chemotherapy regimens used for squamous and non-squamous cancers. Non-squamous cancers (particularly adenocarcinomas) are also suitable for targeted therapy if the epidermal growth factor receptor (EGFR) genetic mutation is present. Diagnosis is frequently made  by fine needle aspiration from lymph node metastases. We have evaluated the adequacy of material obtained by EBUS-TBNA for subtyping of NSCLC. METHODS: All EBUS-TBNA procedures performed at Leeds Teaching Hospitals between February 2009  and November 2011 were analysed. Data was collected on the indication, final cytological diagnosis and whether EGFR mutation testing was possible. We analysed the data to establish our rate of NSCLC-NOS diagnoses and to determine the technical success of EGFR testing. RESULTS: Data from 391 procedures was analysed. The indication was staging of malignancy in 345 patients and suspected  non-malignant disease in 48 patients. Malignant disease was diagnosed in 204 patients (53.7%), small cell 43, squamous cell 64, adenocarcinoma 40, adenosquamous 2, large cell 12, NSCLC-NOS 31 and malignant disease of non-lung primary 12. EBUS-TBNA identified 149 patients with NCSLC. Subtyping could be obtained in 118 (79.2%). The number of patients with a diagnosis of NSCLC NOS on  EBUS-TBNA was 31 (20.8%, 95%CI 15-28%). Of the 204 specimens with a malignant diagnosis immunohistochemistry was performed in 149 (73.0%). It was not performed in 52 (25.5%) cases and there was insufficient material available in 3 (1.5%) cases. EGFR testing was requested in 36 patients. Our test success rate for EGFR  mutation testing on EBUS-TBNA samples was 88.8% (95%CI 74.7-95.6%). CONCLUSION: EBUS-TBNA samples when made into cell blocks and subjected to a panel of immunohistochemical stains returned adequate tissue for cytological analysis in over 97% of cases, with an NOS rate of 20.8%. We have also shown that cytology specimens are adequate for EGFR mutation testing in over 88% of cases. We conclude that EBUS-TBNA is an accurate diagnostic test both for determining NSCLC subtype and performing EGFR mutation analysis to tailor treatment in lung cancer  patients.

 

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[369]

TÍTULO / TITLE:  - Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2012 Dec 18. pii: S0169-5002(12)00642-3. doi: 10.1016/j.lungcan.2012.11.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.021

AUTORES / AUTHORS:  - Choi H; Paeng JC; Kim DW; Lee JK; Park CM; Kang KW; Chung JK; Lee DS

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - INTRODUCTION: ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation. METHODS: Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic  characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status. RESULTS: Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK(+)),  156 were EGFR mutation positive (EGFR(+)), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK(+) tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P<0.01). In a subgroup analysis of advanced stage  (stage IIIb and IV), ALK(+) lung cancer showed significantly higher SUVmax (P<0.05) than EGFR(+) tumors. In another subgroup analysis of size matched groups, ALK(+) tumors showed significant difference in SUVmax, lymph node and distant metastasis (P<0.01), particularly in the moderate-sized tumors (1.5-3cm). CONCLUSION: ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement.

 

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[370]

TÍTULO / TITLE:  - Cucurbitacin B potently suppresses non-small-cell lung cancer growth: Identification of intracellular thiols as critical targets.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 19. pii: S0304-3835(13)00030-X. doi: 10.1016/j.canlet.2013.01.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.008

AUTORES / AUTHORS:  - Kausar H; Munagala R; Bansal SS; Aqil F; Vadhanam MV; Gupta RC

INSTITUCIÓN / INSTITUTION:  - James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.

RESUMEN / SUMMARY:  - Cucurbitacin B (CuB), has recently emerged as a potent anticancer agent; however, its efficacy in non-small-cell lung cancer (NSCLC) and the mechanism(s) initiating its biological effects remain largely unclear. In this study, CuB potently suppressed the growth of four NSCLC cells (H1299, A549, HCC-827 and H661) in vitro and the highly aggressive H1299 xenograft in vivo. CuB significantly altered the actin cytoskeletal assembly, induced G2/M cell-cycle arrest and induced mitochondrial apoptosis through the modulation of several key  molecular targets mediating the aforementioned processes. Interestingly, all cellular effects of CuB were completely attenuated only by the thiol antioxidant  N-acetylcysteine (NAC). Furthermore, pretreatment with glutathione synthesis inhibitor butithione-sulfoxime (BSO), significantly exacerbated CuB’s cytotoxic effects. To this end, cells treated with CuB revealed a rapid and significant decrease in the levels of protein thiols and GSH/GSSG ratio, suggesting disruption of cellular redox balance as the primary event in CuB’s cytotoxic arsenal. Using UV and FTICR mass spectrometry we also demonstrate for the first time a physical interaction of CuB with NAC and GSH in a cell-free system suggesting that CuB interacts with and modulates cellular thiols to mediate its anti-cancer effects. Collectively, our data sheds new light on the working mechanisms of CuB and demonstrate its therapeutic potential against NSCLC.

 

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[371]

TÍTULO / TITLE:  - Relation between vascular patterns visualized by narrow band imaging (NBI) videobronchoscopy and histological type of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):374. doi: 10.1007/s12032-012-0374-x. Epub 2012 Dec 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0374-x

AUTORES / AUTHORS:  - Zaric B; Perin B; Stojsic V; Carapic V; Eri Z; Panjkovic M; Andrijevic I; Matijasevic J

INSTITUCIÓN / INSTITUTION:  - Department for Interventional Pulmonology, Faculty of Medicine, Institute for Pulmonary Diseases of Vojvodina, Clinic for Pulmonary Oncology, University of Novi Sad, Put doktora Goldmana 4, 21204, Sremska Kamenica, Serbia, bojanzaric@neobee.net.

RESUMEN / SUMMARY:  - Narrow Band Imaging (NBI) videobronchoscopy is a new technique for visualization  of microvascular changes in bronchial mucosa. The primary aim of this study was to evaluate relation between vascular patterns visualized by NBI and histology of lung cancer. We prospectively evaluated 65 patients with suspected lung cancer scheduled for bronchoscopy. NBI followed conventional WL videobronchoscopy. After identification of endoscopically visible tumor, NBI was used to determine predominant type of pathological vascular pattern (dotted, tortuous, abrupt-ending blood vessels-Shibuya descriptors). All the lesions were biopsied and histologically confirmed. There were 81.5 % male and 18.5 % female patients evaluated in the study. Lung cancer was confirmed in all patients; 63.1 % were diagnosed with squamous cell lung cancer (SCC), 24.6 % had adenocarcinoma, 9.2 %  had small-cell (SCLC) and 3.1 % large-cell lung cancer (LC). Dotted blood vessels were significantly (p < 0.000) associated with adenocarcinoma, identified in 68.4 % adenocarcinoma and 31.6 % SCC. Tortuous blood vessels were identified in 72 % SCC, 8 % adenocarcinoma, 12 % SCLC and 8 % of LC. Tortuous blood vessels were significantly (p < 0.000) associated with SCC. Abrupt-ending vessels were identified in 81 % SCC, 14.3 % SCLC and 4.8 % adenocarcinoma and were significantly associated (p < 0.000) with SCC. Dotted visual pattern of blood vessels identified during NBI videobronchoscopy is highly suggesting adenocarcinoma histology of lung cancer. Tortuous and abrupt-ending blood vessels visualized under NBI videobronchoscopy significantly suggest squamous cell histology of lung cancer. Large-scale studies should be designed in order to determine true relation between visual appearance and histology in lung cancer.

 

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[372]

TÍTULO / TITLE:  - The Choice of Invasive Diagnostic Techniques in Advanced Lung Cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Cardiovasc Surg. 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326776

AUTORES / AUTHORS:  - Turk F; Yuncu G; Atinkaya C; Semerkant T; Ozturk G; Ekinci Y

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Faculty of Medicine, Pamukkale University, Denizli, Turkey.

RESUMEN / SUMMARY:  - Background We retrospectively evaluated the invasive diagnostic techniques that were not suitable for transthoracic biopsy or bronchoscopy and the results of these techniques for advanced lung cancer cases.Methods The files of patients operated at the Department of Thoracic Surgery, Faculty of Medicine, Pamukkale University for advanced lung cancer (stages III and IV) between 2006 and 2010 were retrospectively reviewed for the analysis of definite diagnostic methods.Results The mean age of 59 patients who underwent invasive diagnostic techniques was 56.55 +/- 9.42 years (32 to 75) and the female to male ratio was 1:4 (11 female:48 male). Mediastinoscopy was the most commonly used invasive techniques with 20 patients (34%) while the second most common techniques was video-assisted thoracoscopic surgery with 10 patients (17%). Thoracotomy was the  most invasive diagnostic techniques with four patients (6.5%).Conclusions Although it would be desirable to use noninvasive and minimally invasive diagnostic techniques in the diagnosis of lung cancers, we should not try to avoid using invasive diagnostic techniques in surgical practice in advanced lung  cancers where other techniques may be inadequate.

 

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[373]

TÍTULO / TITLE:  - Prognostic significance of serum miR-17-5p in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):353. doi: 10.1007/s12032-012-0353-2. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0353-2

AUTORES / AUTHORS:  - Chen Q; Si Q; Xiao S; Xie Q; Lin J; Wang C; Chen L; Chen Q; Wang L

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Fuzhou Pulmonary Hospital, Fujian Medical University, Fuzhou, 350008, China, chenqun88@hotmail.com.

RESUMEN / SUMMARY:  - miR-17-5p is abnormally expressed in various tumor types. The aim of this study was to investigate the expression level of miR-17-5p in serum of patients with lung cancer and to determine whether serum miR-17-5p expression is related to the prognosis of patients with lung cancer. RT-qPCR was used to examine expression of miRNA-17-5p in 20 pairs of lung cancer and adjacent normal tissues, and sera from 221 patients with lung cancer and 54 matched controls. The correlation of serum miR-17-5p with clinicopathological factors or prognosis of patients with lung cancer was analyzed. The expression level of miR-17-5p obviously increased in lung cancer tissues (P = 0.004). Furthermore, serum miR-17-5p expression also significantly increased in patients with lung cancer compared with healthy individuals (P = 0.03). The survival analysis showed that serum miR-17-5p expression was closely related to the survival of patients with lung cancer. Patients with high miR-17-5p expression had shorter survival times [hazard ratio  (HR) = 1.767, 95 %CI 1.039-3.005, P = 0.035]. A lower expression level of serum miR-17-5p helps extend the survival of patients with lung cancer. Thus, miR-17-5p may be potential biomarker for prediction the prognosis in patients with lung cancer.

 

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[374]

TÍTULO / TITLE:  - The present and future of thermal ablation for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs612

AUTORES / AUTHORS:  - Fernando HC

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Boston Medical Center, Boston University, Boston, MA, USA.

 

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[375]

TÍTULO / TITLE:  - Semiautomated laser capture microdissection of lung adenocarcinoma cytology samples.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):622-31. doi: 10.1159/000342984. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000342984

AUTORES / AUTHORS:  - Roy Chowdhuri S; Hanson J; Cheng J; Rodriguez-Canales J; Fetsch P; Balis U; Filie AC; Giaccone G; Emmert-Buck MR; Hipp JD

INSTITUCIÓN / INSTITUTION:  - Laboratory of Pathology, National Cancer Institute, Bethesda, Md., USA.

RESUMEN / SUMMARY:  - Objective: In the past decade molecular diagnostics has changed the clinical management of lung adenocarcinoma patients. Molecular diagnostics, however, is largely dependent on the quantity and quality of the tumor DNA that is retrieved  from the tissue or cytology samples. Frequently, patients are diagnosed on cytology specimens where the tumor cells are scattered within the cell block, making selecting for tumor enrichment difficult. In the past we have used laser capture microdissection (LCM) to select for pure populations of tumor cells to increase the sensitivity of molecular assays. This study explores several methods for semiautomated computer-guided LCM. Study Design: Hematoxylin and eosin- or TTF-1-immunostained slides from a pleural effusion cell block with metastatic lung adenocarcinoma were used for LCM with either AutoScan or a recently described pattern-matching algorithm, spatially invariant vector quantization (SIVQ), to define morphologic predicates (vectors) to select cells of interest. Results: We retrieved pure populations of tumor cells using both algorithm-guided LCM approaches with slight variations in cellular retrievals. Both methods were semiautomated, requiring minimum technical supervision. Conclusion: In this study we demonstrate the first semiautomated, computer-guided LCM of a cytology specimen using SIVQ and AutoScan, a first step towards the long-term goal of integrating LCM into the clinical cytology-molecular workflow.

 

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[376]

TÍTULO / TITLE:  - A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathology. 2013 Jan;45(1):44-8. doi: 10.1097/PAT.0b013e32835bc848.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAT.0b013e32835bc848

AUTORES / AUTHORS:  - Segal A; Sterrett GF; Frost FA; Shilkin KB; Olsen NJ; Musk AW; Nowak AK; Robinson BW; Creaney J

INSTITUCIÓN / INSTITUTION:  - *PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Perth daggerSchool of Population Health, University of Western Australia, Nedlands double daggerNational Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands section signDepartment of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands,  Western Australia, Australia.

RESUMEN / SUMMARY:  - AIMS: : Cytological diagnosis of malignant pleural mesothelioma (MPM) is controversial, but has been used in our institution for over 30 years. To assess  the role of effusion cytology in mesothelioma diagnosis we conducted an audit of  pleural fluid cytology results over a 20 year period (1988-2007). METHODS: : Pleural samples were received from 6285 patients; data linkage with Western Australian Cancer and Mesothelioma Registries demonstrated that 815 of these patients had a diagnosis of MPM. Cytological examination of a pleural effusion specimen had been performed in 517 (63%) of these 815 patients. RESULTS: : Definitive cytological diagnosis of MPM was made in 377/517 cases, resulting in an ‘absolute’ sensitivity of 73%. An additional 66 patients were diagnosed as atypical/suspicious, resulting in a ‘complete’ sensitivity of 86%. If only biopsy/necropsy proven cases are considered, the absolute sensitivity is 68% and  the complete sensitivity is 82%. There were no false positive diagnoses of malignancy; two patients with metastatic adenocarcinoma were initially diagnosed  as MPM, prior to the availability of specific mesothelial markers, resulting in a positive predictive value of 99%. CONCLUSIONS: : Effusion cytology is an inexpensive, minimally invasive procedure which should be included in the diagnostic work-up of cases of suspected MPM.

 

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[377]

TÍTULO / TITLE:  - Concurrent chemoradiotherapy for large-volume locally-advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 25. pii: S0169-5002(13)00013-5. doi: 10.1016/j.lungcan.2013.01.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.006

AUTORES / AUTHORS:  - Wiersma TG; Dahele M; Verbakel WF; van de Ven PM; de Haan PF; Smit EF; van Reij EJ; Slotman BJ; Senan S

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.

RESUMEN / SUMMARY:  - PURPOSE: Patients with large volume stage III non-small cell lung cancer (NSCLC)  are often excluded from concurrent chemoradiotherapy (CRT) protocols due to fears about excessive toxicity and poor survival. Patients with N3 nodal disease may be excluded for the same reason. We have routinely accepted fit patients in both the above groups for CRT if they met our planning parameters. We analyzed toxicity and survival outcomes for patients undergoing CRT with a planning target volume (PTV) exceeding 700cc, either with or without N3 nodal disease, or a PTV less then 700cc with N3 disease. MATERIALS AND METHODS: Single center, retrospective study of patients with stage III NSCLC treated with CRT between 2004 and 2011. RESULTS: 121 patients were eligible, with 81% (98/121) having a PTV>700cc (of whom 33% (32/98) had N3 nodal disease) and 19% (23/121) having N3 disease and a PTV</=700cc. Grade >/=3 esophagitis and pneumonitis were recorded in respectively 34% and 4% of all patients. Median follow-up for all patients was 37.6 months (mo). Median overall (OS) and progression-free (PFS) survivals were 15.7 mo and 11.6 mo, respectively, OS for all patients with PTV>700cc was 14.5 mo (19.5 mo with N3 and 13.2 mo without N3), compared to 26.5 mo for PTV</=700cc with N3 (p=0.009). About 1 in 4 patients with PTV>700cc died within 6 mo of starting radiotherapy (this was associated with Charlson comorbidity index [CCI]>/=1), while about 18% were alive at 3 years. CONCLUSION: Patients undergoing CRT for stage III NSCLC with a PTV>700cc, with or without N3 nodal disease, had a significantly shorter OS than patients with PTV</=700cc with N3. Patients with PTV>700cc and with CCI>/=1, had a significantly higher risk of early death but longer-term survivors with PTV>700cc are observed. The PTV and CCI should be considered in clinical decision making and used as stratification factors in future trials.

 

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[378]

TÍTULO / TITLE:  - Farletuzumab in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung Cancer. 2013 Jan 25. pii: S0169-5002(13)00004-4. doi: 10.1016/j.lungcan.2012.12.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.021

AUTORES / AUTHORS:  - Thomas A; Maltzman J; Hassan R

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.

RESUMEN / SUMMARY:  - Folate is essential for proliferating cells and folate transport pathways and folate-dependent metabolic processes show promise as targets for anti-neoplastic  therapy. Folate receptor alpha (FOLR1), a folate transporter, is an attractive target for anti-neoplastic therapy due to its high affinity for folate, restricted range of expression in normal tissue and differential over-expression  in malignant tissue. FOLR1 is expressed in non-small cell lung cancer, with a higher expression in adenocarcinoma compared with squamous cell carcinoma. Farletuzumab is a monoclonal antibody targeting FOLR1 which in pre-clinical studies led to cytotoxicity of FOLR1-expressing cells, inhibited tumor growth in  animal models and showed limited reactivity with normal tissue. In phase I/II trials, farletuzumab was well tolerated as a single-agent and in combination, without additive toxicity with chemotherapy. An ongoing phase II, double blind, placebo-controlled study is evaluating farletuzumab in patients with FOLR1 expressing metastatic adenocarcinoma of lung.

 

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[379]

TÍTULO / TITLE:  - Brain abscess mimicking lung cancer metastases; a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Imaging. 2013 Jan-Feb;37(1):147-50. doi: 10.1016/j.clinimag.2012.04.020. Epub 2012 Jun 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.04.020

AUTORES / AUTHORS:  - Asano M; Fujimoto N; Fuchimoto Y; Ono K; Ozaki S; Kimura F; Kishimoto T

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, 1-10-25 Chikkomidorimachi, Minamiku, Okayama 7028055, Japan.

RESUMEN / SUMMARY:  - A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases.

 

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[380]

TÍTULO / TITLE:  - Role of Fluorescence in situ Hybridization in Lung Cancer Cytology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Cytol. 2012;56(6):611-21. doi: 10.1159/000339792. Epub 2012 Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000339792

AUTORES / AUTHORS:  - Savic S; Bubendorf L

INSTITUCIÓN / INSTITUTION:  - Division of Cytopathology, Institute for Pathology, University Hospital Basel, Basel, Switzerland.

RESUMEN / SUMMARY:  - There are several challenges in lung cytology including equivocal cytological findings, lung cancer subclassification, and predictive marker analysis. Fluorescence in situ hybridization (FISH) detects chromosomal alterations that underlie the development and progression of cancer, and pinpoints targets of new  anticancer drugs. Detection of such targets by FISH can be of diagnostic utility  in morphologically difficult cases. Multitarget FISH with four different chromosomal probes improves the sensitivity of cytology in the diagnosis of lung  cancer and clarifies equivocal cytological findings. FISH is becoming increasingly important in the field of predictive marker analysis. FISH is the gold standard to identify ALK rearrangements for treatment with the ALK inhibitor crizotinib (Xalkori). EGFR mutation analysis is the method of choice for selecting patients for therapy with EGFR tyrosine kinase inhibitors (TKIs), whereas the EGFR gene copy number has not been confirmed as a reliable predictive marker. MET amplification is an important mechanism of secondary resistance to EGFR TKIs and a candidate predictive marker for targeted second-line treatment of TKI-resistant non-squamous non-small cell lung cancer. FGFR1 amplification is a promising new marker in squamous cell carcinoma that may predict the response to  FGFR1 inhibitors. In conclusion, there are an increasing number of clinically relevant FISH applications in lung cytology. We provide an overview on the current role of FISH in respiratory cytology.

 

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[381]

TÍTULO / TITLE:  - Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Today. 2012 Dec 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00595-012-0470-8

AUTORES / AUTHORS:  - Eguchi T; Fukui D; Takasuna K; Wada Y; Amano J; Yoshida K

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Ina Central Hospital, Ina, Japan, tks1976@shinshu-u.ac.jp.

RESUMEN / SUMMARY:  - Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient’s postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered.

 

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[382]

TÍTULO / TITLE:  - Podoplanin overexpression in human mesothelioma cell lines enhances the tumorigenic phenotype.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):932-40. doi: 10.3892/or.2013.2225. Epub 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2225

AUTORES / AUTHORS:  - Yamaki E; Yajima T; Kosaka T; Mogi A; Tanaka S; Kuwano H

INSTITUCIÓN / INSTITUTION:  - Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.

RESUMEN / SUMMARY:  - Podoplanin, a small type I integral membrane mucin-type sialoglycoprotein, serves as a useful marker for diagnosing malignant pleural mesothelioma (MPM); however,  the physiological function of podoplanin in mesothelioma cells is not known. To elucidate the role of podoplanin in the pathogenesis of MPM, we generated two mesothelioma cell lines (PODO1 and PODO2) that stably express high levels of podoplanin. Although PODO1 cells proliferated to the same extent in culture or in nude mice, the survival rate of the mice was significantly reduced compared with  that of the controls. We demonstrated that PODO1 and PODO2 cells had increased invasive ability in in vitro assays and induced upregulation of matrix metalloproteinase-1. PODO1 and PODO2 cultures could not be induced to undergo apoptosis when starved or treated with cis-diamminedichloroplatinum(II) (CDDP) compared with the controls. Moreover, silencing of podoplanin expression using RNA interference restored the ability of CDDP to induce apoptosis. Consistent with their growth properties, we detected constitutive activation of extracellular signal-regulated kinase in PODO1 and PODO2 cultures. These findings suggest that constitutive expression of podoplanin contributes to the invasive growth properties of mesothelioma cells and their resistance to apoptosis. Moreover, our data suggest that podoplanin or components of its signaling pathway, or both, may serve as important targets for developing novel treatments  for MPM.

 

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[383]

TÍTULO / TITLE:  - Reliable categorisation of visual scoring of coronary artery calcification on low-dose CT for lung cancer screening: validation with the standard Agatston score.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Radiol. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-012-2726-5

AUTORES / AUTHORS:  - Huang YL; Wu FZ; Wang YC; Ju YJ; Mar GY; Chuo CC; Lin HS; Wu MT

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan, Republic of China.

RESUMEN / SUMMARY:  - OBJECTIVES: To validate the reliability of the visual coronary artery calcification score (VCACS) on low-dose CT (LDCT) for concurrent screening of CAC and lung cancer. METHODS: We enrolled 401 subjects receiving LDCT for lung cancer screening and ECG-gated CT for the Agatston score (AS). LDCT was reconstructed with 3- and 5-mm slice thickness (LDCT-3mm and LDCT-5mm respectively) for VCACS to obtain VCACS-3mm and VCACS-5mm respectively. After a training session comprising 32 cases, two observers performed four-scale VCACS (absent, mild, moderate, severe) of 369 data sets independently, the results were compared with  four-scale AS (0, 1-100, 101-400, >400). RESULTS: CACs were present in 39.6 % (146/369) of subjects. The sensitivity of VCACS-3mm was higher than for VCACS-5mm (83.6 % versus 74.0 %). The median of AS of the 24 false-negative cases in VCACS-3mm was 2.3 (range 1.1-21.1). The false-negative rate for detecting AS >/=  10 on LDCT-3mm was 1.9 %. VCACS-3mm had higher concordance with AS than VCACS-5mm (k = 0.813 versus k = 0.685). An extended test of VCACS-3mm for four junior observers showed high inter-observer reliability (intra-class correlation = 0.90) and good concordance with AS (k = 0.662-0.747). CONCLUSIONS: This study validated the reliability of VCACS on LDCT for lung cancer screening and showed that LDCT-3mm was more feasible than LDCT-5mm for CAD risk stratification. KEY POINTS  : * Low-dose computed tomography (LDCT) rarely misses significant coronary artery calcification (CAC). * Visual scoring of CAC on LDCT is highly concordant with Agatston scoring. * LDCT-3mm is more feasible than LDCT-5mm for CAD risk stratification. * CAC assessment enriched the screening information for LDCT lung cancer screening.

 

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[384]

TÍTULO / TITLE:  - Surgery on Extracorporeal Circulation in Early and Advanced Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Cardiovasc Surg. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1331041

AUTORES / AUTHORS:  - Kauffmann M; Kruger T; Aebert H

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic, Cardiac and Vascular Surgery, University Hospital of Tubingen, Tubingen, Germany.

RESUMEN / SUMMARY:  - Background Locally advanced (T4) non-small cell lung cancer (NSCLC) is principally amenable to surgery. For radical resection of cardiovascular structures, extracorporeal circulation (ECC) may be required. Tumor dissemination is a concern in this situation. In this study, we evaluate the long-term results  of T4 NSCLC surgery with ECC and compare them with combined cardiopulmonary surgery for early-stage NSCLC and heart disease.Methods We retrospectively analyzed 16 patients undergoing surgery on ECC over a 13-year period. Eight patients suffered from T4 NSCLC (group A), and another eight patients suffered from coincidental T1-T2 NSCLC and heart disease (group B).Results In group A, five patients received neoadjuvant radiochemotherapy. Complete resection was achieved in all patients. Thirty-day mortality was one patient (12.5%) in each group. Six patients died from recurrent cancer with a median survival of 13.6 months in group A. Prognosis in patients with direct tumor invasion of the aortopulmonary window was a lot worse compared to those with atrial infiltration. One T4 patient who had only received surgery survived for 155 months without relapse. In group B, no NSCLC relapse occurred, and median survival was 21.6 months. All but one death in group B occurred due to cardiovascular incidents.Conclusions Surgery on ECC for T4 NSCLC gives satisfactory results. The site of infiltration appears to be most important for local tumor relapse. Long-term survival is possible in some cases. Simultaneous cardiac and pulmonary  surgery resulted in good early and midterm outcomes without surgery-induced tumor propagation.

 

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[385]

TÍTULO / TITLE:  - Autophagy and Bcl-2/BNIP3 death regulatory pathway in non-small cell lung carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - APMIS. 2012 Dec 8. doi: 10.1111/apm.12026.

            ●● Enlace al texto completo (gratuito o de pago) 1111/apm.12026

AUTORES / AUTHORS:  - Karpathiou G; Sivridis E; Koukourakis M; Mikroulis D; Bouros D; Froudarakis M; Bougioukas G; Maltezos E; Giatromanolaki A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.

RESUMEN / SUMMARY:  - We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and  autophagy, guiding new pathways in future lung carcinoma research.

 

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[386]

TÍTULO / TITLE:  - Sarcomatoid non-small cell lung cancer responding to sunitinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Pharmacol Ther. 2013 Jan;51(1):87-8.

AUTORES / AUTHORS:  - Schultheis B; Kummer G; Strumberg D

INSTITUCIÓN / INSTITUTION:  - Department of Hematology and Oncology, Marienhospital Herne, Ruhr University Bochum, Germany.

 

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[387]

TÍTULO / TITLE:  - Management of primary hepatopancreatobiliary small cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Surg Oncol. 2012 Dec 27. doi: 10.1002/jso.23305.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23305

AUTORES / AUTHORS:  - Groeschl RT; Christians KK; Turaga KK; Gamblin TC

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: Primary small cell carcinomas (SCC) of the pancreas, liver, gallbladder, and bile ducts have only been described in case reports. We hypothesized that surgical treatment was associated with improved overall survival (OS) for patients with localized hepatopancreatobiliary SCC. METHODS: The Surveillance, Epidemiology, and End-Results (SEER) database was queried for patients with SCC from 1998 to 2008. Survival was analyzed with Cox proportional  hazards models. RESULTS: Eighty-five patients had nonmetastatic hepatopancreatobiliary SCC and operative treatment data. Hepatic SCC was associated with a 2 month median OS, and no patient underwent surgery. Stage-adjusted median OS for pancreatobiliary SCC patients undergoing resection (19 months, 95% confidence interval [CI]: 10-42 months) was greater than those who were not resected (8 months, 95% CI: 4-12 months, P = 0.0052). Both surgical  resection (hazard ratio [HR]: 0.42, 95% CI: 0.29-0.63, P < 0.001) and administration of radiation therapy (HR: 0.50, 95% CI: 0.35-0.71, P < 0.001) independently predicted prolonged OS in adjusted models. CONCLUSION: Surgical resection was associated with prolonged survival for patients with localized pancreatic, gallbladder, and biliary primaries. While we recognize several biases inherent in a population-based study, these results provide insight into the survival that can be achieved with surgical resection of SCC in these specific locations. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

 

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[388]

TÍTULO / TITLE:  - Ground glass opacity and T-factor in staging lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cardiothorac Surg. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezs642

AUTORES / AUTHORS:  - Baisi A; De Simone M; Raveglia F; Cioffi U

INSTITUCIÓN / INSTITUTION:  - Thoracic Surgery Unit, Azienda Ospedaliera San Paolo, University of Milan, Milan, Italy.

 

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[389]

TÍTULO / TITLE:  - A rare tumor of the lung: Pulmonary sclerosing hemangioma (pneumocytoma).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respir Med. 2013 Jan 1. pii: S0954-6111(12)00455-6. doi: 10.1016/j.rmed.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.rmed.2012.12.005

AUTORES / AUTHORS:  - Baysak A; Oz AT; Mogulkoc N; Bishop PW; Ceylan KC

INSTITUCIÓN / INSTITUTION:  - Faculty of Medicine, Izmir University, Chest Diseases Dept., Izmir, Turkey. Electronic address: drbaysak@gmail.com.

RESUMEN / SUMMARY:  - A 67-year-old woman was referred to our department for further evaluation of her  abnormal, chest radiogram. Thorax computed tomography revealed a well-circumscribed, round mass in the middle lobe of the right lung. A thoracotomy was performed and pulmonary sclerosing hemangioma was diagnosed. We herein present a rare tumor of the lung.

 

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[390]

TÍTULO / TITLE:  - Protective effects of ADAM8 against cisplatin-mediated apoptosis in non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Biol Int. 2013 Jan;37(1):47-53. doi: 10.1002/cbin.10011. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10011

AUTORES / AUTHORS:  - Zhang W; Wan M; Ma L; Liu X; He J

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou  Medical College, State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.

RESUMEN / SUMMARY:  - A disintegrin, metalloproteinase 8 (ADAM8), is overexpressed in the vast majority of lung cancers and can be a diagnostic marker of lung cancer. We have investigated the effect of ADAM8 on the cisplatin resistance in non-small-cell lung cancer (NSCLC) cell lines. Stable cell lines overexpressing ADAM8 in A549 and H460 cells were generated, both of which have low endogenous ADAM8. Ectopic expression of ADAM8 rendered cells more resistant to cisplatin-induced toxicity,  increasing the half maximal inhibitory concentration (IC(50) ) values by 1.85-fold in A549 cells and 3.91-fold in H460 cells relative to mock-transfected  cells. Moreover, silencing of ADAM8 in H647 cells with high endogenous level of ADAM8 sensitised them to cisplatin-induced toxicity, with a lower IC(50) value of 11.2 microM relative to an IC(50) of 25.3 microM in mock-transfected cells. Moreover, knockdown of ADAM8 caused a significant increase in cisplatin-induced apoptosis assessed by annexin-V/propidium iodide double staining, accompanying with enhanced cleavage of caspase-3 and poly(ADP-ribose) polymerase. Western blot analysis showed that a greater amount of phosphorylated signal transducer and activator of transcription 3 (STAT3) in ADAM8-overexpressing A549 cells compared  to parental or mock-transfected cells. STAT3 silencing increased the susceptibility of ADAM8-overexpressing A549 cells to cisplatin. Both Bcl-2 and Mcl-1 in ADAM8-overexpressing A549 cells were profoundly diminished by STAT3 knockdown. Thus, ADAM8 is implicated in cisplatin resistance of NSCLC cells through activation of the STAT3 signalling pathway, and thus represents a potential therapeutic target in this malignancy.

 

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[391]

TÍTULO / TITLE:  - The role of Necl-5 in the invasive activity of lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Mol Pathol. 2012 Dec 28. pii: S0014-4800(12)00178-5. doi: 10.1016/j.yexmp.2012.12.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexmp.2012.12.003

AUTORES / AUTHORS:  - Tane S; Maniwa Y; Hokka D; Tauchi S; Nishio W; Okita Y; Yoshimura M

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Japan.

RESUMEN / SUMMARY:  - Nectin-like molucule-5 (Necl-5) is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor and is often upregulated in cancer cells. It has been said that Necl-5 plays a role in not only cell-cell adhesion,  but also cell migration, proliferation, and metastasis. In this study, we used a  bronchioloalveolar carcinoma (BAC) cell line and fibroblasts to assess the expression of Necl-5 in the development of cancer-stroma communication by using an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enables visualization of cell migration during invasion. The expression of Necl-5 was higher in BAC cells than in fibroblasts. This tendency didn’t change even when the BAC cells were mixed with fibroblasts. To assess the role of Necl-5 in the invasive activity of the BAC cells, we knocked down its expression using RNA  interference (RNAi). The invasion assay with DL-CGH revealed that inhibition of Necl-5 expression in the BAC cells was associated with suppressed invasiveness. In addition, Necl-5 knockdown inhibited the movement and proliferation of the BAC cells. Necl-5 expression in lung cancer cells is crucial for their invasiveness in the cancer-stromal interaction, suggesting that Necl-5 could be a favorable molecular target for the suppression of invasiveness in lung adenocarcinoma.

 

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[392]

TÍTULO / TITLE:  - Management of Malignant Pleural Effusion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00408-012-9445-1

AUTORES / AUTHORS:  - Kastelik JA

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Hull and East Yorkshire Hospitals NHS Trust,  Hull York Medical School, Castle Hill Hospital, University of Hull, Castle Road,  Cottingham, East Yorkshire, HU16 5JQ, UK, j.a.kastelik@hull.ac.uk.

RESUMEN / SUMMARY:  - Malignancy is one of the most common causes of pleural effusion. Malignant pleural effusion is defined by the presence of malignant cells in the pleural fluid. Development of malignant pleural effusion usually defines advanced malignancy. Pathophysiology of malignant pleural effusion is not fully understood and may involve complex interactions between the mesothelial and malignant cells. Investigations and management of patients with malignant pleural effusion require a multidisciplinary approach. In this review, current practice for management of  patients with malignant pleural effusion will be discussed. In addition, imaging  techniques will be covered, including the use of thoracic ultrasound and its role in image-guiding pleural procedures. Moreover, interventional techniques will be  described, such as medical thoracoscopy, the use of indwelling pleural catheters, or surgery for investigation and management of malignant pleural effusion.

 

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[393]

TÍTULO / TITLE:  - Cucurbitacin B and Its Rapidly Emerging Role in the Management of Systemic Malignancies Besides Lung Carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biother Radiopharm. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1373

AUTORES / AUTHORS:  - Kapoor S

 

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[394]

TÍTULO / TITLE:  - Sphingosine Suppresses Mesothelioma Cell Proliferation by Inhibiting PKC-delta and Inducing Cell Cycle Arrest at the G(0)/G(1) Phase.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Physiol Biochem. 2012 Sep 20;30(4):995-1004.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000341476

AUTORES / AUTHORS:  - Okuwa H; Kanno T; Fujita Y; Gotoh A; Tabata C; Fukuoka K; Nakano T; Nishizaki T

INSTITUCIÓN / INSTITUTION:  - Division of Bioinformation, Department of Physiology, Hyogo College of Medicine,  1-1 Mukogawa-cho, Nishinomiya, Japan.

RESUMEN / SUMMARY:  - Background/Aims: Sphingosine regulates cellular differentiation, cell growth, and apoptosis. The present study aimed at understanding sphingosine-regulated mesothelioma cell proliferation. Methods: Human malignant mesothelioma cells such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells were cultured. The siRNA to silence the protein kinase C (PKC)-delta-targeted gene was constructed and transfected into cells. MTT assay, cell cycle analysis using a flow cytometry, and cell-free PKC-delta assay were carried out. Results: For all the cell types sphingosine inhibited cell growth in a concentration (1-100 microM)-dependent manner. The sphingosine effect was not prevented by rottlerin, an inhibitor of protein kinase C-delta (PKC-delta); conversely, rottlerin further enhanced the sphingosine effect or rottlerin suppressed mesothelioma cell growth without sphingosine. In the cell-free PKC assay, sphingosine attenuated PKC-delta activity. Knocking-down PKC-delta induced cell cycle arrest at the G0/G1 phase and inhibited cell growth. Conclusion: The results of the present study show that sphingosine suppressed mesothelioma cell proliferation by inhibiting PKC-delta, to induce cell cycle arrest at the G0/G1 phase.

 

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[395]

TÍTULO / TITLE:  - Key molecular mechanisms in lung cancer invasion and metastasis: A comprehensive  review.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Crit Rev Oncol Hematol. 2013 Jan 16. pii: S1040-8428(12)00253-3. doi: 10.1016/j.critrevonc.2012.12.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.critrevonc.2012.12.007

AUTORES / AUTHORS:  - Perlikos F; Harrington KJ; Syrigos KN

INSTITUCIÓN / INSTITUTION:  - 12th Pulmonary Medicine Department, “Sotiria” General Hospital, Athens School of  Medicine, Greece.

RESUMEN / SUMMARY:  - Lung cancer remains one of the most common and malignant cancers worldwide. It is most often diagnosed at late stages, when it has already presented local invasion and distal metastases. The basic stages of invasion and metastasis involve the detachment of tumor cells from the extracellular matrix, invasion of surrounding  tissues and basal lamina, intravasation into the blood stream, survival and transport through the blood stream, migration, arrest and extravasation at a distal site and formation of a metastatic lesion. These steps require fundamental mechanisms such as angiogenesis, degradation of matrix barriers, disruption of cell-cell and cell-matrix adhesion and inducement of cellular motility. Genes that regulate functions like unlimited growth potential, survival, genomic instability, angiogenesis, epithelial to mesenchymal transition and apoptosis evasion, are involved in giving lung cancer tumors invasive and metastatic competence. Improving of understanding of the underlying molecular and cellular mechanisms remains an urgent and essential issue, in order to develop new more effective strategies in preventing and treating lung cancer.

 

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[396]

TÍTULO / TITLE:  - The effects of increased provision of thoracic surgical specialists on the variation in lung cancer resection rate in England.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):68-72. doi: 10.1097/JTO.0b013e3182762315.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182762315

AUTORES / AUTHORS:  - Lau KK; Rathinam S; Waller DA; Peake MD

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Glenfield Hospital, University Hospitals of Leicester, Leicester, UK.

RESUMEN / SUMMARY:  - INTRODUCTION: There is a wide variation in the lung cancer resection rate in England. We assessed the effect of the regional provision of thoracic surgery service on the variation in lung cancer resection rate. METHODS: A retrospective  observational study correlating National Lung Cancer Audit data with thoracic surgery workforce data was performed to review the lung cancer resection rate in  England in 2008 and 2009. RESULTS: In 2008, there was a sixfold variation in resection rate, with a higher resection rate in hospitals where surgeons were based (base hospitals) than in peripheral hospitals (20.0% versus 11.6%, p < 0.001). The resection rate was also higher in cancer networks, which were served  by two or more specialist thoracic surgeons (14.6% versus 12.7%, p = 0.028), and  where surgeons were present in more than two-thirds of the lung cancer multidisciplinary team meetings (14.4% versus 12.0%, p = 0.046). In 2009, the overall resection rate increased from 14.5% to 18.4%. Four units increased their  number of specialist thoracic surgeons and had a significantly higher increase in resection rate than units without expansion (relative rise 66.3% versus 19.2%; p  = 0.022). CONCLUSIONS: The large variation in the resection rate seems, in part,  to be related to the local availability of specialist thoracic surgeons. The greatest improvement in the resection rate was in units with expansion of specialist thoracic surgeons. We suggest the expansion of specialist thoracic surgeons will improve the resection rate and thereby the overall survival of lung cancer in England. This has significant implications for the future of training in cardiothoracic surgery and organization of cancer services.

 

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[397]

TÍTULO / TITLE:  - SOX1 antibodies in Lambert-Eaton myasthenic syndrome and screening for small cell lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann N Y Acad Sci. 2012 Dec;1275(1):70-7. doi: 10.1111/j.1749-6632.2012.06772.x.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1749-6632.2012.06772.x

AUTORES / AUTHORS:  - Lipka AF; Verschuuren JJ; Titulaer MJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. Department of Neuroimmunology, Institut d’Investigacio Biomedica August Pi I Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, España.

RESUMEN / SUMMARY:  - Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular synapse. About half of LEMS patients have an associated small cell  lung carcinoma (SCLC), which is usually detected after diagnosis of LEMS. This short review summarizes clinical and serological markers shown to predict the presence of SCLC in LEMS patients. SOX1 antibodies are a specific marker for SCLC-LEMS but they are also found in SCLC patients without paraneoplastic neurological syndromes. No relation to any clinical characteristic or survival effect has been found for SOX1-positive patients. Several clinical markers also discriminate between SCLC-LEMS and nontumor LEMS. Detailed analysis of these clinical and demographic characteristics from two independent patient cohorts has led to development of the DELTA-P score. This prediction model has provided for a simple clinical tool to indicate the presence of SCLC early in the course of the  disease. The DELTA-P score can be used to guide tumor screening in individual patients.

 

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[398]

TÍTULO / TITLE:  - Immunohistochemistry of cytokeratins 7, 8, 17, 18, and 19, and GLUT-1 aids differentiation of desmoplastic malignant mesothelioma from fibrous pleuritis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histol Histopathol. 2012 Dec 10.

AUTORES / AUTHORS:  - Horiuchi T; Ogata S; Tominaga S; Hiroi S; Kawahara K; Hebisawa A; Irei I; Ito I; Kameya T; Tsujimura T; Nakano T; Nakanishi K; Kawai T

INSTITUCIÓN / INSTITUTION:  - 1Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa. Japan.

RESUMEN / SUMMARY:  - It is difficult to distinguish desmoplastic malignant mesothelioma (DMM) from fibrous pleuritis (FP). We investigated the utility of immunohistochemistry as a  way of differentiating between DMM and FP. We examined 11 DMMs and 46 FPs with the aid of antibodies against 18 cytokeratin (CK) subtypes, calponin, caldesmon,  desmin, and GLUT-1. The best sensitivity and specificity cut-off values in the receiver operating characteristic curves (ROC) for CKs 7, 8, 17, 18, and 19, and  GLUT-1 were each above 60%. When cases with either DMM or FP were partitioned by  the staining score associated with the best sensitivity and specificity cut-off values in ROC, the incidence of a positive expression for CKs 7, 8, 17, 18, and 19, and GLUT-1 was significantly higher in DMM than in FP. In conclusion, immunohistochemistry for CKs 7, 8, 17, 18, and 19, and GLUT-1 may be useful, alongside histological characteristics, for separating DMM from FP.

 

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[399]

TÍTULO / TITLE:  - Recurrent solitary fibrous tumor of the pleura with malignant transformation and  non-islet cell tumor-induced hypoglycemia due to paraneoplastic overexpression and secretion of high-molecular-weight insulin-like growth Factor II.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Intern Med. 2012;51(23):3267-72. Epub 2012 Dec 1.

AUTORES / AUTHORS:  - Tominaga N; Kawarasaki C; Kanemoto K; Yokochi A; Sugino K; Hatanaka K; Uekusa T; Fukuda I; Aiba M; Hizuka N; Uda S

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology and Metabolism, Kanto Rosai Hospital, Japan.

RESUMEN / SUMMARY:  - A 41-year-old man was diagnosed with a solitary fibrous tumor (SFT) of the pleura in the posterior mediastinum. Despite two surgeries for excision, the SFT recurred and progressed with direct invasion of the chest wall and bone metastases. He was hospitalized because of cerebral infarction and presented with recurrent severe hypoglycemia fourteen years later. High-molecular-weight (HMW) insulin-like growth factor II (IGF-II) was identified in the serum and tumor using Western blotting and immunohistochemistry. These findings suggested that the cause of the recurrent severe hypoglycemia was SFT production of HMW IGF-II,  a mediator of non-islet cell tumor-induced hypoglycemia (NICTH).

 

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[400]

TÍTULO / TITLE:  - Primary malignant sarcomatoid mesothelioma in the pericardium.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Intern Med. 2013;52(2):249-53. Epub 2013 Jan 15.

AUTORES / AUTHORS:  - Tateishi K; Ikeda M; Yokoyama T; Urushihata K; Yamamoto H; Hanaoka M; Kubo K; Sakai Y; Nakayama J; Koizumi T

INSTITUCIÓN / INSTITUTION:  - The First Department of Internal Medicine, Shinshu University School of Medicine, Japan.

RESUMEN / SUMMARY:  - Primary malignant pericardial mesothelioma is an exceptionally rare tumor, and making an antemortem diagnosis of this disease is notoriously difficult. We herein report the case of a 61-year-old woman with pericardial mesothelioma who presented with shortness of breath and peripheral edema of the lower limbs. Chest computed tomography (CT) showed an anterior mass and thickened pericardium with multiple pericardial nodules. A biopsy of the mediastinal mass was performed using right thoracotomy, and the histological findings indicated a sarcomatoid tumor. The patient was treated with chemotherapy; however, she but died three months after diagnosis. An autopsy confirmed a final diagnosis of sarcomatoid type primary malignant pericardial mesothelioma following extensive immunohistopathological examinations.

 

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[401]

TÍTULO / TITLE:  - Primary sarcomatoid malignant pericardial mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Intern Med. 2013;52(1):157-8. Epub 2013 Jan 1.

AUTORES / AUTHORS:  - Jiang D; Kong M; Li J; Qian J

INSTITUCIÓN / INSTITUTION:  - Department of Heart Center, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China.

 

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[402]

TÍTULO / TITLE:  - Lung cancer: an update on current surgical strategies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tex Heart Inst J. 2012;39(6):844-5.

AUTORES / AUTHORS:  - Mehran RJ

INSTITUCIÓN / INSTITUTION:  - Thoracic Center, MD Anderson Cancer Center, Houston, Texas 77030.

 

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[403]

TÍTULO / TITLE:  - MiR-138 Inhibits Tumor Growth Through Repression of EZH2 in Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Physiol Biochem. 2013 Jan 15;31(1):56-65.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000343349

AUTORES / AUTHORS:  - Zhang H; Zhang H; Zhao M; Lv Z; Zhang X; Qin X; Wang H; Wang S; Su J; Lv X; Liu H; Du W; Zhou W; Chen X; Fei K

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University, Shanghai.

RESUMEN / SUMMARY:  - Background/Aims: MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC). Methods: The expression of miR-138 was first examined in NSCLC cell lines and tumourtissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2). Results: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various  human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3’ untranslated region (3’ UTR) of EZH2 and suppress the expression of EZH2 at both  mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. Conclusion: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.

 

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[404]

TÍTULO / TITLE:  - Results of surgery for lung cancer compared with radiotherapy: do we speak the same language.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):129-30. doi: 10.1097/JTO.0b013e31827ec6a5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ec6a5

AUTORES / AUTHORS:  - Van Schil PE

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Belgium.

 

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[405]

TÍTULO / TITLE:  - Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to alpha-tocopheryl succinate.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Apoptosis. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10495-012-0795-1

AUTORES / AUTHORS:  - Prochazka L; Koudelka S; Dong LF; Stursa J; Goodwin J; Neca J; Slavik J; Ciganek M; Masek J; Kluckova K; Nguyen M; Turanek J; Neuzil J

INSTITUCIÓN / INSTITUTION:  - Veterinary Research Institute, Brno, Czech Republic, lubomir.pr@gmail.com.

RESUMEN / SUMMARY:  - alpha-Tocopheryl succinate (alpha-TOS) is a promising anti-cancer agent due to its selectivity for cancer cells. It is important to understand whether long-term exposure of tumour cells to the agent will render them resistant to the treatment. Exposure of the non-small cell lung carcinoma H1299 cells to escalating doses of alpha-TOS made them resistant to the agent due to the upregulation of the ABCA1 protein, which caused its efflux. Full susceptibility of the cells to alpha-TOS was restored by knocking down the ABCA1 protein. Similar resistance including ABCA1 gene upregulation was observed in the A549 lung cancer cells exposed to alpha-TOS. The resistance of the cells to alpha-TOS  was overcome by its mitochondrially targeted analogue, MitoVES, that is taken up  on the basis of the membrane potential, bypassing the enhanced expression of the  ABCA1 protein. The in vitro results were replicated in mouse models of tumours derived from parental and resistant H1299 cells. We conclude that long-term exposure of cancer cells to alpha-TOS causes their resistance to the drug, which  can be overcome by its mitochondrially targeted counterpart. This finding should  be taken into consideration when planning clinical trials with vitamin E analogues.

 

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[406]

TÍTULO / TITLE:  - EGFR mutations in squamous cell lung cancer in never-smokers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):e6-7. doi: 10.1097/JTO.0b013e3182762d49.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182762d49

AUTORES / AUTHORS:  - Baik CS; Pritchard CC; Eaton KD; Chow LQ

INSTITUCIÓN / INSTITUTION:  - Thoracic, Head and Neck Program, Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington, USA. cbaik2@u.washington.edu

 

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[407]

TÍTULO / TITLE:  - Mouse models of lung squamous cell carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Metastasis Rev. 2012 Nov 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10555-012-9406-4

AUTORES / AUTHORS:  - You MS; Rouggly LC; You M; Wang Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and The Alvin J Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA.

RESUMEN / SUMMARY:  - Although many mouse models of lung adenocarcinoma exist, only a few mouse lung squamous cell carcinoma models have been developed. Since most clinical chemoprevention trials of lung cancer are performed in subjects with bronchial dysplasia, development of a lung squamous cell carcinoma mouse model sufficient for chemoprevention studies is a high priority. We have shown that lung squamous  cell carcinomas can be induced chemically in several strains of mice (1), and that this chemically induced lung squamous cell carcinoma model is applicable to  cancer chemoprevention studies. Recently, Ji et al. (2) have shown that simultaneous activation of KrasG12D and inactivation of Lkb1 results in a broader histological range of lung tumors, with approximately 50 % of the lung tumors being squamous cell carcinomas. Here, we review the application of mouse lung squamous cell carcinoma models with different stages of squamous lesions and squamous cell carcinomas to cancer development and chemoprevention studies.

 

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[408]

TÍTULO / TITLE:  - Synchronous presentation of hepatoid alpha-fetoprotein-producing lung cancer and  colorectal adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumori. 2012 Sep-Oct;98(5):130e-134e. doi: 10.1700/1190.13214.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1190.13214

AUTORES / AUTHORS:  - Valentino F; Torchio M; Morbini P; Danova M

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. f.valentino@smatteo.pv.it

RESUMEN / SUMMARY:  - We describe the synchronous presentation of hepatoid adenocarcinoma of the lung and colorectal adenocarcinoma in a patient with elevated alpha-fetoprotein (AFP)  serum levels. Our patient was treated after surgery with a conventional chemotherapy regimen including bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, which was demonstrated to improve the clinical results in the treatment of colorectal and lung cancer compared with chemotherapy alone, and is today approved both for colon and lung cancer. Besides the unconventional association of the two cancer types in our patient and the unsatisfactory clinical benefit obtained with the medical treatment administered, we report on the significance of AFP serum levels as a tumor marker in this peculiar situation. In our patient these levels, monitored from the first clinical symptoms through the last chemotherapy course, did not show any correlation with the response to treatment or with the patient’s overall outcome. In particular, the serum marker remained essentially unchanged after the surgical removal of the lung mass and the subsequent chemotherapy.

 

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[409]

TÍTULO / TITLE:  - Natural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182779d18

AUTORES / AUTHORS:  - Oxnard GR; Lo PC; Nishino M; Dahlberg SE; Lindeman NI; Butaney M; Jackman DM; Johnson BE; Janne PA

INSTITUCIÓN / INSTITUTION:  - *Department of Medical Oncology, Dana-Farber Cancer Institute; daggerDepartment of Medicine, Brigham and Women’s Hospital; double daggerDepartment of Radiology,  Dana-Farber Cancer Institute and Brigham and Women’s Hospital; section signDepartment of Biostatistics, Dana-Farber Cancer Institute; ||Department of Pathology, Brigham and Women’s Hospital; and paragraph signBelfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA.

RESUMEN / SUMMARY:  - INTRODUCTION: : Exon 20 insertions are the third most common family of epidermal  growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. METHODS: : NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. RESULTS: : One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. CONCLUSIONS: : Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is  similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.

 

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[410]

TÍTULO / TITLE:  - Development of non-small-cell lung cancer in a father and his son who never smoked.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):e13-4. doi: 10.1097/JTO.0b013e318279e97a.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318279e97a

AUTORES / AUTHORS:  - Kurahara Y; Utsumi T; Kawaguchi T

INSTITUCIÓN / INSTITUTION:  - Departments of *Internal Medicine, and daggerDepartment of Surgery, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan.

 

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[411]

TÍTULO / TITLE:  - Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Feb;8(2):140-6. doi: 10.1097/JTO.0b013e3182725ff9.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182725ff9

AUTORES / AUTHORS:  - Isobe T; Onn A; Morgensztern D; Jacoby JJ; Wu W; Shintani T; Itasaka S; Shibuya K; Koo PJ; O’Reilly MS; Herbst RS

INSTITUCIÓN / INSTITUTION:  - Departments of *Thoracic and Head and Neck Medical Oncology, and daggerDepartment of Pulmonary Oncology, Sheba Medical Center, Sheba, Israel; double daggerDepartment of Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut; section signDepartment of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas; and vertical lineDepartment of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.

RESUMEN / SUMMARY:  - INTRODUCTION: : Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed. METHODS: : To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were  established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size. RESULTS: : In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent. CONCLUSIONS: : We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.

 

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[412]

TÍTULO / TITLE:  - Lambert-Eaton myasthenic syndrome in mixed small cell carcinoma and adenocarcinoma of extrapulmonary origin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 5. pii: S0967-5868(12)00388-8. doi: 10.1016/j.jocn.2012.02.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.02.039

AUTORES / AUTHORS:  - Chang A; Wang HC; Hsu WC

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Shin-Kong WHS Memorial Hospital, 95 Wen-Chang Road, Shin-Lin District, Taipei, Taiwan.

RESUMEN / SUMMARY:  - A patient with typical Lambert-Eaton myasthenic syndrome (LEMS) has a clinical manifestation of proximal muscle weaknesses, a larger-than-100% incremental change in repetitive nerve stimulation on high-rate stimulation electrophysiological testing, and a paraneoplastic origin from small cell carcinoma of the lung. Here, we present a patient with an atypical myasthenic syndrome with an oculobulbar-predominant muscle involvement, a borderline incremental change in repetitive nerve stimulation at high frequencies, and a paraneoplastic origin from extrapulmonary mixed small cell carcinoma and adenocarcinoma. The purpose of this report is to emphasize the importance of painstaking scrutiny in the examination of a patient with a less-common presentation of LEMS.

 

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[413]

TÍTULO / TITLE:  - Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):45-51. doi: 10.1097/JTO.0b013e318274a83e.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318274a83e

AUTORES / AUTHORS:  - Conklin CM; Craddock KJ; Have C; Laskin J; Couture C; Ionescu DN

INSTITUCIÓN / INSTITUTION:  - University of British Columbia, Vancouver, British Columbia, Canada.

RESUMEN / SUMMARY:  - INTRODUCTION: Fluorescence in situ hybridization (FISH) is the standard procedure for the detection of anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement in non-small-cell lung carcinoma (NSCLC) but is expensive and time  consuming. We tested three antibodies to ALK, using various detection systems, and hypothesized that ALK immunohistochemistry (IHC) may represent a cost-effective and efficient means of screening for ALK rearrangement in NSCLC. METHODS: We screened 377 stage I or II NSCLC cases in a tissue microarray by FISH and IHC (5A4 [Leica Biosystems Newcastle Ltd, Newcastle upon Tyne, UYnited Kingdom] by Nichirei’s N-Histofine ALK detection kit [Nichirei Biosciences inc.,  Tokyo, Japan], 5A4 by Novocastra with ADVANCE [Dako Canada inc., Burlington, Ontario, Canada], D5F3 by Cell Signaling Technology with ADVANCE [Cell Signalling Technologies inc., Danvers, MA], and DAKO clone ALK1 with FLEX [Dako Canada inc., Burlington, Ontario, Canada] and ADVANCE). IHC was scored as 0, 1+, 2+, or 3+. Possibly positive or positive cases were further analyzed by IHC and FISH on whole section. RESULTS: Tissue microarray results were available on 377 cases by  IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods. Three cases were ALK-positive by FISH on whole section validation. There was no correlation between semiquantitative IHC score (1+, 2+, 3+) and ALK rearrangement by FISH. D5F3 (Cell Signaling by ADVANCE) and 5A4 (Novocastra by ADVANCE) showed the greatest combination of sensitivity (100%) and specificity (87.5% for 5A4 by Novocastra and 75% for D5F3 by Cell Signaling), and produced no false-negative results. CONCLUSIONS: IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. D5F3 (Cell Signaling) and 5A4 (Novocastra) can be used with FISH for identification of IHC-positive cases to reduce screening costs.

 

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[414]

TÍTULO / TITLE:  - Evaluating beliefs associated with late-stage lung cancer presentation in minorities.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Oncol. 2013 Jan;8(1):12-8. doi: 10.1097/JTO.0b013e3182762ce4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182762ce4

AUTORES / AUTHORS:  - Bergamo C; Lin JJ; Smith C; Lurslurchachai L; Halm EA; Powell CA; Berman A; Schicchi JS; Keller SM; Leventhal H; Wisnivesky JP

INSTITUCIÓN / INSTITUTION:  - Doris Duke Clinical Research Fellow, UMDNJ-Robert Wood Johnson Medical School, Camden, New Jersey, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Minority patients in the United States present with later stages of lung cancer and have poorer outcomes. Cultural factors, such as beliefs regarding lung cancer and discrimination experiences, may underlie this disparity. METHODS: Patients with a new diagnosis of lung cancer were recruited from four medical centers in New York City. A survey, using validated items, was conducted on the minority (black and Hispanic) and nonminority patients about their beliefs regarding lung cancer, fatalism, and medical mistrust. Univariate and logistic regression analyses were used to compare beliefs among minorities and nonminorities and to assess the association of these factors with late-stage (III and IV) presentation. RESULTS: Of the 357 lung cancer patients, 40% were black or Hispanic. Minorities were more likely to be diagnosed with advanced-stage lung cancer (53% versus 38%, p = 0.01). Although beliefs about lung cancer etiology, symptoms, and treatment were similar between groups (p > 0.05), fatalistic views  and medical mistrust were more common among minorities and among late-stage lung  cancer patients (p < 0.05, for all comparisons). Adjusting for age, sex, education, and insurance, minorities had increased odds of advanced-stage lung cancer (odds ratio: 1.79; 95% confidence interval, 1.04-3.08). After controlling  for fatalism and medical mistrust, the association between minority status and advanced stage at diagnosis was attenuated and no longer statistically significant (odds ratio: 1.56; 95% confidence interval, 0.84-2.87). CONCLUSIONS:  Fatalism and medical mistrust are more common among minorities and may partially  explain the disparities in cancer stage at diagnosis. Addressing these factors may contribute to reducing disparities in lung cancer diagnosis and outcomes.

 

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[415]

TÍTULO / TITLE:  - Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Res. 2012;20(2-3):131-7.

AUTORES / AUTHORS:  - Hirose T; Murata Y; Oki Y; Sugiyama T; Kusumoto S; Ishida H; Shirai T; Nakashima M; Yamaoka T; Okuda K; Ohnishi T; Ohmori T

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan. thirose@med.showa-u.ac.jp

RESUMEN / SUMMARY:  - The aim of this study was to investigate the relationship of the number of circulating tumor cells (CTCs) with the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We prospectively  evaluated CTCs in the peripheral blood of patients with previously untreated metastatic NSCLC. From May 2008 through August 2010, 33 patients (23 men and 10 women; median age, 64 years; range, 46-74 years) were enrolled. All patients received combination chemotherapy with gemcitabine and carboplatin. The CTCs were captured from samples of peripheral blood with a semiautomated system using an antibody against epithelial cell adhesion molecule. Blood samples with one or more CTC per 7.5 ml were defined as positive. Of total 33 patients, 12 (36.4%) had positive CTCs and 5 (15.2%) had five or more CTCs before chemotherapy. There  were no differences in response rates to cytotoxic chemotherapy between CTC-positive patients and CTC-negative patients. On the other hand, the rate of progressive disease in cytotoxic chemotherapy was significantly higher in CTC-positive patients (66.7%) than in CTC-negative patients (23.8%, p = 0.02). In conclusion, the number of CTCs could be a useful predictive factor for the effectiveness of cytotoxic chemotherapy in patients with metastatic NSCLC.

 

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[416]

TÍTULO / TITLE:  - Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the ‘common arm’ approach.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2012 Dec;12(12):1591-6. doi: 10.1586/era.12.135.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.135

AUTORES / AUTHORS:  - Mack PC; Gandara DR; Lara PN Jr

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA.

RESUMEN / SUMMARY:  - Historically, notable variability has been observed in clinical trial outcomes between different regions and populations worldwide, even when employing the same cytotoxic regimen in lung cancer. These divergent results underscore the inherent challenges in interpreting trials conducted abroad and raise questions regarding  the general applicability of transnational clinical trials. Various reasons have  been postulated to account for these differences in efficacy and toxicity, including trial design, eligibility criteria, patient demographics and, perhaps most intriguingly, population-related pharmacogenomics. However, without methodology to control for such variables, these hypotheses remain largely untested. The authors previously developed the ‘common arm’ approach in order to  directly compare efficacy and toxicity results of trials simultaneously performed in different countries. By standardizing clinical trial-associated variables such as treatment regimens (dose, schedule, and so on), eligibility, staging, response and toxicity criteria, this approach has the potential to determine the underlying reasons for divergences in trial outcomes across countries, and whether population-associated polymorphisms contribute to these differences. In the past decade, Japanese and US investigators have applied the common arm analytic method to trials in both extensive-stage small-cell lung cancer (SCLC) and advanced nonSCLC. In the SCLC analysis, a comparison of the cisplatin/irinotecan arms from both trials revealed significant differences in response rates and overall survival. Significant differences were also observed in the distribution of gender and performance status. The common arm analysis in  nonSCLC included two trials from Japan and one from the USA, each containing a ‘common’ carboplatin/paclitaxel arm. Clinical results were similar in the two Japanese trials, but were significantly different from the US trial with regard to survival, neutropenia, febrile neutropenia and anemia. The underlying basis for these divergent outcomes is discussed. The common arm methodology provides a  template for identifying and interpreting patient outcome differences across populations, and is an instructive lesson in the burgeoning era of clinical trials globalization.

 

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[417]

TÍTULO / TITLE:  - Effects of treatment regimens on survival in patients with malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Rev Med Pharmacol Sci. 2013 Jan;17(1):19-24.

AUTORES / AUTHORS:  - Abakay A; Abakay O; Tanrikulu AC; Sezgi C; Sen H; Kaya H; Kucukoner M; Kaplan MA; Celik Y; Senyigit A

INSTITUCIÓN / INSTITUTION:  - Department of Chest Disease, Department of Medical Oncology and Department of Biostatistics; School of Medicine, Dicle University, Diyarbakir, Turkey. arahmanabakay@hotmail.com

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE: In this study, we aimed to investigate the factors affecting the survival of patients with malignant pleural mesothelioma (MPM) according to their treatment regimens, including best supportive care (BSC), chemotherapy, surgical group and multimodality (MM) therapy. PATIENTS: A retrospective analysis was performed on clinical data and treatment outcomes of 400 patients registered in our hospital with MPM between January 1989 and April 2010. RESULTS: Mean age (p < 0.001), presence of asbestos exposure (p = 0.0014),  presence of smoking history (p < 0.001), Karnofsky performance status (p < 0.001), histological subtype (p = 0.034) and stage (p < 0.001) variables were found to be significantly different among the four treatment regimens. Mean survival time of all patients was 12.32 months. Mean survival time 10.5 months for the BSC group, 15.7 for the surgical group, 16.02 for the chemotherapy group, and 26.55 for the MM group. There were significant differences in mean survival time among the four treatment regimens. In addition, a significant difference was found in survival time between the two chemotherapy groups (p = 0.032). Mean survival time for cisplatin + gemcitabine was found to be 14.49 months and for cisplatin + pemetrexed, 18.34 months. CONCLUSIONS: The MM group had better survival rates than the other groups. The new chemotherapy combination, cisplatin + pemetrexed, can be helpful in improving survival time.

 

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[418]

TÍTULO / TITLE:  - Paclitaxel plus platinum or gemcitabine plus platinum in first-line treatment of  advanced non-small-cell lung cancer: results from 6 randomized controlled trials.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Oncol. 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10147-012-0502-9

AUTORES / AUTHORS:  - Jiang J; Liang X; Zhou X; Huang R; Chu Z; Zhan Q

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai, 200040, China.

RESUMEN / SUMMARY:  - AIM: The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis. METHODS: An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg’s funnel plot and Egger’s test using Stata/SE version 10.1 software. RESULTS: Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88-1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90-1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90-1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00-1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97-1.14, p = 0.20). Grade 3-4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35-0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30-0.45, p < 0.00001; RR = 0.20, 95 % CI = 0.14-0.27, p < 0.00001; respectively). Grade 3-4 sensory neuropathy, fatigue and neutropenia were comparable between the two groups. Sensitivity analyses in studies of paclitaxel compared with gemcitabine combined with the same platinum strengthened the above conclusion. CONCLUSIONS: Our meta-analysis showed that paclitaxel plus  platinum had similar efficacy and less toxicity compared with gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer.

 

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[419]

TÍTULO / TITLE:  - Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Transl Med. 2013 Jan 11;11(1):13.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-13

AUTORES / AUTHORS:  - Castanon E; Bosch-Barrera J; Lopez I; Collado V; Moreno M; Lopez-Picazo JM; Arbea L; Lozano MD; Calvo A; Gil-Bazo I

RESUMEN / SUMMARY:  - ABSTRACT: : Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related  with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy). METHODS: We have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy. RESULTS: Id1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R = 0.579, p = 0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p = 0.002). A trend towards significance for a worse progression free survival (30  vs 1 months, p = 0.219) and a lower response rate to the treatment (RR = 50% vs 87.5%, p = 0.07) was also observed. CONCLUSIONS: A correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.

 

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[420]

TÍTULO / TITLE:  - Year in review 2012: Lung cancer, respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respirology. 2013 Jan 15. doi: 10.1111/resp.12048.

            ●● Enlace al texto completo (gratuito o de pago) 1111/resp.12048

AUTORES / AUTHORS:  - Porcel JM; Leung CC; Restrepo MI; Takahashi K; Lee P

INSTITUCIÓN / INSTITUTION:  - Pleural Diseases Unit, Department of Internal Medicine, Arnau de Vilanova University Hospital, Biomedical Research Institute of Lleida, Lleida, España.

RESUMEN / SUMMARY:  - This Year in Review series addresses the most relevant articles published in Respirology and other respiratory medicine journals during 2012 concerning five specific areas that we consider to be of importance to practicing pulmonologists, namely lung cancer, respiratory infections, tuberculosis (TB), pleural diseases,  and interventional pulmonology and imaging. Some important findings that will be  commented on more in depth are that: 1) screening for lung cancer using low-dose  computed tomography (CT) in high risk populations is promising, although not firmly established, 2) an enhanced CURB (which stands for confusion, urea, respiratory rate, blood pressure) score as well as the Japanese A-DROP (age, dehydration, respiratory failure, orientation disturbance, and pressure) prognostic scale are as accurate as the pneumonia severity index (PSI) scoring system to predict mortality in patients with community-acquired pneumonia (CAP),  3) randomized trials are urgently needed to optimize multidrug-resistant (MDR)-TB treatment, 4) the use of video-assisted thoracoscopic surgery (VATS) to quantify  pleural tumor burden and, if feasible, perform an intrathoracic cytoreduction in  patients with malignant effusions secondary to ovarian cancer (OC) may have a significant impact on further patient management plans, and 5) respiratory endoscopy and its different diagnostic and therapeutic modalities, is a safe procedure with overall complication rates less than 1%.

 

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[421]

TÍTULO / TITLE:  - Assessment of the effect of occupational exposure to formaldehyde on the risk of  lung cancer in two Canadian population-based case-control studies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Scand J Work Environ Health. 2013 Jan 17. pii: 3344. doi: 10.5271/sjweh.3344.

            ●● Enlace al texto completo (gratuito o de pago) 5271/sjweh.3344

AUTORES / AUTHORS:  - Mahboubi A; Koushik A; Siemiatycki J; Lavoue J; Rousseau MC

INSTITUCIÓN / INSTITUTION:  - INRS-Institut Armand-Frappier, 531, boulevard des Prairies, Laval, QC, Canada H7V 1B7. marie-claude.rousseau@iaf.inrs.ca.

RESUMEN / SUMMARY:  - OBJECTIVE: This study aimed to explore the possible association between formaldehyde exposure and lung cancer risk. METHODS: Data were collected in two population-based case-control studies conducted in Montreal, Canada. Cases were individuals diagnosed with incident, histologically-confirmed lung cancer. Controls were randomly selected from electoral lists and frequency-matched to cases by age, sex, and electoral district of residence. Interviews for the two studies were conducted in 1979-1986 and 1996--2002, using a virtually identical questionnaire to obtain lifetime occupational and smoking history and several lifestyle covariates. Experts reviewed the detailed work history for each participant to assess exposure to several occupational agents, including formaldehyde. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between several metrics of formaldehyde exposure and lung cancer, adjusting for smoking and occupational and sociodemographic factors. RESULTS: In all, 2060 lung cancer cases and 2046 population controls were interviewed and assessed for exposure. About 25% of subjects had ever been occupationally exposed to formaldehyde. The adjusted OR for lung cancer was 1.06 (95% CI 0.89--1.27) comparing ever versus never exposure to formaldehyde. Analyses for age at first exposure, average, and peak intensity  of exposure also suggested an absence of association between formaldehyde exposure and lung cancer risk. Results did not vary by sex, lifetime smoking intensity, or histological subtype. CONCLUSIONS: No marked increases in lung cancer risk related to workplace formaldehyde exposure were observed. Study participants were mainly exposed at low concentration levels, which should be considered in the interpretation of our findings.

 

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[422]

TÍTULO / TITLE:  - Analgesic Effect of Switching From Oral Opioids to a Once-a-Day Fentanyl Citrate  Transdermal Patch in Patients With Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Hosp Palliat Care. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1049909112470020

AUTORES / AUTHORS:  - Takakuwa O; Oguri T; Maeno K; Yokoyama M; Hijikata H; Uemura T; Ozasa H; Ohkubo H; Miyazaki M; Niimi A

RESUMEN / SUMMARY:  - A new once-a-day fentanyl citrate transdermal patch was developed in Japan. We retrospectively investigated analgesic and adverse effects of this drug in 24 patients with lung cancer. All patients were started on this patch by switching from an oral opioid. The mean pain score before switching was 2.45 (0-5); 48 hours after switching, 15 of the 24 patients showed a decreased pain score and the mean score (2.00) was significantly lower than that before switching. Of the  16 patients who had adverse effects of oral opioids, 7 patients showed improvement in their symptoms after switching. Two patients showed adverse effects of the drug but their symptoms were mild, and no patient required dose decrease. This new transdermal patch could be a useful treatment option for cancer pain.

 

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[423]

TÍTULO / TITLE:  - A Clinical Study of Shrinking Field Radiation Therapy Based on (18)F-FDG PET/CT for Stage III Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Technol Cancer Res Treat. 2012 Dec 26.

AUTORES / AUTHORS:  - Ding X; Li H; Wang Z; Huang W; Li B; Zang R; Sun H; Yi Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, P.R. China. baoshli@yahoo.com.

RESUMEN / SUMMARY:  - The aim is to investigate the feasibility of shrinking field technique after 40 Gy for stage III non-small cell lung cancer (NSCLC) during radiation therapy. Eighty-seven consecutive patients treated with intensity-modulated radiation therapy or three-dimensional conformal radiation therapy were enrolled in this study. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography  ((18)F-FDG PET/CT) scanning was performed prior to treatment and repeated after 40 Gy, and the delineation of target volume was based on fused images of PET and  CT. After 40 Gy of conventional fractionated radiotherapy to the initial planning target volume (PTV), a boost of 19.6-39.2 Gy was delivered to the shrunken PTV through late course accelerated hyperfractionated radiotherapy, and the median total dose was 66.0 Gy (range, 59.6-79.2 Gy). Gross tumor volume (GTV) and PTV regressions were recorded, and prescription doses with or without shrinking field were calculated. Local recurrence patterns were investigated through follow-up. The tumor volumes regressed in 84 (96.6%) patients and increased in 3 (3.4%) patients after 40 Gy. The mean GTV and PTV reduction was 38% (range, -13-95%) and 30% (range, -5-95%). Mean total prescription dose escalated from 62.0 Gy to 68.5  Gy through shrinking field technique. The median follow-up was 17 months, ranging from 5 to 46 months, and the 1- and 2-year overall survival rates in our study were 74.7% and 34.6%. The response rate was 79.5%, and radiation toxicity was acceptable. Tumor progression occurred in 67.8% (59/87) patients. Numbers of patients who had outfield, infield and both infield and outfield recurrences were 3 (3.4%), 26 (29.5%), and 3 (3.4%), respectively. In conclusion, significant tumor regression was observed after 40 Gy, and radiation dose escalated after shrinking field with acceptable toxicity and outfield relapse. Shrinking field radiotherapy based on (18)F-FDG PET/CT after 40 Gy was safe and feasible for stage III NSCLC.

 

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[424]

TÍTULO / TITLE:  - Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer. 2012 Dec 12;11:90. doi: 10.1186/1476-4598-11-90.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-11-90

AUTORES / AUTHORS:  - Kimura S; Paiz J; Yoneda M; Kido T; Vinson C; Ward JM

INSTITUCIÓN / INSTITUTION:  - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA. kimuras@mail.nih.gov.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The CCAAT/enhancer binding proteins (C/EBPs) play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs  are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. METHODS: A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP) gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis  bioassay in the presence and absence of doxycycline, and the effect of abolition  of DNA binding activities of C/EBPs on lung carcinogenesis was examined. RESULTS: A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for  lung carcinomas in mouse. CONCLUSIONS: The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

 

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[425]

TÍTULO / TITLE:  - Infectious complications in patients with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Rev Med Pharmacol Sci. 2013 Jan;17(1):8-18.

AUTORES / AUTHORS:  - Akinosoglou KS; Karkoulias K; Marangos M

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Department of Pulmonology and Department of Infectious Diseases, University General Hospital of Patras, Rio, Patras, Greece.  k.akinosoglou07@imperial.ac.uk

RESUMEN / SUMMARY:  - Infections remain a part of the natural course of cancer. During the course of their disease, patients with lung cancer frequently present with an infection that can ultimately be fatal. Pathogenesis of infectious syndromes is usually determined by the underlying disease, as well as, the iatrogenic manipulations that occur during its management. Hence, lung cancer infections include lower respiratory tract infections in the context of COPD, aspiration, obstruction and  opportunistic infections due to immunosuppression. Moreover, treatment-related infectious syndromes including post operative pneumonia, febrile neutropenia and  superimposed infection following radiation/chemotherapy toxicity is common. Importantly, diagnosis of infection in the febrile lung cancer patient is challenging and requires a high index of suspicion in order to distinguish from other causes of fever, including malignant disease and pulmonary embolism. Prompt initiation of treatment is pivotal to avoid increased mortality. Careful consideration of infection pathogenesis can predict most likely pathogens and guide antibiotic management, thus, ensuring most favourable outcome.

 

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[426]

TÍTULO / TITLE:  - The Role of MET Receptor Tyrosine Kinase in Non-Small Cell Lung Cancer and Clinical Development of Targeted Anti-MET Agents.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncologist. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1634/theoncologist.2012-0262

AUTORES / AUTHORS:  - Robinson KW; Sandler AB

INSTITUCIÓN / INSTITUTION:  - Portland, Oregon, USA.

RESUMEN / SUMMARY:  - A better understanding of the pathophysiology and evolution of non-small cell lung cancer (NSCLC) has identified a number of molecular targets and spurred development of novel targeted therapeutic agents. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are implicated in tumor cell proliferation, migration, invasion, and angiogenesis in a broad spectrum of human cancers, including NSCLC. Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Resistance to EGFR inhibitors is likely mediated through downstream activation of the phosphoinositide 3-kinase /AKT pathway. Simultaneous treatment of resistant tumors with a MET inhibitor plus an EGFR inhibitor can abrogate activation of downstream effectors of cell growth, proliferation, and survival, thereby overcoming acquired resistance to EGFR inhibitors. Development and preclinical testing of multiple agents targeting the HGF-MET pathway, including monoclonal antibodies targeting HGF or the MET receptor and small-molecule inhibitors of the MET tyrosine kinase, have confirmed the crucial role of this pathway in NSCLC. Several agents are now in phase III clinical development for the treatment of NSCLC. This review summarizes the role  of MET in the pathophysiology of NSCLC and in acquired resistance to EGFR inhibitors and provides an update on progress in the clinical development of inhibitors of MET for treatment of NSCLC.

 

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[427]

TÍTULO / TITLE:  - Dacomitinib , a new therapy for the treatment of non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Opin Pharmacother. 2013 Feb;14(2):247-53. doi: 10.1517/14656566.2013.758714. Epub 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.758714

AUTORES / AUTHORS:  - Brzezniak C; Carter CA; Giaccone G

INSTITUCIÓN / INSTITUTION:  - Walter Reed National Military Medical Center , 8901 Wisconsin Ave, Bethesda, MD 20889 , USA.

RESUMEN / SUMMARY:  - Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is characterized by a poor prognosis and few second- or third-line treatments. First-generation reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI) has paved the way for targeted treatment in lung cancer.  These drugs result in excellent responses in patients with activating EGFR mutations. Unfortunately, resistance often develops. Second-generation irreversible inhibitors hope to prevent mutational progression to a resistant clone or delay the use of alternative non-targeted therapies. Areas covered: This article focuses on the current published ongoing research using the second-generation irreversible TKI, dacomitinib . The use of dacomitinib, a pan inhibitor of the HER family of tyrosine kinases, will be reviewed along with its  efficacy in the advanced or metastatic NSCLC population. Expert opinion: Data available suggest dacomitinib is effective in NSCLC patients both in initial treatment and after failure of first-generation inhibitors. Furthermore, preclinical data suggest dacomitinib can achieve responses in tumors harboring the T790M, gatekeeper mutation, present in up to 50% of tumors that have acquired resistant to first-generation inhibitors. Its usefulness in potentially delaying  development of resistant clones as well as in combination with other targeting strategies is under investigation.

 

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[428]

TÍTULO / TITLE:  - Is vaccine therapy a renewed strategic approach for non-small-cell lung cancer therapy?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Vaccines. 2013 Jan;12(1):5-7. doi: 10.1586/erv.12.131.

            ●● Enlace al texto completo (gratuito o de pago) 1586/erv.12.131

AUTORES / AUTHORS:  - Rossi A

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, S.G. Moscati Hospital, Contrada Amoretta, 8, Avellino, Italy. arossi_it@yahoo.it.

 

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[429]

TÍTULO / TITLE:  - EGF receptor tyrosine kinase inhibitors in the treatment of brain metastases from non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2012 Nov;12(11):1429-35. doi: 10.1586/era.12.121.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.121

AUTORES / AUTHORS:  - Bartolotti M; Franceschi E; Brandes AA

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Azienda Unita Sanitaria Locale, Bologna, Italy.

RESUMEN / SUMMARY:  - The incidence of brain metastasis (BM) is high in patients with non-small-cell lung cancer. Available standard therapeutic options, such as whole-brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. Novel agents, such as EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs), have now been included in standard non-small-cell lung cancer treatments. In a small subset of patients harboring EGFR-activating mutations, erlotinib and gefitinib administration was followed by a response rate of 70-80%, and a longer progression-free and overall  survival than those obtained with standard chemotherapeutic regimens. However, since most of the larger studies on these agents have excluded BM patients from their series, few prospective data are available on the efficacy of these agents  in this setting. In recent years, however, several authors have reported a growing number of cases of partial and complete response in BM patients treated with EGFR TKIs. Data from retrospective series and Phase II studies also suggest  that a response can be obtained using EGFR TKI treatment for patients with BM, especially those harboring EGFR mutations.

 

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[430]

TÍTULO / TITLE:  - Back to EGF+61 genetic polymorphisms and lung cancer risk: looking to the future!

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Sao Paulo Med J. 2012;130(6):415-6.

AUTORES / AUTHORS:  - De Mello RA

 

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[431]

TÍTULO / TITLE:  - Clinicopathologic Correlations of Liver Kinase B1, E-Cadherin, and N-Cadherin Expression in Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e31826b128b

AUTORES / AUTHORS:  - Liu S; Miao Y; Fan C; Liu Y; Yu J; Zhang Y; Dai S; Wang E

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.

RESUMEN / SUMMARY:  - The role of liver kinase B1 (LKB1) as a tumor suppressor has emerged from the observation of increased risk of malignancy in gastrointestinal tract in Peutz-Jeghers syndrome patients harboring LKB1 gene mutations. LKB1 gene inactivation has recently been demonstrated in a subset of lung carcinoma and has been proven to trigger epithelial-mesenchymal transition in lung adenocarcinoma cells. However, the clinicopathologic significance, particularly prognosis, of LKB1 protein expression remains largely unclear. Using immunohistochemistry, we investigated the correlations between LKB1, E-cadherin, and N-cadherin expression and clinicopathologic parameters of lung cancer patients. Immunohistochemistry on specimens of the normal bronchial epithelium revealed that LKB1 was strongly or moderately expressed in the cytoplasm, and E-cadherin was expressed clearly on the cell membrane, whereas N-cadherin was absent or only weakly expressed at the  membrane and/or in the cytoplasm. In contrast, in lung cancer samples, LKB1 expression was absent or decreased in 25.7% (29/113) cases accompanied with loss  of membranous E-cadherin expression (25/29, P=0.009) and increased membranous and/or cytoplasmic N-cadherin expression (18/29, P=0.007). Loss of LKB1 expression positively correlated with histologic type (P=0.001), poor differentiation (P=0.004), and adverse prognosis (P<0.001). Moreover, loss of LKB1 expression correlated with lymph node metastasis (P=0.022) in lung adenocarcinoma samples and was an independent factor that impacted lung adenocarcinoma patients’ prognosis (P=0.003). Therefore, loss of LKB1 expression  correlates with epithelial-mesenchymal transition markers and may be a useful marker of poor survival for the patient with lung adenocarcinoma.

 

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[432]

TÍTULO / TITLE:  - Importance of the cytological samples for the epidermal growth factor receptor gene mutation test for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2012 Dec 13. doi: 10.1111/cas.12081.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12081

AUTORES / AUTHORS:  - Hagiwara K; Kobayashi K

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.

RESUMEN / SUMMARY:  - Mutations in the epidermal growth factor receptor (EGFR) gene confer it with cancer driver gene functions in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor -tyrosine kinase inhibitors are effective agents against NSCLC with a mutated EGFR gene. Accordingly, many guidelines recommend the use of an EGFR mutation test in NSCLC. However, not all patients are tested in most countries where tissue samples are mainly used for the test. As of 2011, most of  the patients with advanced NSCLC are tested in Japan, and the use of cytological  samples has significantly contributed to this success. A portion of samples used  to determine a definite diagnosis of NSCLC, either tissue samples or cytological  samples, is ensured to contain cancer cells, and is then investigated by an EGFR  mutation test that is applicable to both tissue samples and cytological samples.  Cytological samples now account for one-third of all the samples investigated. EGFR mutation is detected in cytological samples at a similar rate with tissue samples. The criterion ensuring an EGFR mutation test to have satisfactory sensitivity and specificity for use in both tissue and cytological samples is presented. Cytological samples are valuable clinical sources being collected less invasively than tissue samples, and should therefore be extensively used in EGFR  mutation testing.

 

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[433]

TÍTULO / TITLE:  - Sublobar/wedge resection or stereotactic body radiation therapy for stage I marginally operable non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2012 Nov;12(11):1375-7. doi: 10.1586/era.12.123.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.123

AUTORES / AUTHORS:  - Suppiah S; Linden P; Robke J; Schroeder C; Yao M; Machtay M; Lo SS

INSTITUCIÓN / INSTITUTION:  - Southern Illinois University Medical School, Springfield, IL, USA.

 

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[434]

TÍTULO / TITLE:  - Foxp3+ regulatory T cells coexisting with cancer associated fibroblast are correlated with a poor outcome in lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2013 Jan 10. doi: 10.1111/cas.12099.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12099

AUTORES / AUTHORS:  - Kinoshita T; Ishii G; Hiraoka N; Hirayama S; Yamauchi C; Aokage K; Hishida T; Yoshida J; Nagai K; Ochiai A

INSTITUCIÓN / INSTITUTION:  - Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

RESUMEN / SUMMARY:  - Recently, an association between tumor infiltrating Foxp3(+) regulatory T cells (Tregs) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of Treg induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between Tregs and the patient outcome and to investigate whether Treg induction is influenced by the characteristics of cancer-associated fibroblasts (CAFs) in lung adenocarcinoma. The numbers of Tregs in both the tumor stroma and the tumor nest  were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAFs influence Treg induction, we selected and cultured CAFs from “low Treg” and “high Treg” adenocarcinoma. The number of Tregs was much higher in the stroma than in the nest (P < 0.01). The patients with “high Treg” has significantly poorer prognosis than those with “low Treg” (OS: P = 0.03, RFS: P = 0.02, 5-year overall survival: 85.4% vs. 93.0%). Compared with the CAFs from “low Treg” adenocarcinoma, culture  supernatant of the CAFs from “high Treg” adenocarcinoma induced more Tregs (P = 0.01). CAFs from “high Treg” adenocarcinoma expressed significantly higher mRNA levels of TGF-beta (P = 0.01) and VEGF (P = 0.01), both of which are involved in  Treg induction. Our studies suggest the possibility that CAFs expressing immunoregulatory cytokines may induce Tregs in the stroma, creating a tumor-promoting microenvironment in lung adenocarcinoma and leading to a poor outcome.

 

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[435]

TÍTULO / TITLE:  - Chemoradiotherapy for Limited-disease Small-cell Lung Cancer in Elderly Patients  Aged 75 Years or Older.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Clin Oncol. 2013 Feb;43(2):176-83. doi: 10.1093/jjco/hys197. Epub 2012 Dec  5.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hys197

AUTORES / AUTHORS:  - Shukuya T; Takahashi T; Harada H; Ono A; Akamatsu H; Taira T; Kenmotsu H; Naito T; Murakami H; Endo M; Takahashi K; Yamamoto N

INSTITUCIÓN / INSTITUTION:  - *Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-chou, Suntou-gun, Shizuoka 411-8777, Japan. tshukuya@juntendo.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: As clinical trials for limited-disease small-cell lung cancer often exclude elderly patients due to comorbidities and a decline in organ function, the most suitable treatment for limited-disease small-cell lung cancer patients aged 75 years or older still remains unclear. METHODS: From July 2002 to June 2011, 20 consecutive patients aged 75 years or older, with Stage II to IIIB limited-disease small-cell lung cancer, were scheduled to be treated with concurrent or sequential chemoradiotherapy at the Shizuoka Cancer Center. We reviewed the medical charts of the patients and evaluated their characteristics,  treatment compliance, toxicity and antitumor efficacy. RESULTS: Five patients were treated with concurrent chemoradiotherapy and the other 15 patients were scheduled to be treated with sequential chemoradiotherapy. Of these 15 patients,  12 were treated with four cycles of etoposide (80 mg/m(2), days 1-3, q3-4w) plus  carboplatin (area under the curve 5, day 1, q3-4w), followed by thoracic radiotherapy. Of the five patients treated with concurrent chemoradiotherapy, discontinuation of chemotherapy/thoracic radiotherapy occurred in two patients due to toxicity and they suffered a prolonged decrease in performance status. Of  the 12 patients treated with etoposide plus carboplatin followed by sequential thoracic radiotherapy, the response rate, median progression-free survival and median overall survival time were 91%, 244 and 601 days. CONCLUSIONS: These results suggest that concurrent chemoradiotherapy is not feasible for all limited-disease small-cell lung cancer patients aged 75 years or older. The alternative of four cycles of etoposide plus carboplatin followed by thoracic radiotherapy is a candidate for the standard treatment of limited-disease small-cell lung cancer patients in this age group. A further trial is warranted to develop and evaluate the optimal treatment for elderly patients with limited-disease small-cell lung cancer.

 

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[436]

TÍTULO / TITLE:  - Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Res Notes. 2013 Jan 3;6:3. doi: 10.1186/1756-0500-6-3.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1756-0500-6-3

AUTORES / AUTHORS:  - Minami S; Kijima T; Shiroyama T; Okafuji K; Hirashima T; Uchida J; Imamura F; Osaki T; Nakatani T; Ogata Y; Yamamoto S; Namba Y; Otsuka T; Tachibana I; Komuta K; Kawase I

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan. tkijima@imed3.med.osaka-u.ac.jp.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC). However, the optimal maintenance strategy is  still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance. METHODS: Chemonaive patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1) plus carboplatin (AUC 6 mg/mL/min, day 1) every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8) plus carboplatin (AUC 5 mg/mL/min, day1) every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks. (Trial registration: UMIN000008252) RESULTS: The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned  50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS) was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95%  CI, 0.45-2.27; p = 0.95) and median overall survival (OS) was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40-1.51; p = 0.60), showing no  difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25), 64.0% (16/25), and 48% (12/25) for arm A vs. 16.7% (4/24), 50.0% (12/24), and 33% (8/24) for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively). Both induction regimens were tolerable, except that  more patients experienced peripheral neuropathy in arm A. Toxicities during the maintenance phase were also minimal. CONCLUSION: Survival and overall response were not significantly different between the two arms. Gemcitabine may be well-tolerable and feasible for maintenance therapy.

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[437]

TÍTULO / TITLE:  - Multiplexed Gene Expression and Fusion Transcript Analysis to Detect ALK Fusions  in Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Mol Diagn. 2013 Jan;15(1):51-61. doi: 10.1016/j.jmoldx.2012.08.006. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jmoldx.2012.08.006

AUTORES / AUTHORS:  - Lira ME; Kim TM; Huang D; Deng S; Koh Y; Jang B; Go H; Lee SH; Chung DH; Kim WH; Schoenmakers EF; Choi YL; Park K; Ahn JS; Sun JM; Ahn MJ; Kim DW; Mao M

INSTITUCIÓN / INSTITUTION:  - Pfizer Oncology, San Diego, California.

RESUMEN / SUMMARY:  - Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib. Because of this profound therapeutic implication, the latest National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend upfront ALK screening for all patients with NSCLC. The Food and Drug Administration-approved companion diagnostic test (ie, fluorescence in situ hybridization) for identification of ALK-positive patients,  however, is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen many patients. To explore alternative screening modalities for detecting ALK fusions, we designed a combination of two  transcript-based assays to detect for presence or absence of ALK fusions using NanoString’s nCounter technology. By using this combined gene expression and ALK  fusion detection strategy, we developed a multiplexed assay with a quantitative scoring modality that is highly sensitive, reproducible, and capable of detecting low-abundant ALK fusion transcripts, even in samples with a low tumor cell content. In 66 archival NSCLC samples, our results were highly concordant to prior results obtained by fluorescence in situ hybridization and IHC. Our assay offers a cost-effective, easy-to-perform, high-throughput, and FFPE-compatible screening alternative for detection of ALK fusions.

 

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[438]

TÍTULO / TITLE:  - Clinico-Pathological Features and Management of Lung Cancer Patients with Atherosclerotic Vascular Diseases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 13.

AUTORES / AUTHORS:  - Shoji F; Morodomi Y; Kyuragi R; Okamoto T; Matsumoto T; Yano T; Maehara Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Purpose: Increased numbers of patients with both lung cancer and atherosclerotic  vascular disease (AVD) may be expected in the future. The aim of this study was to report the incidence of lung cancer in patients with AVD and to discuss patient characteristics and management.Method: A total of 638 patients who underwent AVD treatment were investigated.Results: Lung cancer was observed in 17 (2.7%) of 638 patients studied. The proportion of smoking history was significantly higher in patients with lung cancer (p = 0.0091).The pack-year index in patients with lung cancer was significantly higher than that in patients without lung cancer (p = 0.0073). Although 4 of 6 (66.7%) patients with concomitant lung cancer and AVD had stage I or II lung cancer, 5 of 7 (71.4%) patients with lung cancer diagnosed after AVD treatment had stage III or IV lung  cancer. In patients with lung cancer found after AVD treatment, only 1 of 7 patients underwent surgical resections. The time until lung cancer was 12 to 198  months with a mean of62.5 months after AVD treatment. In concomitant cases, priority was given to AVD treatment in all 5 cases, and there were no serious events after the postoperative course.Conclusions: Both patients with a smoking history and heavy smokers were at high risk for lung cancer, and most lung cancers found after AVD treatment were in the advanced stages and had poor prognoses. Therefore, we recommend careful and routine follow-up for screening lung cancer after AVD treatment.

 

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[439]

TÍTULO / TITLE:  - Apigenin-induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Biol Med (Maywood). 2012 Dec 1;237(12):1433-48. doi: 10.1258/ebm.2012.012148.

            ●● Enlace al texto completo (gratuito o de pago) 1258/ebm.2012.012148

AUTORES / AUTHORS:  - Das S; Das J; Samadder A; Boujedaini N; Khuda-Bukhsh AR

INSTITUCIÓN / INSTITUTION:  - Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University  of Kalyani, Kalyani 741235, India.

RESUMEN / SUMMARY:  - We isolated apigenin (5,7,4’-trihydroxy flavone) from ethanolic extract of Lycopodium clavatum (LC) used as a homeopathic mother tincture for treatment of various diseases. We assessed the anticancer potentials of the compound using human malignant melanoma cell line A375 and a lung carcinoma cell line A549 and focussed on its putative molecular mechanism of action on apoptosis induction. We examined the cytotoxicity of apigenin in both cancer cells and normal peripheral  blood mononuclear cells (PBMC). A375 cells were more prone to apigenin-induced apoptosis, as compared with A549 cells after 24 h of treatment, while PBMC showed little or no cytotoxicity to apigenin. We also evaluated the effects of apigenin  on interaction with DNA by comparative analysis of circular dichroism spectral data and melting temperature profiles ™ of calf thymus DNA (CT-DNA) treated with or without apigenin. Reactive oxygen species (ROS) accumulation in mitochondria, super-oxide dismutase and total thiol group (GSH) activities were also analyzed. The apoptotic process involved mitochondrial pathway associated with apigenin-DNA interaction, DNA fragmentation, ROS accumulation, cytochrome c  (cyt c) release and mitochondrial transmembrane potential depolarization, Bax, caspase 3, 9, PARP, up-regulation, Bcl-2 down-regulation and down-regulation of cyt c in the mitochondrial fraction. Results of mitochondrial inner membrane swelling measurements, intracellular ADP/ATP ratio and ATPase activity showed that in A549 cells, apigenin did not appear to directly target the mitochondrial  oxidative phosphorylation system but rather acted at an upstream step to activate the mitochondrial apoptotic pathway. However, apigenin could directly target and  impair mitochondrial function in A375 cells by breaking down their oxidative phosphorylation system. Collectively, these results suggest that apigenin exhibits anticancer potential in A375 and A549 cells that may be mediated through DNA interaction, damage and mitochondrial dysfunction either by direct or indirect action on mitochondrial oxidative phosphorylation system.

 

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[440]

TÍTULO / TITLE:  - COX-2 and PPAR-gamma Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Ther. 2013 Jan;12(1):69-82. doi: 10.1158/1535-7163.MCT-12-0335. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0335

AUTORES / AUTHORS:  - Ramer R; Heinemann K; Merkord J; Rohde H; Salamon A; Linnebacher M; Hinz B

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Burkhard Hinz, Institute of Toxicology and Pharmacology, University of Rostock, Schillingallee 70, D-18057 Rostock, Germany. burkhard.hinz@med.uni-rostock.de.

RESUMEN / SUMMARY:  - The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-gamma in cannabidiol’s proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by  NS-398 (COX-2 inhibitor), GW9662 (PPAR-gamma antagonist), and siRNA targeting COX-2 and PPAR-gamma. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-gamma mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-gamma mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-gamma to the nucleus and induced a PPAR-gamma-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-gamma in tumor tissue and tumor regression that was reversible  by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol  involving initial upregulation of COX-2 and PPAR-gamma and a subsequent nuclear translocation of PPAR-gamma by COX-2-dependent PGs. Mol Cancer Ther; 12(1); 69-82. ©2012 AACR.

 

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[441]

TÍTULO / TITLE:  - Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Exp Toxicol. 2013 Feb;32(2):186-95. doi: 10.1177/0960327112459206.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0960327112459206

AUTORES / AUTHORS:  - Ahamed M

INSTITUCIÓN / INSTITUTION:  - King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.

RESUMEN / SUMMARY:  - In medicine, the use of silica nanoparticles (SiO(2) NPs) offers new perspectives in biosensor, drug delivery and cancer therapy. However, questions about potential toxic and deleterious effects of SiO(2) NPs have also been raised. The  aim of this study was to investigate the induction of cytotoxicity, oxidative stress and apoptosis by SiO(2) NPs (size 15 nm) in human skin epithelial (A431) and human lung epithelial (A549) cells. SiO(2) NPs (concentration range 25-200 microg/ml) induced dose-dependent cytotoxicity in both types of cells, which was  demonstrated by cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) and lactate dehydrogenase leakage assays. SiO(2) NPs were also found to induce oxidative stress in a dose-dependent manner, indicated by depletion of glutathione and induction of reactive oxygen species (ROS) generation and lipid peroxidation. Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to SiO(2) NPs, the messenger RNA level of apoptotic genes (caspase-3 and caspase-9) were upregulated in a dose-dependent manner. Moreover,  activities of caspase-3 and caspase-9 enzymes were also significantly higher in both kinds of cells exposed to SiO(2) NPs. This study suggested that SiO(2) NPs induce cytotoxicity and apoptosis in A431 and A549 cells, which is likely to be mediated through ROS generation and oxidative stress.

 

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[442]

TÍTULO / TITLE:  - Targeting signaling pathways in lung cancer therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Opin Ther Targets. 2013 Feb;17(2):107-11. doi: 10.1517/14728222.2013.729043. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1517/14728222.2013.729043

AUTORES / AUTHORS:  - Cho WC

INSTITUCIÓN / INSTITUTION:  - Chartered Scientist, Queen Elizabeth Hospital, Department of Clinical Oncology ,  Room 1305, 13/F, Block R, 30 Gascoigne Road, Kowloon , Hong Kong williamcscho@gmail.com.

RESUMEN / SUMMARY:  - Understanding the oncogenic signaling pathways and their underlying mechanisms may lead to new opportunities for developing therapeutic strategies for cancer treatment. In recent years, some molecular targeted agents have emerged for the inhibition of specific targets in signaling pathways. There are also studies examining whether the combination of these pathway-based therapeutics with standard therapies can produce synergistic effects in lung cancer treatment. On the other hand, it has been reported that some predictive biomarkers have been identified for the triage of patients most likely to benefit from these targeted  drugs. This article discusses the features and targeting of some dysregulated signaling pathways in lung cancer therapy intending to provide up-to-date information of the recent discoveries in lung cancer signaling pathway research and the most promising developments of pathway-based therapies, which may lead to substantial improvements for the clinical treatment of lung cancer.

 

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[443]

TÍTULO / TITLE:  - Lobar lung resection in elderly patients with non-small cell lung carcinoma: impact of cardiac comorbidity on surgical outcome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Swiss Med Wkly. 2012 Dec 21;142:0. doi: 10.4414/smw.2012.13742.

            ●● Enlace al texto completo (gratuito o de pago) 4414/smw.2012.13742

AUTORES / AUTHORS:  - Senbaklavaci O; Taspinar H; Hartert M; Ergun S; Keranen S; Vahl CF

INSTITUCIÓN / INSTITUTION:  - Johannes Gutenberg University Mainz, Germany; senbak@hotmail.com.

RESUMEN / SUMMARY:  - PRINCIPLES: The aim of this study was to evaluate the impact of cardiac comorbidity on the perioperative morbidity and mortality after lobar lung resection for lung cancer in patients aged 70 years and older. METHODS: The medical records of all 68 patients >/=70 years, who underwent lobar lung resection for non-small cell lung cancer (NSCLC) from 2003 to 2011 at our department, were reviewed retrospectively. Twenty-two patients with a mean age of 76.3 years had cardiac comorbidities (Group A) including previous cardiac operations in 4 patients, previous myocardial infarction in 5 patients, previous  coronary stent insertion in 3 patients, medically treated coronary artery disease in 10 patients and medically treated valvular heart disease in 2 patients whereas 46 patients (mean age = 74.5 years) had no previous cardiac history (Group B). RESULTS: There were no significant differences in postoperative morbidity (13.6%  in Group A vs. 17.4% in Group B) between both groups. No in-hospital mortality was observed in both groups. CONCLUSION: In our experience lobar lung resections  for NSCLC in elderly patients with cardiac comorbidity seem to be a safe therapy  option for this increasing subpopulation. Though, our retrospective data with the small number of study objects require further confirmation in larger prospective  trials.

 

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[444]

TÍTULO / TITLE:  - Circulating endothelial cells and tumor blood volume as predictors in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Sci. 2013 Jan 9. doi: 10.1111/cas.12097.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cas.12097

AUTORES / AUTHORS:  - Wang J; Xiao J; Wei X; Wang L; Lin L; Liu Z; Wang X; Sun B; Li K

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and  Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

RESUMEN / SUMMARY:  - The current criteria for evaluating antiangiogenic efficacy is insufficient as tumor shrinkage occurs after blood perfusion decreases. Tumor blood volume (BV) in CT perfusion imaging, and circulating endothelial cells (CECs) may predict the status of angiogenesis. The present study aimed to validate their representation  as feasible predictors in non-small-cell lung carcinoma (NSCLC). A total of 74 patients were categorized randomly into two arms undergoing regimens of vinorelbine and cisplatin (Navelbine and platinum, NP) with rh-endostatin or single NP. The response rate, perfusion imaging indexes, and activated CECs (aCECs) during treatment were recorded. Progression free survival (PFS) was determined through follow-up. The correlations among above indicators, response,  and PFS were analyzed: aCECs increased significantly in cases of progressive disease (PD) after single NP chemotherapy (P = 0.024). The tumor BV decreased significantly in cases with clinical benefit in combined arm (P = 0.026), whereby inverse correlations existed between aCECs (the post-therapeutic value minus the  pre-therapeutic value) and PFS (P = 0.005), and between BV and PFS (P = 0.044); and positive correlation existed between aCECs and BV. Therefore, both aCECs and  tumor BV can serve as predictors, and detection of both indicators can help evaluate the chemo-antiangiogenic efficacy in NSCLC more accurately.

 

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[445]

TÍTULO / TITLE:  - Ultra-sensitive assay for paclitaxel in intracellular compartments of A549 cells  using liquid chromatography-tandem mass spectrometry.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Jan 1;912:93-7. doi: 10.1016/j.jchromb.2012.10.033. Epub 2012 Nov 2.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jchromb.2012.10.033

AUTORES / AUTHORS:  - Wang T; Ma W; Sun Y; Yang Y; Zhang W; Fawcett JP; Du H; Gu J

INSTITUCIÓN / INSTITUTION:  - Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Bethune Hospital of Jilin University, Dongminzhu Street, Changchun 130061,  PR China; Research Center for Drug Metabolism, College of Life Science, Jilin University, Qianjin Street, Changchun 130012, PR China.

RESUMEN / SUMMARY:  - A high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of paclitaxel in intracellular compartments using docetaxel as internal standard (IS) has been developed and validated. A549 cancer cells (10(6)) were incubated with paclitaxel (2ng/mL) for up to 4h and then subjected to sequential extraction of cytosolic, membrane/organelle, nuclear and  cytoskeleton soluble protein. Fractions were ultrasonicated to release protein bound paclitaxel after which drug was extracted using liquid-liquid extraction with diethyl ether:dichloromethane (2:1, v/v). Chromatographic separation was then carried out on an Ascentis Express C18 column (50mmx4.6mm, 2.7mum) with a mobile phase of acetonitrile:0.1% formic acid in water (50:50, v/v). Detection involved electrospray positive ionization followed by multiple reactions monitoring of the precursor-to-product ion transitions of paclitaxel at m/z 854.4-->286.3 and docetaxel at m/z 808.6-->226.1. Assay validation based on samples of total cell extract in the same buffer as protein fractions showed the  assay was linear over the range 2-600pg/mL with intra- and inter-day precision (as relative standard deviation) and accuracy (as relative error) of <7% and <+/-12%, respectively. Recovery was approximately 70% and matrix effects were minimal. The distribution of paclitaxel in subcellular components of A549 cancer  cells was mainly into the cytoskeletal compartment.

 

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[446]

TÍTULO / TITLE:  - CD133+ cancer stem cells in lung cancer .

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Biosci. 2013 Jan 1;18:447-53.

AUTORES / AUTHORS:  - Wang S; Xu ZY; Wang LF; Su W

INSTITUCIÓN / INSTITUTION:  - Department of Oncology Part II, Longhua Hospital, Shanghai University of Traditional Chinese Medicine,Shanghai,725South Wan Ping Road, Xuhui District, Shanghai City, China 200032.

RESUMEN / SUMMARY:  - Lung cancer is the most preventable cancer worldwide but has a poor prognosis. Recent advances in the study of lung cancer stem cell (CSC) populations has led to a growing recognition of the central importance of cells with stem cell-like properties in lung tumorigenesis. High number of CD133+ cells is associated with  the maintenance, metastasis and drug-resistance of lung cancer. CD133 serves as a stemness biomarker for CD133+ CSCs, which have been found in lung cancer tissues. This article reviews the major studies supporting the existence and importance of CD133+ CSCs in the maintenance, metastasis and drug resistance of lung cancer. Continued research in the field of CD133+ CSCs biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets.

 

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[447]

TÍTULO / TITLE:  - Nonlinear motion compensation using cubature Kalman filter for in vivo fluorescence microendoscopy in peripheral lung cancer intervention.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Biomed Opt. 2013 Jan;18(1):16008. doi: 10.1117/1.JBO.18.1.016008.

            ●● Enlace al texto completo (gratuito o de pago) 1117/1.JBO.18.1.016008

AUTORES / AUTHORS:  - He T; Xue Z; Alvarado MV; Wong KK; Xie W; Wong ST

INSTITUCIÓN / INSTITUTION:  - Methodist Hospital Research Institute, Weill Cornell Medical College, Department  of Systems Medicine and Bioengineering, Houston, Texas, USA.

RESUMEN / SUMMARY:  - Fluorescence microendoscopy can potentially be a powerful modality in minimally invasive percutaneous intervention for cancer diagnosis because it has an exceptional ability to provide micron-scale resolution images in tissues inaccessible to traditional microscopy. After targeting the tumor with guidance by macroscopic images such as computed tomorgraphy or magnetic resonance imaging, fluorescence microendoscopy can help select the biopsy spots or perform an on-site molecular imaging diagnosis. However, one challenge of this technique for percutaneous lung intervention is that the respiratory and hemokinesis motion often renders instability of the sequential image visualization and results in inaccurate quantitative measurement. Motion correction on such serial microscopy  image sequences is, therefore, an important post-processing step. We propose a nonlinear motion compensation algorithm using a cubature Kalman filter (NMC-CKF)  to correct these periodic spatial and intensity changes, and validate the algorithm using preclinical imaging experiments. The algorithm integrates a longitudinal nonlinear system model using the CKF in the serial image registration algorithm for robust estimation of the longitudinal movements. Experiments were carried out using simulated and real microendoscopy videos captured from the CellVizio 660 system in rabbit VX2 cancer intervention. The results show that the NMC-CKF algorithm yields more robust and accurate alignment results.

 

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[448]

TÍTULO / TITLE:  - LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to  the Metabolism Drug Phenformin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell. 2013 Jan 15. pii: S1535-6108(12)00518-1. doi: 10.1016/j.ccr.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2012.12.008

AUTORES / AUTHORS:  - Shackelford DB; Abt E; Gerken L; Vasquez DS; Seki A; Leblanc M; Wei L; Fishbein MC; Czernin J; Mischel PS; Shaw RJ

INSTITUCIÓN / INSTITUTION:  - Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA; Pulmonary and Critical Care Medicine, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA. Electronic address: dshackelford@mednet.ucla.edu.

RESUMEN / SUMMARY:  - The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in approximately 20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient  cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial  inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors.

 

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[449]

TÍTULO / TITLE:  - The PARAMOUNT Trial: A Phase III Randomized Study Of Maintenance Pemetrexed Versus Placebo Immediately Following Induction First-Line Treatment With Pemetrexed Plus Cisplatin For Advanced Nonsquamous Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rev Recent Clin Trials. 2012 Dec 11.

AUTORES / AUTHORS:  - Gridelli C; Maione P; Rossi A

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, “S.G. Moscati” Hospital, Avellino Italy.

RESUMEN / SUMMARY:  - The search for new agents and for innovative strategies is warranted in the treatment of advanced non small cell lung cancer (NSCLC) because the outcomes remain unsatisfactory for most patients. Maintenance treatment with either a chemotherapeutic agent or a molecularly targeted agent after first-line chemotherapy is a very interesting strategy that has been largely investigated in the last years. Maintenance treatment can consist of drugs included in the induction regimen (continuation maintenance) or other noncross-resistant agents not included in the induction regimen (switch maintenance). The switch maintenance strategy with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor erlotinib (in all the histologies) or with pemetrexed (in non-squamous  histologies) have been demonstrated to be two possible effective options versus the classic break from cytotoxic chemotherapy after a fixed course in the treatment of advanced NSCLC. However some biases may have influenced the outcomes of switch maintenance trials as the low rate of patients treated with erlotinib and pemetrexed in the placebo arms. Very recently, a randomized phase III trial named PARAMOUNT has demonstrated a clinically significant benefit in overall survival with a good safety profile versus placebo in favour of continuation maintenance with pemetrexed after four cycles of induction with cisplatin plus pemetrexed. Continuation maintenance can be considered the true maintenance strategy because switch maintenance is an early second-line treatment. Continuation maintenance with pemetrexed after cisplatin plus pemetrexed induction for patients selected for a maintenance strategy is recommended as first-line treatment of advanced non-squamous NSCLC.

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[450]

TÍTULO / TITLE:  - Bevacizumab as first-line therapy in advanced non-small-cell lung cancer: a brazilian center experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Drugs R D. 2012 Dec 1;12(4):207-16. doi: 10.2165/11636760-000000000-00000.

            ●● Enlace al texto completo (gratuito o de pago) 2165/11636760-000000000-00000

AUTORES / AUTHORS:  - Jardim DL; Gagliato Dde M; Ribeiro KB; Shimada AK; Katz A

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil. jardimde@gmail.com

RESUMEN / SUMMARY:  - OBJECTIVES: Bevacizumab has been approved by the US Food and Drug Administration  as a first-line therapy for metastatic non-small-cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel. A single Latin American center experience was reviewed to determine the safety and efficacy of adding bevacizumab to first-line chemotherapy in a local population. METHODS: We retrospectively identified patients with non-squamous NSCLC treated with bevacizumab plus chemotherapy combinations as first-line chemotherapy between July 1, 2006, and January 30, 2011, at Sirio Libanes Hospital in Sao Paulo, Brazil. We collected data on patient characteristics, treatment combinations, toxicities, response to treatment, and survival. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis, and prognostic factors were identified by the Cox regression model. RESULTS: A total  of 56 patients were included in the final analysis (median age 62.4 years; 70% male). In 35 patients (62.5%), bevacizumab was combined with carboplatin and paclitaxel, and in 16 patients (28.6%), it was combined with pemetrexed and carboplatin. The response rate evaluated by the reference clinical team reached 74.5%, the median PFS was 5.3 months, and the median OS was 14.8 months. In multivariate analysis, use of maintenance therapy was the only predictive factor  for OS (hazard ratio 6.85, 95% confidence interval 2.94-15.22). No treatment-related deaths were identified, and the overall incidence of grade 3-4  non-hematologic toxicities was 16%. CONCLUSION: Our results confirm the efficacy  and safety data of bevacizumab first-line combinations for NSCLC in a Brazilian population.

 

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[451]

TÍTULO / TITLE:  - Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Oncol. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10147-012-0503-8

AUTORES / AUTHORS:  - Sakamoto J; Sonobe M; Kobayashi M; Ishikawa M; Kikuchi R; Nakajima D; Yamada T; Nakayama E; Takahashi T; Sato T; Chen F; Bando T; Date H

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University Hospital, 54 Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Postoperative recurrence in non-small cell lung cancer (NSCLC) reduces the life expectancy of patients. In this retrospective study, we investigated the prognostic factors in patients with postoperative brain metastases from surgical resected non-small cell lung cancer (NSCLC). METHODS: We conducted a retrospective chart review of patients who had undergone resection for NSCLC between April 2004 and February 2009 and found 65 had experienced postoperative brain metastases by March 2010. We reviewed these patients for clinicopathological information, treatments and responses to treatment, and overall survival. RESULTS: The 5-year survival rate after the diagnosis of brain  metastases was 15.4 %. Significantly favorable prognostic factors for patients after a diagnosis of brain metastases included female gender, adenocarcinoma, a small number (1-3) of brain metastases, no extracranial metastasis at the diagnosis of brain metastases, radiation treatment (whole-brain radiation and/or  stereotactic irradiation), and local treatment [stereotactic irradiation and/or surgical operation (craniotomy)]. Furthermore, in patients with only brain metastases as the postoperative initial recurrence, the favorable positive prognostic factors included a small number (1-3) of brain metastases, adjuvant chemotherapy, chemotherapy (including adjuvant and other chemotherapy and excluding epidermal growth factor receptor-tyrosine kinase inhibitors), and local treatment. CONCLUSIONS: Our study found that the foregoing clinical characteristics in postoperative brain metastases and the administration of treatment contributed to patient life expectancy.

 

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[452]

TÍTULO / TITLE:  - Expression of SHP2 and Related Markers in Non-Small Cell Lung Cancer: A Tissue Microarray Study of 80 Cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e31827da3f9

AUTORES / AUTHORS:  - Tang C; Luo D; Yang H; Wang Q; Zhang R; Liu G; Zhou X

INSTITUCIÓN / INSTITUTION:  - Departments of *Respiratory Medicine daggerPathology, Southwest Hospital, Third Military Medical University, Chongqing, China.

RESUMEN / SUMMARY:  - The purpose of this study was to assess the relationships between the expression  of SHP2 and VEGF, VEGFR-1, VEGFR-2, MMP-2, MMP-9, TIMP-1, TIMP-2, and microvessel density (MVD), as well as the clinicopathologic parameters of these markers in non-small cell lung cancer (NSCLC). Using a tissue microarray, the expression of  these 8 markers in 80 NSCLC cases was detected by immunohistochemistry. The expression of the markers was higher in cancer tissues when compared with the surrounding tissues. The MVD was lower in the CD34-positive cancer tissues than in the surrounding tissues. Significantly higher positive rates of expression for SHP2, MMP-9, and MMP-2 were observed in patients with lymph node metastases. The  later the clinical stage was, the higher the expression of MMP-9 and MMP-2. The expression of VEGF in patients with lung squamous cell carcinomas was significantly higher than in patients with lung adenocarcinomas. The positive expression of SHP2 correlated significantly with that of VEGFR-2 and the MVD and  a survival disadvantage was noted in the patients with SHP2-positive tumors. Therefore, our data suggest that the expression of SHP2 in NSCLC has high specificity and sensitivity and is closely related to lymph node metastasis and the expression of VEGFR-2 and the MVD in patients with NSCLC. SHP2 expression may promote the invasion and metastasis of NSCLC through angiogenesis and the lymphatic system.

 

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[453]

TÍTULO / TITLE:  - Prevention of Needle-Tract Seeding by Two-Step Freezing after Lung Cancer Biopsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Oncol Res. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9601-1

AUTORES / AUTHORS:  - Mu F; Liu SP; Zhou XL; Chen JB; Li HB; Zuo JS; Xu KC

INSTITUCIÓN / INSTITUTION:  - Guangzhou Fuda Hospital, Institutes of Biomedicine and Health, Chinese Academy of Science, No. 91 Judezhong Road, Haizhu District, Guangzhou, Guangdong, 510305, China.

RESUMEN / SUMMARY:  - Fine-needle aspiration biopsy is a method to detect malignancy for undetermined pulmonary nodules, but has the potential to spread malignant cells from the tumor to the pleural cavity or chest wall. We developed a two-step freezing method to avoid needle-tract seeding, by use of percutaneous cryoablation after biopsy but  before the biopsy needle was removed. A man aged 72 years was admitted because of a large mass in right upper lobe. After biopsy, the patient underwent surgery. Pathological assessment of the resected tumor showed that tissue around the biopsy probe and cryoprobe had been killed before needle withdrawal.

 

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[454]

TÍTULO / TITLE:  - Testing for lung cancer in people at high risk.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - CA Cancer J Clin. 2013 Jan 11. doi: 10.3322/caac.21177.

            ●● Enlace al texto completo (gratuito o de pago) 3322/caac.21177

 

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[455]

TÍTULO / TITLE:  - 20-second CT scans cuts lung cancer deaths, but is it right for you? High-risk current and former smokers may benefit. Before having your scan, carefully consider the pros and cons.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Harv Mens Health Watch. 2012 Nov;17(4):4-5.

 

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[456]

TÍTULO / TITLE:  - Prognostic implications of volume-based measurements on FDG PET/CT in stage III non-small-cell lung cancer after induction chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2321-7

AUTORES / AUTHORS:  - Soussan M; Chouahnia K; Maisonobe JA; Boubaya M; Eder V; Morere JF; Buvat I

INSTITUCIÓN / INSTITUTION:  - University Paris 13, Sorbonne Paris Cite, Bobigny, France, michael.soussan@avc.aphp.fr.

RESUMEN / SUMMARY:  - PURPOSE: We sought to determine whether metabolic volume-based measurements on FDG PET/CT scans could provide additional information for predicting outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with induction chemotherapy. METHODS: Included in the study were 32 patients with stage III NSCLC who were treated with induction platinum-based chemotherapy followed in 21  by surgery. All patients had an FDG PET/CT scan before and after the induction chemotherapy. Tumours were delineated using adaptive threshold methods. The SUVmax, SUVpeak, SUVmean, tumour volume (TV), total lesion glycolysis (TLG), and  volume and largest diameter on the CT images (CTV and CTD, respectively) were calculated. Index ratios of the primary tumour were calculated by dividing the follow-up measurements by the baseline measurements. The prognostic value of each parameter for event-free survival (EFS) was determined using Cox regression models. RESULTS: The median follow-up time was 19 months (range 6-43 months). Baseline PET and CT parameters were not significant prognostic factors. After induction therapy, only SUVmax, SUVpeak, SUVmean, TV, TLG and CTV were prognostic factors for EFS, in contrast to CTD. Of the index ratios, only TV and TLG ratios  were prognostic factors for EFS. Patients with a TLG ratio <0.48 had a longer EFS than those with a TLG ratio >0.48 (13.9 vs. 9.2 months, p = 0.04). After adjustment for the effect of surgical treatment, all the parameters significantly correlated with EFS remained significant. CONCLUSION: SUV, metabolic volume-based indices, and CTV after induction chemotherapy give independent prognostic information in stage III NSCLC. However, changes in metabolic TV and TLG under induction treatment provide more accurate prognostic information than SUV alone,  and CTD and CTV.

 

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[457]

TÍTULO / TITLE:  - First report of upfront treatment with Gefitinib in comparison with chemotherapy  in advanced non-small cell lung cancer patients from south India: Analysis of 120 patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Med Paediatr Oncol. 2012 Jul;33(3):146-54. doi: 10.4103/0971-5851.103141.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0971-5851.103141

AUTORES / AUTHORS:  - Louis RA; Rajendranath R; Ganesan P; Sagar TG; Krishnamurthy A

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Cancer Institute (WIA), Sardar Patel Road, Adyar, Chennai, Tamil Nadu, India.

RESUMEN / SUMMARY:  - BACKGROUND: Lung cancer is the most common cause of cancer deaths in males and sixth among females in south India. Lung cancer is being increasingly recognized  among non-smokers. MATERIALS AND METHODS: Stage IIIB and IV advanced non-small cell lung cancer (NSCLC) patients (n=120) treated from January 2009 to December 2010 were retrospectively analyzed. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. Decision to use upfront Gefitinib was based on parameters like female sex, non-smoking status, adenocarcinoma histology and poor PS. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method and prognosis by log rank  test and Cox regression. RESULTS: BASELINE PARAMETERS: median age: 60 years (22-78 years); male sex: 83 (69.2%); Stage IV: 95(79.2%); adenocarcinoma: 109 (90.8%); smokers: 66 (55%); PS 2/3: 65(54.2%); first-line therapy: Gefitinib: 47  (39.2%), chemotherapy: 73 (60.8%). Among those progressing after chemotherapy, 17 (23%) received second-line Gefitinib. After a median follow-up of 7.5 months (1-26 months), median PFS and OS were 5 months (0-23 months) and 7.5 months (1-26 mo), respectively. On univariate analysis, PFS was significantly improved for non-smokers (7 months vs 4 months, P=0.010), females (7 months vs 5 months, P=0.024) and upfront treatment with Gefitinib (10 months vs 4 months, P=0.014). The only significant factor that affected OS was female sex (18 months vs 9 months, P=0.042). No factors were significant on multivariate analysis. Among PS  2/3 patients, PFS was significantly higher with Gefitinib (n=36) than with single-agent chemotherapy (n=29) [median PFS of 10 months vs 4 months (P=0.017)]. CONCLUSION: In the largest series on the use of first-line Gefitinib from India,  we found it to be a useful agent in the treatment of NSCLC, especially in females patients with poor PS and non-smokers, even without Epidermal Growth Factor Receptor (EGFR) mutation testing. Second-line Gefitinib may have negated the OS differences. However, EGFR mutation studies may help in further individualization of therapy.

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[458]

TÍTULO / TITLE:  - Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Jun;24(2):97-102. doi: 10.1007/s11670-012-0097-8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-012-0097-8

AUTORES / AUTHORS:  - Yang JJ; Zhou Q; Liao RQ; Huang YS; Xu CR; Wang Z; Wang BC; Chen HJ; Wu YL

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Cancer Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non-small cell lung cancer (NSCLC). METHODS: Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were  randomly assigned to the NG arm (n=30) and the CG arm (n=32). Only patients (24 and 25 in the NG and CG arms, respectively) who completed >/=2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate (ORR). The secondary outcome measures included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: There were no statistically significant differences in the efficacy measures (ORR, P=0.305; median PFS, P=0.198; median OS, P=0.961) or in the major  adverse events (grade ¾ neutropenia, P=0.666; grade ¾ anemia, P=0.263; grade  ¾ thrombocytopenia, P=0.212) between the two treatment arms. However, there was a trend towards higher ORR (37.5% vs. 24.0%), longer PFS (6.0 vs. 5.0 months), and less adverse events in the NG arm. CONCLUSION: NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

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[459]

TÍTULO / TITLE:  - Synthesis and antiproliferative evaluation of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Med Chem. 2013 Jan;59:274-82. doi: 10.1016/j.ejmech.2012.11.027. Epub 2012  Nov 24.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejmech.2012.11.027

AUTORES / AUTHORS:  - Tseng CH; Chen YL; Hsu CY; Chen TC; Cheng CM; Tso HC; Lu YJ; Tzeng CC

INSTITUCIÓN / INSTITUTION:  - Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.

RESUMEN / SUMMARY:  - Certain 3-phenylquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) and (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one  (11) were identified as potential lead compounds for further development. Compound 6a was active against the growth of H1299 and SKBR-3 with IC(50) values  of 1.41 and 0.70 muM respectively which was more active than the positive topotecan (IC(50) values of 6.02 and 8.91 muM respectively). Compound 11 exhibited an IC(50) value of less than 0.10 muM against the growth of MDA-MB231,  and non-cytotoxic to the normal mammary epithelial cell (H184B5F5/M10). Mechanism studies indicated that compound 11 induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and consequently caused the cell death.

 

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[460]

TÍTULO / TITLE:  - Asymptomatic multiple splenic cysts in a pulmonary neoplasm patient.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nippon Med Sch. 2012;79(6):468-70.

AUTORES / AUTHORS:  - Yuan SM; Lin JS

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, The First Hospital of Putian, Teaching Hospital, Fujian Medical University.

RESUMEN / SUMMARY:  - Splenic cysts are rare, and their treatment remains challenging. A 66-year-old man scheduled to undergo surgical treatment for a pulmonary neoplasm was found with abdominal computed tomography and ultrasonography to have multiple cysts in  the body of the spleen. He underwent pulmonary wedge resection, and histological  examination showed that the lesion of the left lung was an adenocarcinoma. The patient recovered without complications after the operation. Because the splenic  cysts were small and caused no abdominal symptoms, the patient was advised to undergo careful follow-up. Large splenic cysts warrant surgical treatment, whereas careful follow-up is recommended for small asymptomatic splenic cysts.

 

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[461]

TÍTULO / TITLE:  - Pneumonectomy with and without induction chemo-radiotherapy for non-small cell lung cancer: short and long-term results from a single centre.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Rev Med Pharmacol Sci. 2013 Jan;17(1):29-40.

AUTORES / AUTHORS:  - Margaritora S; Cesario A; Cusumano G; Dall’armi V; Porziella V; Meacci E; Lococo F; D’Angelillo R; Congedo MT; Granone P

INSTITUCIÓN / INSTITUTION:  - Division of General Thoracic Surgery, School of Medicine, Catholic University of  the Sacred Heart, Rome, Italy. vporziella@rm.unicatt.it

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: Pneumonectomy for non small cell lung cancer (NSCLC) after induction radio-chemotherapy (IT) has been associated with high peri-operative risk and its safety and efficacy is still debated. The aim of this retrospective study was to compare short and long-term results of pneumonectomy in patients treated with and without IT (radiotherapy plus chemotherapy) for NSCLC. MATERIALS AND METHODS: From 1995 to 2008, 85 consecutive patients underwent pneumonectomy: 49 received pre-operative radiotherapy and chemotherapy  (IT group), and 36 patients did not (non-IT group). Peri-operative and long-term  outcomes were compared. RESULTS: Major complications rate was 14.3% for IT group  and 16.7% for non-IT group (p = n.s.). Mortality rate was 2% in IT group and 5.5% in non-IT group (p = n.s.). Post-operative hospital stay was significantly longer in the IT group (p < 0.0001) as the need for blood transfusion (p = 0.002). Indeed, the mortality rate was similar in the left- and right-sided operations. 5 years survival was 45.3% for IT group and 38.4% for non-IT group (p = n.s.) and 5 year disease free survival rates were 42.3% vs. 37.8% for the two groups, respectively (p = n.s.). Among the clinical, surgical and pathological features no differences on long term outcomes were found with regards to IT. DISCUSSION: Pneumonectomy is a feasible and safe procedure even after pre-operative IT. Our results showed a prolonged hospitalization and the need for blood transfusion in  the IT group.

 

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[462]

TÍTULO / TITLE:  - Differentiation of tumor recurrence from radiation-induced pulmonary fibrosis after stereotactic ablative radiotherapy for lung cancer: characterization of (18)F-FDG PET/CT findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Nucl Med. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12149-012-0682-4

AUTORES / AUTHORS:  - Nakajima N; Sugawara Y; Kataoka M; Hamamoto Y; Ochi T; Sakai S; Takahashi T; Kajihara M; Teramoto N; Yamashita M; Mochizuki T

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, National Hospital Organization Shikoku Cancer Center, Kou-160, Minamiumemoto-machi, Matsuyama, Ehime, 791-0280, Japan, haruhi0321@gmail.com.

RESUMEN / SUMMARY:  - OBJECTIVE: Stereotactic ablative radiotherapy (SABR), also known as stereotactic  body radiotherapy (SBRT), is now a standard treatment option for patients with stage I non-small cell lung cancer or oligometastatic lung tumor who are medically inoperable or medically operable but refuse surgery. When mass-like consolidation is observed on follow-up CT after SABR, it is sometimes difficult to differentiate tumor recurrence from SABR-induced pulmonary fibrosis. In this study, we evaluated the role of (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) in differentiating tumor recurrence from radiation fibrosis after SABR. METHODS: Between June 2006 and June 2009, 130 patients received SABR for stage I non-small cell lung cancer  or metastatic lung cancer at our institution. Fifty-nine patients of them were imaged with FDG-PET/CT after SABR. There were a total of 137 FDG-PET/CT scans for retrospective analysis. The FDG uptake in the pulmonary region was assessed qualitatively using a 3-point scale (0, none or faint; 1, mild; or 2, moderate to intense), and the shape (mass-like or non mass-like) was evaluated. For semi-quantitative analysis, the maximum standardized uptake value (SUV(max)) was  calculated. RESULTS: Sixteen of 59 patients had local failure. In recurrent tumor, the combination of intensity grade 2 and mass-like shape was most common (21/23; 91 %). By contrast, in cases of radiation fibrosis, the combination of intensity grade 0 or 1 and non mass-like shape was most common (48/59; 81 %). The SUV(max) of tumor recurrence after 12 months was significantly higher than that of radiation fibrosis (8.0 +/- 3.2 vs. 2.1 +/- 0.9, p < 0.001), and all tumor recurrence showed the SUV(max) > 4.5 at diagnosis of local failure. At >/=12 months after SABR, these two variables, the combination of intensity 2 and mass-like FDG uptake or SUV(max) > 4.5 acquired a significant high predictive value of local recurrence, finding sensitivity 100 % and specificity 100 % for both of them. CONCLUSIONS: The combination of FDG uptake patterns and SUV(max) was useful for distinguishing tumor recurrence from radiation fibrosis after SABR.

 

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[463]

TÍTULO / TITLE:  - Case report: Metastatic small-cell lung carcinoma of the external auditory canal.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ear Nose Throat J. 2012 Nov;91(11):476-8.

AUTORES / AUTHORS:  - Hain M; Feldberg E; Halperin D

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Kaplan Medical Center, Rehovot, POB 1, Israel. rmhain@gmail.com.

RESUMEN / SUMMARY:  - We report the case of a 73-year-old man who developed metastatic small-cell lung  cancer to the bony external auditory canal (EAC). The patient had only recently been diagnosed with his primary carcinoma. The metastasis presented as a bulky, fleshy, bleeding mass in the right EAC. Biopsy of the metastasis revealed that its histologic characteristics were identical to those of the primary. This case  is of interest because this was a unique type of metastasis to the EAC. Although  there are reports in the literature of lung cancer and even small-cell cancer metastasizing to the temporal bone, we could find no previously published report  of a small-cell lung carcinoma metastasizing to the EAC.

 

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[464]

TÍTULO / TITLE:  - Video-assisted thoracoscopic surgery with posterior spinal reconstruction for the resection of upper lobe lung tumors involving the spine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Spine J. 2013 Jan 4. pii: S1529-9430(12)01407-6. doi: 10.1016/j.spinee.2012.11.026.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.spinee.2012.11.026

AUTORES / AUTHORS:  - Stoker GE; Buchowski JM; Kelly MP; Meyers BF; Patterson GA

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedic Surgery, Washington University in St. Louis, 660 S. Euclid Ave., West Pavilion Suite 11300, Campus Box 8233, St. Louis, MO 63110, USA.

RESUMEN / SUMMARY:  - BACKGROUND CONTEXT: Video-assisted thoracoscopic surgery (VATS) is associated with less morbidity and recovery time compared with traditional open thoracotomy  (OT) for the resection of early stage non-small cell lung cancer (NSCLC). Local invasion of NSCLC into adjacent vertebrae confers a TNM T status of T4. Anatomical lobectomy by VATS with simultaneous posterior spinal reconstruction (PSR), as a single procedure, offers advantages to selected patients judged as suitable candidates for resection. PURPOSE: To report the preliminary results of  a novel, multidisciplinary surgical technique for the treatment of upper lobe lung cancers with direct extension to the spine. STUDY DESIGN: Consecutive case series. PATIENT SAMPLE: Eight adults who underwent PSR with either VATS or OT for the treatment of a T4 (vertebral body invasion) NSCLC. OUTCOME MEASURES: Total operative time, estimated blood loss, length of hospital stay, postoperative tumor recurrence and metastasis, survival, reoperations, and any other intraoperative or postoperative complication. METHODS: Eight consecutive patients who underwent instrumented PSR with corpectomy for the treatment of an upper lobe NSCLC at a single institution were identified. Either VATS (n=4) or OT (n=4) was  performed at the time of the reconstruction in each patient. All tumors were stage III NSCLC without metastasis. RESULTS: Patients who underwent VATS and OT were aged 54+/-11 and 54+/-2.9 years, respectively. Mean operative time and blood loss were similar between the groups: VATS: 367+/-117 minutes versus OT: 518+/-264 minutes; VATS: 813+/-463 mL versus OT: 1,250+/-1,500 mL. Mean follow-up was 16+/-13 months after surgery. Complications occurred in all eight patients. One OT patient had wound dehiscence requiring a tissue flap, and another suffered from a septic shock. No wound complications developed after VATS. Death secondary to tumor recurrence occurred once in each group. For the six surviving patients,  23+/-15 months (range, 4.5-43 months) have elapsed since surgery. CONCLUSIONS: Video-assisted thoracoscopic surgery with PSR is a novel and viable method for the complete resection of T4 NSCLC.

 

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[465]

TÍTULO / TITLE:  - The efficacy of bronchial washings in diagnosis of lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathologica. 2012 Aug;104(4):175-6.

AUTORES / AUTHORS:  - Mlika M; Ayadi-Kaddour A; Chebbi C; Boudaya S; Kilani T; Mezni F

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Abderrahman Mami Hospital, University of Medicine, Tunis El Manar, Tunisia. mlika.zorgati.mona@hotmail.com

RESUMEN / SUMMARY:  - BACKGROUND: The accurate diagnosis of lung carcinoma has become compulsory, especially after the introduction of new targeted therapies. The majority of these patients are non-operable, highlighting the importance of the cytology specimen. Our aim was to assess the diagnostic efficacy of bronchial washings in  low income countries where this low cost technique is widely performed. MATERIAL  AND METHODS: We conducted a study of 118 bronchial washings collected in the Department of Pathology. Bronchial washings were smeared on 5-6 clean slides. These were fixed in 95% ethyl alcohol for haematoxylin and eosin staining. Cases  were retrospectively reviewed by two pathologists (FM and MM) together with the corresponding biopsies. False negative cases were reviewed twice, and the diagnosis was reassessed in one case. We calculated the sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and Yoden index. CONCLUSIONS: Our study showed a sensitivity of 56%, specificity of 90%, PPV of 55%, NPV of 76% and a Yoden index of 0.45. These results emphasise the diagnostic efficacy of bronchial washings and the possibility of performing molecular tests on cytology specimens.

 

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[466]

TÍTULO / TITLE:  - The Effect of the Extent of Lymph Node Dissection for Stage IA Non-Small-Cell Lung Cancer on Patient Disease-Free Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Nov 27. pii: S1525-7304(12)00199-4. doi: 10.1016/j.cllc.2012.09.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.09.002

AUTORES / AUTHORS:  - Xu F; Qi L; Yue D; Wang C

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Cancer Prevention of Tianjin, Cancer Institute and Hospital of  Tianjin Medical University, Tianjin, China.

RESUMEN / SUMMARY:  - BACKGROUND: Systematic LN dissection has been proposed as 1 of the important parts of the standard surgery for NSCLC for decades. However, controversy exists  as to whether extensive LN dissection has benefit for early stage NSCLC patients. The aim of the present study was to investigate whether the extent of dissection  affects the DFS of stage IA patients. PATIENTS AND METHODS: The stations dissected and the LN obtained during operations from stage IA NSCLC patients were recorded and the patients were grouped according to the number of dissected LN (N), total stations (NS) and mediastinal stations (N(2)). The DFS curve of patients from each group were generated by the Kaplan-Meier method and compared with the log-rank test. The correlation between the patients’ clinical features and N retrieval were also analyzed. RESULTS: A total of 203 stage IA NSCLC patients were grouped (N </= 10, 10 < N </= 20, and N > 20; NS >/= 6 and NS < 6;  N(2) >/= 3 and N(2) < 3) and analyzed. Right-sided disease, tumor maximal diameter > 2 cm, and more NS or N(2) dissected correlated with more retrieval of  LN (P = .001, .003, < .001, < .001). The increase of N, NS, and N(2) dissected were found to predict improved DFS (P = .001, .019, < .001), but there were no significant survival differences between the N </= 20 and N > 20 patients within  the NS >/= 6 subset (P = .140). CONCLUSION: The dissection of more stations did increase the harvest of LN, which could achieve better survival for a stage IA NSCLC patient. The number of dissected (mediastinal) stations served as a more significant prognostic factor.

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[467]

TÍTULO / TITLE:  - Correlation between [(18)F]FDG PET/CT and volume perfusion CT in primary tumours  and mediastinal lymph nodes of non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2318-2

AUTORES / AUTHORS:  - Sauter AW; Spira D; Schulze M; Pfannenberg C; Hetzel J; Reimold M; Klotz E; Claussen CD; Horger MS

INSTITUCIÓN / INSTITUTION:  - Diagnostic and Interventional Radiology, Department of Radiology, Eberhard Karls  University, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany, alexander.sauter@klinikum.uni-tuebingen.de.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this study was to investigate correlations between glucose metabolism as determined by [(18)F]FDG PET/CT and tumour perfusion as quantified  by volume perfusion CT in primary tumours and mediastinal lymph nodes (MLN) of patients with non-small-cell lung cancer (NSCLC). METHODS: Enrolled in the study  were 17 patients with NSCLC. [(18)F]FDG uptake was quantified in terms of SUV(max) and SUV(avg). Blood flow (BF), blood volume (BV) and flow extraction product (K(trans)) were determined as perfusion parameters. The correlations between the perfusion parameters and [(18)F]FDG uptake values were subsequently evaluated. RESULTS: For the primary tumours, no correlations were found between perfusion parameters and [(18)F]FDG uptake. In MLN, there were negative correlations between BF and SUV(avg) (r = -0.383), BV and SUV(avg) (r = -0.406),  and BV and SUV(max) (r = -0.377), but not between BF and SUV(max), K(trans) and SUV(avg), or K(trans) and SUV(max). Additionally, in MLN with SUV(max) >2.5 there were negative correlations between BF and SUV(avg) (r = -0.510), BV and SUV(avg)  (r = -0.390), BF and SUV(max) (r = -0.536), as well as BV and SUV(max) (r = -0.346). CONCLUSION: Perfusion and glucose metabolism seemed to be uncoupled in large primary tumours, but an inverse correlation was observed in MLN. This information may help improve therapy planning and response evaluation.

 

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[468]

TÍTULO / TITLE:  - Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer. 2012 Dec 12;11(1):91.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-11-91

AUTORES / AUTHORS:  - Cavazzoni A; Alfieri RR; Cretella D; Saccani F; Ampollini L; Galetti M; Quaini F; Graiani G; Madeddu D; Mozzoni P; Galvani E; La Monica S; Bonelli M; Fumarola C; Mutti A; Carbognani P; Tiseo M; Barocelli E; Petronini PG; Ardizzoni A

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or  tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. RESULTS: In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited  tumour growth when compared with erlotinib and cetuximab alone. CONCLUSION: Our results indicate that erlotinib increases surface expression of EGFR and/or HER2  only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

 

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[469]

TÍTULO / TITLE:  - Paclitaxel-Loaded Polymeric Micelle (230 mg/m(2)) and Cisplatin (60 mg/m(2)) vs.  Paclitaxel (175 mg/m(2)) and Cisplatin (60 mg/m(2)) in Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase IIB Trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 2. pii: S1525-7304(12)00257-4. doi: 10.1016/j.cllc.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.005

AUTORES / AUTHORS:  - Lee SY; Park HS; Lee KY; Kim HJ; Jeon YJ; Jang TW; Lee KH; Kim YC; Kim KS; Oh IJ; Kim SY

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Guro Hospital, Korea University Medical School,  Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - INTRODUCTION:: The development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin. PATIENTS AND METHODS: Patients with stage IIIB/IV or recurrent non-small-cell lung cancer (NSCLC) who were chemonaive were eligible for participation. The patients were randomly assigned to receive PPM 230 mg/m(2) plus cisplatin 60 mg/m(2) or paclitaxel 175 mg/m(2) plus cisplatin 60 mg/m(2) once every 3-week cycle. The primary endpoint was to compare the response rate (RR) between the groups with coprimary analyses to assess noninferiority. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 276 patients were randomized to PPM plus cisplatin (n = 140) or paclitaxel plus cisplatin (n = 136). RR was 43.6% in the PPM plus cisplatin group and 41.9% in the paclitaxel plus cisplatin group. Noninferiority  of PPM plus cisplatin compared with paclitaxel plus cisplatin was confirmed for RR. There were no differences in progression-free survival and overall survival between the groups. Although there was a higher rate of grade 3 neutropenia in the PPM plus cisplatin group, the overall rate of adverse events was comparable between the 2 groups. CONCLUSION: PPM in combination with cisplatin was well tolerated, and its response rate was noninferior to that of paclitaxel plus cisplatin in patients with advanced NSCLC and who were chemonaive.

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[470]

TÍTULO / TITLE:  - Malignant pleural effusion research provides insights to improve surgical study design.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Bull Am Coll Surg. 2012 Nov;97(11):52-3.

AUTORES / AUTHORS:  - Demmy T; Nelson H

 

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[471]

TÍTULO / TITLE:  - Monoclonal antibodies in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Opin Biol Ther. 2013 Feb;13(2):209-26. doi: 10.1517/14712598.2012.748742.  Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1517/14712598.2012.748742

AUTORES / AUTHORS:  - Wang Y; Deng G; Liu X; Cho WC

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of the Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China , Yinchuan, Ningxia , China lxm1966@nxu.edu.cn.

RESUMEN / SUMMARY:  - Introduction: Lung cancer is the leading cause of cancer death worldwide. As clinical benefits to conventional cancer therapies are still formidable, there is an urgent need for novel agents and approaches to improve the overall clinical outcomes for patients with lung cancer. Areas covered: This article reviews the current understanding of targeted therapy for lung cancer with monoclonal antibodies (mAbs), mainly bevacizumab and cetuximab. The results from several key clinical trials validating the effectiveness and safety of bevacizumab and cetuximab, the relation of cancer biomarkers, the polymorphic correlation of targeted genes with the therapeutic outcome of mAb-based treatment, as well as the impact of Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial on personalised treatment of lung cancer are discussed. Expert opinion: The addition of bevacizumab or cetuximab to chemotherapy has shown promising benefits to the patients with non-small-cell lung cancer. However, the overall benefits of mAb-based targeted therapy to lung  cancer patients vary among individuals. It is therefore necessary to define reliable predictive biomarkers in an effort to better identify patients who are most likely to benefit from treatment with these novel agents in lung cancer.

 

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[472]

TÍTULO / TITLE:  - Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Jan 16;13(1):22.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-22

AUTORES / AUTHORS:  - Federico R; Adolfo F; Giuseppe M; Lorenzo S; Martino DT; Anna C; Adriano P; Gino C; Francesca R; Matteo C; Gbenga K; Paolo M; Francesco F

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Malignant pleural mesothelioma is an aggressive tumor that  has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results. METHODS: Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m2+cisplatin 75 mg/m2 IV every 21 days x 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3--8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4--8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation. RESULTS: Fifty-four treatment-naive patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy,  45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including  90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while  median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively.  The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%).Following two cardiopulmonary radiation-related  deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended. CONCLUSIONS: The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation.Trial registration: Clinicaltrial.com registrationID #NCT00087698.

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[473]

TÍTULO / TITLE:  - A549 lung cell line activity of biosynthesized silver nanoparticles using Albizia adianthifolia leaf.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Colloids Surf B Biointerfaces. 2013 Jan 7;105C:87-91. doi: 10.1016/j.colsurfb.2012.12.044.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.colsurfb.2012.12.044

AUTORES / AUTHORS:  - Gengan RM; Anand K; Phulukdaree A; Chuturgoon A

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa. Electronic address: genganrm@dut.ac.za.

RESUMEN / SUMMARY:  - Stable AgNPs were formed in vitro by reacting AgNO(3) (aq) solution with the aqueous plant leaf extract. UV-vis revealed the surface plasmon resonance lambda(max) at 448nm and the absorbance steadily increased in intensity as a function of reaction time. Transmission electron microscope (TEM) and XRD studies were used to characterize the AgNPs; the size was 4-35nm. Dynamic light scattering (DLS) was used as supporting evidence to determine hydrodynamic size and zeta potential recorded as 80.27nm and -24.7mV, respectively. FT-IR spectra suggest that AgNPs are capped with protein molecules and other water soluble phytocompounds such as saponins and glycosides which also behave as stabilizing agents; TEM images indicate a visible layer surrounding the AgNPs. Prominent absorption bands at 3380 and 1642cm(-1) are assigned to alcohol and carbonyl groups, respectively. (1)H NMR of the neat aqueous plant extract indicates presence of a complex mixture of compounds; however the chemical shift at delta 6.0-8.0 and 1.0-4.0ppm indicates the presence of few aromatic but abundant aliphatic compounds, respectively. Toxicity of AgNPs on lung cancer cells (A549)  and normal healthy peripheral lymphocytes (PLs) at 10mug/ml and 50mug/ml was assessed using the MTT, ATP and lactate dehydrogenase assays. Viability data for  A549 cells showed a 21% (10mug/ml) and 73% (50mug/ml) cell viability after 6h exposure to AgNPs compared to 117% (10mug/ml) and 109% (50mug/ml) cell viability  of normal peripheral lymphocytes. Lactate dehydrogenase was only significantly altered at 50mug/ml AgNPs treated cells from 2.43+/-0.04 units to 0.77+/-0.04 units.

 

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[474]

TÍTULO / TITLE:  - Aflibercept in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Opin Biol Ther. 2013 Jan;13(1):115-20. doi: 10.1517/14712598.2013.745847.  Epub 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1517/14712598.2013.745847

AUTORES / AUTHORS:  - Neal JW; Wakelee HA

INSTITUCIÓN / INSTITUTION:  - Stanford University/Stanford Cancer Institute, Department of Medicine (Oncology), Stanford, CA, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Angiogenesis, the recruitment and growth of blood vessels, is a process central to the growth of solid tumors. One of the key mediators of angiogenesis is the vascular endothelial growth factor (VEGF) family of ligands.  An antibody to VEGF-A, bevacizumab, has demonstrated a survival benefit in conjunction with platinum-based doublet chemotherapy in non-small-cell lung cancer (NSCLC). Aflibercept (VEGF Trap) is a recombinant VEGF receptor-antibody protein fusion with higher affinity for VEGF-A than bevacizumab, plus affinity for VEGF-B and placental growth factor (PlGF). AREAS COVERED: This article reviews recent clinical trials investigating the role of aflibercept in the treatment of lung cancer, both published in the literature and those for which preliminary data have been presented at major scientific meetings. EXPERT OPINION: Aflibercept has proven Phase III efficacy in metastatic colorectal cancer, but in lung cancer, large clinical trials have not yielded positive results. There remains hope that identification of biomarkers of response will one day help select patients most likely to benefit from antiangiogenesis therapy.

 

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[475]

TÍTULO / TITLE:  - Management of advanced lung cancer in resource-constrained settings: a perspective from India.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2012 Nov;12(11):1479-95. doi: 10.1586/era.12.119.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.119

AUTORES / AUTHORS:  - Singh N; Aggarwal AN; Behera D

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India.

RESUMEN / SUMMARY:  - Advanced lung cancer (LC) is an important cause of cancer-related morbidity and mortality in resource-constrained settings (RCSs). Cytological/pathological confirmation of diagnosis of LC is essential prior to treatment initiation for ruling out mimickers such as pulmonary tuberculosis. Accurate staging is necessary for optimal management, and investigations should be prioritized based  on availability and cost-effectiveness. Platinum-based doublet chemotherapy remains the standard of care for advanced LC. Cost of therapy, lack of medical insurance and frequency of visits are important determinants of treatment regimen. EGF receptor mutation testing may not be readily available in RCSs and chemotherapy should be preferred for unselected patients with advanced non-small-cell lung cancer. Generic drugs may be more affordable than innovator brands. Treatment efficacy should be assessed with traditional end points (survival and objective response rates) as well as those relevant to RCSs (quality of life, toxicity profile and healthcare facility utilization). Issues related to LC treatment in first- and subsequent-line settings in RCSs are discussed in detail in this evidence-based review.

 

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[476]

TÍTULO / TITLE:  - PARP1 inhibition affects pleural mesothelioma cell viability and uncouples AKT/mTOR axis via SIRT1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Mol Med. 2013 Jan 10. doi: 10.1111/jcmm.12000.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jcmm.12000

AUTORES / AUTHORS:  - Pinton G; Manente AG; Murer B; De Marino E; Mutti L; Moro L

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, University of Piemonte Orientale A. Avogadro, Novara, Italy.

RESUMEN / SUMMARY:  - Malignant Pleural Mesothelioma (MMe) is a rare but increasingly prevalent, highly aggressive cancer with poor prognosis. The aetiology of MMe is essentially a function of previous exposure to asbestos fibres, which are considered to be an early-stage carcinogen. Asbestos is toxic to human mesothelial cells (HMCs), that activate the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP1) to repair DNA.  The targeting of PARP1 is showing considerable potential for delivering selective tumour cell kill while sparing normal cells, and offers a scientifically rational clinical application. We investigated PARP1 expression in normal mesothelial and  MMe tissues samples. Immunohistochemical analysis revealed low PARP1 staining in  peritumoural mesothelium. As opposite, a progressive increase in epithelioid and  in the most aggressive sarcomatoid MMe tissues was evident. In MMe cell lines, we correlated increased PARP1 expression to sensitivity to its inhibitor CO-338 and  demonstrated that CO-338 significantly reduced cell viability as single agent and was synergistic with cis-platin. Interestingly, we described a new correlation between PARP1 and the AKT/mTOR axis regulated by SIRT1. SIRT1 has a role in the modulation of AKT activation and PARP1 has been described to be a gatekeeper for  SIRT1 activity by limiting NAD+ availability. Here, we firstly demonstrate an inverse correlation between AKT acetylation and phosphorylation modulated by SIRT1 in MMe cells treated with CO-338. In conclusion, this study demonstrates that PARP1 overexpression defines increased responsiveness to its inhibition, then these results imply that a substantial fraction of patients could be candidates for therapy with PARP inhibitors.

 

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[477]

TÍTULO / TITLE:  - On the horizon for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Manag Care. 2012 Dec;18(5 Spec No.):SP237-41.

AUTORES / AUTHORS:  - Comeau JM; Mohundro MM; Mohundro BL

INSTITUCIÓN / INSTITUTION:  - Assistant Professor, University of Louisiana at Monroe College of Pharmacy-Shreveport, 1725 Claiborne Ave, Shreveport, LA 71103. E-mail: comeau@ulm.edu.

 

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[478]

TÍTULO / TITLE:  - The optimality of different strategies for supplemental staging of non-small-cell lung cancer: a health economic decision analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Value Health. 2013 Jan;16(1):57-65. doi: 10.1016/j.jval.2012.09.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jval.2012.09.007

AUTORES / AUTHORS:  - Sogaard R; Fischer BM; Mortensen J; Rasmussen TR; Lassen U

INSTITUCIÓN / INSTITUTION:  - Centre for Health Services Research and Technology Assessment, Institute for Public Health, University of Southern Denmark, Odense, Denmark. Electronic address: ris@cast.sdu.dk.

RESUMEN / SUMMARY:  - OBJECTIVES: To assess the expected costs and outcomes of alternative strategies for staging of lung cancer to inform a Danish National Health Service perspective about the most cost-effective strategy. METHODS: A decision tree was specified for patients with a confirmed diagnosis of non-small-cell lung cancer. Six strategies were defined from relevant combinations of mediastinoscopy, endoscopic or endobronchial ultrasound with needle aspiration, and combined positron emission tomography-computed tomography with F18-fluorodeoxyglucose. Patients without distant metastases and central or contralateral nodal involvement (N2/N3) were considered to be candidates for surgical resection. Diagnostic accuracies were informed from literature reviews, prevalence and survival from the Danish Lung Cancer Registry, and procedure costs from national average tariffs. All parameters were specified probabilistically to determine the joint decision uncertainty. The cost-effectiveness analysis was based on the net present value of expected costs and life years accrued over a time horizon of 5 years. RESULTS: At threshold values of around euro30,000 for cost-effectiveness, it was found to  be cost-effective to send all patients to positron emission tomography-computed tomography with confirmation of positive findings on nodal involvement by endobronchial ultrasound. This result appeared robust in deterministic sensitivity analysis. The expected value of perfect information was estimated at  euro52 per patient, indicating that further research might be worthwhile. CONCLUSIONS: The policy recommendation is to make combined positron emission tomography-computed tomography and endobronchial ultrasound available for supplemental staging of patients with non-small-cell lung cancer. The effects of  alternative strategies on patients’ quality of life, however, should be examined  in future studies.

 

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[479]

TÍTULO / TITLE:  - miRNA-mRNA network detects hub mRNAs and cancer specific miRNAs in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - In Silico Biol. 2011-2012;11(5-6):281-95. doi: 10.3233/ISB-2012-0444.

            ●● Enlace al texto completo (gratuito o de pago) 3233/ISB-2012-0444

AUTORES / AUTHORS:  - Devaraj S; Natarajan J

INSTITUCIÓN / INSTITUTION:  - Data Mining and Text Mining Laboratory, Dept. of Bioinformatics, Bharathiar University, Coimbatore, India.

RESUMEN / SUMMARY:  - MicroRNA expression profiles can improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. In this paper, we  undertook to develop a miRNA-mRNA network and uncover unique growth suppressive miRNAs in lung cancer using microarray data. The miRNA-mRNA network was developed based on a bipartite graph theory approach, and a number of miRNA-mRNA modules have been identified to mine associations between miRNAs and mRNAs. From the network, we identified totally 29 protective miRNA-mRNA regulatory modules, since we restricted our search to protective miRNAs. Subsequently we analyzed the pathways for the target genes in the protective miRNA-mRNA modules using Pathway-Express. The miRNA-mRNA network efficiently detects hub mRNAs deregulated by the protective miRNAs and identifies cancer specific miRNAs in lung cancer. From the pathway analysis results, the ECM receptor pathway, Focal adhesion pathway and cell adhesion molecules pathway seem to be more interesting to investigate, since these pathways were related to all the ten protective miRNAs.  Furthermore, protective miRNA target analysis revealed that genes VCAN, SIL, CD44 and MMP14 were found to have an important role in these pathways. Hence, it was inferred that these genes can be important putative targets for those protective  miRNAs. A greater understanding of the mechanisms regulating VCAN, SIL, CD44 and  MMP14 expression and activity will assist in the development of specific inhibitors of cancer cell metastasis. Thus these observations are expected to have an intense implication in cancer and may be useful for further research.

 

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[480]

TÍTULO / TITLE:  - A woman with a solitary pulmonary nodule: is it a lung cancer?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Rev Med Pharmacol Sci. 2012 Oct;16 Suppl 4:38-41.

AUTORES / AUTHORS:  - Conti V; Petroianni A; Halili I; Lemontzi E; Dal V; Lagalla M; Vitolo D; Paone G; Terzano C

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular and Respiratory Sciences, Sapienza University of Rome, Rome, Italy.

RESUMEN / SUMMARY:  - BACKGROUND: Solitary pulmonary nodules present a real challenge for physicians. Due to the clinical implications and prognosis of a certain diagnosis, it should  be pursued with any cost; a clear definition is not always simple and further investigations are often necessary to exclude the possibility of a malignancy. A  diagnostic path must be followed and the clinical hypothesis should be reconsidered on the basis of the new information provided by the tests, always keeping in mind their limits! Sometimes only the surgical resection permits a definitive diagnosis. A 68 year-old non-smoker female with a pulmonary solitary nodule highly suspicious to be malignant at the chest CT, performed a FBS with BAL, negative for neoplastic cells and for infective agents, and a CT guided pulmonary biopsy that was inconclusive. The patient underwent then a video-thoracoscopic atypical lung resection that demonstrated the reactive nature of the lesion, definitely excluding the presence of a malignancy.

 

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[481]

TÍTULO / TITLE:  - Relation between nitrate and nitrite food habits with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Exp Ther Oncol. 2012;10(2):107-12.

AUTORES / AUTHORS:  - Karimzadeh L; Koohdani F; Siassi F; Mahmoudi M; Moslemi D; Safari F

INSTITUCIÓN / INSTITUTION:  - Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - Nitrites, a probable human carcinogen, generate reactive nitrogen species that may cause damage to the lung. We evaluated the association between nutritional habits related to nitrite and nitrate intake and risk of lung cancer in Mazandaran, Northern Province of Iran. In this case-control study the two groups  were matched for gender and age (+/- 5 years). A semi -quantitative food frequency questionnaire (FFQ) was used to collect dietary data about nutritional  habits related to nitrate, nitrite, vitamins E and C intake, from 40 lung cancer  cases and 40 control subjects admitted at Mazanaran hospitals. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of lung cancer using logistic regression. Mean score of nutritional habits in case group was significantly lower than that in control group (P less than or equal 0.001). We observed a positive association between animal sources of nitrate and nitrite intake (OR = 2.7, 95% CI: 0.13-0.96) and risk of lung cancer. Decreased risk of lung cancer was also observed with fruit intake (OR = 0.26, 95% CI: 1.3-11). Our  results indicate a probable association between nutritional habits related to animal sources of nitrate and nitrite intake and the risk of lung cancer that requires to be confirmed by other studies.

 

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[482]

TÍTULO / TITLE:  - Virtual bronchoscopy using FDG-PET/CT images for the evaluation of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Rev Med Pharmacol Sci. 2012 Dec;16(14):1951-60.

AUTORES / AUTHORS:  - Yildirim D; Tamam M; Sanli Y; Ozgul MA; Somay A

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Kasimpasa Military Hospital, Istanbul, Turkey. yildirimduzgun@yahoo.com

RESUMEN / SUMMARY:  - <strong> PURPOSE: </strong> We aimed to put forward the contribution of virtual bronchoscopy in the determination and diagnosis of tracheobronchial system pathologies. We compared the data obtained from PET/CT and virtual bronchoscopy (VB) with the fiberoptic bronchoscopy (FOB) data of the cases with a diagnosis or pre-diagnosis of lung tumor. <strong> MATERIALS AND METHODS: </strong> A total of 261 (male=238, female=23) lung cancer cases with a mean age of 53+/-7.3 years (range =35-77 years), who had undergone FOB and had bronchoalveolar lavage and/or biopsy results, were included in this multicenter, prospective study conducted between 2006 and 2008. FOB data confirmed with cytohistopathology were considered as the gold standard. Five cases that had peripheral lesions, with negative cytopathological results were excluded from the study. Positron emission tomography images were fused with 16/slice multi-detector computed tomography system images (Discovery ST PET/16 slice CT fusion system HPOWER 60; General Electric Medical Systems, Milwaukee, WI, USA). Thereafter, all of the cases were  evaluated with virtual bronchoscopy, using a special multidisplay workstation with multiplanar reformatting (MPR) and minimum intensity projection (MINIP) to see the fused images simultaneously. The data obtained with both virtual bronchoscopy (PET/CT VB) and FOB in different centers were recorded, and the evaluation and comparison of these data were done by an independent researcher. The sensitivity, specificity, and positive and negative predictive values of making an accurate diagnosis and defining concomitant pathologies by both methods, were calculated. <strong> RESULTS: </strong> The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy values of VB and PET/CT-VB in determining the segment involved by malignancy were as follows, 91%, 83%, 94%, 77%, and 89%, and 95%, 97%, 99%, 87%, and 96%, respectively. <strong> CONCLUSIONS: </strong> The sensitivity of PET/CT-VB in determining the involved tracheobronchial segment(s) in malignancy and concomitant pathologies in cases with lung tumor was remarkably higher than that  with CT-VB. Therefore, PET/CT-VB is recommended to be included in routine lung cancer examinations since it provides similar outcomes to that of FOB+cytohistopathological examination.

 

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[483]

TÍTULO / TITLE:  - Clinical Significance of EML4-ALK Fusion Gene and Association with EGFR and KRAS  Gene Mutations in 208 Chinese Patients with Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e52093. doi: 10.1371/journal.pone.0052093. Epub 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052093

AUTORES / AUTHORS:  - Li Y; Li Y; Yang T; Wei S; Wang J; Wang M; Wang Y; Zhou Q; Liu H; Chen J

INSTITUCIÓN / INSTITUTION:  - Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Heping District, Tianjin, China.

RESUMEN / SUMMARY:  - The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK,  EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in  primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the  NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites.

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[484]

TÍTULO / TITLE:  - Long-term survival rates of patients with stage IIIB and IV non-small cell lung cancer treated with cisplatin plus vinorelbine or gemcitabine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Dec;4(6):1035-1038. Epub 2012 Sep 18.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.714

AUTORES / AUTHORS:  - Ozkaya S; Findik S; Dirican A; Atici AG

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Faculty of Medicine, Rize University, Rize;

RESUMEN / SUMMARY:  - Limited data exist concerning the long-term (>/=5 year) survival rates of patients with stage IIIB and IV non-small cell lung carcinoma (NSCLC) receiving chemotherapy. We aimed to determine the long-term results of cisplatin plus third-generation (vinorelbine or gemcitabine) cytotoxic chemotherapy in patients  with locally advanced and advanced NSCLC. The study included 141 patients, and all patients were followed up from the time of diagnosis until death. The median  age of the patients was 59.1+/-9.9 years. The male-to-female ratio was 124/17; 62.4% of the patients had stage IIIB and 37.6% had stage IV NSCLC. Squamous cell  carcinoma, adenocarcinoma and undifferentiated NSCLC subtypes accounted for 69.5, 17.7 and 12.7% of the cases, respectively. The overall response rate was 32.6% and the median survival time was 12.3 months (95% CI, 10.2-14.5). The median survival times for stages IIIB and IV were 12.6+/-1.4 and 11.9+/-1.7 months, respectively. The 1-, 2-, 3- and 5-year survival rates were 33, 7.5, 4.3 and 2.8%, respectively. In conclusion, cisplatin-based new-generation cytotoxic agents for combined modality therapy offer an increased hope of long-term survival for patients with locally advanced and advanced NSCLC.

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[485]

TÍTULO / TITLE:  - Towards Mechanism Classifiers: Expression-anchored Gene Ontology Signature Predicts Clinical Outcome in Lung Adenocarcinoma Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AMIA Annu Symp Proc. 2012;2012:1040-9. Epub 2012 Nov 3.

AUTORES / AUTHORS:  - Yang X; Li H; Regan K; Li J; Huang Y; Lussier YA

INSTITUCIÓN / INSTITUTION:  - Center for Biomedical Informatics, Dept. of Medicine, Section of Hematology/Oncology, Department of Pediatrics; The University of Chicago, Chicago, IL 60637;

RESUMEN / SUMMARY:  - We aim to provide clinically applicable, reproducible, mechanistic interpretations of gene expression changes that lack in gene overlap among predictive gene-signatures. Using a method we recently developed, Functional Analysis of Individual Microarray Expression (FAIME), we provide evidence that Gene Ontology-anchored signatures (GO-signatures) show reliable prognosis in lung cancer. In order to demonstrate the biological congruence and reproducibility of  FAIME-derived mechanism classifiers, we chose a disease where gene expression classifiers signatures alone had failed to significantly stratify a larger collection of samples and that exhibited poor or no genetic overlap. For each patient in the two lung adenocarcinoma studies, personalized FAIME-profiles of GO biological processes are generated from genome-wide expression profiles. For both training studies, GO-signatures significantly associated to patient mortality were identified (Prediction Analysis for Microarrays; three-fold cross-validation). These two GO-signatures could effectively stratify patients from an independent validation cohort into sub-groups that show significant differences in disease-free survival (log-rank test P=0.019; P=0.001). Importantly, significant mechanism overlaps assessed by information-theory similarity were detected between the two GO-signatures (Fischer Exact Test p=0.001). Hence, together with machine learning technologies, FAIME could be utilized to develop an ontology-driven and expression-anchored prognostic signature that is personalized for an individual patient.

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[486]

TÍTULO / TITLE:  - A Randomized Phase II Study of Pemetrexed in Combination With Cisplatin or Carboplatin as First-line Therapy for Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 15. pii: S1525-7304(12)00249-5. doi: 10.1016/j.cllc.2012.10.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.001

AUTORES / AUTHORS:  - Schuette WH; Groschel A; Sebastian M; Andreas S; Muller T; Schneller F; Guetz S; Eschbach C; Bohnet S; Leschinger MI; Reck M

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine II, Hospital Martha-Maria, Halle-Dolau, Halle, Germany. Electronic address: wolfgang.schuette@martha-maria.de.

RESUMEN / SUMMARY:  - BACKGROUND: Pemetrexed plus cisplatin was approved for first-line treatment of non-small-cell lung cancer (NSCLC) in patients with nonsquamous histology after initiation of this study. This phase II study evaluated pemetrexed plus cisplatin and pemetrexed plus carboplatin as first-line treatments for stage IIIB/IV NSCLC. PATIENTS AND METHODS: The patients were randomized (1:1) to 2 parallel arms: pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) or pemetrexed (500 mg/m(2))  plus carboplatin (area under the curve 6) day 1 every 3 weeks (maximum, 6 cycles). Progression-free survival (PFS) was the primary objective; secondary objectives included overall survival (OS), 1-year survival, and safety. RESULTS:  Sixty-five patients were randomized to each treatment arm. The patients treated with pemetrexed plus cisplatin had a median age of 64 years and were predominantly men (42 [64.6%]) with nonsquamous histology (53 [81.5%]), stage IV  (61 [92.4%]) disease, and a performance status of 0 (40 [61.5%]). Median PFS was  6.0 months, 6-month PFS rate was 50.5%, median OS was 11.7 months, and 1-year survival rate was 47.5%. Drug-related grade ¾ toxicities included neutropenia (11 [16.9%]), anemia (5 [7.7%]), thrombocytopenia (2 [3.1%]), and nausea (3 [4.6%]). Patients treated with pemetrexed plus carboplatin had a median age of 63 years, were predominantly men (46 [70.8%]) with nonsquamous histology (52 [80.0%]), stage IV (58 [86.6%]) disease, and a performance status of 0 (45 [69.2%]). The median PFS was 4.7 months, the 6-month PFS rate was 34.9%, median OS was 8.9 months, and 1-year survival rate was 39.2%. Drug-related grade ¾ toxicities included neutropenia (17 [26.2%]), thrombocytopenia (11 [16.9%]), anemia (7 [10.8%]), and nausea (5 [7.7%]). CONCLUSIONS: Both the pemetrexed plus  cisplatin and pemetrexed plus carboplatin arms met their primary endpoints and demonstrated efficacy and tolerability as first-line therapy in patients with advanced NSCLC. http://ClinicalTrials.gov: NCT00402051.

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[487]

TÍTULO / TITLE:  - Prognostic factors for survival of patients with extensive stage small cell lung  cancer—a retrospective single institution analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):4959-62.

AUTORES / AUTHORS:  - Wu C; Li F; Jiao SC

INSTITUCIÓN / INSTITUTION:  - Department of General Hospital of Chinese PLA (People’s Liberation Army), Beijing, China.

RESUMEN / SUMMARY:  - The objective of this retrospective study was to investigate prognostic factors associated with survival of patients with extensive stage small cell lung cancer  (ES-SCLC). Included were 200 patients admitted to the Liberation Army General Hospital with a diagnosis of ES-SCLC. The demographics of patients, disease characteristics, pre-treatment biochemical parameters and therapeutic plan were assessed or evaluated. Univariate analysis found that second-line chemotherapy, radiotherapy, and no liver metastasis were associated with improved survival. Tumor response to first-line chemotherapy and normal initial hemoglobin levels were also associated with a survival benefit (all P-values </= 0.0369). Multivariate Cox regression analysis indicated that liver metastasis and the total number of all chemotherapy cycles were independent prognostic factors of survival. The morbidity risk in patients with liver metastasis was 2.52-fold higher than that in patients without liver metastasis (hazard ratio (HR)=2.52 (1.69-3.76); P<0.0001). However, one unit increase in the total number of chemotherapy cycles decreased the risk of death by 0.86-fold (HR=0.86 (0.80-0.92); P<0.0001). Absence of liver metastasis and ability of a patient to receive and tolerate multiple lines of chemotherapy were associated with longer survival.

 

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[488]

TÍTULO / TITLE:  - The relationship between tyrosine kinase inhibitor therapy and overall survival in patients with non-small cell lung cancer carrying EGFR mutations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer. 2012 Dec 7. doi: 10.5732/cjc.012.10160.

            ●● Enlace al texto completo (gratuito o de pago) 5732/cjc.012.10160

AUTORES / AUTHORS:  - Suzuki H; Hirashima T; Okamoto N; Yamadori T; Tamiya M; Morishita N; Shiroyama T; Otsuka T; Kitai K; Kawase I

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino Habikino-shi Osaka, 583-8588 Japan. suzukih@ra.opho.jp.

RESUMEN / SUMMARY:  - For patients with epidermal growth factor receptor (EGFR) mutation-positive lung  cancer, the relationship between the dose or duration of treatment with tyrosine  kinase inhibitor (TKI) and overall survival remains unclear. Here, we retrospectively analyzed clinical data for 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was  553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) =  0.263- 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.

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[489]

TÍTULO / TITLE:  - A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Case Rep. 2012 Dec 28;6(1):427. doi: 10.1186/1752-1947-6-427.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-6-427

AUTORES / AUTHORS:  - Okonogi N; Ebara T; Ishikawa H; Yoshida D; Ueno M; Maeno T; Suga T; Nakano T

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. noriyukiokonogi@gmail.com.

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Malignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy. CASE PRESENTATION: A 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent  with a diagnosis of malignant pleural mesothelioma (sarcomatoid type). The tumor  was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies  including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years. CONCLUSIONS: The combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be  considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to confirm the effects of this treatment on malignant pleural mesothelioma.

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[490]

TÍTULO / TITLE:  - Gene therapy using the human telomerase catalytic subunit gene promoter enables targeting of the therapeutic effects of vesicular stomatitis virus matrix protein against human lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Nov;4(5):859-864. Epub 2012 Aug 23.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.679

AUTORES / AUTHORS:  - Zhang P; Tan J; Yang DB; Luo ZC; Luo S; Chen P; Sun P; Zhou Y; Chen XC; Wei YQ; Wen YJ

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041;

RESUMEN / SUMMARY:  - The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is highly active in immortalized cells and more than 90% of human cancer cells, but is quiescent in the majority of normal somatic cells. Thus, the hTERT  promoter has been extensively used in targeted cancer gene therapy. Vesicular stomatitis virus (VSV) matrix protein (MP) induces the apoptosis of tumor cells in the absence of other viral components. In our previous studies, we successfully constructed the pVAX-M plasmid from the pVAX plasmid, which expressed wild-type VSV MP (VSV MP is under the control of the CMV promoter) and  demonstrated that pVAX-M efficiently suppresses the growth of malignant tumors via the induction of apoptosis in vitro and in vivo. The present study was designed to construct the plasmid phTERTM (VSV MP is under the control of the hTERT promoter) and investigate whether it had a targeted antitumor effect in nude mice bearing human lung adenocarcinoma. In vitro, A549 human lung adenocarcinoma cells were treated with NS, Lip-null, etoposide, Lip-pVAX-M or Lip-phTERT-M, and examined for cell viability through MTT assays or for apoptosis by flow cytometry and TUNEL assays. In vivo, A549 human lung carcinoma models in  nude mice were established. Mice were treated with 10 4-weekly intravenous administrations of NS, Lip-null, etoposide (2 mg/kg), Lip-pVAX-M or Lip-phTERT-M. Subsequently, Lip-phTERT-M was found to be the most efficient inhibitor of tumor  growth and inducer of tumor cell apoptosis when compared with the other groups in vivo and in vitro (P<0.05). Notably, immunohistochemical staining showed that Lip-phTERT-M significantly limited the overexpression of VSV MP to the tumor tissues and reduced VSV MP expression in other organs in comparison with Lip-pVAX-M (P<0.05). Therefore, it can be concluded that phTERT-M demonstrates a  targeted antitumor effect on A549 human lung adenocarcinoma cells. These observations suggest that phTERT-M gene therapy may be a novel and potent strategy for targeting human lung adenocarcinoma.

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[491]

TÍTULO / TITLE:  - Virtual Reality Bringing a New Reality to Postthoracotomy Lung Cancer Patients Via a Home-Based Exercise Intervention Targeting Fatigue While Undergoing Adjuvant Treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Nurs. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NCC.0b013e318278d52f

AUTORES / AUTHORS:  - Hoffman AJ; Brintnall RA; Brown JK; von Eye A; Jones LW; Alderink G; Ritz-Holland D; Enter M; Patzelt LH; Vanotteren GM

INSTITUCIÓN / INSTITUTION:  - Author Affiliations: College of Nursing, Michigan State University, East Lansing  (Dr Hoffman); Kirkhof College of Nursing, Grand Valley State University, Grand Rapids, Michigan (Dr Brintnall); School of Nursing, University at Buffalo, State  University of New York (Dr Brown); Psychology Department, Michigan State University, East Lansing (Dr von Eye); Duke Center for Cancer Survivorship, Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (Dr Jones); Frederik Meijer Honors College, Grand Valley State University, Grand Rapids, Michigan (Dr Alderink); Lemmen-Holton Cancer Pavilion,  Spectrum Health, Grand Rapids (Ms Ritz-Holland and Mr Enter), Michigan; and Spectrum Health, Grand Rapids, Michigan, and College of Human Medicine, Michigan  State University, East Lansing (Drs Patzelt and VanOtteren).

RESUMEN / SUMMARY:  - BACKGROUND:: Little is known about rehabilitation for postthoracotomy non-small cell lung cancer (NSCLC) patients. This research uses a perceived self-efficacy-enhancing light-intensity exercise intervention targeting a priority symptom, cancer-related fatigue (CRF), for postthoracotomy NSCLC patients. This article reports on phase II of a 2-phase study. Phase I focused on initiation and tolerance of exercise during the 6 weeks immediately after thoracotomy, whereas phase II addressed maintenance of exercise for an additional 10 weeks including participants initiating and completing chemotherapy and/or radiation therapy. OBJECTIVE:: The objective of this study was to investigate the feasibility, acceptability, and preliminary efficacy of an exercise intervention  for postthoracotomy NSCLC patients to include those initiating and completing adjuvant therapy. INTERVENTIONS/METHODS:: A single-arm design composed of 7 participants postthoracotomy for NSCLC performed light-intensity exercises using  an efficacy-enhancing virtual-reality approach using the Nintendo Wii Fit Plus. RESULTS:: Despite most participants undergoing chemotherapy and/or radiation therapy, participants adhered to the intervention at a rate of 88% with no adverse events while giving the intervention high acceptability scores on conclusion. Likewise, participants’ CRF scores improved from initiation through the conclusion of the intervention with perceived self-efficacy for walking at a  light intensity continuously for 60 minutes, improving significantly upon conclusion over presurgery values. CONCLUSIONS:: Postthoracotomy NSCLC patients maintained exercise for an additional 10 weeks while undergoing adjuvant therapy  showing rehabilitation potential because the exercise intervention was feasible,  safe, well tolerated, and highly acceptable showing positive changes in CRF self-management. IMPLICATIONS FOR PRACTICE:: A randomized controlled trial is needed to further investigate these relationships.

 

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[492]

TÍTULO / TITLE:  - Applied research on serum protein fingerprints for prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Tradit Chin Med. 2012 Sep;32(3):350-4.

AUTORES / AUTHORS:  - Liu Z; Yu Z; Ouyang X; Du J; Lan X; Zhao M

INSTITUCIÓN / INSTITUTION:  - Academy of Integrative Medicine of Fujian University ofTCM, Fuzhou, Fujian 350122, China.

RESUMEN / SUMMARY:  - OBJECTIVE: This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer; and as diagnostic model of Chinese medicine. METHODS: Serum samples from 63 lung  cancer patients with Qi deficiency syndrome and phlegm and blood stasis, and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis  were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader. Protein profiles were generated using immobilized metal affinity capture (IMAC3) protein  chips. Differentially-expressed proteins were screened. Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages, respectively. RESULTS: A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened (P<0.05). The decision tree model was M 2284.97, with a sensitivity of 96.2% and a specificity of 66.7%. CONCLUSION: SELDI-TOF-MS techniques, combined with a decision tree model, can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients; and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.

 

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[493]

TÍTULO / TITLE:  - Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR  mutation-positive Non-small cell lung cancer: an economic analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Jan 29;13(1):39.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-39

AUTORES / AUTHORS:  - Zhu J; Li T; Wang X; Ye M; Cai J; Xu Y; Wu B

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. METHODS: A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained  from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used  to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. RESULTS: After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The  utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. CONCLUSIONS: These  results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

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[494]

TÍTULO / TITLE:  - Analysis of the impact of chest wall constraints on eligibility for a randomized  trial of stereotactic body radiotherapy of peripheral stage I non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Imaging Radiat Oncol. 2012 Dec;56(6):654-60. doi: 10.1111/j.1754-9485.2012.02437.x. Epub 2012 Sep 5.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1754-9485.2012.02437.x

AUTORES / AUTHORS:  - Siva S; Shaw M; Chesson B; Gill S; Ball D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University of Melbourne, Melbourne, Victoria, Australia. shankar.siva@petermac.org

RESUMEN / SUMMARY:  - INTRODUCTION: Chest wall toxicities are recognized complications of stereotactic  radiotherapy (SBRT) in non-small cell lung cancer. To minimize toxicity, the Trans-Tasman Radiation Oncology Group (TROG) 09.02 ‘CHISEL’ study protocol excluded patients with tumours within 1 cm of the chest wall. The purpose of this study is to evaluate the implication of chest wall proximity constraints on patient eligibility, toxicity and potential accrual. METHODS: Exclusion zones of  1 cm beyond the mediastinum and 2 cm beyond the bifurcation of the lobar bronchi  were incorporated into the CHISEL credentialing CT dataset. Volumes of lung within which tumours varying from 1 cm to 5 cm in diameter may occupy and remain  eligible for the CHISEL study were calculated. These volumes were compared to a hypothetical model in which the 1 cm chest wall proximity restriction was removed. RESULTS: The percentage of lung area in which a tumour mass can occupy and be suitable for CHISEL in the left and right lung were 54% and 60% respectively. Removing the constraint increased the percentage of available lung  to 83% and 87% respectively. Considering a 2 cm spherical tumour, only 21% and 31% of tumours in the left and right lung would be eligible with the chest wall constraint, whilst 39% and 50% respectively would be eligible without the constraint. CONCLUSIONS: The exclusion of tumours less than 1 cm to chest wall significantly reduces the proportion of patients eligible for the CHISEL protocol. A review of the literature pertaining to chest wall toxicity after stereotactic radiotherapy supports a change in chest wall exclusion criteria for  the CHISEL study.

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[495]

TÍTULO / TITLE:  - Clinical characteristics, treatment and survival outcomes in malignant mesothelioma: eighteen years’ experience in Turkey.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(11):5735-9.

AUTORES / AUTHORS:  - Berk S; Dogan OT; Kilickap S; Epozturk K; Akkurt I; Seyfikli Z

INSTITUCIÓN / INSTITUTION:  - Department of Chest Diseases, Faculty of Medicine, Cumhuriyet University, Sivas,  Turkey E-mail : serdar_berk@mynet.com.

RESUMEN / SUMMARY:  - Background: Malignant mesothelioma (MM) is an insidious tumor with poor prognosis, arising from mesothelial surfaces such as pleura, peritoneum and pericardium. We here aimed to evaluate the demographic, clinical, and radiological features of patients with MM followed in our center as well as their survival. Methods: The study included 228 patients (131 male, 97 female) who were followed up in our institution between 1993 and 2010 with the diagnosis of MM. Results: The mean age was 59.1 years in men and 58.7 years in women and the sex ratio was 1.4:1 in favor of males. Environmental asbestos exposure was present in 86% of the patients for a mean duration of 40+/-20 years (range: 3-70). Pleural effusion and thoracic/abdominal pain were the most common presenting signs and symptoms (70.2% and 57.8%, respectively). One hundred-thirteen (66%) patients were treated with platinum-based combination chemotherapy (PBCT) plus supportive  care (SC) and 67 (34%) patients received SC alone. The median follow-up time was  10.0 months. The median overall survival was significantly improved with PBCT plus SC compared to SC alone (11.4 vs. 5.1 months; p=0.005). The 6, 12, 18, and 24-month survival rates were significantly improved with PBCT plus SC compared to SC alone (72%, 43%, 19%, and 2% vs. 49%, 31%, 11%, and 1%). Conclusion: The survival of patients with MM improved in patients treated with PBCT. The survival advantage continued 12- and 24-month after the initial time of combination chemotherapy.

 

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[496]

TÍTULO / TITLE:  - Molecular targeted therapy in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minn Med. 2012 Oct;95(10):38-41.

AUTORES / AUTHORS:  - Fujioka N; Bitterman PB

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Masonic Cancer Center, University of Minnesota, USA.

RESUMEN / SUMMARY:  - Genetic sequencing has allowed better understanding of non-small-cell lung cancer, leading to improvements in the ability to diagnose and treat the disease  through targeted therapy. This article describes some of the past and ongoing studies of targeted therapies for lung cancers, the genetic mutations in lung cancers that develop in people who never smoked, and the role of Minnesota researchers in understanding the pathogenesis of lung cancer.

 

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[497]

TÍTULO / TITLE:  - Prognostic Value of Gross Tumor Volume for Definitive Radiation Therapy in Patients With Locoregionally Recurrent Non-Small-Cell Lung Cancer After Surgical  Resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Dec 28. pii: S1525-7304(12)00252-5. doi: 10.1016/j.cllc.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.002

AUTORES / AUTHORS:  - Lee NK; Moon SH; Kim TH; Han JY; Yun T; Kim HT; Lee HS; Kim MS; Lee JM; Cho KH; Lee JS

INSTITUCIÓN / INSTITUTION:  - Proton Therapy Center, Research Institute Hospital, National Cancer Center, Goyang, Republic of Korea.

RESUMEN / SUMMARY:  - PURPOSE: To investigate the prognostic value of gross tumor volume (GTV) for predicting survival outcomes and to present the results of definitive radiation therapy (RT) in patients with postsurgical locoregionally recurrent non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between April 2001 and September 2009, 38 patients with postsurgical locoregionally recurrent NSCLC underwent definitive RT with curative intent. Median follow-up time for surviving patients was 54.9 months. The primary endpoint was postrecurrence overall survival (OS). The effect of tumor volume on clinical outcome was assessed by using 2 cutoff values of GTV, 20 and 80 cm(3). RESULTS: Median postrecurrence survival time was 27.9 months, and the 2-, 3-, and 5-year estimated OS rates were 56.0%, 39.8% and 33.2%, respectively. The median GTV was 26.8 cm(3). Patients with a GTV <20 cm(3) had significantly higher 2-year (69.0% vs. 28.6%) and 3-year (61.4% vs. 14.3%) OS rates than patients with a GTV >/=80 cm(3) (P = .004). Patients with isolated local or regional recurrence had significantly better OS than patients with combined local and regional recurrence (P = .001). Multivariate analysis showed that smaller GTV and isolated local or regional recurrence were independent favorable prognostic factors for OS. CONCLUSIONS: Postrecurrence OS of patients with postsurgical locoregionally recurrent NSCLC treated with definitive RT was excellent compared with previous findings. The GTV as a continuous variable was a better predictor of OS than stage at recurrence and may be useful for stratifying the risk in patients with postsurgical recurrent NSCLC.

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[498]

TÍTULO / TITLE:  - Editorial Comment from Dr Schreiber and Dr Rineer to Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Urol. 2012 Dec 11. doi: 10.1111/iju.12059.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iju.12059

AUTORES / AUTHORS:  - Schreiber D; Rineer J

INSTITUCIÓN / INSTITUTION:  - Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, New  York. david.schreiber@va.gov.

 

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[499]

TÍTULO / TITLE:  - Editorial Comment from Dr Koga to Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Urol. 2012 Dec 11. doi: 10.1111/iju.12058.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iju.12058

AUTORES / AUTHORS:  - Koga F

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. f-koga.uro@tmd.ac.jp.

 

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[500]

TÍTULO / TITLE:  - Editorial Comment from Dr Ismaili to Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Urol. 2012 Dec 11. doi: 10.1111/iju.12057.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iju.12057

AUTORES / AUTHORS:  - Ismaili N

INSTITUCIÓN / INSTITUTION:  - Department of Oncology and Radiotherapy, Medical Oncology, Oncology Center, University Hospital Mohammed VI, and Faculty of Medicine, Cadi Ayyad University;  Faculty of Medicine, Cadi Ayyad University, Marrakech, Morocco. ismailinabil@yahoo.fr.

 

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[501]

TÍTULO / TITLE:  - Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Urol. 2012 Dec 11. doi: 10.1111/iju.12038.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iju.12038

AUTORES / AUTHORS:  - Meijer RP; Meinhardt W; van der Poel HG; van Rhijn BW; Kerst JM; Pos FJ; Horenblas S; Bex A

INSTITUCIÓN / INSTITUTION:  - Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.

RESUMEN / SUMMARY:  - OBJECTIVES: To assess the long-term outcome and the risk for local recurrence of  patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation).  METHODS: All consecutive patients with primary small cell carcinoma of the bladder (n = 66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n = 27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. RESULTS: Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n = 19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival  0.0% for incomplete responders (n = 8; P = 0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. CONCLUSIONS: Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population.

 

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[502]

TÍTULO / TITLE:  - Radiotherapy Alone vs. Radiochemotherapy in Patients With Favorable Prognosis of  Clinical Stage IIIA Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 4. pii: S1525-7304(12)00250-1. doi: 10.1016/j.cllc.2012.10.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.002

AUTORES / AUTHORS:  - Jeremic B; Milicic B; Milisavljevic S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University Hospital, Kragujevac, Serbia. Electronic address: b.jeremic@sun.ac.za.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the outcome of radiotherapy (RT) vs. radiochemotherapy (RT-CHT) in patients with locally advanced, inoperable non-small-cell lung cancer who had a “favorable” prognosis (stage IIIA, Karnofsky performance score 70-100,  no weight loss >5%). PATIENTS AND METHODS: A total of 222 patients with these characteristics were among 600 patients enrolled into 5 prospective trials between 1988 and 1998, and were treated with either hyperfractionated RT alone (doses of 69.6 and 67.6 Gy when using 1.2 and 1.3 Gy twice a day, respectively) (n = 45) or the same hyperfractionated RT and concurrent CHT (n = 177), which consists of either carboplatin-etoposide (or paclitaxel-carboplatin. RESULTS: The median times and 5-year overall survival, local progression-free survival, and the distant metastasis-free survival rates for all 222 patients were 33 months, 31 months, and not attained yet, respectively, and 36%, 43%, and 57%, respectively. RT-CHT was superior to RT alone in terms of both overall survival (median survival time, 38 vs. 21 months, respectively; 5-year, 41% vs. 16%, respectively; P < .001) and local progression-free survival (median time to local progression, 38 vs. 22 months, respectively, 5-year local progression-free survival, 48% vs. 23%, respectively; P < .001) but not the distant metastasis-free survival. The most frequent acute high-grade (>3) toxicity was esophageal and bronchopulmonary (8% each) and the most frequent late high-grade toxicity was esophageal (6%). RT-CHT caused only significantly more hematologic high-grade toxicity. CONCLUSIONS: RT-CHT achieved excellent results in this favorable patient population (median survival time, 38 months; 5-year survival, 41%) accompanied with very low toxicity. These results compare favorably with results of other similar studies when using combined RT and CHT, with or without  surgery.

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[503]

TÍTULO / TITLE:  - Aberrant expression of E-cadherin in lung tissues of patients with probable lung  cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5149-53.

AUTORES / AUTHORS:  - Yuan YL; Wang YM; Liu H; Qin GF; Tang AG; Duan Y

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Laboratory, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

RESUMEN / SUMMARY:  - INTRODUCTION: This study assessed the relationship of E-cadherin mRNA and protein expression with the diagnosis of lung cancer with the aim of providing an auxiliary diagnostic method. METHODS: Semi-quantitative nested RT-PCR and western blotting were applied to detect E-cadherin mRNA transcripts and protein, respectively, in 30 cases of diagnostic lung cancer, 30 cases of clinically suspected patients with lung cancer and 30 cases of other disease. Immunohistochemical staining was also used to detect E-cadherin. RESULTS: Remarkably decreased levels of relative E-cadherin mRNA value and increased E-cadherin protein negativity were observed in probable lung cancer, when compared with possible lung cancer and others. With a threshold of 1.45, relative E-cadherin mRNA value showed a sensitivity of 90% and a specificity of 83% for the diagnosis of lung cancer. The combination of decreased relative E-cadherin mRNA value and negative E-cadherin protein increased the specificity and sensitivity. CONCLUSION: These data suggest that Chinese patients with diagnostic lung cancer have similar decreased levels of relative E-cadherin mRNA and E-cadherin protein value in the lung cancer tissues as in lung cancer patients in other countries. Measurement of relative E-cadherin mRNA and protein values in lung cancer tissues has potential for lung cancer diagnosis.

 

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[504]

TÍTULO / TITLE:  - Ciliated Muconodular Papillary Tumor of the Lung: A Newly Defined Low-grade Malignant Tumor with CT Findings Reminiscent of Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Clin Oncol. 2013 Feb;43(2):205-7. doi: 10.1093/jjco/hys218. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hys218

AUTORES / AUTHORS:  - Hata Y; Yuasa R; Sato F; Otsuka H; Goto H; Isobe K; Mitsuda A; Wakayama M; Shibuya K; Takagi K; Watanabe Y

INSTITUCIÓN / INSTITUTION:  - *Department of Chest Surgery, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8584, Japan. yoshinobuhata@hotmail.com.

RESUMEN / SUMMARY:  - A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors  have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography  findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

 

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[505]

TÍTULO / TITLE:  - Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Korean J Intern Med. 2013 Jan;28(1):94-7. doi: 10.3904/kjim.2013.28.1.94. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 3904/kjim.2013.28.1.94

AUTORES / AUTHORS:  - Kwon YS; Han J; Jung KH; Kim JH; Koh WJ

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous  inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin.

 

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[506]

TÍTULO / TITLE:  - A huge cemento-ossifying fibroma of paranasal sinus: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Medica (Hradec Kralove). 2012;55(3):146-9.

AUTORES / AUTHORS:  - Erdim I; Yazici ZM; Yilmazer R; Sever N; Kayhan FT

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, Bakirkoy Dr. Sadi Konuk Training and Research  Hospital, Istanbul, Turkey. ibrahim_erdim@hotmail.com

RESUMEN / SUMMARY:  - Cemento-ossifying fibroma is a well-bordered, slow-growing, benign fibro-osseous  disease. Although its localization is generally in the mandible, it can be seen in any area of the craniofacial region. Radiology and histopathology help to diagnose the condition. Treatment is based on close observation and/or surgical excision. In this case, we report the case of a 62-year-old male patient who had  a large radiological appearance, cemento-ossifying fibroma in the paranasal sinuses.

 

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[507]

TÍTULO / TITLE:  - Gemcitabine plus paclitaxel as second-line chemotherapy in patients with advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5119-24.

AUTORES / AUTHORS:  - Baykara M; Coskun U; Berk V; Ozkan M; Kaplan MA; Benekli M; Karaca H; Inanc M; Isikdogan A; Sevinc A; Elkiran ET; Demirci U; Buyukberber S

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Sakarya University Training and Research Hospital, Sakarya, Turkey. meltembaykara@yahoo.com

RESUMEN / SUMMARY:  - PURPOSE: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. METHODS: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or  metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine 1500 mg/m2 and paclitaxel 150 mg/m2 administered every two weeks. RESULTS: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range  38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3  and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. CONCLUSION: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

 

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[508]

TÍTULO / TITLE:  - Molecular mechanisms underlying the antitumor activity of 3-aminopropanamide irreversible inhibitors of the epidermal growth factor receptor in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2013 Jan;15(1):61-72.

AUTORES / AUTHORS:  - Galvani E; Giovannetti E; Saccani F; Cavazzoni A; Leon LG; Dekker H; Alfieri R; Carmi C; Mor M; Ardizzoni A; Petronini PG; Peters GJ

INSTITUCIÓN / INSTITUTION:  - Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy ; Department Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.

RESUMEN / SUMMARY:  - Overcoming the emergence of acquired resistance to clinically approved epidermal  growth factor receptor (EGFR) inhibitors is a major challenge in the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to investigate the effects of a series of novel compounds affecting viability of NSCLC NCI-H1975 cells (carrying the EGFR T790M mutation). The inhibition of the autophosphorylation of EGFR occurred at nanomolar concentrations and both UPR1282 and UPR1268 caused a significant induction of apoptosis. Targeting of EGFR and downstream pathways was confirmed by a peptide substrate array, which highlighted the inhibition of other kinases involved in NSCLC cell aggressive behavior. Accordingly, the drugs inhibited migration (about 30% vs. control), which could be, in part, explained also by the increase of E-cadherin expression. Additionally, we observed a contraction of the volume of H1975 spheroids, associated with the reduction of the cancer stem-like cell hallmark CD133. The activity of UPR1282 was retained in H1975 xenograft models where it determined tumor shrinkage (P < .05) and resulted well tolerated compared to canertinib. Of  note, the kinase activity profile of UPR1282 on xenograft tumor tissues showed overlapping results with respect to the activity in H1975 cells, unraveling the inhibition of kinases involved in pivotal proliferation and invasive signaling pathways. In conclusion, UPR1282 and UPR1268 are effective against various processes involved in malignancy transformation and progression and may be promising compounds for the future treatment of gefitinib-resistant NSCLCs.

 

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[509]

TÍTULO / TITLE:  - Changes in the demographics and prognoses of patients with resected non-small cell lung cancer: a 20-year experience at a single institution in Korea.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Korean Med Sci. 2012 Dec;27(12):1486-90. doi: 10.3346/jkms.2012.27.12.1486. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 3346/jkms.2012.27.12.1486

AUTORES / AUTHORS:  - Lee JG; Lee CY; Bae MK; Byun CS; Kim DJ; Chung KY

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - The demographics and prognosis of non-small cell lung cancer patients have changed during the last few decades. We conducted this study to assess the change in demographics and prognosis in resected non-small cell lung cancer patients during a 20-yr single-institution study in Korea. We retrospectively reviewed the medical records of 2,076 non-small cell lung cancer patients who underwent pulmonary resection between 1990 and 2009. Their clinical characteristics and survival were analyzed over a five-year period. With time, the proportions of female, adenocarcinoma, stage IA, and lobectomy patients increased, whereas the proportions of male, squamous cell carcinoma, stage IIIA, and pneumonectomy patients decreased. These demographic changes caused improved prognosis. The five-year survival rate of all patients was 53.9%. The five-year survival rate increased from 31.9% in 1990-1994, to 43.6% in 1995-1999, 51.3% in 2000-2004, and 69.7% in 2005-2009 (P < 0.001). In conclusion, among patients with resected non-small cell lung cancer, the proportions of female, adenocarcinoma, stage IA,  and lobectomy patients have increased, and the five-year survival rate has gradually improved during the last 20 yr in Korea.

 

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[510]

TÍTULO / TITLE:  - Tumor Burden is Predictive of Survival in Patients With Non-Small-Cell Lung Cancer and With Activating Epidermal Growth Factor Receptor Mutations Who Receive Gefitinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 9. pii: S1525-7304(12)00259-8. doi: 10.1016/j.cllc.2012.10.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.007

AUTORES / AUTHORS:  - Park JH; Kim TM; Keam B; Jeon YK; Lee SH; Kim DW; Chung DH; Kim YT; Kim YW; Heo DS

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Although activating epidermal growth factor receptor (EGFR) mutations are excellent predictors of gefitinib outcome in non-small-cell lung cancer (NSCLC), most patients become resistant to gefitinib. Despite our knowledge of the molecular basis of acquired resistance, clinical predictors have not been well elucidated. This study was undertaken to evaluate predictors of clinical outcome in patients with NSCLC and with EGFR mutations treated with gefitinib. PATIENTS AND METHODS: A total of 170 patients with NSCLC and with EGFR mutations  received gefitinib as a first-line (n = 50) and a second-line or more (n = 120) treatment at Seoul National University Hospital. Treatment outcomes were compared between groups based on clinicopathologic factors, such as treatment line, metastatic site, and mutation subtype. RESULTS: Survival outcomes were similar between first-line and second-line or greater gefitinib treatment (overall response rate, 2P = .832; progression-free survival [PFS], 2P = .373; and overall survival [OS], 2P = .290). When the number of metastatic sites was at least 3, significantly reduced survival was observed (median PFS 8.5 vs. 14.0 months, 2P < .001; median OS 21.4 vs. 25.6 months, 2P = .002). In addition, the presence of at least 3 organs with metastases was an independent predictor of PFS (hazard ratio  [HR] 1.97 [95% CI, 1.37-2.85]; 2P < .001) and OS (HR 2.00 [95% CI, 1.18-3.39]; 2P = .010). Patients who failed to respond to gefitinib within 6 months of treatment had more lymph node metastases and more sites of metastasis than those who responded later. CONCLUSIONS: Tumor burden, expressed as the number of metastatic sites, is predictive of inferior survival in patients with NSCLC and with activating EGFR mutations who are treated with gefitinib.

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[511]

TÍTULO / TITLE:  - Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53081. doi: 10.1371/journal.pone.0053081. Epub 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053081

AUTORES / AUTHORS:  - Scheffler M; Zander T; Nogova L; Kobe C; Kahraman D; Dietlein M; Papachristou I; Heukamp L; Buttner R; Boellaard R; Lammertsma AA; Querings S; Stoelben E; Engel-Riedel W; Neumaier B; Wolf J

INSTITUCIÓN / INSTITUTION:  - Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany ; Center for Integrated Oncology Koln Bonn, Cologne, Germany.

RESUMEN / SUMMARY:  - 3’-deoxy-3’-[(18)F]fluoro-L-thymidine (FLT) and 2’-deoxy-2’-[(18)F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1-25.4 months]) compared to patients with an FDG SUVmax >/=6.6 (3.1 months [95% CI 0.6-5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer  survival (10.3 months (0-23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0-8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT  PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR). TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT00568841.

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[512]

TÍTULO / TITLE:  - Video-Assisted Thoracoscopic Surgery for Lung Cancer in Patients on Hemodialysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Nov 15.

AUTORES / AUTHORS:  - Matsuoka K; Kuroda A; Kang A; Imanishi N; Nagai S; Ueda M; Miyamoto Y

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, National Hospital Organization Himeji Medical Center, Himeji, Hyogo, Japan.

RESUMEN / SUMMARY:  - Purpose: Surgical treatment of lung cancer in patients receiving hemodialysis carries a high risk because of poor cardiac function and a fragile electrolyte balance. Because the number of patients receiving hemodialysis has increased, the proportion of such patients with lung cancer is expected to rise. However, few studies have examined the results of surgery for lung cancer in hemodialysis patients, especially by video-assisted thoracoscopic surgery (VATS).Methods: We conducted a retrospective analysis of 5 hemodialysis patients who underwent VATS  for lung cancer.Results: All patients were men, and the mean age was 70.4 years.  The operative procedure was lobectomy in 4 patients and segmentectomy in 1. During the perioperative period, none required urgent hemodialysis. There were no critical complications and in-hospital deaths. Three of the 5 patients are currently alive and recurrence-free. One patient died of recurrence at 4 month after surgery, and the other patient died at17 months after surgery without cancer recurrence.Conclusions: VATS appears to be a safe procedure for hemodialysis patients with lung cancer, and the long-term outcome is satisfactory.

 

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[513]

TÍTULO / TITLE:  - Hope for progress after 40 years of futility? Novel approaches in the treatment of advanced stage III and IV non-small-cell-lung cancer: Stereotactic body radiation therapy, mediastinal lymphadenectomy, and novel systemic therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Carcinog. 2012;11:20. doi: 10.4103/1477-3163.105340. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1477-3163.105340

AUTORES / AUTHORS:  - Fung SF; Warren GW; Singh AK

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Medicine, Roswell Park Cancer Institute, University at Buffalo School of Medicine, Elm and Carlton Streets, Buffalo, New York, 14263, USA.

RESUMEN / SUMMARY:  - Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality. The majority of patients present with advanced (stage III-IV) disease. Such patients are treated with a variety of therapies including surgery, radiation, and chemotherapy. Despite decades of work, however, overall survival in this group has been resistant to any substantial improvement. This review briefly details the evolution to the current standard of care for advanced NSCLC, advances in systemic therapy, and novel techniques (stereotactic body radiation therapy [SBRT], and transcervical extended mediastinal lymphadenectomy [TEMLA] or video-assisted mediastinal lymphadenectomy [VAMLA]) that have been used in localized NSCLC. The utility of these techniques in advanced stage therapy and potential methods of combining these novel techniques with systemic therapy to improve survival are discussed.

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[514]

TÍTULO / TITLE:  - Genetic and Prognostic Differences of Non-small Cell Lung Cancer between Elderly  Patients and Younger Counterparts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Aging Dis. 2012 Dec;3(6):438-43. Epub 2012 Oct 23.

AUTORES / AUTHORS:  - Suda K; Tomizawa K; Mizuuchi H; Ito S; Kitahara H; Shimamatsu S; Kohno M; Yoshida T; Okamoto T; Maehara Y; Yatabe Y; Mitsudomi T

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka;

RESUMEN / SUMMARY:  - Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged >/=75 years with  those of patients aged </= 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis, we retrospectively analyzed 405 surgically treated non-small cell lung cancers (NSCLCs) before the era of routine clinical application of post-surgical adjuvant chemotherapy. Postsurgical recurrence-free survival (RFS)  was compared between elderly patients and younger counterparts. The genetic analysis showed elderly non-squamous cell lung cancer patients to have higher prevalence of EGFR mutations (53.1 % vs 42.0%, P = 0.15) and lower prevalence of  the ALK translocation (0 % vs 4.5%, P = 0.23) than their younger counterparts. The prognostic analysis showed postsurgical RFS was similar between the elderly NSCLC patients and the younger patients. However in multivariate analysis, adjusting for gender, smoking status, pathological stage, and histology, elderly  patients had significantly worse prognoses (HR 1.57, 95% CI, 1.08-2.29; P = 0.02) compared with younger patients. These results suggest differences in genetic and  prognostic aspects between elderly lung cancer patients and younger lung cancer patients.

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[515]

TÍTULO / TITLE:  - Physical health, mental health, and life changes among family caregivers of patients with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Nurs Forum. 2013 Jan 1;40(1):53-61. doi: 10.1188/13.ONF.53-61.

            ●● Enlace al texto completo (gratuito o de pago) 1188/13.ONF.53-61

AUTORES / AUTHORS:  - Mosher CE; Bakas T; Champion VL

INSTITUCIÓN / INSTITUTION:  - Department of Psychology, Indiana University-Purdue University in Indianapolis.

RESUMEN / SUMMARY:  - Purpose/Objectives: To describe physical health, mental health, and life changes  among family caregivers of patients with lung cancer.Design: Cross-sectional quantitative study.Setting: A university outpatient oncology center, two Veterans Affairs outpatient clinics, and a private outpatient oncology practice in Indianapolis, IN.Sample: 91 family caregivers of patients with lung cancer.Methods: Data were collected using standardized instruments and analyzed using descriptive statistics and hierarchical multiple regression.Main Research Variables: Demographic and medical factors, physical health, mental health, and life changes from caregiving.Findings: Caregivers’ physical health and mental health were below population norms, whereas social functioning did not differ from norms. More than 50% of caregivers reported negative emotional effects of caregiving, and more than 33% reported negative physical health effects of caregiving. About 40% of caregivers, however, reported positive changes in their  relationships with the patients with lung cancer and other family members as a result of caregiving. Caregivers’ mental health was more strongly associated with life changes than physical health.Conclusions: Findings suggest that many family  caregivers of patients with lung cancer experience negative physical and mental health effects of caregiving, whereas relations with family members improve for a substantial minority of caregivers. These positive and negative consequences of caregiving should be jointly considered when developing self-report measures and  interventions for this population.Implications for Nursing: Nurses can conduct brief screening assessments to identify caregivers with probable distress and can provide practical and psychosocial support, as well as referrals to support services.Knowledge Translation: Findings suggest that interventions are needed to address the negative physical and emotional health consequences of caring for family members with lung cancer. Such interventions could build on the relational benefits of caregiving to improve the patient-caregiver relationship and expand caregivers’ support system.

 

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[516]

TÍTULO / TITLE:  - Respiratory Complications during Mid- and Long-Term Follow-Up Periods in Patients Who Underwent Pneumonectomy for Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 13.

AUTORES / AUTHORS:  - Seok Y; Lee E; Cho S

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Cardiovascular Surgery, Kyungpook National University  Hospital, Daegu, Korea.

RESUMEN / SUMMARY:  - Background: Pneumonectomy is associated with higher early mortality and morbidity, and it is also known to predispose the patient to respiratory complications during mid- and long-term follow-up. Therefore, the purpose of this study was to identify risk factors associated with respiratory complications during the follow-up period after pneumonectomy.Methods: We retrospectively reviewed 98 patients who underwent pneumonectomy for non-small cell lung cancer (NSCLC) between Jan 1995 and Dec 2005 Univariate and multivariate analyses were used to identify risk factors of late respiratory complications among preoperative and intraoperative data.Results: The median follow up duration of 98 patients was 33.1 months(4.2-180.0 months). The late mortality rate was 68.4% (n  = 67). Causes of late death were cancer specific in 37 patients (55.2%) and respiratory specific in 25 patients(37.3%). Compared with 59 patients who had no  respiratory infection after pneumonectomy during mid- or long-term follow-up, being male, a lower BMI (<22 kg/m(2)), presence of chronic obstructive pulmonary  disease (COPD) and preoperative pneumonia were significant risk factors by univariate analysis. Multivariate analysis revealed that presence of preoperative pneumonia was the only independent factor associated with late mortality from respiratory complications during the mid- and long-term follow-up periods (OR = 2.41, 95% CI = 1.10-5.32, p = 0.028).Conclusion: Respiratory infection was a comparable risk factor of mortality in the mid- and long-term after pneumonectomy with cancer recurrence. The presence of preoperative pneumonia was an independent factor related to respiratory infection.Careful follow-up for these patients may  be required.

 

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[517]

TÍTULO / TITLE:  - Wedge resection versus lobectomy for T1N0 non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Minerva Chir. 2012 Dec;67(6):489-98.

AUTORES / AUTHORS:  - Stefani A; Nesci J; Casali C; Morandi U

INSTITUCIÓN / INSTITUTION:  - Unit of Thoracic Surgery, Modena and Reggio Emilia University, Modena, Italy - alessandro.stefani@unimore.it.

RESUMEN / SUMMARY:  - AIM: Advances in imaging techniques and screening protocols can detect more small lung cancers. Controversy exists regarding surgical management of these small tumors. METHODS: Records and long-term outcome of all patients with T1N0 (</=2 cm) non-small cell lung cancer undergoing wedge resection with curative intent from 1996 through 2010 were retrospectively reviewed. Those patients were compared with a group of patients treated with lobectomy during the same period and for a disease at the same stage. Sublobar resections were performed in compromised patients in all cases. RESULTS: The study included 206 patients: 82 received wedge resection, 124 lobectomy. Morbidity and mortality were similar between the two groups. Locoregional recurrence rate was significantly higher for wedge resection compared with lobectomy (22% versus 8% respectively), cancer-specific survival and disease-free survival were significantly poorer for  wedge resection with respect to lobectomy: 5-year survival of 74% versus 85% respectively, 5-year disease-free survival of 62% versus 77%. The type of operation resulted as an independent prognostic factor of cancer-specific survival. CONCLUSION: We found poorer outcome for wedge resection compared to lobectomy. We believe that caution should be used when suggesting the use of wedge resection as intentional limited resection for patients with small non-small cell lung cancer who may otherwise tolerate lobectomy. Two randomized trials comparing limited resection and lobectomy are ongoing in Japan and in United States: they will better clarify the role of limited resection, especially segmentectomy, in the treatment of T1aN0 tumors. Wedge resection may remain a valid option for compromised patients.

 

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[518]

TÍTULO / TITLE:  - Prognostic Factors for Survival of Stage IB Upper Lobe Non-small Cell Lung Cancer Patients: A Retrospective Study in Shanghai, China.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2011 Dec;23(4):265-70. doi: 10.1007/s11670-011-0265-2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-011-0265-2

AUTORES / AUTHORS:  - Wang WL; Shen-Tu Y; Wang ZQ

INSTITUCIÓN / INSTITUTION:  - Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To identify clinical and pathologic factors that were associated with  the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients.  METHODS: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received  any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. RESULTS: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1-6.5] and 4.6 (95% CI: 1.9-11) for those aged 58-68 years and those >68 years, respectively, relative to those aged <58 years.  HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI:  2.3-18) and 1.4 (95% CI: 0.7-2.8), respectively. HRs for those with tumor size 3.1-5 cm and >5 cm (vs</=3.0 cm) were 2.3 (95% CI: 1.1-4.9) and 4.3 (95% CI: 1.9-10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3-12). CONCLUSION: Advanced age, larger  tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.

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[519]

TÍTULO / TITLE:  - Clinical investigation of EGFR mutation detection by pyrosequencing in lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):271-276. Epub 2012 Oct 1.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.950

AUTORES / AUTHORS:  - Kim HJ; Oh SY; Kim WS; Kim SJ; Yoo GH; Kim WD; Lee KY

INSTITUCIÓN / INSTITUTION:  - Departments of Internal Medicine and.

RESUMEN / SUMMARY:  - Direct sequencing is the standard method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer, however, its relatively low sensitivity limits its clinical use. Pyrosequencing is a bioluminometric, real-time non-electrophoretic DNA sequencing technique with a number of advantages compared with direct sequencing, including higher sensitivity, speed,  automation and cost-effectiveness. Clinical specimens from 202 lung cancer patients were analyzed for EGFR mutations in exons 18, 19, 20 and 21 using the pyrosequencing method following genomic DNA extraction from paraffin-embedded tissue specimens. All clinical data and tumor specimens were obtained from the Konkuk University Hospital (Korea) between July 2006 and December 2008. The results and clinical responses to EGFR-tyrosine kinase inhibitors (TKIs) were compared. Overall, EGFR mutation-positive rate was 26.7% (54/202). Activating EGFR mutations were observed more frequently in female (52.1 vs. 13.0%), non-smoking (47.8 vs. 15.8%) and adenocarcinoma (35.2 vs. 5.2%) patients. However, significant numbers of EGFR mutation-positive patients were identified as male, former or current smokers and non-adenocarcinoma patients. The combinations of favorable clinicopathological factors, including female, non-smoking and adenocarcinoma, were not identified to significantly increase the positive EGFR mutation rate (female, 52.1%; female and non-smoker, 52.6%; female, non-smoker and adenocarcinoma, 51.9%). The present findings indicate that EGFR mutation analysis is a highly useful method for the prediction of response to EGFR-TKI and the use of favorable clinicopathological factors to perform this analysis is not suitable. Exon 19 deletion was the most common mutation (63.6%) and exon 21 L858R substitution was measured at 32.7%. The exon 20 T790M mutation  was identified in 1 patient prior to EGFR-TKI treatment. EGFR mutation status is  associated with response to EGFR-TKI and the overall response rate in patients who have the activating EGFR mutation was 82.4 vs. 5.9% in patients with a wild-type EGFR. The present study demonstrates that EGFR mutations analyzed by the pyrosequencing method are well correlated with clinicopathological parameters and that this method may be useful in the clinical practice.

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[520]

TÍTULO / TITLE:  - Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberc Respir Dis (Seoul). 2012 Dec;73(6):303-11. doi: 10.4046/trd.2012.73.6.303. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 4046/trd.2012.73.6.303

AUTORES / AUTHORS:  - Lee KH; Lee KY; Jeon YJ; Jung MH; Son C; Lee MK; Ryu JS; Yang SH; Lee JC; Kim YC; Kim SY

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea.

RESUMEN / SUMMARY:  - BACKGROUND: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). METHODS: In this Phase IV observational  study, we recruited patients, previously failed first-line chemotherapy, who had  locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient’s characteristics of modified intent-to-treat population. RESULTS: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable,  the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). CONCLUSION: Gefitinib was  observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

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[521]

TÍTULO / TITLE:  - Uptake and tolerance of chemotherapy in elderly patients with small cell lung cancer and impact on survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Epidemiol. 2012;2012:708936. doi: 10.1155/2012/708936. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/708936

AUTORES / AUTHORS:  - Fisher S; Al-Fayea TM; Winget M; Gao H; Butts C

INSTITUCIÓN / INSTITUTION:  - School of Public Health, University of Alberta, Edmonton, Alberta, Canada T6G 1C9.

RESUMEN / SUMMARY:  - The treatment of elderly cancer patients is complicated by many factors. We sought to assess the uptake and tolerance of chemotherapy among patients 75 years and older diagnosed with small cell lung cancer (SCLC) in years 2004-2008 in Alberta, Canada, and assess their survival. All patients who met the above criteria and had an oncologist-consult were included. Data were obtained from the Alberta Cancer Registry and chart review. A total of 171 patients were included in the study, 117 (68%) of whom began chemotherapy. Of those, 52% completed all cycles, 66% did not have any dose reductions, and 31% completed all cycles at the recommended dose. The risk of death for patients who did not complete all cycles  of chemotherapy was 2.72 (95% CI: 1.52-4.87) and for those who completed all cycles but with a reduced dose was 1.02 (95% CI: 0.57-1.82) relative to those who completed chemotherapy at full dose after adjusting for several demographic/clinical factors. Our results suggest that a significant proportion of elderly patients are able to tolerate chemotherapy and receive a survival benefit from it while those who experience toxicity may receive a survival benefit from a reduction in chemotherapy dose as opposed to stopping treatment.

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[522]

TÍTULO / TITLE:  - Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 5;12:580. doi: 10.1186/1471-2407-12-580.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-580

AUTORES / AUTHORS:  - Heuvers ME; Aerts JG; Cornelissen R; Groen H; Hoogsteden HC; Hegmans JP

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Erasmus Medical Center, Postbox 2040, 3000 CA,  Rotterdam, The Netherlands. j.hegmans@erasmusmc.nl.

RESUMEN / SUMMARY:  - ABSTRACT: Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recently it was often thought that tumors are more or less undetected or tolerated by the patient’s immune system causing the neoplastic cells to divide and spread without resistance. However, it is without  any doubt that the tumor environment contains a wide variety of recruited host immune cells. These tumor infiltrating immune cells influence anti-tumor responses in opposing ways and emerges as a critical regulator of tumor growth. Here we provide a summary of the relevant immunological cell types and their complex and dynamic roles within an established tumor microenvironment. For this, we focus on both the systemic compartment as well as the local presence within the tumor microenvironment of late-stage non-small cell lung cancer (NSCLC), admitting that this multifaceted cellular composition will be different from earlier stages of the disease, between NSCLC patients. Understanding the paradoxical role that the immune system plays in cancer and increasing options for their modulation may alter the odds in favor of a more effective anti-tumor immune response. We predict that the future standard of care of lung cancer will  involve patient-tailor-made combination therapies that associate (traditional) chemotherapeutic drugs and biologicals with immune modulating agents and in this  way complement the therapeutic armamentarium for this disease.

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[523]

TÍTULO / TITLE:  - Comparison of the GTV coverage by PTV and isodose of 90% in 2D and 3D planning during endobronchial brachytherapy in the palliative treatment of patients with advanced lung cancer. Pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Contemp Brachytherapy. 2012 Jun;4(2):113-5. doi: 10.5114/jcb.2012.29369. Epub 2012 Jun 30.

            ●● Enlace al texto completo (gratuito o de pago) 5114/jcb.2012.29369

AUTORES / AUTHORS:  - Lyczek J; Kazalski D; Kowalik L; Sawicki M

INSTITUCIÓN / INSTITUTION:  - Brachytherapy Department, Brzozow Hospital, Subcarpathian Cancer Center, Brzozow, Poland.

RESUMEN / SUMMARY:  - PURPOSE: Endobronchial brachytherapy (EB) is one way of treatment of patients with advanced lung cancer. Technological progress and the introduction of computed tomography for use in 3D planning allows one to define the area being treated very precisely, which gives an opportunity to extend survival, even in groups of patients receiving palliative care. MATERIAL AND METHODS: In 2011, in the Brachytherapy Department of the Subcarpathian Oncological Center, a group of  12 consecutive patients with advanced cancer of the bronchus underwent palliative EB. We compared the coverage of GTV (gross tumor volume), seen in the computed tomography study with intravenous contrast, by the PTV (planning target volume) planned in 3D and 2D. RESULTS: In 2D planning GTV coverage ranged from 15% to 89%. By analyzing the isodose of 90%, it was found that 2D planning covered GTV in 15-35% of the dose. In 3D planning, this coverage changed positively, and ranged from 85% to 100%. The GTV coverage in 3D planning was 100% by definition.  In addition, it should be noted that in the 3D planning one can spare critical organs or pacemakers. CONCLUSIONS: Planning for HDR brachytherapy in all locations should be based on dynamic imaging at present, especially in centers that are equipped with CT. Evaluation should be a routine test in treatment planning. The use of CT, even in palliative treatment planning, allows for much better coverage of GTV areas as well, which is very important to reduce radiation doses to critical organs and thereby reduce the toxic effects of treatment.

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[524]

TÍTULO / TITLE:  - Re-challenge treatment of small-molecular inhibitors in NSCLC patients beyond progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):647-9. doi: 10.3978/j.issn.2072-1439.2012.10.14.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.14

AUTORES / AUTHORS:  - Tu L; Sun L

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Cancer, Cancer Center, West China Hospital, West China School of Clinical Medicine, Sichuan University, Chengdu, China;

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[525]

TÍTULO / TITLE:  - Polymorphisms in intron 1 of the EGFR gene in non-small cell lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Nov;4(5):785-789. Epub 2012 Aug 23.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.681

AUTORES / AUTHORS:  - Shitara M; Sasaki H; Yokota K; Okuda K; Hikosaka Y; Moriyama S; Yano M; Kawaguchi T; Kubo A; Takada M; Kitahara N; Okumura M; Matsumura A; Iuchi K; Fujii Y

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601;

RESUMEN / SUMMARY:  - The epidermal growth factor receptor (EGFR) gene is highly polymorphic and its expression and activity may be affected by various polymorphisms. There have been several studies examining associations between EGFR polymorphisms and clinical outcome of lung cancer therapy; however, the underlying mechanism is largely unknown. The present study investigated EGFR polymorphism status and its correlation with clinicopathological features in Japanese non-small cell lung cancer (NSCLC) patients. We investigated 5 polymorphisms in the EGFR gene (-216G/T, -191C/A, 8227G/A, D994D and R497K) in 274 surgically-treated NSCLC patients. TaqMan single nucleotide polymorphism (SNP) genotyping assays and a PCR-based assay were used to analyze these polymorphisms. In our cohort of patients we did not find any evidence of the -191C/A polymorphism. Our results showed that the patients with the 8227GA or AA type in intron 1 had a significantly better prognosis with the anti-EGFR therapy than the patients with  the GG type (p=0.0448) in terms of recurrence of lung cancer. No significant association was observed between 3 other SNPs (-216G/T, D994D and R497K) and clinicopathological features. The EGFR 8227G/A polymorphism in intron 1 may be associated with clinical outcome in NSCLC patients treated with EGFR tyrosine kinase inhibitors.

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[526]

TÍTULO / TITLE:  - Early-stage lung cancer: trial compares radiosurgery to standard surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncology (Williston Park). 2012 Nov;26(11):1072-3.

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[527]

TÍTULO / TITLE:  - Association between chronic obstructive pulmonary disease and lung cancer: the missing link.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Jan;126(1):154-65.

AUTORES / AUTHORS:  - Wang ZL

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China (Email: wangzengli@tom.com).

RESUMEN / SUMMARY:  - OBJECTIVE: This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer. DATA SOURCES: The data used in this review were obtained mainly from studies reported in the PubMed database (1997 - 2012) using the terms of COPD and lung cancer. STUDY SELECTION:  Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified, retrieved  and reviewed. RESULTS: COPD prevalence, morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important. COPD is characterized by a chronic inflammation of lower airway and, importantly, the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers. COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50% - 90% of patients with lung cancer. CONCLUSIONS: Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age, and 50% - 70% of patients diagnosed with lung cancer have declined spirometric evidence of COPD. Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lung diseases and for people at risk.

 

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[528]

TÍTULO / TITLE:  - SNPs in the TGF-beta Signaling Pathway Are Associated with Increased Risk of Brain Metastasis in Patients with Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51713. doi: 10.1371/journal.pone.0051713. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051713

AUTORES / AUTHORS:  - Li Q; Wu H; Chen B; Hu G; Huang L; Qin K; Chen Y; Yuan X; Liao Z

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

RESUMEN / SUMMARY:  - PURPOSE: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-beta signaling pathway could be a predictive biomarker of brain metastasis. PATIENTS AND METHODS: We genotyped 33 SNPs from 13 genes in the TGF-beta signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis. RESULTS: The median age of the 116 men and 45 women in the study was  58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001). CONCLUSIONS: We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to  identify patients at high risk of brain metastasis.

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[529]

TÍTULO / TITLE:  - Enriching the molecular definition of the airway “field of cancerization:” establishing new paradigms for the patient at risk for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Prev Res (Phila). 2013 Jan;6(1):4-7. doi: 10.1158/1940-6207.CAPR-12-0470.  Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0470

AUTORES / AUTHORS:  - Gomperts BN; Walser TC; Spira A; Dubinett SM

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, 37-131 Center for Health Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095. sdubinett@mednet.ucla.edu.

RESUMEN / SUMMARY:  - The “field of cancerization” refers to histologically normal-appearing tissue adjacent to neoplastic tissue that displays molecular abnormalities, some of which are the same as those of the tumor. Improving our understanding of these molecular events is likely to increase our understanding of carcinogenesis. Kadara and colleagues attempt to characterize the molecular events occurring temporally and spatially within the field of cancerization of patients with early-stage non-small cell lung cancer (NSCLC) following definitive surgery. They followed patients with bronchoscopies annually after tumor resection and extracted RNA from the serial brushings from different endobronchial sites. They  then conducted microarray analysis to identify gene expression differences over time and in different sites in the airway. Candidate genes were found that may have biologic relevance to the field of cancerization. For example, expression of phosphorylated AKT and ERK1/2 was found to increase in the airway epithelium with time. Although there are limitations in the study design, this investigation demonstrates the utility of identifying molecular changes in histologically normal airway epithelium in lung cancer. In addition to increasing our understanding of lung cancer biology, studying the field of cancerization has the potential to identify biomarkers from samples obtained in a minimally invasive manner. Cancer Prev Res; 6(1); 4-7. ©2013 AACR.

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[530]

TÍTULO / TITLE:  - Descent into quiet chaos: the story of Mr. F.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Conn Med. 2012 Aug;76(7):423-4.

AUTORES / AUTHORS:  - Sloshower J

INSTITUCIÓN / INSTITUTION:  - Yale University, USA.

 

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[531]

TÍTULO / TITLE:  - Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):562-8. doi: 10.3978/j.issn.2072-1439.2012.10.16.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.16

AUTORES / AUTHORS:  - Muraki K; Koyama R; Honma Y; Yagishita S; Shukuya T; Ohashi R; Takahashi F; Kido K; Iwakami S; Sasaki S; Iwase A; Takahashi K

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Juntendo University, School of Medicine, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline  with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against  nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed. RESULTS: Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (P=0.0004) and a decrease in the serum creatinine level (P=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (P=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in  patients with advanced NSCLC [HR 0.232 (95% CI: 0.055-0.986), P=0.039]. CONCLUSIONS: These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.

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[532]

TÍTULO / TITLE:  - The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 10;12:588. doi: 10.1186/1471-2407-12-588.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-588

AUTORES / AUTHORS:  - Hu M; Ye L; Ruge F; Zhi X; Zhang L; Jiang WG

INSTITUCIÓN / INSTITUTION:  - Cardiff University-Capital Medical University Joint Centre for Biomedical Research, Cardiff, UK. yel@cf.ac.uk.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Psoriasin (S100A7) is a member of the S100 gene family. Alteration of Psoriasin expression has previously been reported to play an important role in cancer aggressive behaviour. The current study sought to investigate the level of Psoriasin expression at the mRNA level in a cohort of patients with non-small cell lung cancer (NSCLC), the association with clinical implication and outcomes, and the molecular and cellular impact of the protein on lung cancer cells. METHODS: Fresh frozen NSCLC cell carcinoma tissues, along with matched normal tissues were obtained from 83 NSCLC patients who received curative resection from January 2003 to December 2011. The expression of Psoriasin in the  NSCLC specimens was assessed using both quantitative real time PCR (QPCR) and immunochemical staining. Knockdown and forced expression of Psoriasin in NSCLC cell lines were carried out using constructed plasmid vectors carrying either ribozyme transgenes targeting human Psoriasin or full-length coding sequence, respectively. The effect of Psoriasin on the functions of NSCLC cells was determined using a variety of in vitro cell function assays. RESULTS: Higher mRNA levels of Psoriasin were observed in tumour tissues when compared to both the paired normal background tissues and none paired normal tissues (p = 0.0251 and 0.0195). The mRNA level of Psoriasin was found to be higher in the squamous carcinoma (P=0.035). Higher Psoriasin expression is associated with poor prognosis. The cell function tests had supportive results to the clinical findings. Over-expression of Posriasin in lung cancer cells (SK-MES-1) resulted in an increase in in vitro growth and invasiveness. In contrast, Psoriasin knockdown suppressed cell growth and invasion (P<0.05), but increased cell adhesion (P<0.05). CONCLUSIONS: Psoriasin expression is increased in lung cancer, more specifically in lung squamous carcinoma compared with adenocarcinoma, and is associated with poor prognosis. Psoriasin plays crucial roles in regulating the growth and invasion of lung cancer cells.

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[533]

TÍTULO / TITLE:  - Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Jan 10;4:e454. doi: 10.1038/cddis.2012.188.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.188

AUTORES / AUTHORS:  - Stahl S; Kaminskyy VO; Efazat G; Hyrslova Vaculova A; Rodriguez-Nieto S; Moshfegh A; Lewensohn R; Viktorsson K; Zhivotovsky B

INSTITUCIÓN / INSTITUTION:  - Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

RESUMEN / SUMMARY:  - Radiation therapy is frequently used to treat non-small cell lung cancers (NSCLCs). We have previously shown that a combination of ionizing radiation (IR)  and the staurosporine analog PKC 412, but not Ro 31-8220, increases cell death in NSCLC cells. To identify genes involved in the enhancement of cell death, a total gene profiling in response to co-administration of (i) PKC 412 with IR, or (ii) Ro 31-8220 with IR was implemented. These combined treatments caused upregulation of 140 and 179 genes and downregulation of 253 and 425 genes, respectively. Certain genes were selected and verified by real-time quantitative PCR and, of these genes, robust suppression of Ephrin B3 expression was suggested as a possible cell death-inducing mechanism of combined treatment with IR and PKC 412. Indeed, silencing of Ephrin B3 using siRNA in NSCLC cells resulted in a major alteration of their morphology with an elongated phenotype, decreased proliferation and increased cell death signaling. Moreover, silencing of Ephrin B3 in combination with IR caused a decrease in IR-mediated G(2)-arrest, induced cellular senescence, inhibited MAPK ERK and p38 phosphorylation, and caused an upregulation of p27(kip1) expression. Finally, silencing of Ephrin B3 in combination with IR sensitized U-1810 cells to IR-induced apoptosis. In conclusion, we identify and describe Ephrin B3 as a putative signaling molecule involved in the response of NSCLC cells to combined treatment with PKC 412 and ionizing radiation.

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[534]

TÍTULO / TITLE:  - Perceptions of smoking and lung cancer in New Castle County, Delaware.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Del Med J. 2012 Oct;84(10):311-7.

AUTORES / AUTHORS:  - Abramson-Chen E; Khan O; Raman T

INSTITUCIÓN / INSTITUTION:  - Department of Family and Community Medicine at Christiana Care Health System in Newark, DE, USA.

RESUMEN / SUMMARY:  - There is no standardized survey tool to capture adult respondents’ knowledge of risks for lung cancer. We sought to develop such a tool and developed a test survey for this purpose. We designed and implemented this survey to identify knowledge of issues relating to smoking and lung cancer among patients of primary care practices in New Castle County, Delaware. Our study demonstrated the successful piloting of a standardized tool to assess patient knowledge of lung cancer risks. Most respondents (71.6 percent) were knowledgeable of the cluster relating to association between smoking and lung cancer; fewer (38.6 percent) were knowledgeable about the relationship between smoking cessation and lung cancer. The areas relating to lung cancer diagnosis and treatment identified the  greatest gaps in understanding, with only 15.8 percent displaying a moderate level of knowledge. Implications for care and for policy are discussed.

 

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[535]

TÍTULO / TITLE:  - Evaluation of current methods to detect the mutations of epidermal growth factor  receptor in non-small cell lung cancer patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Multidiscip Respir Med. 2012 Dec 11;7(1):52. doi: 10.1186/2049-6958-7-52.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2049-6958-7-52

AUTORES / AUTHORS:  - Obradovic J; Jurisic V

INSTITUCIÓN / INSTITUTION:  - Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34 000, Kragujevac, Serbia. vdvd@mailcity.com.

RESUMEN / SUMMARY:  - ABSTRACT: Many different methods were developed to detect commonly known mutations and to screen new mutations of the epidermal growth factor receptor in  non-small cell lung cancer patients. Some of these methods are so sensitive as to be able to detect even one epidermal growth factor receptor mutant tumor cell among up to 1000-2000 normal cells. We have considered current methods chronologically reported to detect mutations in epidermal growth factor receptor  in patients with non-small cell lung cancer. We also gave a short preview of their significance for routine clinical works. A Pub Med literature search was performed in order to demonstrate what methods are mostly used in mutation detection and to show their distribution through the last 10 years.

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[536]

TÍTULO / TITLE:  - Changes of acute-phase protein levels in the serum of lung cancer patients following radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Med. 2013;6(1):50-6. Epub 2012 Nov 18.

AUTORES / AUTHORS:  - Maria TG; Vasileios KE; Panagiotis PS; Kostas SN

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Radiation Oncology Unit, Medical School Rimini 1, Haidari, Athens 12462, Greece.

RESUMEN / SUMMARY:  - PURPOSE: the assessment of serum level changes of C-reactive protein (CRP), ferritin (FER), and albumin (ALB) as inflammation markers in Non Small Cell Lung  Cancer patients (stages IIIA - inoperable and stage IIIB) treated with radiotherapy. Significant findings: Normal pre-radiotherapy levels of CRP were found in 18 patients, of FER in 17, and of ALB in 22. Higher levels of CRP were found in 9 patients and of FER in 10. Lower ALB was found in 5 patients.Post-radiotherapy CRP levels were significantly higher (compared to the  pre-radiotherapy levels) in 25 patients. The same was observed regarding FER in 18 patients whereas 12 patients had lower post-radiotherapy levels. The statistical analysis (non parametrical Wilcoxon test) revealed that these differences were statistically significant (p-value< 0.001). CONCLUSIONS: The levels of CRP, FER, and ALB are reliable and useful biomarkers correlated with the acute complication of lung parenchyma damage induced by radiotherapy.

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[537]

TÍTULO / TITLE:  - Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Ophthalmol. 2012 Dec 18;12:65. doi: 10.1186/1471-2415-12-65.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2415-12-65

AUTORES / AUTHORS:  - Sabater AL; Sadaba LM; de Nova E

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Clinica Universidad de Navarra, Navarra, Apartado 4209, Pamplona, 31008, España. lmsadaba@unav.es.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Meningeal carcinomatosis (MC) is a rare complication associated with hematologic and solid tumors. MC develops when malignant cells gain access to the leptomeningeal space, producing several clinical symptoms. Loss of vision and ocular motility deficit are the most frequent ocular symptoms  reported. Fundus examination usually appears normal, although optic nerve alterations like optic atrophy or papilledema have been described. MC diagnosis is usually completed by magnetic resonance imaging (MRI) and cerebrospinal fluid  (CSF) analysis. Indicated treatment for MC usually involves intrathecal chemotherapy combined with radiotherapy, although survival rate is extremely low. CASE PRESENTATION: A 66-year old man with stage IV metastatic lung adenocarcinoma, presented to the Ophthalmology Department with a two-month history of double vision, soft headaches and dizziness episodes. The patient presented a best visual corrected acuity of 0.7 in his right eye and 0.8 in his left eye. Diplopia was corrected with 6-prism diopters base-out prism in right eye. Funduscopy showed a bilateral papilledema, juxtapapillary exudates and splinter hemorrhages. Brain MRI showed a diffuse leptomeningeal enhancement in cortical sulcus. Lumbar puncture was performed and cerebrospinal fluid (CSF) cytology revealed malignant cells compatible with a diagnosis of MC. Intrathecal  chemotherapy was administered. CONCLUSION: MC is a serious complication of systemic cancer patients, involving a poor prognosis. Early diagnosis is extremely important, although treatment is frequently aimed to reduce the symptoms and extend survival. Eye symptoms may be the chief complaint, so MC should be considered in any patient with vision loss or diplopia accompanied by neurologic symptoms and in the absence of an intraocular cause, especially in the context of systemic cancer.

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[538]

TÍTULO / TITLE:  - The transcriptional consequences of somatic amplifications, deletions, and rearrangements in a human lung squamous cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2012 Nov;14(11):1075-86.

AUTORES / AUTHORS:  - Stead LF; Berri S; Wood HM; Egan P; Conway C; Daly C; Papagiannopoulos K; Rabbitts P

INSTITUCIÓN / INSTITUTION:  - Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.

RESUMEN / SUMMARY:  - Lung cancer causes more deaths, worldwide, than any other cancer. Several histologic subtypes exist. Currently, there is a dearth of targeted therapies for treating one of the main subtypes: squamous cell carcinoma (SCC). As for many cancers, lung SCC karyotypes are often highly anomalous owing to large somatic structural variants, some of which are seen repeatedly in lung SCC, indicating a  potential causal association for genes therein. We chose to characterize a lung SCC genome to unprecedented detail and integrate our findings with the concurrently characterized transcriptome. We aimed to ascertain how somatic structural changes affected gene expression within the cell in ways that could confer a pathogenic phenotype. We sequenced the genomes of a lung SCC cell line (LUDLU-1) and its matched lymphocyte cell line (AGLCL) to more than 50x coverage. We also sequenced the transcriptomes of LUDLU-1 and a normal bronchial epithelium cell line (LIMM-NBE1), resulting in more than 600 million aligned reads per sample, including both coding and non-coding RNA (ncRNA), in a strand-directional manner. We also captured small RNA (<30 bp). We discovered significant, but weak, correlations between copy number and expression for protein-coding genes, antisense transcripts, long intergenic ncRNA, and microRNA (miRNA). We found that miRNA undergo the largest change in overall expression pattern between the normal bronchial epithelium and the tumor cell line. We found evidence of transcription  across the novel genomic sequence created from six somatic structural variants. For each part of our integrated analysis, we highlight candidate genes that have  undergone the largest expression changes.

 

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[539]

TÍTULO / TITLE:  - Influence of Comorbidities on the Efficacy of Radiotherapy with or without Chemotherapy in Elderly Stage III Non-small Cell Lung Cancer Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

            ●● Enlace a la Editora de la Revista http://cancerres.aacrjournals.org/ 

            ●● Cita: Cancer Research: <> Treat. 2012 Dec;44(4):242-50. doi: 10.4143/crt.2012.44.4.242. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4143/crt.2012.44.4.242

AUTORES / AUTHORS:  - Lee JH; Wu HG; Kim HJ; Kim DW; Lee SH; Kim TM; Kim YW; Heo DS

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Seoul National University College of Medicine,  Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: The current study was conducted in order to evaluate the clinical outcome of radical radiotherapy (RT) with or without chemotherapy for elderly patients with stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between 1990 and 2010, 125 patients, aged 70 years or more, received radical RT with or without chemotherapy for treatment of stage III NSCLC. We reviewed the patients’ prognostic factors, including comorbidities. Comorbidity status was evaluated using a simplified comorbidity score (SCS). Of the patients  reviewed, 82 received radical RT alone, whereas the other 43 patients underwent chemoradiotherapy (CRT). A platinum-based chemotherapy regimen was most commonly  used (42/43). RESULTS: The two-year overall-survival (OS) and progression-free survival (PFS) rates were 32.2% and 21.8%, respectively. SCS was the independent  prognostic factor for OS. In the frail elderly subgroup with a SCS of >/=10, CRT  demonstrated a significant difference in PFS, but not in OS. In contrast, OS and  PFS following CRT were significantly superior to RT in the fit elderly subgroup with a SCS of <10. The incidence of severe pulmonary toxicities in the frail elderly subgroup was significantly higher than that in the fit elderly subgroup.  CONCLUSION: Multiple comorbidities evaluated according to the SCS are related to  poor OS in elderly patients with stage III NSCLC. CRT improved clinical outcome when compared to RT in the fit elderly subgroup, however, the gain from this treatment was negated in the frail elderly subgroup with multiple comorbidities.  Therefore, evaluation of comorbidity is necessary in order to determine whether chemotherapy should be combined with RT in elderly patients with stage III NSCLC.

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[540]

TÍTULO / TITLE:  - Generalized peritonitis arising from small bowel metastasis in a lung cancer patient.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Korean Surg Soc. 2013 Jan;84(1):57-60. doi: 10.4174/jkss.2013.84.1.57. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 4174/jkss.2013.84.1.57

AUTORES / AUTHORS:  - Park YJ; Kim KY; Park JY; Cho JS; Kim Y; Shin SH

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Chonnam National University Hwasun Hospital, Hwasun, Korea.

RESUMEN / SUMMARY:  - Symptomatic gastrointestinal metastasis from lung malignancy is rarely reported.  In this report, we present a case of lung adenocarcinoma with acute abdominal pain from small bowel perforation. The patient underwent small bowel resection and the final diagnosis was metastatic adenocarcinoma originating from lung. Immunohistochemistry was positive for thyroid transcription factor-1 and cytokeratin 7 (CK7), and negative for CK20. We present this rare case and briefly review the literature.

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[541]

TÍTULO / TITLE:  - Detection of Rib Metastases in Patients with Lung Cancer: A Comparative Study of  MRI, CT and Bone Scintigraphy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52213. doi: 10.1371/journal.pone.0052213. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052213

AUTORES / AUTHORS:  - Chen YQ; Yang Y; Xing YF; Jiang S; Sun XW

INSTITUCIÓN / INSTITUTION:  - Soochow University School of Medicine, Suzhou, Jiangsu, China ; Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - We retrospectively investigated the imaging findings of bone scintigraphy, chest  CT and chest MRI in 55 cases of lung cancer. The sensitivity, specificity and accuracy of the detection of rib metastases were compared between imaging modalities on both a per-lesion and a per-patient basis. On a per-lesion basis, MRI sensitivity and accuracy were significantly higher than that of bone scintigraphy and CT (P<0.05). The sensitivities, specificities, and accuracy levels between CT and bone scintigraphy did not differ on either a per-lesion or  per-patient basis (P>0.05). MRI appears to be superior for the detection of ribs  metastases in lung cancer.

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[542]

TÍTULO / TITLE:  - A case of typhlitis developed after chemotherapy with irinotecan and Cisplatin in a patient with small cell lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberc Respir Dis (Seoul). 2012 Nov;73(5):288-91. doi: 10.4046/trd.2012.73.5.288. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 4046/trd.2012.73.5.288

AUTORES / AUTHORS:  - Ji EH; Kim YM; Kim SJ; Yeom SJ; Ha SE; Kang HH; Kang JY; Lee SH; Moon HS

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Typhlitis is a necrotizing colitis that usually occurs in neutropenic patients and develops most often in patients with hematologic malignancies such as leukemia and lymphoma. Typhlitis may proceed to bowel perforation, peritonitis and sepsis, which requires immediate treatment. Irinotecan is a semisynthetic analogue of the natural alkaloid camptothecin which prevents DNA from unwinding by inhibition of topoisomerase I. It is mainly used in colon cancer and small cell lung carcinoma (SCLC), of which the most common adverse effects are gastrointestinal toxicities. To the best of our knowledge, no case of typhlitis after chemotherapy with a standard dose of irinotecan in a solid tumor has been reported in the literature. We, herein, report the first case of typhlitis developed after chemotherapy combining irinotecan and cisplatin in a patient with SCLC.

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[543]

TÍTULO / TITLE:  - Patients with advanced lung cancer: is there scope to discontinue inappropriate medication?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Pharm. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11096-012-9731-2

AUTORES / AUTHORS:  - Todd A; Williamson S; Husband A; Baqir W; Mahony M

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy, Health and Well-being, Faculty of Applied Sciences, University of Sunderland, Wharncliffe Street, Sunderland, SR1 3SD, UK, adam.todd@durham.ac.uk.

RESUMEN / SUMMARY:  - Background Polypharmacy-taking five or medications per day-is common in lung cancer patients. This patient group is prescribed medication to control acute symptoms associated with cancer and also to prevent or treat other long-term conditions. These medications increase the pill burden for the patient and also the probability of developing a drug-related toxicity. Objective To assess the prevalence of inappropriate medication in patients taking erlotinib for the treatment of advanced non-small cell lung cancer. Method This was a multicentre study across three sites in the North of England. Medication histories for patients receiving erlotinib were retrospectively extracted from medical notes and assessed by the clinical team (a consultant pharmacist, nurse specialist and  clinical oncologist) to determine if the medication was appropriate or inappropriate. The clinical team considered the following factors when deciding if the medication was appropriate or inappropriate: remaining life expectancy of  the patient, time until benefit of the treatment, goals of care and treatment targets. Results Among the 20 patients assessed, 19 (95 %) according to the clinical team were taking medications that were inappropriate. The mean number of medications the patients were taking was 8 (range 1-16) and the most common class of medication used were drugs affecting the Central Nervous System. In addition,  there were 11 patients (55 %) who were taking erlotinib in combination with a proton pump inhibitor (PPI)-a clinically significant drug interaction that impairs the absorption of erlotinib. Conclusions Patients taking erlotinib for the treatment of advanced non-small cell lung cancer take many inappropriate medications for the treatment or prevention of long-term conditions. These patients should have their medications reviewed in the context of their original  therapeutic goals.

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[544]

TÍTULO / TITLE:  - Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 22;12(1):615.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-615

AUTORES / AUTHORS:  - Petrausch U; Schuberth PC; Hagedorn C; Soltermann A; Tomaszek S; Stahel R; Weder W; Renner C

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. METHODS: This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and  re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT). No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. DISCUSSION: Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in  patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports  of severe toxicity in patients who received T cells intravenously due to unexpected expression of the target antigen (on-target) in other tissues than the tumor (off-tissue). To minimize the risk of on-target off-tissue toxicity and to  maximize the on-target anti-tumor effect we propose a clinical protocol with loco-regional administration of re-directed T cells. FAP-specific T cells will be directly injected in the pleural effusion of patients with MPM.Trial registration: ClinicalTrials.gov (NCT01722149).

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[545]

TÍTULO / TITLE:  - Activation of Thromboxane A(2) Receptor (TP) Increases the Expression of Monocyte Chemoattractant Protein -1 (MCP-1)/Chemokine (C-C motif) Ligand 2 (CCL2) and Recruits Macrophages to Promote Invasion of Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54073. doi: 10.1371/journal.pone.0054073. Epub 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054073

AUTORES / AUTHORS:  - Li X; Tai HH

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, United States of America.

RESUMEN / SUMMARY:  - Thromboxane synthase (TXAS) and thromboxane A(2) receptor (TP), two critical components for thromboxane A(2) (TXA(2)) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA(2) promotes these processes are still unclear. Here we show that TXA(2) mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor alpha isoform (A549-TPalpha). The induction of MCP-1 was also found in other lung cancer cells  H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPalpha cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA(2) may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment.

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[546]

TÍTULO / TITLE:  - Syk is low-expressed in non-small-cell lung cancer and inversely correlates with  patient’s survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Biochim Biophys Sin (Shanghai). 2013 Feb;45(2):149-51. doi: 10.1093/abbs/gms102. Epub 2012 Dec 2.

            ●● Enlace al texto completo (gratuito o de pago) 1093/abbs/gms102

AUTORES / AUTHORS:  - Peng C; Sun Q; Hao Y; Cong B; Zhao Y; Zhao X

INSTITUCIÓN / INSTITUTION:  - Thoracic Department, Second Hospital of Shandong University, Jinan 250033, China.

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[547]

TÍTULO / TITLE:  - Epidermal Growth Factor Recetor mutation study for 5 years, in a population of patients with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rev Port Pneumol. 2013 Jan;19(1):7-12. doi: 10.1016/j.rppneu.2012.08.002. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.rppneu.2012.08.002

AUTORES / AUTHORS:  - Castro AS; Parente B; Goncalves I; Antunes A; Barroso A; Conde S; Neves S; Machado JC

INSTITUCIÓN / INSTITUTION:  - Unidade de Pneumologia Oncologica, Servico de Pneumologia, Centro Hospitalar Vila Nova de Gaia-Espinho, Vila Nova de Gaia, Portugal. Electronic address: anasfcastro@gmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: In 2006, the Vila Nova de Gaia/Espinho Hospital Centre Pulmonary Oncology Unit started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010, regardless of histology, smoking habits, age or sex. The aim of this  study was to characterize the group of patients that carried out the sequencing between 2006-2010, to determine EGFR mutation frequency, to evaluate the overall  survival and the survival after the use of tyrosine kinase inhibitors (TKI), in patients who performed this therapy in second and third line, knowing the EGFR mutation status. METHODS: Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy. Record of the material available for analysis and average delay of exam results, according to the material submitted. RESULTS: The  sequencing was performed in 374 patients, 71,1% males, 67,1% non/ex-smokers, 32,9% smokers, 57,8% adenocarcinoma and 23,5% squamous cell carcinoma (SCC). The  mutation was detected in 49 patients (13,1%). In all studied patients, the mutation rate was 9% in males and 23% in females. Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6  months in not mutated patients (p = 0.003). CONCLUSION: Our group had an overall  mutation rate of 13.1% with female, non-smokers, adenocarcinoma histology predominance. In selected patients (2006/2009), the mutation rate was 16%, in not selected patients (2010) the mutation rate was 10.4%. This study has permitted a  better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors, in second and third line therapy with previous knowledge of the EGFR mutational status. Statistical significant differences in survival were  found in the two patient groups (EGFR mutated and non mutated). The EGFR mutation research should be performed in all patients with NSCLC, giving the possibility to a considerable number of patients to perform a first line treatment with TKI (EGFR mutated patients) and the advantage of performing other chemotherapy schemes, when progression occurs.

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[548]

TÍTULO / TITLE:  - Early Response to Chemotherapy in Patients With Non-Small-Cell Lung Cancer Assessed by [18F]-Fluoro-Deoxy-D-Glucose Positron Emission Tomography and Computed Tomography.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Dec 28. pii: S1525-7304(12)00254-9. doi: 10.1016/j.cllc.2012.10.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.004

AUTORES / AUTHORS:  - Novello S; Vavala T; Giaj Levra M; Solitro F; Pelosi E; Veltri A; Scagliotti GV

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University of Turin, AOU San Luigi Orbassano (TO), Italy. Electronic address: silvia.novello@unito.it.

RESUMEN / SUMMARY:  - BACKGROUND: This study aimed to demonstrate that patients who exhibit a tumor metabolic response to first-line chemotherapy seen on FDG-PET and computed tomography (CT) would survive longer than those who did not show such a response, comparing this evaluation with the morphologic response seen on CT. PATIENTS AND  METHODS: Images were acquired in 22 consecutive patients with advanced non-small-cell lung cancer (NSCLC) randomized to receive carboplatin/paclitaxel/sorafenib or placebo. FDG-PET was performed within 4 weeks before (PET1) and 2 weeks after starting treatment (PET2). Similarly, CT (CT1) was performed at baseline and then every 2 cycles (6 weeks) during treatment (CT2). Responders and nonresponders were identified with FDG-PET, and metabolic response was then compared with morphologic changes detected by spiral CT. RESULTS: Twenty-one of 22 patients completed this study. In terms of progression-free survival (PFS) (45 vs. 22.2 weeks) and overall survival (OS) (77 vs. 47.7 weeks), we observed a trend that was not statistically significant for patients whose response after 2 weeks of treatment was seen on FDG-PET (P = .22 for PFS; P = .15 for OS). CONCLUSION: Patients with advanced NSCLC who had a positive outcome, as evidenced by prolonged survival, were those who showed a tumor metabolic response seen on FDG-PET.

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[549]

TÍTULO / TITLE:  - Neoadjuvant Chemotherapy With Docetaxel-Cisplatin in Patients With Stage III N2 Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 3. pii: S1525-7304(12)00251-3. doi: 10.1016/j.cllc.2012.10.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.003

AUTORES / AUTHORS:  - Liao WY; Chen JH; Wu M; Shih JY; Chen KY; Ho CC; Yang JC; Yu CJ

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

RESUMEN / SUMMARY:  - INTRODUCTION: To assess the efficacy and potential prognostic factors of patients with stage III N2 non-small-cell lung cancer (NSCLC) treated with neoadjuvant docetaxel-cisplatin (DP) chemotherapy followed by surgical resection. METHODS: Sixty-two patients with NSCLC treated with DP as neoadjuvant chemotherapy between November 2003 and December 2009 were identified and reviewed in this study. Tumor response, survival, and clinicopathologic data were collected retrospectively. The time to event was analyzed by fitting Cox proportional hazards models. RESULTS: Fifty-eight (94%) of 62 patients eventually underwent surgical resection after DP. The overall clinical response rate to induction DP chemotherapy was 42%. Patients with squamous cell carcinoma (SCC) histology were more likely to response to the DP regimen than those with adenocarcinoma histology (68% vs. 33%, P = .006). With a median follow-up of 82.4 months among the 58 patients, there were 41 (71%) tumor relapses and 27 (47%) deaths. The median event-free survival  was 27.5 months (95% CI, 22.3-32.7 months), and the median overall survival was 66.7 months (95% CI, 35.1-98.3 months). In multivariate analysis, when fitting the Cox proportional hazards model, SCC histology (hazard ratio [HR] 0.234 [95% CI, 0.098-0.560]; P = .001) and mediastinal downstaging to N0 (HR 0.451 [95% CI,  0.226-0.898]; P = .024) were independent predictors of better event-free survival. CONCLUSIONS: Neoadjuvant chemotherapy with the DP regimen is both active and well tolerated in patients with stage III N2 NSCLC. SCC histology predicted a better treatment response and survival outcome than adenocarcinoma histology in this patient group. Further investigation of combined-modality treatment is warranted to improve survival in the adenocarcinoma subset of stage  III N2 NSCLC.

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[550]

TÍTULO / TITLE:  - Asymptomatic primary tuberculous pleurisy with intense 18-fluorodeoxyglucose uptake mimicking malignant mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Infect Dis. 2013 Jan 14;13(1):12.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2334-13-12

AUTORES / AUTHORS:  - Shinohara T; Shiota N; Kume M; Hamada N; Naruse K; Ogushi F

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by mycobacterial proliferation. Although it has been shown that pulmonary tuberculosis induces 18-fluorodeoxyglucose (FDG) uptake in active lesions, little is known about the application of FDG positron emission/computed tomography (FDG  PET/CT) to the management of primary tuberculous pleurisy. CASE PRESENTATION: We  report a case of asymptomatic primary tuberculous pleurisy presenting with diffuse nodular pleural thickening without distinct pleural effusion and parenchymal lung lesions mimicking malignant mesothelioma. An initial FDG PET/CT  scan demonstrated multiple lesions of intense FDG uptake in the right pleura and  thoracoscopic biopsy of pleural tissue revealed caseous granulomatous inflammation. The patient received antituberculous therapy for 6 months, with clearly decreased positive signals on a repeated FDG PET/CT scan. CONCLUSION: FDG PET/CT imaging may be useful for evaluating disease activity in tuberculous pleurisy patients with an unknown time of onset.

 

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[551]

TÍTULO / TITLE:  - Silibinin In Vitro Protects A549 Cells from Staphylococcus aureus-Mediated Injury and In Vivo Alleviates the Lung Injury of Staphylococcal Pneumonia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Planta Med. 2013 Jan;79(2):110-5. doi: 10.1055/s-0032-1328068. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1328068

AUTORES / AUTHORS:  - Wang X; Dong J; Dai X; Zhang Y; Wang J; Li H; Lu C; Tan W; Gao X; Deng X; Bu S; Niu X

INSTITUCIÓN / INSTITUTION:  - College of Quartermaster Technology, Jilin University, Changchun, PR China.

RESUMEN / SUMMARY:  - In this study, hemolysis, Western blot, and real-time RT-PCR assays were performed to evaluate silibinin’s activity against S. aureus alpha-toxin secretion. In addition, live/dead cell staining and lactate dehydrogenase activity assays were introduced to examine the influence of silibinin on alpha-toxin-induced cell injury in human alveolar epithelial cells. Furthermore,  we tested the influence of silibinin on S. aureus pneumonia in a mouse model. We  show that silibinin inhibits the expression of alpha-toxin in a dose-dependent manner and alleviates alpha-toxin-induced lung cell injury. The IC50 of silibinin that inhibits the hemolytic activity of S. aureus was 14.33 microg/mL for strain  8325-4. Moreover, this compound provides effective protection on the lung injury  of staphylococcal pneumonia.

 

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[552]

TÍTULO / TITLE:  - ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE(2) Expression in A549 Cells: Role of P2 Receptor-Dependent STAT3 Activation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54125. doi: 10.1371/journal.pone.0054125. Epub 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054125

AUTORES / AUTHORS:  - Cheng SE; Lee IT; Lin CC; Wu WL; Hsiao LD; Yang CM

INSTITUCIÓN / INSTITUTION:  - Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.

RESUMEN / SUMMARY:  - BACKGROUND: Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E(2) (PGE(2)) are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE(2) release remain unclear. PRINCIPAL FINDINGS: Here, we showed that ATPgammaS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin), PKC (Go6983, Go6976, Ro318220, and Rottlerin), ROS (Edaravone), NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin], Jak2 (AG490), and STAT3 [cucurbitacin E (CBE)] and transfection with siRNAs of PKCalpha, PKCiota, PKCmu, p47(phox), Jak2, STAT3, and cPLA(2) markedly reduced ATPgammaS-induced COX-2 expression and PGE(2) production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPgammaS. Moreover, ATPgammaS-induced ROS generation and p47(phox) translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPgammaS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Go6983, Go6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells. SIGNIFICANCE: Taken together, these results showed that ATPgammaS induced COX-2 expression and PGE(2) production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA(2) signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation  will create opportunities for the development of anti-inflammation therapeutic strategies.

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[553]

TÍTULO / TITLE:  - Video-assisted thoracic surgery lobectomy for right lung cancer in a patient with right aortic arch: report of a case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gen Thorac Cardiovasc Surg. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11748-013-0205-9

AUTORES / AUTHORS:  - Kodate M; Osaki T; Ono K

INSTITUCIÓN / INSTITUTION:  - Department of Chest Surgery, Iizuka Hospital, 3-83,Yoshiomachi, Iizuka, Fukuoka,  820-8505, Japan, mkodateh1@aih-net.com.

RESUMEN / SUMMARY:  - A 57-year-old man with an anomalous right aortic arch presented with cancer of the right lung. The right recurrent laryngeal nerve was found to be hooked around the right aortic arch. Right lower lobectomy with systematic mediastinal lymph node dissection was successfully performed using video-assisted thoracic surgery  to provide close intraoperative attention to the branching of recurrent laryngeal nerve.

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[554]

TÍTULO / TITLE:  - Quantitative analysis of survivin protein expression and its therapeutic depletion by an antisense oligonucleotide in human lung tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Ther Nucleic Acids. 2012 Jun 19;1:e30. doi: 10.1038/mtna.2012.19.

            ●● Enlace al texto completo (gratuito o de pago) 1038/mtna.2012.19

AUTORES / AUTHORS:  - Olsen AL; Davies JM; Medley L; Breen D; Talbot DC; McHugh PJ

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

RESUMEN / SUMMARY:  - RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber  optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies.

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[555]

TÍTULO / TITLE:  - Radiation port erythema multiforme: erythema multiforme localized to the radiation port in a patient with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Skinmed. 2012 Nov-Dec;10(6):390-2.

AUTORES / AUTHORS:  - Chodkiewicz HM; Cohen PR

INSTITUCIÓN / INSTITUTION:  - The Medical School, The University of Texas-Houston Medical School, USA.

RESUMEN / SUMMARY:  - A 75-year-old man was treated with stereotactic radiation to 50 gray units in 4 fractions for stage IB non-small cell lung cancer. Radiotherapy was directed at the right lower lobe segment of the lung and lasted 4 days. He developed radiodermatitis, which completely resolved within a few weeks after radiotherapy  was finished. Three months after completing radiation therapy, he developed a pruritic red lesion within his radiation port on his right mid back with the formation of blisters a week later. Two weeks after the onset of the patient’s blisters, cutaneous examination showed individual and convergent erythematous papules and plaques with superficial scaling at sites of resolving vesicles located within the radiated area (Figures 1 and 2). The patient had neither symptoms of mycoplasma pneumoniae, nor lesions or history of present or past herpetic infection. Also, he had not recently been placed on any new medications, and he did not have any other erythema multiforme-associated risk factors. A biopsy from the erythematous lesions showed a band-like infiltrate of lymphocytes in the dermis. The overlying epidermis contained necrotic keratinocytes and there was alteration of the basal layer. Correlation of the clinical presentation and pathologic changes established a diagnosis of erythema multiforme localized to the radiation port. The patient was treated with topical triamcinolone acetonide  0.1% cream twice daily for 10 days and once daily for 4 days. His lesions resolved and there was mild hyperpigmentation of the affected area.

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[556]

TÍTULO / TITLE:  - Prospective Study of Urinary and Serum Cross-Linked N-Telopeptide of Type I Collagen (NTx) for Diagnosis of Bone Metastasis in Patients With Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Dec 28. pii: S1525-7304(12)00261-6. doi: 10.1016/j.cllc.2012.11.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.006

AUTORES / AUTHORS:  - Tamiya M; Tokunaga S; Okada H; Suzuki H; Kobayashi M; Sasada S; Okamoto N; Morishita N; Matsuura Y; Miyamoto N; Hattori M; Taira K; Daga H; Takeda K; Hirashima T

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan. Electronic address: moto19781205@yahoo.co.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Many cancers metastasize to bone, which may cause an increase in bone resorption because of the direct effects of the tumor itself or osteoclastic activation. PATIENTS AND METHODS: Levels of urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum cross-linked N-telopeptide of type I collagen (sNTx) were measured in 100 patients with lung cancer and 50 patients with benign respiratory disease using the Osteomark NTx urine and serum assays (Osteomark, Princeton, NJ). Bone metastasis was diagnosed by bone scintigraphy. Receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity to detect bone metastasis were calculated when cutoff points were set to 64 nmol bone collagen equivalents (BCE)/mmol Cr for uNTx and 22 nmol BCE/L for sNTx. RESULTS: Patients with lung cancer and bone metastasis had significantly higher levels of both uNTx and sNTx  (uNTx median [range], 61.3 [22.7-593.1] nmol BCE/mmol creatinine [Cr]; sNTx median [range], 19.7 [10.7-97.1] nmol BCE/L) than did patients with lung cancer without bone metastasis (uNTx median [range], 45.2 [19.8-153.0] nmol BCE/mmol Cr; sNTx median [range], 16.7 [11.0-28.4] nmol BCE/L), or patients with benign respiratory diseases (uNTx median [range], 40.6 [15.2-155.9] nmol BCE/mmol Cr; sNTx median [range], 14.8 [9.5-55.5] nmol BCE/L.). There was good correlation between uNTx and sNTx (R = 0.807). Area under the curve (AUC) for ROC was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis were 48.0% and 86.0%, respectively, using uNTx, and 40.0% and 87.0%, respectively, using sNTx. CONCLUSION: This prospective study indicates equivalency between sNTx and uNTx in sensitivity and specificity to detect bone metastasis, and both uNTx and sNTx may have value as aids in the diagnosis of bone metastasis in patients with lung cancer.

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[557]

TÍTULO / TITLE:  - Improving referral of patients for consideration of adjuvant chemotherapy after surgical resection of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Oncol. 2012 Dec;19(6):e422-7. doi: 10.3747/co.19.1133.

            ●● Enlace al texto completo (gratuito o de pago) 3747/co.19.1133

AUTORES / AUTHORS:  - Zuccato JA; Ellis PM

INSTITUCIÓN / INSTITUTION:  - Faculty of Medicine, University of Toronto, Toronto, ON.

RESUMEN / SUMMARY:  - BACKGROUND: Clinical trials demonstrate improved survival for patients with completely resected non-small-cell lung cancer (nsclc) who receive adjuvant chemotherapy. Concerns have been raised about the implementation of those data. The present study measured rates of referral for adjuvant chemotherapy and barriers to referral, and it also evaluated a knowledge translation strategy to change practice. METHODS: An audit and feedback approach was used. Using a retrospective cohort of patients undergoing thoracotomy at St. Joseph’s Hospital  in Hamilton, Ontario, during January-December 2008, anonymized data were presented to a group of thoracic surgeons for evaluation and feedback. RESULTS: Among 150 thoracotomies performed, 55 patients with nsclc were potentially eligible for adjuvant chemotherapy, but only 27 (49%) were referred for it. Significant variability in referral between surgeons (19%-100%) was observed. Reasons for non-referral were poorly documented in the medical record, but appeared to be primarily the surgeon’s decision. The feedback session with surgeons produced a number of constructive suggestions to implement change in practice. CONCLUSIONS: Our findings suggest that surgeon choice was the most significant barrier to implementation of adjuvant chemotherapy for nsclc. Audit and feedback was a useful knowledge translation strategy. However, longer follow-up is needed to document change in practice.

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[558]

TÍTULO / TITLE:  - KIT (CD117) Expression in a Subset of Non-Small Cell Lung Carcinoma (NSCLC) Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52885. doi: 10.1371/journal.pone.0052885. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052885

AUTORES / AUTHORS:  - Donnenberg AD; Zimmerlin L; Landreneau RJ; Luketich JD; Donnenberg VS

INSTITUCIÓN / INSTITUTION:  - Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America ; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

RESUMEN / SUMMARY:  - We have previously described the expression of CD44, CD90, CD117 and CD133 in NSCLC tumors, adjacent normal lung, and malignant pleural effusions (MPE). Here we describe the unique subset of tumors expressing CD117 (KIT), a potential therapeutic target. Tumor and adjacent tissue were collected from 58 patients. Six MPE were obtained before therapy. Tissue was paraffin embedded for immunofluorescent microscopy, disaggregated and stained for flow cytometry or cryopreserved for later culture. The effect of imatinib on CD117(high)/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Primary tumors divided into KIT(neg) and KIT(+) by immunofluorescence. By more sensitive flow cytometric analysis, CD117+ cytokeratin+ cells were detected in all tissues (1.1% of cytokeratin+ cells in normal lung, 1.29% in KIT “negative” tumors, 40.7% in KIT(+) tumors, and 0.4% in MPE). In KIT(+)/CD117(high), but not KIT(+)/CD117(low) tumors, CD117 was overexpressed 3.1-fold compared to normal lung. Primary cultures of CD117(high) tumors were sensitive to imatinib (5 microM) in short term culture. We conclude that NSCLC tumors divide into CD117(low) and CD117(high). Overexpression of CD117 in CD117(high) NSCLC supports exploring KIT  as a therapeutic target in this subset of patients.

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[559]

TÍTULO / TITLE:  - An update on molecularly targeted therapies in second- and third-line treatment in non-small cell lung cancer: focus on EGFR inhibitors and anti-angiogenic agents.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0964-2

AUTORES / AUTHORS:  - Majem M; Pallares C

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Service, Hospital de la Santa Creu i Sant Pau, c/Sant Antoni Maria Claret 167, 08025, Barcelona, España, mmajem@santpau.cat.

RESUMEN / SUMMARY:  - Docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (gefitinib and erlotinib) are recommended second-line therapy for advanced non-small cell lung cancer (NSCLC) patients with disease progression. Although erlotinib is the only recommended third-line therapy, several drugs are  being used in the clinic. Recent studies have focused on combining targeted agents with approved therapies, including broad-spectrum multikinase inhibitors targeting multiple ErbB Family receptors and multitargeted anti-angiogenic agents targeting the vascular endothelial growth factor receptor, platelet-derived growth factor receptor and fibroblast growth factor receptor pathways. Here, we review targeted therapies that are being evaluated in second- and third-line settings in NSCLC, including the ErbB Family Blocker afatinib (BIBW 2992), multityrosine kinase inhibitors (pelitinib [EKB-56]), neratinib [HKI-272], canertinib [CI-1033], lapatinib [GW-572016], dacomitinib [PF-299804]) and multitargeted anti-angiogenic agents (vandetanib [ZD6474], sunitinib [SU11248], sorafenib [BAY43-9006], nintedanib [BIBF1120], axitinib [AG-013736], cediranib [AZD2171], motesanib [AMG 706], linifanib [ABT869] and pazopanib [GW786034]).

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[560]

TÍTULO / TITLE:  - Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with advanced non-small cell lung cancer: Single center experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J BUON. 2012 Oct-Dec;17(4):724-8.

AUTORES / AUTHORS:  - Inal A; Kucukoner M; Kaplan MA; Urakci Z; Karakus A; Komek H; Dostbil Z; Isikdogan A

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Dicle University, Diyarbakir, Turkey.

RESUMEN / SUMMARY:  - Purpose: The purpose of this retrospective single-center study was to evaluate the prognostic implication on overall survival (OS) of the F-18 FDG PET scan in locally advanced or metastatic non small cell lung cancer (NSCLC) patients. Methods: We retrospectively reviewed 120 locally advanced or metastatic NSCLC patients (December 2004-November 2011) treated/followed at the Dicle University,  School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables (n=18) were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors for OS. Results: Among 18  variables of univariate analysis, 6 were identified to bear prognostic significance: sex (p=0.01), performance status (PS) (p =0.03), stage (p=0.04), bone metastases (p=0.002), serum albumin (p=0.01) and blood glucose level (p=0.03). Multivariate analysis showed that PS, bone metastases and serum albumin level were independent prognostic factors for OS (p=0.01, p=0.004, p=0.003, respectively). Conclusion: PS, serum albumin levels and bone metastases were independent prognostic factors, while FDG uptake of the primary lesion was not associated with prognosis of OS in locally advanced or metastatic NSCLC patients.

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[561]

TÍTULO / TITLE:  - Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Sep;24(3):226-31. doi: 10.1007/s11670-012-0226-4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-012-0226-4

AUTORES / AUTHORS:  - Ren SX; Li AW; Zhou SW; Zhang L; Wang YS; Li B; Chen XX; Zhang J; Xu JF; Zhou CC

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology.

RESUMEN / SUMMARY:  - OBJECTIVE: Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 (BRCA1) gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 (RRM1) gene overexpression enhances resistance to gemcitabine. To further examine the effect  of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer (NSCLC), we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy. METHODS: RNA was isolated from fresh tumor tissue. Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels: both low-cisplatin plus gemcitabine (GP); both high-vinorelbine plus cisplatin (NP); BRCA1 low and RRM1 high-cisplatin plus docetaxel (TP); BRCA1 high and RRM1  low-vinorelbine plus gemcitabine (GN). RESULTS: From Dec 2005 to Nov 2008, 94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study. The median age was 58 years old. Among them, 21 patients received  GP, 30 patients received TP and 43 patients received NP chemotherapy. GP group had a higher response rate, and longer median time to progression (TTP) and median overall survival (OS) time than the other 2 groups. The response rates in  the GP, TP and NP groups were 42.9%, 36.7% and 27.9%, respectively (P=0.568). The median TTP was 5.6, 5.0, 4.8 months (P=0.975), respectively, and the median OS time was 12.5, 11.0, 9.7 months (P=0.808), respectively. CONCLUSION: Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group. This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

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[562]

TÍTULO / TITLE:  - Effectiveness and response predictive factors of erlotinib in a non-small cell lung cancer unselected European population previously treated: A retrospective, observational, multicentric study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Oncol Pharm Pract. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1078155212465994

AUTORES / AUTHORS:  - Cioffi P; Marotta V; Fanizza C; Giglioni A; Natoli C; Petrelli F; Grappasonni I

INSTITUCIÓN / INSTITUTION:  - Hospital Pharmacy, SS Annunziata Hospital, Chieti, Italy.

RESUMEN / SUMMARY:  - Aims and background:Erlotinib approval was supported by the positive results of a large multicentric phase III trial (BR.21 study) that included 10% Asiatic patients and the remaining were North-American Caucasian. It is well-known that the efficacy of tyrosine kinase inhibitors is strongly influenced by ethnicity and other genetic factors. It is, therefore, relevant to establish whether the same profile of efficacy is seen in an unselected population and whether the results of BR.21 can be generalized to other patient populations, such as that described here. METHODS: In this retrospective, observational, multicentric study, we assessed effectiveness and potentially response predictive factors in 222 unselected Italian patients, with stage IIIB/IV non-small-cell lung cancer, with performance status from 0 to 3, who had received at least one line of chemotherapy, treated with the standard dose of erlotinib (150 mg once daily) until disease progression or unacceptable toxicity. RESULTS: The disease control  rate was 60.9% (135 patients). Median progression-free survival and overall survival times were 3.1 months and 7.97 months, respectively. The characteristics of non-smoker, female gender, performance status 0 or 1 were associated with a significantly better prognosis in terms of disease control rate and were also predictive of longer overall survival and progression-free survival. The 1-year survival rate was 38.79%. Even though Italian patients baseline characteristics were strongly different to those reported in pivotal BR.21 trial in terms of age, performance status, line treatment and ethnic group, our study confirms the favorable effectiveness profile in real clinical practice of erlotinib according  to results from the pivotal study BR.21. CONCLUSIONS: Today, we know that epidermal growth factor receptor (EGFR) status assessment is mandatory before starting first-line therapy and that the presence of only certain clinical characteristics initially associated with sensitivity to EGFR-tyrosine kinase inhibitors, as reported in this study, is not sufficient in selecting patients candidates to such treatments.

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[563]

TÍTULO / TITLE:  - EZH2 Promotes Malignant Behaviors via Cell Cycle Dysregulation and Its mRNA Level Associates with Prognosis of Patient with Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52984. doi: 10.1371/journal.pone.0052984. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052984

AUTORES / AUTHORS:  - Cao W; Ribeiro Rde O; Liu D; Saintigny P; Xia R; Xue Y; Lin R; Mao L; Ren H

INSTITUCIÓN / INSTITUTION:  - Shanghai Key Laboratory of Stomatology, Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ; Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland, United States of America.

RESUMEN / SUMMARY:  - BACKGROUND: Epigenetic silencing is a common mechanism to inactivate tumor suppressor genes during carcinogenesis. Enhancer of Zeste 2 (EZH2) is the histone methyltransferase subunit in polycomb repressive complex 2 which mediates transcriptional repression through histone methylation. EZH2 overexpression has been linked to aggressive phenotypes of certain cancers. However, the mechanism that EZH2 played in promoting malignancy in non-small cell lung cancer (NSCLC) remains unclear. In addition, the correlation of EZH2 overexpression and the prognosis of NSCLC patients in non-Asian cohort need to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Up-regulation of EZH2 was found in NSCLC cells compared with normal human bronchial epithelial cells by western blot assay. Upon EZH2 knockdown using small interfering RNA (siRNA), the proliferation, anchorage-independent growth and invasion of NSCLC cells were remarkably suppressed with profound induction of G1 arrest. Furthermore, the expression of cyclin D1 was notably reduced whereas p15(INK4B), p21(Waf1/Cip1) and p27(Kip1) were increased in NSCLC cells after EZH2-siRNA delivery. To determine whether EZH2 expression contributes to disease progression in patients with NSCLC, Taqman quantitative real-time RT-PCR was used to measure the expression of EZH2 in paired tumor and normal samples. Univariate analysis revealed that patients with  NSCLC whose tumors had a higher EZH2 expression had significantly inferior overall, disease-specific, and disease-free survivals compared to those whose tumors expressed lower EZH2 (P = 0.005, P = 0.001 and P = 0.003, respectively). In multivariate analysis, EZH2 expression was an independent predictor of disease-free survival (hazard ratio = 0.450, 95% CI: 0.270 to 0.750, P = 0.002).  CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that EZH2 overexpression is critical for NSCLC progression. EZH2 mRNA levels may serve as a prognostic predictor for patients with NSCLC.

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[564]

TÍTULO / TITLE:  - Effect of trichostatin A and paclitaxel on the proliferation and apoptosis of lung adenocarcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Jan;126(1):129-34.

AUTORES / AUTHORS:  - Zhang S; Zhang QC; Jiang SJ

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Diseases, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

RESUMEN / SUMMARY:  - BACKGROUND: Histone deacetylase inhibitors can regulate gene expression through modulation of the degree of acetylation of histone and non-histone, thus affecting cell proliferation, survival and chemosensitivity. Histone deacetylase  inhibitors combined with paclitaxel may enhance the inhibitory effect of drugs on lung cancer cells. This study aimed to observe the effect of trichostatin A (TSA)/paclitaxel on the proliferation and apoptosis in human A549 lung adenocarcinoma cells, and to investigate its mechanism. METHODS: A549 cells were  cultured in Dulbecco modified Eagle’s medium (DMEM) in the presence of paclitaxel and the histone deacetylase inhibitor TSA, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst  33258 staining and flow cytometry analysis, and cell cycle was detected by flow cytometry analysis. The proteins poly ADP-ribose polymerase (PARP), caspase-3, survivin, and tubulin acetylation were detected by Western blotting. RESULTS: A significant reduction of proliferation was observed in A549 lung adenocarcinoma cells treated by paclitaxel or TSA. Combined treatment with TSA/paclitaxel caused the greatest inhibition of cell proliferation. The combined treatment with TSA and paclitaxel induced more severe apoptosis, and significantly more cells were arrested in G2/M phase (P < 0.05) then with a single drug. Using Western blotting, we demonstrated that treatment with TSA/paclitaxel led to synergistic increase in acetylated tubulin, PARP, caspase-3, and reduced the expression of survivin. CONCLUSION: TSA and paclitaxel have a synergistic activity that can inhibit cell growth and induce apoptosis.

 

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[565]

TÍTULO / TITLE:  - Fluorescence In Situ Hybridization and Immunohistochemistry as Diagnostic Methods for ALK Positive Non-Small Cell Lung Cancer Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e52261. doi: 10.1371/journal.pone.0052261. Epub 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052261

AUTORES / AUTHORS:  - Martinez P; Hernandez-Losa J; Cedres S; Castellvi J; Martinez-Marti A; Tallada N; Murtra-Garrell N; Navarro-Mendivill A; Rodriguez-Freixinos V; Canela M; Ramon Y Cajal S; Felip E

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Department, Vall d’Hebron University Hospital, Universidad Autonoma de Barcelona, Barcelona, España.

RESUMEN / SUMMARY:  - BACKGROUND: Anaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients. METHODS: NSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored. RESULTS: ninety-nine patients were identified. Median age was 61.5 years (range 35-83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative. CONCLUSIONS: ALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients.

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[566]

TÍTULO / TITLE:  - Surgical treatment of early stage small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Cardiovasc Thorac Ann. 2012 Dec;20(6):694-8. doi: 10.1177/0218492312453348.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0218492312453348

AUTORES / AUTHORS:  - Ploenes T; Osei-Agyemang T; Krohn A; Kayser G; Burger M; Passlick B

INSTITUCIÓN / INSTITUTION:  - Till.Ploenes@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - Background: Chemotherapy with radiation has to be considered the standard therapy for limited-stage small cell lung cancer but surgical resection is possible in a  small subgroup in which it may improve survival. Surgery is not recommended as the standard treatment, but a few small studies have demonstrated a benefit of surgery in highly selected cases of limited-stage small cell lung cancer. Methods: We conducted a retrospective study of 29 patients with limited-stage small cell lung cancer undergoing surgical resection in our department. There were 7 (24%) women and 22 (76%) men with a median age of 62 years (range, 46-82 years). Medical history, histology and survival status were extracted from the medical database of the University Medical Center Freiburg. Results: The median overall survival was 20.7 months. In 15 patients who received neoadjuvant treatment, the median survival was 89.4 months. Karnofsky performance status and  neoadjuvant chemotherapy had a significant influence on median survival (p <0.0004). Conclusions: We concluded that surgical resection can be beneficial in  a highly selected group of patients as a part of a multidisciplinary approach. In addition, surgical resection is safe with acceptable mortality and morbidity.

 

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[567]

TÍTULO / TITLE:  - Potentiation of in vitro and in vivo antitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Jan 23;13(1):29.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-29

AUTORES / AUTHORS:  - Rathos MJ; Khanwalkar H; Joshi K; Manohar SM; Joshi KS

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: In the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells. METHODS: Synergistic effects of P276-00 and doxorubicin on growth inhibition was  studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model. RESULTS: The combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-kappaB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited  tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model. CONCLUSION: These findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-kappaB signaling and inhibition of Cdk-1 which is involved in cell cycle progression.

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[568]

TÍTULO / TITLE:  - Successful Chemoradiotherapy for Small-Cell Carcinoma of the Esophagus in an Octogenarian Japanese Woman: Report of the Oldest Case and Review of Long-Term Survival Cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 26.

AUTORES / AUTHORS:  - Shinohara Y; Takeno S; Takahashi Y; Moroga T; Yamashita SI; Kawahara K

INSTITUCIÓN / INSTITUTION:  - Department of Surgery II, Oita University Faculty of Medicine, Oita, Japan.

RESUMEN / SUMMARY:  - Small-cell carcinoma of the esophagus (SCCE) is a rare and rapidly progressive malignant tumor with an extremely unfavorable prognosis. We report a case of long-term survival and review similar cases in the literature. An 84-year-old Japanese woman visited a clinic complaining of tarry stools. Type-1 tumor was detected in the left posterior wall of the middle thoracic esophagus on endoscopic examination, and the pathological diagnosis following immunohistochemical examination was SCCE. Chemoradiotherapy was adopted after taking the characteristics of poor prognosis, rapid progression, and patient age  into consideration. Chemoradiotherapy comprised 56 Gy of irradiation over43 days  and two courses chemotherapy with cisplatin and vincristine. Therapeutic effect was evaluated as complete response after endoscopic examination and computed tomography at one month after treatment. No recurrence or metastasis has been identified as of more than five years after achieving complete response, with endoscopic examination every six months and computed tomography every three months. To date, long-term survival has only been reported in octogenarian patients with SCCE, and the present case describes the oldest patient for whom successful radical therapy has been reported.

 

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[569]

TÍTULO / TITLE:  - A chrono-target chemotherapy treatment model for lung cancer treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ther Deliv. 2013 Jan;4(1):5-8. doi: 10.4155/tde.12.137.

            ●● Enlace al texto completo (gratuito o de pago) 4155/tde.12.137

AUTORES / AUTHORS:  - Zarogoulidis P; Trakada G; Zarogoulidis K

INSTITUCIÓN / INSTITUTION:  - Pulmonary Department - Oncology Unit, ‘G. Papanikolaou’ General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece and University Pulmonary Department-Interventional Unit, ‘Ruhrland’ Klinik, University of Duisburg-Essen, Essen, Germany. pzarog@hotmail.com.

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[570]

TÍTULO / TITLE:  - CT-Guided Percutaneous Cordotomy for Intractable Pain in What is More than a Disease: Lung Malignancies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Turk Neurosurg. 2013;23(1):81-7. doi: 10.5137/1019-5149.JTN.6980-12.0.

            ●● Enlace al texto completo (gratuito o de pago) 5137/1019-5149.JTN.6980-12.0

AUTORES / AUTHORS:  - Kanpolat Y; Ozdemir M; Al-Beyati E

INSTITUCIÓN / INSTITUTION:  - President of the Turkish Academy of Sciences, Emeritus, Ankara University, Faculty of Medicine, Department of Neurosurgery, Ankara, Turkey.

RESUMEN / SUMMARY:  - AIM: Lung cancer is the leading cause of cancer-related mortality worldwide. Pain is a common problem in these patients, yet inadequate or dissatisfactory management is prevalent. MATERIAL and METHODS: Between 1987 and 2012, 224 patients with intractable pain were treated with computerized tomography (CT)- guided cordotomy. Among them, 210 had intractable pain due to malignancies. The majority of the cases were diagnosed as pulmonary malignancies (108 patients). Sixty-seven were pulmonary carcinoma, 26 mesothelioma and 15 Pancoast tumors. RESULTS: After cordotomy, 98.13% of cancer patients reported initial pain relief. Minimum and maximum preoperative scores of the Karnofsky Performance Scale were 20 and 70, versus postoperative scores of 40 and 90 (p < 0.001). The median preoperative VAS score was 8 (6-9). On the first postoperative day, the score dropped sharply to 0 (0-8) (p < 0.001). In this selected series of 108 percutaneous cordotomy procedures, as well as in the total series of 224 patients, there was no mortality or major morbidity. CONCLUSION: CT-guided percutaneous cordotomy is an effective procedure that should be used in the treatment of cancer-related pain problems. We suggest that cordotomy should be preferred as soon as possible in patients who fail to respond to the classic analgesic therapy.

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[571]

TÍTULO / TITLE:  - CT Densitometry as a Predictor of Pulmonary Function in Lung Cancer Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Open Respir Med J. 2012;6:139-44. doi: 10.2174/1874306401206010139. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 2174/1874306401206010139

AUTORES / AUTHORS:  - Moloney F; McWilliams S; Crush L; Laughlin PD; Kenneddy M; Henry M; O’ Connor O; Maher MM

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Cork University Hospital and University College Cork, Cork, Ireland.

RESUMEN / SUMMARY:  - PURPOSE: Preoperative pulmonary assessment is undertaken in patients with resectable lung cancer to identify those at increased risk of perioperative complications. Guidelines from the American College of Chest Physicians indicate  that if the FEV(1) and DLCO are >/=60% of predicted, patients are suitable for resection without further evaluation. The aim of our study is to determine if quantitative measures of lung volume and density obtained from pre-operative CT scans correlate with pulmonary function tests. This may allow us to predict pulmonary function in patients with lung cancer and identify patients who would tolerate surgical resection. MATERIALS AND METHODS: Patients were identified retrospectively from the lung cancer database of a tertiary hospital. Image segmentation software was utilized to estimate total lung volume, normal lung volume (values -500 HU to -910 HU), emphysematous volume (values less than -910 HU), and mean lung density from pre-operative CT studies for each patient and these values were compared to contemporaneous pulmonary function tests. RESULTS:  A total of 77 patients were enrolled. FEV1 was found to correlate significantly with the mean lung density (r=.762, p<.001) and the volume of emphysema (r= -.678, p<.001). DLCO correlated significantly with the mean lung density (r =.648, p<.001) and the volume of emphysematous lung (r= -.535, p<.001). CONCLUSION: The results of this study suggest that both FEV1 and DLCO correlate significantly with volume of emphysema and mean lung density. We now plan to prospectively compare these CT parameters with measures of good and poor outcome  postoperatively to identify CT measures that may predict surgical outcome preoperatively.

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[572]

TÍTULO / TITLE:  - The dynamics of selected local inflammatory markers to talc in the treatment of malignant pleural effusions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Dec 7. doi: 10.5507/bp.2012.095.

            ●● Enlace al texto completo (gratuito o de pago) 5507/bp.2012.095

AUTORES / AUTHORS:  - Habal P; Jankovicova K; Omran N; Kondelkova K; Krejsek J; Mandak J

INSTITUCIÓN / INSTITUTION:  - Department of Cardiac Surgery, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital in Hradec Kralove, Czech Republic.

RESUMEN / SUMMARY:  - BACKGROUND: Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H(2)Mg(3)(SiO(3))(4)) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. METHODS: The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. RESULTS: Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in  pleural fluid before the talc poudrage. This showed limited ability to create an  adequate inflammatory response to external stimuli. This group also showed lower  levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect  of the treatment was not influenced by morphologic tumour type. No statistically  significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. CONCLUSIONS: There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.

 

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[573]

TÍTULO / TITLE:  - Role of Ku70 and Bax in epigallocatechin-3-gallate-induced apoptosis of A549 cells in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):101-106. Epub 2012 Oct 16.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.972

AUTORES / AUTHORS:  - Li JJ; Gu QH; Li M; Yang HP; Cao LM; Hu CP

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

RESUMEN / SUMMARY:  - EGCG (epigallocatechin-3-gallate), the major catechin found in green tea, has been demonstrated to inhibit proliferation and induce apoptosis in a number of types of tumors. Recent studies reveal that EGCG has various anticancer effects.  This study investigated a further possible molecular mechanism of the anticancer  effects of EGCG in murine lung cancer xenografts. In the study, A549 human lung cancer cells were injected into nude mice. Tumor volume was used to measure cancer cell growth. The weight of the animals was used to assess the toxicity of  the drugs. The expression of protein and mRNA was assayed by western blot analysis and RT-PCR, respectively. The interaction between Bax and Ku70 was determined by immunoprecipitation. Our results suggest that EGCG induced A549 lung cancer cell apoptosis in vivo, and had less toxic effects compared to classical anticancer drugs. EGCG may inhibit the surrogate markers of proliferation and apoptosis (caspase 3) in A549 tumor xenografts in vivo. In addition, EGCG downregulated the expression of Bcl-xl and upregulated the expression of Bax mRNA and protein. Further experiments indicated that EGCG downregulated the protein expression of Ku70 and interrupted the binding of Ku70  and Bax. This is the first study demonstrating that the induction of apoptosis by EGCG may be caused by the downregulation of Ku70 and that EGCG disrupts the interaction between Ku70 and Bax in lung cancer.

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[574]

TÍTULO / TITLE:  - Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2013 Jan 17;11(1):9.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-9

AUTORES / AUTHORS:  - Okur HK; Yuksel M; Lacin T; Baysungur V; Okur E

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate  and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. METHODS: Fifteen patients (all male, mean age 63.6 +/- 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at -20 [degree sign]C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. RESULTS: Both luminol (specific for .OH, H2O2, and HOCl-) and lucigenin (selective for O2.-) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 +/- 0.71 and 2.5 +/- 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). CONCLUSION: In patients with  lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which  is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.

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[575]

TÍTULO / TITLE:  - Linear EBUS in Staging Non-Small Cell Lung Cancer and Diagnosing Benign Diseases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2013 Jan;20(1):66-76. doi: 10.1097/LBR.0b013e31827d1514.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e31827d1514

AUTORES / AUTHORS:  - Dincer HE

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, MN.

RESUMEN / SUMMARY:  - As an evolving technique, linear endobronchial ultrasound is becoming the first choice and standard of care not only to diagnose the malignant and benign mediastinal lesions but also to stage non-small cell lung cancer. Lung cancer is  the leading cause of cancer-related mortality in both men and women. The disease  causes more death compared with colorectal, breast, and prostate cancers combined in the United States. Staging of lung cancer determines the prognosis. The type of lung cancer has changed in the past few decades. The frequency of adenocarcinoma has increased, whereas squamous cell carcinoma now is less frequent. Determining the cell type and its molecular characteristics allow targeted treatments in adenocarcinoma. The diagnosis of indeterminate mediastinal lymph nodes or masses and staging lung cancer might be challenging. This article  will review the principles and clinical utility of endobronchial ultrasound in mediastinal lesions.

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[576]

TÍTULO / TITLE:  - Down-regulation of heparanase leads to the inhibition of invasion and proliferation of A549 cells in vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Biochim Biophys Sin (Shanghai). 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/abbs/gms109

AUTORES / AUTHORS:  - Chen Z; Zhu L; Li X; Tian H; Fang Y; Liu H; Li S; Li L; Yue W; Li W

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Shandong University, Jinan 250013, China.

RESUMEN / SUMMARY:  - Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with  tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small  cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in  vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which  might be the mechanism responsible for the inhibition of A549 cell proliferation  in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.

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[577]

TÍTULO / TITLE:  - Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Jan 3;8:4. doi: 10.1186/1748-717X-8-4.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-4

AUTORES / AUTHORS:  - Badiyan SN; Bierhals AJ; Olsen JR; Creach KM; Garsa AA; Dewees T; Bradley JD; Robinson CG

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University in St, Louis, 4921 Parkview Place, Campus Box 8224, St, Louis, MO, 63110, USA. crobinson@radonc.wustl.edu.

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. METHODS: One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004-2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. RESULTS: Median follow-up was 29 months. The median  SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and  five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053). CONCLUSIONS: Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be  an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

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[578]

TÍTULO / TITLE:  - Surgical Treatment for Metachronous Second Primary Lung Cancer after Radical Resection of Primary Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 13.

AUTORES / AUTHORS:  - Ishigaki T; Yoshimasu T; Oura S; Ota F; Nakamura R; Hirai Y; Okamura Y

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.

RESUMEN / SUMMARY:  - Purpose: We retrospectively reviewed our experience of surgical resection for second primary lung cancer (SPLC) in our institute. And to clarify whether periodic follow-up after resection of first primary lung cancer (FPLC) is associated with earlier detection of SPLC.Methods: From January 2003 to March 2011, a total of 386 patients underwent surgical resection for primary lung cancer in our institute. Of these patients, 21 (5.4%) with SPLC were observed during follow-up after surgery. Radiation therapy was selected instead of surgical resection in 7 patients to preserve respiratory function. The other14 patients are reviewed in this paper.Results: Histological types were different between FPLC and SPLC in only one patient(FPLC: adenosquamous carcinoma, SPLC: squamous cell carcinoma). The average SPLC tumor size (18+/-8 mm) was smaller (P  = 0.07) than the average FPLC tumor size (26+/-14 mm). Recurrence was not observed in these patients.The follow-up period after resection of SPLC was 31+/-30 (5-94) months. During followup, 2 patients died of de novo malignancies,  and the other 12 patients were alive without recurrence.Conclusion: Systematic and periodic long-term follow-up after FPLC probably resulted in earlier detection of SPLC and yielded this good prognosis.

 

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[579]

TÍTULO / TITLE:  - Experience of significant hemodynamic instability that occurred during excisional biopsy in a patient with unrecognized bronchial carcinoid tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Korean J Anesthesiol. 2012 Nov;63(5):475-6. doi: 10.4097/kjae.2012.63.5.475. Epub 2012 Nov 16.

            ●● Enlace al texto completo (gratuito o de pago) 4097/kjae.2012.63.5.475

AUTORES / AUTHORS:  - Lee S; Lee KH; Kim JY; Choe WJ; Kim JW

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology and Pain Medicine, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, Korea.

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[580]

TÍTULO / TITLE:  - Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 4;12:568. doi: 10.1186/1471-2407-12-568.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-568

AUTORES / AUTHORS:  - Suzumura T; Kimura T; Kudoh S; Umekawa K; Nagata M; Matsuura K; Tanaka H; Mitsuoka S; Yoshimura N; Kira Y; Nakai T; Hirata K

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kimutats@med.osaka-cu.ac.jp.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Rash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials  with gefitinib have reported different proportions of adverse events compared to  trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown  to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies. METHODS: The frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of  CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can  detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types. RESULTS: A total of 232  patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21-0.94; *p = 0.03), but not diarrhea >/= grade 2 (OR, 0.49; 95% CI, 0.17-1.51; *p = 0.20) or liver dysfunction >/= grade 2 (OR, 1.08; 95% CI, 0.52-2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54-6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21-7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20-5.07; *p = 0.93). CONCLUSIONS: The frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.

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[581]

TÍTULO / TITLE:  - Lung cancer in HIV-infected patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Int AIDS Soc. 2012 Nov 11;15 Suppl 4:18087. doi: 10.7448/IAS.15.6.18087.

AUTORES / AUTHORS:  - Palacios R; Lebron J; Guerrero-Leon M; Del Arco A; Colmenero J; Marquez M; Santos J

INSTITUCIÓN / INSTITUTION:  - Hospital Virgen de la Victoria, Malaga, España.

RESUMEN / SUMMARY:  - Purpose: Several studies have shown that HIV patients are at higher risk of lung  cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods: The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast España (study period 1992-2012) were reviewed, and all patients with a lung cancer were analysed. Results: There were  61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack-years 35.2), with a median age of 48.0 (41.7-52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42-232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85-397), and 66.1%<350/mm3. 66.7% were  on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments  2 (3.4%). Forty-six (76.7%) patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%). Conclusions: The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary  events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma is the most frequent histological type. The diagnosis is usually made at advanced stages of the neoplasm, and mortality is high.

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[582]

TÍTULO / TITLE:  - Advanced lung cancer in the older patient: is there a role for bevacizumab?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):629-30. doi: 10.3978/j.issn.2072-1439.2012.09.07.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.09.07

AUTORES / AUTHORS:  - Marr AS; Ganti AK

INSTITUCIÓN / INSTITUTION:  - Division of Oncology-Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA;

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[583]

TÍTULO / TITLE:  - Airway obstruction following bronchoscopic photodynamic therapy in early centrally located lung cancer requiring extracorporeal membrane oxygenation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Formos Med Assoc. 2013 Jan;112(1):54-6. doi: 10.1016/j.jfma.2012.07.013. Epub 2012 Sep 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jfma.2012.07.013

AUTORES / AUTHORS:  - Chang YC; Lee JM; Ko WJ; Lee YC

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

RESUMEN / SUMMARY:  - Photodynamic therapy (PDT) is a treatment modality of early central located non-small-cell lung cancer, and in patients who are unsuitable for surgical intervention. Most complications of PDT reported in the literature are minor and  can be easily handled. We report a case presenting with nearly fatal complication: airway obstruction following bronchoscopic photodynamic therapy for early endobronchial lung cancer, requiring extracorporeal membrane oxygenation. An 81-year-old man was admitted to thoracic surgery division due to an early centrally located lung cancer. Due to multiple comorbidity and high surgical risk we performed bronchoscopic PDT instead of aggressive lung resection for the patient. After the procedure, he developed severe airway obstruction by tumor debris and required temporary cardiopulmonary support with extracorporeal membrane oxygenation. The patient recovered smoothly after the episode and was free from tumor recurrence for >2 years without any neurological sequelae.

 

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[584]

TÍTULO / TITLE:  - Treatment of Breast and Lung Cancer Cells with a N-7 Benzyl Guanosine Monophosphate Tryptamine Phosphoramidate Pronucleotide (4Ei-1) Results in Chemosensitization to Gemcitabine and Induced eIF4E Proteasomal Degradation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Pharm. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1021/mp300699d

AUTORES / AUTHORS:  - Li S; Jia Y; Jacobson BA; McCauley J; Kratzke R; Bitterman PB; Wagner CR

RESUMEN / SUMMARY:  - The development of cancer and fibrotic diseases has been shown to be highly dependent on disregulation of cap-dependent translation. Binding protein eIF4E to N7-methylated guanosine capped mRNA has been found to be the rate-limiting step governing translation initiation; and therefore represents an attractive target for drug discovery. Our group has found that 7-benzyl guanosine monophosphate (7Bn-GMP) is a potent antagonist of eIF4E cap binding (Kd = 0.8 uM). Recent X-ray crystallographic studies have revealed that the cap-dependent pocket undergoes a  unique structural change in order to accommodate the benzyl group. Unfortunately, 7Bn-GMP is not cell permeable. Recently, we have prepared a tryptamine phosphoramidate prodrug of 7Bn-GMP, 4ei1, and shown that it is a substrate for human histidine triad nucleotide binding protein (hHINT1) and is inhibit eIF4E initiated epithelial-mesenchymal transition (EMT) by Zebra fish embryo cells. To  assess the intracellular uptake of 4ei1 and conversion to 7Bn-GMP by cancer cells, we developed a sensitive assay using LC-ESI-MS/MS for the intracellular quantitation of 4ei1 and 7Bn-GMP. When incubated with the breast cancer cell line MDA-231; or lung cancer cell lines H460, H383 and H2009, 4ei1 was found to be rapidly internalized and converted to 7Bn-GMP. Since oncogenic mRNAs are predicted to have the highest eIF4E requirement for translation, we carried out chemosensitization studies with 4ei1. The prodrug was found to chemosensitize both breast and lung cancer cells to non-toxic levels of gemcitabine. Further mechanistic studies revealed that the expressed levels of eIF4E were substantially reduced in cells treated with 4ei1 in a dose dependent manner. The  levels of eI4E could be restored by treatment with the proteasome inhibitor MG-132. Taken together, our results demonstrate that 4ei1 is likely to inhibit translation initiation by eIF4E cap binding by both antagonizing eIF4E cap binding and initiating eIF4E proteasomal degradation.

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[585]

TÍTULO / TITLE:  - Preliminary experience of CyberKnife treatment of primary non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Assoc Thai. 2012 Oct;95(10):1335-43.

AUTORES / AUTHORS:  - Swangsilpa T; Yongvithisatid P; Pairat K; Dechsupa P; Dhanachai M; Dangprasert S; Narkwong L; Sitathanee C; Puataweepong P; Puddhikarant P; Jiarpinitnun C; Witoonpanich P; Ukhumpun T; Khaophong J

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology Division, Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. swangsilpa@yahoo.com

RESUMEN / SUMMARY:  - OBJECTIVE: Provide the effectiveness of treatment protocol, radiotherapy plan, technique, and early clinical results of inoperable primary non-small cell lung cancer (NSCLC) in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases of inoperable primary NSCLC patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was 45 gray (Gy) in three consecutive fractions for peripherally located tumor and 50 Gy in five fractions within two weeks for centrally located tumor (biological equivalent dose, BED, 112.5 Gy 10, and 100 Gy 10, respectively). The response to treatment was evaluated from roentgenographic  study during follow-up period along with clinical outcome and adverse event. RESULTS: Overall response after the treatment was demonstrated in five cases with roentgenographic complete response (CR, disappearance of tumor) and partial response (PR, 50% decrease in size) in two and three cases, respectively without  any severe adverse event. The treatment planning parameters demonstrated the effectiveness of radiation dose homogeneity and conformity coverage of the target volume. CONCLUSION: This preliminary report has provided the effectiveness of treatment plan and local tumor controlled without severe adverse event for primary inoperable NSCLC patients receiving CyberKnife treatment.

 

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[586]

TÍTULO / TITLE:  - Treatment results of diffuse malignant peritoneal mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gan To Kagaku Ryoho. 2012 Nov;39(12):2416-9.

AUTORES / AUTHORS:  - Yonemura Y; Ishibashi H; Canbay E; Sako S; Tsukiyama G; Mizumoto Y; Ichinose M; Takao N; Yabuki S; Tanaka H; Hirano M; Fushida S; Endou Y

INSTITUCIÓN / INSTITUTION:  - Kishiwada Tokushukai Hospital, Japan.

RESUMEN / SUMMARY:  - During the last 7 years, 21 patients with DMPM were treated. Histologic types were epitheloid type in 18 patients, biphasic type in 2 patients and sarcomatoid  type in 1 patient. Preoperative systemic chemotherapy, hyperthermic intraperitoneal chemotherapy(HIPEC) by laparoscopy(LHIPEC), and intraperitoneal(IP) chemotherapy were done in 14, 3 and 1 patients, respectively. Cytoreductive surgery(CRS) was done in 13 patients. Ten patients received HIPEC after CRS. Partial responses were experienced in 4 of 13 patients treated with preoperative systemic chemotherapy. One of three patients treated by LHIPEC showed complete response. Among 13 patients received laparotomy, complete removal of PC was done in 4(31%) patients. The other 9 patients who received incomplete cytoreduction had diffuse involvement on the small bowel and its mesentery. All over 5-year survival was 17%. Patients treated with HIPEC survived significantly  longer than non-HIPEC group. Neoadjuvant laparoscopic HIPEC may have a great role in the preoperative control of small PC on the surface of small bowel.

 

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[587]

TÍTULO / TITLE:  - Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(11):5363-9.

AUTORES / AUTHORS:  - Zhang EY; Tang XD

INSTITUCIÓN / INSTITUTION:  - Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, China E-mail : txd2599@yahoo.com.cn.

RESUMEN / SUMMARY:  - High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in  Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-1alpha, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling  pathways in lung cancer. This article provides an overview of experiment data on  HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

 

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[588]

TÍTULO / TITLE:  - Lung cancer-initiating cells: a novel target for cancer therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-012-0247-4

AUTORES / AUTHORS:  - Morrison BJ; Morris JC; Steel JC

INSTITUCIÓN / INSTITUTION:  - Division of Hematology-Oncology, Department of Medicine, University of Cincinnati, Cincinnati, OH, 45267, USA, morrisb7@uc.edu.

RESUMEN / SUMMARY:  - Lung cancer is a major public health problem causing more deaths than any other cancer. A better understanding of the biology of this disease and improvements in treatment are greatly needed. Increasing evidence supports the concept that a rare and specialized population of cancer cells, so-called cancer-initiating cells with stem cell-like characteristics, is responsible for tumor growth, maintenance, and recurrence. Cancer-initiating cells also exhibit characteristics that render them resistant to both radiation and chemotherapy, and therefore they are believed to play a role in treatment failure. This has led to the hypothesis  that traditional therapies that indiscriminately kill tumor cells will not be as  effective as therapies that selectively target cancer-initiating cells. Investigating putative cancer-initiating cells in lung cancer will greatly benefit the understanding of the origins of this disease and may lead to novel approaches to therapy by suggesting markers for use in either further isolating this population for study or for selectively targeting these cells. This review will discuss (1) lung cancer, (2) stem cells, and the role of cancer-initiating cells in tumorigenesis; (3) markers and functional characteristics associated with lung cancer-initiating cells; and (4) the potential to selectively target this subpopulation of tumor cells.

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[589]

TÍTULO / TITLE:  - Down-regulation of cellular FLICE-inhibitory protein (Long Form) contributes to apoptosis induced by Hsp90 inhibition in human lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell Int. 2012 Dec 21;12(1):54. doi: 10.1186/1475-2867-12-54.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-12-54

AUTORES / AUTHORS:  - Wang Q; Sun W; Hao X; Li T; Su L; Liu X

INSTITUCIÓN / INSTITUTION:  - Key Laboratory for Experimental Teratology of the Ministry of Education and School of Life Sciences, Shandong University, Jinan, China. suling@sdu.edu.cn.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Cellular FLICE-Inhibitory Protein (long form, c-FLIPL) is a critical negative regulator of death receptor-mediated apoptosis. Overexpression  of c-FLIPL has been reported in many cancer cell lines and is associated with chemoresistance. In contrast, down-regulation of c-FLIP may drive cancer cells into cellular apoptosis. This study aims to demonstrate that inhibition of the heat shock protein 90 (Hsp90) either by inhibitors geldanamycin/17-N-Allylamino-17-demethoxygeldanamycin (GA/17-AAG) or siRNA technique in human lung cancer cells induces c-FLIPL degradation and cellular apoptosis through C-terminus of Hsp70-interacting protein (CHIP)-mediated mechanisms. METHODS: Calu-1 and H157 cell lines (including H157-c-FLIPL overexpressing c-FLIPL and control cell H157-lacZ) were treated with 17-AAG and the cell lysates were prepared to detect the given proteins by Western Blot and the cell survival was assayed by SRB assay. CHIP and Hsp90 alpha/beta proteins were knocked down by siRNA technique. CHIP and c-FLIPL plasmids were transfected  into cells and immunoprecipitation experiments were performed to testify the interactions between c-FLIPL, CHIP and Hsp90. RESULTS: c-FLIPL down-regulation induced by 17-AAG can be reversed with the proteasome inhibitor MG132, which suggested that c-FLIPL degradation is mediated by a ubiquitin-proteasome system.  Inhibition of Hsp90alpha/beta reduced c-FLIPL level, whereas knocking down CHIP expression with siRNA technique inhibited c-FLIPL degradation. Furthermore, c-FLIPL and CHIP were co-precipitated in the IP complexes. In addition, overexpression of c-FLIPL can rescue cancer cells from apoptosis. When 17-AAG was combined with an anti-cancer agent celecoxib(CCB), c-FLIPL level declined further and there was a higher degree of caspase activation. CONCLUSION: We have elucidated c-FLIPL degradation contributes to apoptosis induced by Hsp90 inhibition, suggesting c-FLIP and Hsp90 may be the promising combined targets in  human lung cancer treatment.

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[590]

TÍTULO / TITLE:  - Bronchogenic cyst mimicking ischemic heart disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lung India. 2012 Oct;29(4):376-7. doi: 10.4103/0970-2113.102838.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0970-2113.102838

AUTORES / AUTHORS:  - Michels G; Bovenschulte H; Drebber U; Pfister R

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine III, University of Cologne, Cologne, Germany.

RESUMEN / SUMMARY:  - Bronchogenic cysts are generally asymptomatic and are detected incidentally by radiographic imaging as a smooth homogeneous mediastinal/pulmonary lesion. We present a case of a large bronchogenic cyst in the posterior mediastinum mimicking ischemic heart disease in a 70-year-old man with unknown heart disease. In patients with chest pain the rare case of a bronchogenic cyst has to be considered for management of atypical angina pectoris.

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[591]

TÍTULO / TITLE:  - Mesothelioma: a soon to be forgotten disease in the United States?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2012 Jul;19(3):258-61. doi: 10.1097/LBR.0b013e31825f1aba.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e31825f1aba

AUTORES / AUTHORS:  - Thomas D; Geck R; Rozas D; Muro-Cacho C; Rumbak M

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary, Critical Care and SleepMedicine, Department of Interventional Pulmonology, University of South Florida, Tampa, FL, USA.

RESUMEN / SUMMARY:  - Malignant pleural mesothelioma is an uncommon cancer that commonly presents with  a large unilateral bloody pleural effusion long after asbestos exposure. Its prevalence is decreasing with the decreasing exposure to asbestos in the United States. We present a patient with malignant pleural mesothelioma who underwent evaluation and treatment during medical thoracoscopy. The thoracoscopic evaluation revealed multiple, varied, and severe but characteristic findings of malignant pleural mesothelioma. Medical thoracoscopy is the procedure of choice for the diagnosis of pleural mesothelioma.

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[592]

TÍTULO / TITLE:  - Pulmonary carcinoid tumorlet without underlying lung disease: analysis of its relationship to fibrosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):655-8. doi: 10.3978/j.issn.2072-1439.2012.06.11.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.06.11

AUTORES / AUTHORS:  - He P; Gu X; Wu Q; Lin Y; Gu Y; He J

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China;

RESUMEN / SUMMARY:  - Pulmonary carcinoid tumorlet is a rare pathology and appears to be always associated with other lesions such as bronchiectasis and fibrosis. While the caus e-effect relationship between tumorlet and the accompanying pathological changes  in the surrounding mesenchymal tissue remains to be defined, it has been postulated that pulmonary fibrosis may be the primary pathology underlying the development of tumorlet. In this paper, we present a case where a tumor (<0.5 cm) was detected in the right upper lobe of a 71-year old woman. Cells of the tumor displayed markers characterizing for their neuroendocrine origin. No histological evidence for inflammation, interstitial fibrosis and remodeling of vascular structure was observed. However, immunohistochemistry assay demonstrated a strong production of the profibrotic factors VEGF and TGF-beta1 by tumor cells. These findings suggest that carcinoid tumorlet can be an isolated lesion and pulmonary  fibrosis that “often co-exists” with tumorlet may be secondary to the paracrine effects of fibrotic growth factors produced by tumorlet.

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[593]

TÍTULO / TITLE:  - Clinical significance of E2F1 protein expression in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Hematol. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://www.medicinedirect.com/journal 

            ●● Cita: Experimental Hematology: <> Oncol. 2012 Jul 20;1(1):18. doi: 10.1186/2162-3619-1-18.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2162-3619-1-18

AUTORES / AUTHORS:  - Hung JJ; Hsueh CT; Chen KH; Hsu WH; Wu YC

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112, Taiwan. wuyc@vghtpe.gov.tw.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The transcription factor E2F1 has been implicated in cell cycle control and DNA damage response. Paradoxically, E2F1 can promote apoptosis  and function as tumor suppressor. In non-small cell lung cancer (NSCLC), there are conflicting data for clinical significance of E2F1 expression. In this study, we investigated the protein expression of E2F1 in patients with stage I-III NSCLC, and its correlation with clinical outcome. RESULTS: 56 paired adjacent non-tumor/tumor matched samples were prospectively obtained from patients undergoing surgery for stage I-III NSCLC at Taipei Veterans General Hospital. The protein expression of E2F1 was determined by Western blot analysis. The levels of E2F1 protein were significantly higher in tumor samples than in non-tumor lung specimens (P = 0.008). Overexpression of E2F1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one, and was noted in 21 patients (37.5%). There was no significant difference in overall survival (P = 0.44) or probability of freedom from recurrence (P = 0.378) between patients with E2F1 overexpression vs. non-overexpressors. Additionally, there was no significant association between E2F1 overexpression and any clinicopathologic parameter such as histological type, stage, or angiolymphatic invasion of tumor. CONCLUSION: E2F1 protein is frequently overexpressed in NSCLC. There is no correlation between E2F1 protein expression and clinical outcome such as survival and freedom from progression.

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[594]

TÍTULO / TITLE:  - A Systematic Review of Economic Evaluations in Second and Later Lines of Therapy  for the Treatment of Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Health Econ Health Policy. 2012 Oct 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s40258-012-0001-1

AUTORES / AUTHORS:  - Jakel A; Plested M; Dharamshi K; Modha R; Bridge S; Johns A

INSTITUCIÓN / INSTITUTION:  - Heron Evidence Development Ltd, Building 210a, Butterfield Technology and Business Park, Stopsley, Luton, LU2 8DL, UK.

RESUMEN / SUMMARY:  - INTRODUCTION: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Surgery is generally accepted as the first-line treatment in patients with advanced/metastatic NSCLC, followed by radiotherapy and chemotherapy as second-line treatments. Docetaxel or erlotinib are generally  recommended as the first-line chemotherapy option. The objective of this review was to identify previously published economic evaluations in NSCLC for second- and later-line treatments in order to (i) determine common modelling approaches and (ii) establish the relative cost effectiveness of these treatments. An overview of model critique was also produced to identify common criticisms from health technology assessment (HTA) bodies on the models submitted. METHODS: MEDLINE, Embase, EconLit, MEDLINE in Process(®) and NHS Economic Evaluation Database (NHSEED) were searched (database start-October 2011), along with proceedings from eight major conferences (2007-2011). National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC) and Canadian Agency for Drugs and Technologies in Health (CADTH) websites and the International Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for appraisals in second- or later-line NSCLC. All published studies and HTA appraisals that reported economic evaluations of interventions used in current clinical practice as second- or later-line treatment in patients with advanced/metastatic NSCLC were included. Only studies in English were considered  for inclusion. Studies which met the eligibility criteria after the screening of  full-text articles were extracted by a reviewer and checked by a second party. Where multiple publications were identified describing a single study, the extracted data were compiled into one entry. RESULTS: A total of 29 studies were  included which clearly evaluated second-line or later-line regimens. Most studies were either cost-effectiveness or cost-utility evaluations. Three-state transition Markov models were frequently used in cost-effectiveness and cost-utility evaluations. The model inputs were well reported and commonly consisted of data from pivotal trials. Sensitivity analyses were conducted in the majority of studies and covered variables such as cost, effectiveness, hospitalization and treatment duration. Therapies (docetaxel, pemetrexed and erlotinib) are for the most part cost-effective/cost-saving second-line therapies compared with best supportive care (BSC). Six erlotinib HTAs, across NICE, SMC, and PBAC, and four pemetrexed HTAs, one by NICE and three by SMC, were identified. The CADTH website did not provide sufficient detail on the appraisals and was excluded. Certain aspects of the models and model assumptions, e.g. efficacy inputs, were criticized or determined unjustifiable by the NICE, SMC and PBAC appraisal committees. Erlotinib and pemetrexed were considered to be cost effective versus docetaxel by NICE and SMC in the final submissions. PBAC considered erlotinib to be cost effective versus BSC following a price reduction  in 2008. CONCLUSION: Three-state Markov models are often used to conduct economic analysis in NSCLC and are regarded as appropriate to HTA agencies. Docetaxel, erlotinib and BSC are suitable comparators that should be considered for use in the model in the UK and Australia. Further, manufacturers should carefully select underlying assumptions used in the model, for both costs and clinical inputs, where the latter is derived from direct head-to-head trial data.

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[595]

TÍTULO / TITLE:  - Integrated Therapeutic Approaches in the Treatment of Locally Advanced Non-small  Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Agents Med Chem. 2012 Dec 14.

AUTORES / AUTHORS:  - Di Maio M; Costanzo R; Giordano P; Piccirillo MC; Sandomenico C; Montanino A; Carillio G; Muto P; Jones DR; Daniele G; Perrone F; Rocco G; Morabito A

INSTITUCIÓN / INSTITUTION:  - Clinical Trials Unit, National Cancer Institute, Napoli, Italy. alessandromorabito1@virgilio.it; alessandro.morabito@usc-intnapoli.net.

RESUMEN / SUMMARY:  - Treatment of locally advanced non-small cell lung cancer (NSCLC) remains a significant challenge for oncologists, despite progress made in recent years in early diagnosis and therapy. This review focuses on integrated therapeutic approaches of patients with locally advanced NSCLC, summarizing the available evidence for patients with potentially resectable disease (stage IIIA-0/3) and with unresectable disease (stage IIIA-4/IIIB) and discussing several key questions related to the use of integrated approaches in NSCLC. Based on current  evidence, neoadjuvant platinum-based combination chemotherapy is a treatment option in patients with potentially resectable stage IIIA-0/3: a 2-drug combination of platinum combined with a third-generation drug seems preferable, and at least 3 cycles of chemotherapy should be administered. There are no definitive evidences of clear superiority of surgery compared to radiotherapy for patients obtaining a response with neoadjuvant treatment: however, surgery is associated with a better local control, and subgroup analyses of randomized trials suggest improved outcome in patients in whom a complete resection could be obtained with a lobectomy, avoiding the increased surgical mortality associated with pneumonectomy. Standard treatment for patients with locally advanced, unresectable NSCLC is currently represented by combination of chemotherapy and radiotherapy. Concomitant approach has been proven superior to the sequential administration, although it is associated with higher risk of toxicity. All patients should be evaluated by a multidisciplinary team, skilled in multimodality treatment and should be counselled about risks and potential bene fi ts of the different therapeutic approaches.

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[596]

TÍTULO / TITLE:  - ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-012-0250-9

AUTORES / AUTHORS:  - Casaluce F; Sgambato A; Maione P; Rossi A; Ferrara C; Napolitano A; Palazzolo G; Ciardiello F; Gridelli C

INSTITUCIÓN / INSTITUTION:  - Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.

RESUMEN / SUMMARY:  - The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non-small cell lung cancer (NSCLC). Oncogenic fusion genes, including echinoderm microtubule-associated protein-like 4 (EML4) and ALK, have been detected in approximately 2-7 % of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method for detecting ALK gene rearrangement. EML4-ALK fusion genes define a molecular subset of NSCLC  with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the  receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor). Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement. Preliminary phase II data suggested that crizotinib  is safe and well tolerated with rapid and robust antitumor activity. A phase III  randomized trial in a second-line setting showed response rate and PFS (primary study endpoint) advantage for crizotinib as compared to second-line chemotherapy. Treatment-related adverse events, predominantly restricted to the gastrointestinal and visual systems, are generally self-limiting or easily managed. Crizotinib is a new standard of care for patients with advanced, ALK-positive, NSCLC. In this review, we will discuss the discovery of ALK rearrangements, the clinical epidemiology of lung cancer driven by ALK, the clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based  clinical trials.

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[597]

TÍTULO / TITLE:  - Clinical pathway for surgical treatment of primary lung cancer (2012 Edition).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):671-675.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.15

AUTORES / AUTHORS:  - Zhi XY; He JX; Li H; Zhang X; Jiang GN; Zhao H; Liu LX; Liu DR; Li SQ; Li J; Zhou QH; Wang Q; Wang RW; Fu JH; Xu L; Zhang LY; Zhou NK; Xu SF

INSTITUCIÓN / INSTITUTION:  - Xuanwu Hospital of Capital Medical University;

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[598]

TÍTULO / TITLE:  - CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Braz J Med Biol Res. 2013 Jan 11:1-6.

AUTORES / AUTHORS:  - Shen B; Zhu Q; Zheng MQ; Chen J; Shi MQ; Feng JF

RESUMEN / SUMMARY:  - Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P <  0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.

 

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[599]

TÍTULO / TITLE:  - Prediction of lung cancer risk in a Chinese population using a multifactorial genetic model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Med Genet. 2012 Dec 10;13(1):118.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2350-13-118

AUTORES / AUTHORS:  - Li H; Yang L; Zhao X; Wang J; Qian J; Chen H; Fan W; Liu H; Jin L; Wang W; Lu D

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Lung cancer is a complex polygenic disease. Although recent genome-wide association (GWA) studies have identified multiple susceptibility loci for lung cancer, most of these variants have not been validated in a Chinese population. In this study, we investigated whether a genetic risk score combining multiple. METHODS: Five single-nucleotide polymorphisms (SNPs) identified in previous GWA or large cohort studies were genotyped in 5068 Chinese case—control subjects. The genetic risk score (GRS) based on these SNPs was estimated by two approaches: a simple risk alleles count (cGRS) and a weighted (wGRS) method. The  area under the receiver operating characteristic (ROC) curve (AUC) in combination with the bootstrap resampling method was used to assess the predictive performance of the genetic risk score for lung cancer. RESULTS: Four independent  SNPs (rs2736100, rs402710, rs4488809 and rs4083914), were found to be associated  with a risk of lung cancer. The wGRS based on these four SNPs was a better predictor than cGRS. Using a liability threshold model, we estimated that these four SNPs accounted for only 4.02% of genetic variance in lung cancer. Smoking history contributed significantly to lung cancer (P < 0.001) risk [AUC = 0.619 (0.603-0.634)], and incorporated with wGRS gave an AUC value of 0.639 (0.621-0.652) after adjustment for over-fitting. This model shows promise for assessing lung cancer risk in a Chinese population. CONCLUSION: Our results indicate that although genetic variants related to lung cancer only added moderate discriminatory accuracy, it still improved the predictive ability of the assessment model in Chinese population.

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[600]

TÍTULO / TITLE:  - Zarogouldis, p., et Al., vectors for inhaled gene therapy in lung cancer. Application for nano oncology and safety of bio nanotechnology. Int. J. Mol. Sci. 2012, 13, 10828-10862.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Dec 18;13(12):17290-1. doi: 10.3390/ijms131217290.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms131217290

AUTORES / AUTHORS:  - Zarogoulidis P; Karamanos NK; Porpodis K; Domvri K; Huang H; Hohenforst-Schmidt W; Goldberg EP; Zarogoulidis K

INSTITUCIÓN / INSTITUTION:  - Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece. pzarog@hotmail.com.

RESUMEN / SUMMARY:  - The authors wish to add this correction on their paper published in IJMS [1]. The first author’s name is misspelled and the correct name is Paul Zarogoulidis. In addition, the 6th author’s name is incorrect and should be corrected to Wolfgang  Hohenforst-Schmidt. These errors have been amended in an amended version of the manuscript, which is available from the International Journal of Molecular Sciences website. The authors and publisher apologize for the inconvenience. [..].

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[601]

TÍTULO / TITLE:  - The genetic variant rs401681C/T is associated with the risk of non-small cell lung cancer in a Chinese mainland population.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genet Mol Res. 2013 Jan 22;12(1):67-73. doi: 10.4238/2013.January.22.5.

            ●● Enlace al texto completo (gratuito o de pago) 4238/2013.January.22.5

AUTORES / AUTHORS:  - Wang H; Zhao Y; Ma J; Zhang G; Mu Y; Qi G; Fang Z; Wang L; Fan Q; Ma Z

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China.

RESUMEN / SUMMARY:  - Although lung cancer (LC) is a highly environmentally associated disease, genetic factors are also thought to play a role in this disease. In recent years, genome-wide association studies have identified various susceptible genetic regions for LC. Herein, we used high-resolution melting analysis to genotype 2 significant single nucleotide polymorphisms previously reported in Caucasians, that is, rs401681 at 5p15.33 and rs8034191 at 15q25, in a case-control study with 492 LC cases and 486 cancer-free controls in a Chinese population. We found that  the rs401681C/T allele in the TERT-CLPTM1L gene was associated with the risk of non-small cell lung cancer [NSCLC; P = 0.012, odds ratio (OR) = 1.29, 95% confidence interval (95%CI) = 1.09-1.50], but was not associated with the risk of small cell lung cancer (P = 0.571, OR = 1.15, 95%CI = 0.82-1.47). However, no significant association was found between rs8034191T/C and LC risk. These results suggest that genetic variants in the TERT-CLPTM1L gene may predispose individuals to be susceptible to LC, particularly NSCLC, in the Chinese population.

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[602]

TÍTULO / TITLE:  - Illustrative cases of false positive biopsies after stereotactic body radiation therapy for lung cancer based on abnormal FDG-PET-CT imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 22;2013. pii: bcr2012007967. doi: 10.1136/bcr-2012-007967.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007967

AUTORES / AUTHORS:  - Singhvi M; Lee P

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, 200 UCLA Medical Plaza, David Geffen School of  Medicine at UCLA, Los Angeles, CA, 90095, USA.

RESUMEN / SUMMARY:  - Stereotactic body radiation therapy (SBRT) for early stage lung cancer has made significant strides as an alternative to surgery.1 We present two cases of non-small cell lung cancer treated with SBRT and then followed serially with imaging in which suspicion of recurrence led to biopsies.

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[603]

TÍTULO / TITLE:  - Angiopoietin-like protein ANGPTL2 gene expression is correlated with lymph node metastasis in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1325-1328. Epub 2012 Sep 20.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.924

AUTORES / AUTHORS:  - Sasaki H; Suzuki A; Shitara M; Hikosaka Y; Okuda K; Moriyama S; Yano M; Fujii Y

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

RESUMEN / SUMMARY:  - Inflammation plays key roles at various stages of tumor development, including invasion and metastasis. In mice, the angiopoietin-like protein (ANGPTL2) gene has been implicated in inflammatory carcinogenesis. ANGPTL2 mRNA expression was investigated by real-time polymerase chain reaction (RT-PCR) assay using LightCycler in surgically treated non-small cell lung cancer (NSCLC) cases. In total, 110 surgically resected NSCLC cases were used for mRNA level analyses. The ANGPTL2/beta-actin mRNA levels were not significantly different between lung cancer (1598.481+/-6465.781) and adjacent normal lung tissues (2116.639+/-8337.331, P=0.5453). The tumor/normal (T/N) ratio of ANGPTL2/beta-actin mRNA levels was not different between gender, age, smoking status and pathological stages. The T/N ratio of ANGPTL2/beta-actin mRNA levels was significantly higher in lymph node metastasis-positive cases (2.173+/-3.151)  compared with lymph node metastasis-negative cases (1.212+/-1.778, P=0.0464). However, ANGPTL2 mRNA status was not correlated with tumor invasion status. Thus, ANGPTL2 may drive metastasis and provide a candidate for blockade of its function as a strategy to antagonize the metastatic process in NSCLC.

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[604]

TÍTULO / TITLE:  - Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0258-9

AUTORES / AUTHORS:  - Kobayashi K; Hagiwara K

INSTITUCIÓN / INSTITUTION:  - Saitama Medical University, Moroyama, Japan, kobakuni@saitama-med.ac.jp.

RESUMEN / SUMMARY:  - Before 2009, nonsmall cell lung cancer (NSCLC) was one disease entity treated by  cytotoxic chemotherapy that provided a response rate of 20-35 % and a median survival time (MST) of 10-12 months. In 2004, it was found that activated mutations of the epidermal growth factor receptor (EGFR) gene were present in a subset of NSCLC and that tumors with EGFR mutations were highly sensitive to EGFR tyrosine kinase inhibitors (TKI). Four phase III studies (North East Japan (NEJ)  002, West Japan Thoracic Oncology Group (WJTOG) 3405, OPTIMAL, and EUROTAC) prospectively compared TKI (gefitinib or erlotinib) with cytotoxic chemotherapy as first-line therapy in EGFR-mutated NSCLC. These studies confirmed that progression-free survival (PFS) with TKIs (as the primary endpoint) was significantly longer than that with standard chemotherapy (hazard ratio [HR] = 0.16-0.49) from 2009 to 2011. Although the NEJ 002 study showed identical overall survival (OS) between the arms (HR = 0.89), quality of life (QoL) was maintained  much longer in patients treated with gefitinib. In conclusion, TKI should be considered as the standard first-line therapy in advanced EGFR-mutated NSCLC. Since 2009, a new step has been introduced in the treatment algorithm for advanced NSCLC.

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[605]

TÍTULO / TITLE:  - Adenovirus mediated knockdown of bone morphogenetic protein 2 inhibits human lung cancer growth and invasion in vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):967-76.

AUTORES / AUTHORS:  - Ye XY; Niu XM; Tang NW; Xu YH; Li ZM; Yu YF; Lu S; Chen SW

INSTITUCIÓN / INSTITUTION:  - Department of Shanghai Lung Tumor Clinical Medical Centre, Shanghai Chest Hospital, Huaihai West Road, Shanghai, China.

RESUMEN / SUMMARY:  - Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-beta superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies. BMP-2 has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of BMP-2 in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of BMP-2  in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo. Adenovirus vector-mediated BMP-2 small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of BMP-2 and  tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of BMP-2, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85alpha (PI3Kp85alpha) and phosphorylated AKT (p-AKT). As a result, LAC cell proliferation and invasion  were significantly diminished by knockdown of BMP-2 indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When BMP-2 expression was knocked down, the expression of PI3Kp85alpha, p-AKT, VEGF and MMP-9 was also down-regulated in LAC  cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP  groups. Taken together, our findings indicate that knockdown of BMP-2 inhibits growth and invasion of LAC cells possibly via blockade of the PI3K/AKT signaling  pathway, and BMP-2 may be a potential therapeutic target for lung cancer.

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[606]

TÍTULO / TITLE:  - The trends of relevance about telling lung cancer diagnosis: social constraints,  medical practice in several clinics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberk Toraks. 2012 Dec;60(4):336-43.

AUTORES / AUTHORS:  - Doruk S; Sevinc C; Sever F; Itil O; Akkoclu A

INSTITUCIÓN / INSTITUTION:  - Department of Chest Diseases, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey. sibeldoruk@yahoo.com.

RESUMEN / SUMMARY:  - Introduction: The aim of this study is to assess the opinions of relatives about  telling the lung cancer diagnosis to the patient and evaluate the implementation  in our hospital. Materials and Methods: A survey questionnaire was designed, and  applied on nurses and physicians working in oncology care units, 4th-6th grade medical students, and relatives of cancer and non-cancer patients. Results: Totally 347 (228 males, 119 females) participants (64 physicians, 100 nurses, 61  medical students, and 122 relatives of patients) with a mean age of 28 were enrolled in the study. 62.5% of doctors, 53.2% of nurses, 59.5% of medical students and 45.9% of relatives of lung cancer patients thought that the patient  should be informed about his/her cancer diagnosis. 29.5% of the physicians told their patients about their diagnosis of cancer. Gender, age, abroad experience, academic career, speciality, and period of professional experience were not determined to have any impact on physician’s opinion and clinical practices. Conclusion: It was determined that physicians care more about patients’ right to  be informed than other participating groups. Generally, although physicians agree that the diagnosis of cancer should be told to the patient, their routine clinical practices do not reflect this viewpoint.

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[607]

TÍTULO / TITLE:  - Unexpected Rapid Growth of Estrogen Receptor Positive Lung Cancer during Pregnancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2013 Jan 16.

AUTORES / AUTHORS:  - Hayama M; Chida M; Tamura M; Kobayashi S; Oyaizu T; Honma K

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Dokkyo Medical Uni versity, Tochigi, Japan.

RESUMEN / SUMMARY:  - We report a case with lung cancer during pregnancy, which has a very poor prognosis.A 34-year old female at 30 weeks of pregnancy came to us with a cough and right lower chest pain. Chest computed tomography revealed a mass in the right lower lung lobe and the diagnosis of adenocarcinoma cT2aN1M0 was made. We performed a right sleeve pneumonectomy, as the tumor had progressed to the right  main bronchus near carina. Histological sections of the specimens revealed a poorly differentiated adenocarcinoma that infiltrated surrounding structures. The pathological stage of lung cancer was T4N2M0 stage IIIB. Immunohistochemistry findings for estrogen receptor ? were positive in the nuclei of the adenocarcinoma. She had a rapid recurrence in spite of chemotherapy, and she died 7.5 months after operation. The positive estrogen receptor and hormonal condition during pregnancy might promote cancer and result in her poor prognosis.

 

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[608]

TÍTULO / TITLE:  - Preclinical Rationale for PI3K/Akt/mTOR Pathway Inhibitors as Therapy for Epidermal Growth Factor Receptor Inhibitor-Resistant Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 15. pii: S1525-7304(12)00266-5. doi: 10.1016/j.cllc.2012.12.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.12.001

AUTORES / AUTHORS:  - Gadgeel SM; Wozniak A

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI; Department of Oncology, Karmanos Cancer Institute, Wayne  State University, Detroit, MI. Electronic address: gadgeels@karmanos.org.

RESUMEN / SUMMARY:  - Mutations in the epidermal growth factor receptor gene (EGFR) are frequently observed in non-small-cell lung cancer (NSCLC), occurring in about 40% to 60% of  never-smokers and in about 17% of patients with adenocarcinomas. EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have transformed therapy for patients with EGFR-mutant NSCLC and have proved superior to chemotherapy as first-line treatment for this patient group. Despite these benefits, there are currently 2 key challenges associated with EGFR inhibitor therapy for patients with NSCLC. First, only 85% to 90% of patients with the EGFR mutation derive clinical benefit from EGFR TKIs, with the remainder demonstrating innate resistance to therapy. Second, acquired resistance to EGFR TKIs inevitably occurs in patients who initially respond to therapy, with a median duration of response of about 10 months. Mutant EGFR activates various subcellular signaling  cascades, including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, which demonstrates maintained activity in a variety  of TKI-resistant cancers. Given the fundamental role of the PI3K/Akt/mTOR pathway in tumor oncogenesis, proliferation, and survival, PI3K pathway inhibitors have emerged as a possible solution to the problem of EGFR TKI resistance. However resistance to EGFR TKIs is associated with considerable heterogeneity and complexity. Preclinical experiments investigating these phenomena suggest that in some patients, PI3K inhibitors will have to be paired with other targeted agents  if they are to be effective. This review discusses the preclinical data supporting PI3K/Akt/mTOR pathway inhibitor combinations in EGFR TKI-resistant NSCLC from the perspective of the various agents currently being investigated in  clinical trials.

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[609]

TÍTULO / TITLE:  - Small gamma-Ray Doses Prevent Rather than Increase Lung Tumors in Mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dose Response. 2012 Dec;10(4):527-40. doi: 10.2203/dose-response.12-035.Scott. Epub 2012 Oct 9.

            ●● Enlace al texto completo (gratuito o de pago) 2203/dose-response.12-035.Scott

AUTORES / AUTHORS:  - Scott BR; Bruce VR; Gott KM; Wilder J; March T

INSTITUCIÓN / INSTITUTION:  - Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108.

RESUMEN / SUMMARY:  - We show evidence for low doses of gamma rays preventing spontaneous hyperplastic  foci and adenomas in the lungs of mice, presumably via activating natural anticancer defenses. The evidence partly relates to a new study we conducted whereby a small number of female A/J mice received 6 biweekly dose fractions (100 mGy per fraction) of gamma rays to the total body which prevented the occurrence  of spontaneous hyperplastic foci in the lung. We also analyzed data from a much earlier Oak Ridge National Laboratory study involving more than 10,000 female RFMf/Un mice whereby single gamma-ray doses from 100 to 1,000 mGy prevented spontaneous lung adenomas. We point out the possibility that the decrease in lung cancer mortality observed in The National Lung Screening Trial Research Team study involving lung tumor screening using low-dose computed tomography (CT) may  relate at least in part to low-dose X-rays activating the body’s natural anticancer defenses (i.e., radiation hormesis). This possibility was apparently not recognized by the indicated research team.

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[610]

TÍTULO / TITLE:  - Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Dec;4(6):1045-1050. Epub 2012 Sep 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.702

AUTORES / AUTHORS:  - Hu J; Chen C; Su Y; DU J; Qian X; Jin Y

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China.

RESUMEN / SUMMARY:  - Vascular endothelial growth factor (VEGF) plays a critical role in tumor progression, angiogenesis and metastasis. Cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)2, MMP9 and wild-type (WT) p53 has been found to regulate  the production of VEGF. Whether VEGF regulates the production of COX-2, MMP2, MMP9 and WTp53, however, has yet to be determined. This study examined the influence of the overexpression or knockdown of VEGF on the protein levels of COX-2, MMP2, MMP9 and WTp53 as well as cell growth and cell cycle progression in  Lewis lung carcinoma (LLC) cells. LLC cells were transfected with pIRES2-VEGF-GFP in the VEGF-overexpressing group (LLC-VEGF), pIRES2-GFP in the mock group (LLC-GFP) or pSUPER-VEGF-GFP in the VEGF knockdown group (LLC-RNAi). Protein levels were detected by western blot analysis. LLC cell growth exhibited no marked change in the LLC-VEGF group, but was significantly retarded in the LLC-RNAi group. Further examination revealed that more cells entered the S stage  in the LLC-VEGF group than in the control (or mock) group (45.3 vs. 29.1%, P<0.05), and that cell growth was retarded in the LLC-RNAi group. Moreover, COX-2 and MMP2 and MMP9 proteins were significantly increased in the LLC-VEGF group (approximately 1.84-, 1.89- and 1.83-fold, respectively, vs. control, P<0.05), but significantly decreased in the LLC-RNAi group, whereas the expression of WTp53 exhibited the opposite pattern of change. VEGF expression was positively correlated with COX-2, MMP2 and MMP9 expression (r=0.984, r=0.978, r=0.969, respectively, P<0.01) and negatively correlated with WTp53 (r=-0.833, p<0.01). The activities of MMP2 and MMP9 were increased in the LLC-VEGF group. In conclusion, VEGF overexpression may promote the expression of COX-2 and MMPs, but inhibits WTp53 production in LLC cells; VEGF underexpression may have an inverse  effect. These changes are closely correlated with the infiltration and metastasis of lung cancer.

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[611]

TÍTULO / TITLE:  - Personalized medicine and treatment approaches in non-small-cell lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pharmgenomics Pers Med. 2012;5:113-23. doi: 10.2147/PGPM.S24258. Epub 2012 Sep 25.

            ●● Enlace al texto completo (gratuito o de pago) 2147/PGPM.S24258

AUTORES / AUTHORS:  - Vadakara J; Borghaei H

INSTITUCIÓN / INSTITUTION:  - Fox Chase Cancer Center, Philadelphia, PA, USA.

RESUMEN / SUMMARY:  - Chemotherapy has been the traditional backbone for the management of metastatic lung cancer. Multiple trials have shown the benefits of treatment with platinum doublets in lung cancer. This “one treatment fits all” approach was further refined by the introduction of targeted agents and discovery of subpopulations of patients who benefited from treatment with these agents. It has also become evident that certain histologic subtypes of non-small-cell lung cancer respond better to one cytotoxic chemotherapy versus others. This has led to the concept of using histology to guide therapy. With the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the discovery of activating mutations in the EGFR gene, further personalization of treatment for subgroups of patients has become a reality. More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients. In this article, efforts in personalizing delivery of care based on  the histological subtypes of lung cancer and the role of K-RAS and EGFR mutations, EML4/ALK translocation, and ERCC1 (excision repair cross-complementing 1) and EGFR expression in choosing appropriate treatments for patients with advanced lung cancer are discussed. This article also reviews the problem of resistance to EGFR tyrosine kinase inhibitors and the ongoing trials that target  novel pathways and mechanisms that are implicated in resistance.

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[612]

TÍTULO / TITLE:  - Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Radiat Res. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jrr/rrs136

AUTORES / AUTHORS:  - Duan W; Xu Y; Dong Y; Cao L; Tong J; Zhou X

INSTITUCIÓN / INSTITUTION:  - School of Radiation Medicine and Public Health, Soochow University, Suzhou, Jiangsu 215123, China.

RESUMEN / SUMMARY:  - miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into  A549 and H1299 cells, with or without co-treatment of gamma-irradiation. Results  showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy.

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[613]

TÍTULO / TITLE:  - IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Dec 27;14(1):515-26. doi: 10.3390/ijms14010515.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14010515

AUTORES / AUTHORS:  - Noda M; Yamakawa Y; Matsunaga N; Naoe S; Jodoi T; Yamafuji M; Akimoto N; Teramoto N; Fujita K; Ohdo S; Iguchi H

INSTITUCIÓN / INSTITUTION:  - Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. noda@phar.kyushu-u.ac.jp.

RESUMEN / SUMMARY:  - In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart  of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R) on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab) to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes  was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor  foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that  IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain.

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[614]

TÍTULO / TITLE:  - Gain-of-Function Activity of Mutant p53 in Lung Cancer through Up-Regulation of Receptor Protein Tyrosine Kinase Axl.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Cancer. 2012 Jul;3(7-8):491-502. doi: 10.1177/1947601912462719.

            ●● Enlace al texto completo (gratuito o de pago) 1177_1947601912462719 [pii

            ●● Enlace al texto completo (gratuito o de pago) 1177/1947601912462719

AUTORES / AUTHORS:  - Vaughan CA; Singh S; Windle B; Yeudall WA; Frum R; Grossman SR; Deb SP; Deb S

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry & Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA.

RESUMEN / SUMMARY:  - p53 mutations are present in up to 70% of lung cancer. Cancer cells with p53 mutations, in general, grow more aggressively than those with wild-type p53 or no p53. Expression of tumor-derived mutant p53 in cells leads to up-regulated expression of genes that may affect cell growth and oncogenesis. In our study of  this aggressive phenotype, we have investigated the receptor protein tyrosine kinase Axl, which is up-regulated by p53 mutants at both RNA and protein levels in H1299 lung cancer cells expressing mutants p53-R175H, -R273H, and -D281G. Knockdown of endogenous mutant p53 levels in human lung cancer cells H1048 (p53-R273C) and H1437 (p53-R267P) led to a reduction in the level of Axl as well. This effect on Axl expression is refractory to the mutations at positions 22 and  23 of p53, suggesting that p53’s transactivation domain may not play a critical role in the up-regulation of Axl gene expression. Chromatin immunoprecipitation (ChIP) assays carried out with acetylated histone antibodies demonstrated induced histone acetylation on the Axl promoter region by mutant p53. Direct mutant p53 nucleation on the Axl promoter was demonstrated by ChIP assays using antibodies against p53. The Axl promoter has a p53/p63 binding site, which however is not required for mutant p53-mediated transactivation. Knockdown of Axl by Axl-specific RNAi caused a reduction of gain-of-function (GOF) activities, reducing the cell growth rate and motility rate in lung cancer cells expressing mutant p53. This indicates that for lung cancer cell lines with mutant p53, GOF activities are mediated in part through Axl.

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[615]

TÍTULO / TITLE:  - Parotid small cell carcinoma presenting with long-term survival after surgery alone: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Case Rep. 2012 Dec 28;6(1):431. doi: 10.1186/1752-1947-6-431.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-6-431

AUTORES / AUTHORS:  - Kanazawa T; Fukushima N; Tanaka H; Shiba J; Nishino H; Mineta H; Ichimura K

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University School of Medicine, 3311-1, Shimotsuke, 329-0498, Japan. kanatake@omiya.jichi.ac.jp.

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Primary involvement of the salivary glands in small cell  carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested; the latter have the potential for  spontaneous regression, which is related to a favorable clinical outcome. CASE PRESENTATION: We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was  controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma. CONCLUSION: We believe  this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy.

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[616]

TÍTULO / TITLE:  - Differences in dose-volumetric data between the analytical anisotropic algorithm  and the x-ray voxel Monte Carlo algorithm in stereotactic body radiation therapy  for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Dosim. 2012 Dec 12. pii: S0958-3947(12)00140-9. doi: 10.1016/j.meddos.2012.07.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.meddos.2012.07.007

AUTORES / AUTHORS:  - Mampuya WA; Matsuo Y; Nakamura A; Nakamura M; Mukumoto N; Miyabe Y; Narabayashi M; Sakanaka K; Mizowaki T; Hiraoka M

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

RESUMEN / SUMMARY:  - The objective of this study was to evaluate the differences in dose-volumetric data obtained using the analytical anisotropic algorithm (AAA) vs the x-ray voxel Monte Carlo (XVMC) algorithm for stereotactic body radiation therapy (SBRT) for lung cancer. Dose-volumetric data from 20 patients treated with SBRT for solitary lung cancer generated using the iPlan XVMC for the Novalis system consisting of a 6-MV linear accelerator and micro-multileaf collimators were recalculated with the AAA in Eclipse using the same monitor units and identical beam setup. The mean isocenter dose was 100.2% and 98.7% of the prescribed dose according to XVMC and AAA, respectively. Mean values of the maximal dose (D(max)), the minimal dose (D(min)), and dose received by 95% volume (D(95)) for the planning target volume  (PTV) with XVMC were 104.3%, 75.1%, and 86.2%, respectively. When recalculated with the AAA, those values were 100.8%, 77.1%, and 85.4%, respectively. Mean dose parameter values considered for the normal lung, namely the mean lung dose, V(5), and V(20), were 3.7Gy, 19.4%, and 5.0% for XVMC and 3.6Gy, 18.3%, and 4.7% for the AAA, respectively. All of these dose-volumetric differences between the 2 algorithms were within 5% of the prescribed dose. The effect of PTV size and tumor location, respectively, on the differences in dose parameters for the PTV between the AAA and XVMC was evaluated. A significant effect of the PTV on the difference in D(95) between the AAA and XVMC was observed (p = 0.03). Differences in the marginal doses, namely D(min) and D(95), were statistically significant between peripherally and centrally located tumors (p = 0.04 and p = 0.02, respectively). Tumor location and volume might have an effect on the differences  in dose-volumetric parameters. The differences between AAA and XVMC were considered to be within an acceptable range (<5 percentage points).

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[617]

TÍTULO / TITLE:  - Exposure to welding fumes increases lung cancer risk among light smokers but not  among heavy smokers: evidence from two case-control studies in Montreal.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Med. 2012 Aug;1(1):47-58. doi: 10.1002/cam4.6. Epub 2012 Jun 7.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cam4.6

AUTORES / AUTHORS:  - Vallieres E; Pintos J; Lavoue J; Parent ME; Rachet B; Siemiatycki J

INSTITUCIÓN / INSTITUTION:  - CHUM Research Center, University of Montreal, Montreal Quebec, Canada.

RESUMEN / SUMMARY:  - We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies  were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and  gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9;  95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

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[618]

TÍTULO / TITLE:  - Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Nanomedicine. 2013;8:73-84. doi: 10.2147/IJN.S38221. Epub 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S38221

AUTORES / AUTHORS:  - Chen L; Sha X; Jiang X; Chen Y; Ren Q; Fang X

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - The aim of this work was to establish a novel polymeric mixed micelle composed of Pluronic P105 and F127 copolymers loaded with the poorly soluble antitumor drug docetaxel (DTX) against Taxol-resistant non-small cell lung cancer. A central composite design was utilized to optimize the preparation process, helping to improve drug solubilization efficiency and micelle stability. Prepared by a thin-film hydration method, the average size of the optimized mixed micelle was 23 nm, with a 92.40% encapsulation ratio and a 1.81% drug-loading efficiency. The optimized formulation showed high storage stability in lyophilized form, with 95.7% of the drug content remaining after 6 months’ storage at 4 degrees C. The in vitro cytotoxicity assay showed that the IC50 values for Taxotere(®) and mixed micelles were similar for A549, while on A549/Taxol cell lines, DTX-loaded  P105/F127 mixed micelles showed a superior hypersensitizing effect; their IC50 value (0.059 mug/mL) was greatly reduced compared to those of Taxotere injections (0.593 mug/mL). The in vivo pharmacokinetic study showed that the mixed-micelle formulation achieved a 1.85-fold longer mean residence time in circulation and a  3.82-fold larger area under the plasma concentration-time curve than Taxotere. In addition, therapeutic improvement of mixed micelles in vivo against A549/Taxol was obtained. The tumor inhibition rate of the micelles was 69.05%, versus 34.43% for Taxotere (P < 0.01). Therefore, it could be concluded from the results that DTX-loaded P105/F127 mixed micelles might serve as a potential antitumor drug delivery system to overcome multidrug resistance in lung cancer.

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[619]

TÍTULO / TITLE:  - A rare case of intussusception associated with metastasize small cell carcinoma of lung.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Med Iran. 2012 Nov;50(11):782-4.

AUTORES / AUTHORS:  - Jarmin R; Azman A; Rahim R; Kosai NR; Das S

INSTITUCIÓN / INSTITUTION:  - Department of Surgery Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre,Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.

RESUMEN / SUMMARY:  - Intussusception is common cause of bowel obstruction in the paediatric age group  compared to the elderly population. Many times, The diagnosis may be difficult because of asymptomatic nature of this bowel disorder. We hereby describe the case of a 75-year-old male who presented with lethargy, weakness, loss of movement in the joints and was found to be anemic. The haemoglobin level was low  so he was transfused with packed cells. On gastrointestinal (GI) endoscopy, upper GI bleed was observed. A mass was observed beyond ampulla at the 2nd and 3rd part of the duodenal junction. Computerized tomography (CT) scan also showed a mass at the head of pancreas and the lesion at the left lung. In view of persistent bleed, ‘Whipple’s procedure’ was performed. Histopathological examination showed  small cell carcinoma of the lungs with metastasis to the pancreas and the jejunum. We here discuss the case of intussusception with intestinal metastasis which presented with gastrointestinal bleeding.

 

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[620]

TÍTULO / TITLE:  - A Successful Case of Robotic Bronchoplastic Lobectomy for Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Nov 30.

AUTORES / AUTHORS:  - Nakamura H; Taniguchi Y; Miwa K; Fujioka S; Matsuoka Y; Kubouchi Y

INSTITUCIÓN / INSTITUTION:  - Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Tottori, Japan.

RESUMEN / SUMMARY:  - We performed robotic bronchoplastic upper lobectomy for squamous cell carcinoma of the right hilum of the lung. The patient was a 56-year-old male and surgery was performed using 3 robotic arms and 1 assistance. Deeply wide wedge resection  and interrupted suture were applied to the bronchus of the upper lobe. The pathological stage was pT1bN1M0, IIA. Chest drain tube was removed on postoperative day 2 and no postoperative respiratory complication occurred. The key for success of this procedure is accustoming to robotic manipulation, especially suturing technique because of the absence of a tactile sense.

 

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[621]

TÍTULO / TITLE:  - Intrapulmonary Bronchogenic Cyst in the Thoracic Cavity: A Case Report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 26.

AUTORES / AUTHORS:  - Onuki T; Narita C; Usui S; Inagaki M

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.

RESUMEN / SUMMARY:  - This case report presents an intrapulmonary bronchogenic cyst exhibiting a unique shape. The patient was a 19-year-old man who had been diagnosed with a posterior  mediastinal tumor by computed tomography and magnetic resonance imaging, 2 years  previously. The imaging revealed that the tumor was located on the left side of the posterior mediastinum and was 45 x 25 mm in size. As the size and shape of the tumor did not change in the 2 years after its detection, surgical extraction  was planned. Preoperative diagnosis was, firstly, a neurogenic tumor originating  in the posterior mediastinum.Surgical findings revealed that the tumor formed a bridge between the visceral pleura of the left lower lobe and the chest wall, and most of the tumor was located in the thoracic cavity. Pathological diagnosis was  intrapulmonary bronchogenic cyst. An intrapulmonary bronchogenic cyst with a unique shape, as observed in this case, is very rare.Although preoperative imaging could predict the tumor size, it could not confirm where the tumor originated. Surgical resection of this type of tumor, which is diagnosed preoperatively as a posterior mediastinal tumor, is a superior strategy for precise diagnosis and treatment.

 

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[622]

TÍTULO / TITLE:  - Cisplatin plus oral vinorelbine as first-line treatment for advanced non-small-cell lung cancer: a prospective study confirming that the day-8 hemogram is unnecessary.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0989-6

AUTORES / AUTHORS:  - Provencio M; Sanchez A; Artal A; Sanchez Torres JM; de Castro J; Domine M; Vinolas N; Sanchez A; Perez FJ

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Calle Manuel de Falla 1, 28222, Madrid, España, mprovenciop@gmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: Cisplatin plus oral vinorelbine, one of the standard treatments for metastatic non-small-cell lung cancer (NSCLC), is associated with a high rate of  neutropenia, and a hemogram is performed on day 8. We analyzed the oncologists’ opinions and the result of the hemogram on day 8 to address the question of whether this hemogram could be avoided. MATERIALS AND METHODS: Fifty-eight chemotherapy-naive, advanced NSCLC patients were included. Each received intravenous doses of 75 mg/m(2) cisplatin on day 1 plus oral vinorelbine [60 mg/m(2) in the first cycle (80 mg/m(2) in subsequent cycles) on days 1 and 8], every 3 weeks, for a maximum of six cycles. RESULTS: Out of 257 cycles analyzed,  oral vinorelbine was administered on day 8 in 214 (83.2 %) and the dose was canceled in 6 cycles (2.3 %) due to hematological toxicity. On analyzing the patients to whom chemotherapy had been administered on day 8, based on medical opinion without the doctor knowing the hemogram result, we found that the cycle had been administered with a hemogram showing fewer than 1,500 x 10(6) neutrophils in only 3 of the 185 evaluable cycles [event rate of 1.6 %, with confidence interval 95 % = (0.34-4.67 %)]. CONCLUSION: The hemogram on day 8 can  be avoided and oral vinorelbine administered in relative safety in patients with  good performance status, when confirmed by the clinician’s perception, thereby making this regimen more comfortable for the patient. This is the first prospective study to examine this issue.

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[623]

TÍTULO / TITLE:  - Reduction of Raf Kinase Inhibitor Protein Expression is Associated with Lymph Node Metastasis in Resectable Non-small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Open Respir Med J. 2012;6:135-8. doi: 10.2174/1874306401206010135. Epub 2012 Nov  30.

            ●● Enlace al texto completo (gratuito o de pago) 2174/1874306401206010135

AUTORES / AUTHORS:  - Yan H; Guoqiang L; Shengxi C; Zhenghao D; Lingjin H

INSTITUCIÓN / INSTITUTION:  - Department of Infectious Disease, Xiangya Hospital, Central South University, Xiangya Road, Changsha, China.

RESUMEN / SUMMARY:  - INTRODUCTION: Raf kinase inhibitor protein (RKIP) had been identified as one of prognostic indictor in various malignant diseases. Association of RKIP expression and the clinical-pathological features were not investigated in patients with resectable non-small cell lung cancer (NSCLC). MATERIALS AND METHODOLOGY: 159 sectioned samples from surgical NSCLC patients were investigated by immunohistochemistry in order to reveal the associations between RKIP expression  and clinical-pathologic features. RESULTS: Statistically, Lower RKIP expression level was found in the group with higher N stage (P<0.01) and higher TNM stage (P<0.05). No significant correlation was observed between RKIP expressions and histologic type (P>0.05) and tumor size (P>0.05). CONCLUSIONS: Down expression level of RKIP was found relating to lymph node metastasis in resectable NSCLC patients in this study.

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[624]

TÍTULO / TITLE:  - Ethanolic extract of Thuja occidentalis blocks proliferation of A549 cells and induces apoptosis in vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Zhong Xi Yi Jie He Xue Bao. 2012 Dec;10(12):1451-9. doi: 10.3736/jcim20121218.

            ●● Enlace al texto completo (gratuito o de pago) 3736/jcim20121218

AUTORES / AUTHORS:  - Mukherjee A; Sikdar S; Bishayee K; Paul A; Ghosh S; Boujedaini N; Khuda-Bukhsh AR

INSTITUCIÓN / INSTITUTION:  - Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University  of Kalyani, Kalyani 741235, West Bengal, India; E-mail: prof_arkb@yahoo.co.in, khudabukhsh_48@rediffmail.com.

RESUMEN / SUMMARY:  - OBJECTIVE: To study the possible anticancer and antiproliferative activities of ethanolic leaf extract of Thuja occidentalis (TO) on A549 non-small lung carcinoma cells in vitro. METHODS: Cell viability was ascertained through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after deployment of TO in different doses. The half maximal inhibitory concentration (IC50) dose (282 mug/mL) was determined, and two other doses for dose-dependence  study, one below the IC50 dose (IC35=188 mug/mL) and one above the IC50 dose (IC65=376 mug/mL) were selected. Bromodeoxyuridine (BrdU) incorporation assay and migration studies were performed to elucidate antiproliferative activity of the drug, if any. Fluorescence-activated cell sorting analysis after annexin V-fluorescein isothiocyanate and propidium iodide (annexin V-FITC-PI) dual staining method was done to ascertain early stage of apoptosis, if any. DNA fragmentation assay was done through Hoechst 33258 and acridine orange-ethidium bromide staining. DNA damage was quantified through comet assay. Bax-Bcl2 regulation and expression studies were performed through indirect enzyme-linked immunosorbent assay (ELISA). Caspase 3 activity was measured at gene level through reverse transcription-polymerase chain reaction (RT-PCR) analysis. Its activation at protein level was analyzed through indirect ELISA and Western blot  analysis. RESULTS: TO demonstrated a dose-dependent decrease in viability of A549 cells after 24 h of exposure. Cell proliferation was reduced in a time-dependent  manner of drug exposure as revealed from BrdU incorporation and migration studies. Annexin-V-FITC positivity of cells up to 11.72% as compared to the untreated control revealed early state of TO-induced apoptosis. Occurrence of comet tail and increased fluorescence of Hoechst after 24 h of drug exposure revealed significant DNA nick generation and chromatin condensation. Bax up-regulation and Bcl-2 down-regulation suitably altered ratio of Bax/Bcl-2 in favor of apoptosis. From RT-PCR, indirect ELISA and Western blot studies, caspase 3 activity was also found to be significantly increased along with cleaved poly ADP-ribose polymerase expression. CONCLUSION: Ethanolic leaf extract of TO demonstrated apoptotic and antiproliferative potentials against A549 cell line.

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[625]

TÍTULO / TITLE:  - CUG-binding protein 1 (CUGBP1) expression and prognosis of non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1005-5

AUTORES / AUTHORS:  - Jiao W; Zhao J; Wang M; Wang Y; Luo Y; Zhao Y; Tang D; Shen Y

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, The Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Road, Qingdao, 266003, People’s Republic of China.

RESUMEN / SUMMARY:  - BACKGROUND AND AIMS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. As CUGBP1 may also play a great role in tumor genesis and deterioration, the purpose of this study was to detect the expression of CUGBP1 mRNA and CUGBP1 and assess the prognostic significance of CUGBP1 in NSCLC. METHODS: Expression of CUGBP1 mRNA and CUGBP was detected by Semi-quantitative PCR and Immunohistochemistry, respectively, from 57 NSCLC patients. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using chi (2) test. The prognostic significance was assessed by univariate and multivariate analyses in the Cox hazard model. RESULTS: The expression of CUGBP1 mRNA and CUGBP1 was over-expressed in cancer group and was correlated with TNM stage and Differentiation. By both univariate and multivariate survival analyses, CUGBP1 expression (P = 0.0074, HR = 3.701, 95 % CI 1.420-9.648), TNM-stage (HR = 4.043, 95 % CI 2.098-7.794) and age (HR = 3.207, 95 % CI 1.544-6.664) were noted to be independent indicators of a shorter postsurgical survival. CONCLUSIONS: The expression of CUGBP1 independently predicted a shorter postsurgical survival in NSCLC.

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[626]

TÍTULO / TITLE:  - Role of the extracellular matrix in variations of invasive pathways in lung cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Braz J Med Biol Res. 2013 Jan 11:1-11.

AUTORES / AUTHORS:  - Sa VK; Carvalho L; Gomes A; Alarcao A; Silva MR; Couceiro P; Sousa V; Soares FA; Capelozzi VL

RESUMEN / SUMMARY:  - Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor beta (TGF-beta) may favor invasion, cellular motility, and proliferation. We examined  HAase proteins (Hyal), HAS, E-cadherin, and TGF-beta profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed  by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of  SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01).  Hyal, HAS, E-cadherin, and TGF-beta modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-beta and E-cadherin, may have a greater impact in lung cancer prognosis.

 

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[627]

TÍTULO / TITLE:  - TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-kappaB signalling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(11):e50672. doi: 10.1371/journal.pone.0050672. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050672

AUTORES / AUTHORS:  - Newman AC; Scholefield CL; Kemp AJ; Newman M; McIver EG; Kamal A; Wilkinson S

INSTITUCIÓN / INSTITUTION:  - Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.

RESUMEN / SUMMARY:  - K-Ras dependent non-small cell lung cancer (NSCLC) cells are ‘addicted’ to basal  autophagy that reprograms cellular metabolism in a lysosomal-sensitive manner. Here we demonstrate that the xenophagy-associated kinase TBK1 drives basal autophagy, consistent with its known requirement in K-Ras-dependent NSCLC proliferation. Furthermore, basal autophagy in this context is characterised by sequestration of the xenophagy cargo receptor Ndp52 and its paralogue Tax1bp1, which we demonstrate here to be a bona fide cargo receptor. Autophagy of these cargo receptors promotes non-canonical NF-kappaB signalling. We propose that this TBK1-dependent mechanism for NF-kappaB signalling contributes to autophagy addiction in K-Ras driven NSCLC.

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[628]

TÍTULO / TITLE:  - Adeno-associated virus vector mediated expression of an oncogenic retroviral envelope protein induces lung adenocarcinomas in immunocompetent mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51400. doi: 10.1371/journal.pone.0051400. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051400

AUTORES / AUTHORS:  - Linnerth-Petrik NM; Santry LA; Yu DL; Wootton SK

INSTITUCIÓN / INSTITUTION:  - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.

RESUMEN / SUMMARY:  - Lung cancer is the most common cause of cancer-related death worldwide. A poor overall survival rate of 16% necessitates the need for novel treatment strategies. Mouse models of lung cancer are important tools for analyzing the significance of somatic mutations in the initiation and progression of lung cancer. Of additional importance, however, are animal models of virally induced cancers. JSRV is a simple betaretrovirus that causes contagious lung cancer in sheep known as ovine pulmonary adenocarcinoma and closely resembles human lung adenocarcinoma. Previously we showed that expression of the JSRV envelope (Env) from an AAV vector induced lung tumors in immunodeficient mice, but not in immunocompetent mice. Because of the importance of studying lung cancer in the context of an intact immune system we sought to improve our mouse model. In this  report, we employed the use of a strong JSRV enhancer-promoter combination to express Env at high levels and demonstrate for the first time, lung tumor induction in immunocompetent mice. This occurred despite a robust Env-specific antibody-mediated immune response. The PI3K/Akt and MAPK pathways were activated  in both immunocompetent and immunodeficient mice, however, differential activation of PTEN, GSKalpha, p70S6K, p38MAPK, ATF2 and STAT5 was observed. A JSRV Env lung tumor-derived cell line was shown to have a similar signal transduction activation profile as Env-induced lung tumors in C57BL/6 mice. Given the similarities between our model and pulmonary adenocarcinomas in humans, and the ease with which tumors can be induced in any transgenic mouse, this system can be used to uncover novel mechanisms involved lung tumorigenesis.

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[629]

TÍTULO / TITLE:  - Chondrosarcoma of the larynx.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Isr Med Assoc J. 2012 Nov;14(11):681-4.

AUTORES / AUTHORS:  - Buda I; Hod R; Feinmesser R; Shvero J

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center (Beilinson Campus), Petah Tikva, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. inonb@clalit.org.il

RESUMEN / SUMMARY:  - BACKGROUND: Chondrosarcoma of the larynx is a rare tumor. The most common symptom is hoarseness. Treatment is controversial. OBJECTIVES: To describe six patients with laryngeal chondrosarcoma from a single center. METHODS: The medical records  of a major tertiary hospital were reviewed for all patients with laryngeal chondrosarcoma diagnosed and treated from 1959 to 2010. Data on background, clinical treatment and outcome were collected. RESULTS: Six patients, all males with a mean age of 53.3 years, were identified. Partial laryngectomy was performed in three patients, and total laryngectomy, local excision, and partial  cricoidectomy in one patient each. Four patients had a permanent tracheostomy after surgery. One patient required postoperative chemotherapy and one radiotherapy. Follow-up time was 12-216 months (mean 102 months). Recurrence developed in two patients 2 and 8 years after initial treatment and was treated by salvage surgery in both patients. One patient died during the follow-up from an unrelated cause. The others are currently alive. CONCLUSIONS: This study supports earlier reports recommending initial treatment with partial or total laryngectomy for laryngeal chondrosarcoma. Long-term follow-up for recurrence is  advised. We recommend preserving the larynx, if possible, even if a permanent tracheostomy is necessary.

 

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[630]

TÍTULO / TITLE:  - Middle infrared radiation induces g(2)/m cell cycle arrest in a549 lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54117. doi: 10.1371/journal.pone.0054117. Epub 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054117

AUTORES / AUTHORS:  - Chang HY; Shih MH; Huang HC; Tsai SR; Juan HF; Lee SC

INSTITUCIÓN / INSTITUTION:  - Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.

RESUMEN / SUMMARY:  - There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3-5 microm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased  the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1  (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G(2)/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker gamma-H2AX and sensor 53BP1 was induced by MIR  treatment, it implies the MIR induced G(2)/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression.

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[631]

TÍTULO / TITLE:  - Pulmonary sclerosing hemangioma presenting with dense spindle stroma cells: a potential diagnostic pitfall.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Pathol. 2012 Dec 10;7:174. doi: 10.1186/1746-1596-7-174.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-7-174

AUTORES / AUTHORS:  - Lin XY; Wang Y; Fan CF; Liu Y; Yu JH; Dai SD; Wang L; Wang EH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China. wangeh@hotmail.com.

RESUMEN / SUMMARY:  - ABSTRACT: Pulmonary sclerosing hemangioma (PSH) is an uncommon pulmonary tumor. Histologically, PSH typically consists of two types of cells, surface cuboidal cells and polygonal cells, four architectural patterns including papillary, sclerotic, solid, and hemorrhagic. Herein, we present a case of PSH in a 59-year-old Chinese female. The tumor was predominantly composed of solid area presenting with diffuse spindle cells rather than polygonal cells. Focally, classical papillary and sclerotic area could be seen. Immunohistochemical staining showed that the spindle cells were positive for TTF-1, EMA, Actin(SM) and Vimentin, and negative for cytokeratin, cytokeratin7, cytokeratin5/6, surfactant apoprotein A, surfactant apoprotein B, CD34, CD99, S-100, HMB45, Desmin, Synaptophysin, CD56, ALK and Calretinin. The immunophenotype of the dense spindle cells in this case was similar to that of the polygonal cells, and thus the spindle cells may be the variants of polygonal cells. Based on morphologic features and the immunohistochemical profile, the tumor was diagnosed as a PSH. The significance of spindle cells change is unclear for us. To our knowledge, this is the first reported case of PSH showing dense spindle cells in solid area. This case represents a potential diagnostic pitfall, as it may be misdiagnosed as a mesenchymal tumor such as inflammatory myofibroblastic tumor, synovial sarcoma, solitary fibrous tumor, leiomyoma, or even mesothelioma, especially if the specimen is limited or from fine- needle aspiration. VIRTUAL SLIDES: The virtual  slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1235401622806126.

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[632]

TÍTULO / TITLE:  - Downregulation of ALDH1A1 expression in non-small cell lung carcinomas—its clinicopathologic and biological significance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(1):1-12. Epub 2012 Nov 20.

AUTORES / AUTHORS:  - Okudela K; Woo T; Mitsui H; Suzuki T; Tajiri M; Sakuma Y; Miyagi Y; Tateishi Y; Umeda S; Masuda M; Ohashi K

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan. kojixok@yokohama-cu.ac.jp

RESUMEN / SUMMARY:  - ALDH1A1 metabolizes a variety of endogenous and exogenous aldehyde, and also oxidizes retinol to synthesize retinoic acid and modulate cell differentiation. Moreover, ALDH1A1 is also suggested to participate in the maintenance of cancer stem cells. To investigate the potential role of ALDH1A1 in carcinogenesis of the lung, the present study examined two hundred and sixty eight cases of non-small cell lung carcinoma (NSCLC) for its immunohistochemical expression and analyzed associations between ALDH1A1 levels and a series of clinicopathologic parameters. Also, the biological significance of the aberrant expression of ALDH1A1 was investigated in vitro. ALDH1A1 expression was markedly reduced in 39.9% (107/268) of NSCLCs. The incidence of this reduction was significantly higher in adenocarcinomas (ADC: 41.6%, 85/207) and large cell carcinomas (61.1%, 11/18) than squamous cell carcinomas (25.5%, 11/43). Among ADCs, the downregulation tended to be more remarkable in high grade, poorly differentiated tumors, and tumors with stronger proliferating activity. It also occurred with a significantly higher incidence in smokers than non-smokers. Forced expression of  ALDH1A1 in NSCLC cell lines, which had lost ALDH1A1 expression, markedly attenuated their growth. Taken together, loss of ALDH1A1 expression is suggested  to promote carcinogenesis especially in the smoking-related ADCs.

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[633]

TÍTULO / TITLE:  - RagD gene expression and NRF2 mutations in lung squamous cell carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1167-1170. Epub 2012 Sep 25.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.938

AUTORES / AUTHORS:  - Sasaki H; Shitara M; Yokota K; Hikosaka Y; Moriyama S; Yano M; Fujii Y

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.

RESUMEN / SUMMARY:  - RagD is a member of the small G protein family, which encodes a recently discovered activator of the mTOR pathway. In vitro, RagD plays an important role  in the proliferation of NRF2 gene (NFE2L2) mutated cancer cells. We hypothesized  that tumor RagD expression may be correlated with the mutation status of NRF2 in  lung cancers. RagD mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qPCR) in 90 surgically-treated lung squamous cell cancer cases, including 14 NRF2 mutation cases, and normalized by beta-actin mRNA levels. Mean  RagD/beta-actin mRNA levels of lung squamous cell carcinoma patients did not differ with age (</=65 vs. >65), Brinkman index (<400 vs. >/=400) or gender. RagD/beta-actin mRNA levels were significantly higher in stage III samples (3.204+/-3.623) compared to stage I samples (1.357+/-1.560) (P= 0.0039). In addition, higher RagD/beta-actin mRNA levels were identified in NRF2 mutant samples (3.107+/-3.633) compared to wild-type samples (1.774+/-2.301) (P=0.074).  These results suggest that RagD induction by NRF2 activation plays a role in the  proliferation of lung squamous cell cancers.

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[634]

TÍTULO / TITLE:  - SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2013 Jan 22;11(1):12.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-12

AUTORES / AUTHORS:  - Wang Y; Yue B; Yu X; Wang Z; Wang M

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The role of tumor necrosis factor alpha (TNF-alpha) in cancer is complex with both apoptotic and anti-apoptotic roles proposed. However  the mechanism is not clear. In the study, we designed to investigate the effect of TNF-alpha on the activation and expression of nuclear factor kappa B (NF-kappaB)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-alpha-induced apoptosis. METHODS: We have engineered three A549 cell lines that were transiently transfected with PUMA siRNA, SLUG siRNA and Bcl-2 siRNA, respectively. We have measured the in vitro effects of siRNA on apoptosis, and sensitivity to 20 ng/ml of TNF-alpha treatment for 24--48 h. RESULTS: We found the NF-kappaB activity and PUMA mRNA/protein was significantly  increased after treatment of TNF-alpha for 24 h in untreated A549 cells, and led  to a significant increase in TNF-alpha-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-alpha for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-alpha-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-alpha for 24 h. Inhibition of the NF-kappaB activity could effectively decrease the PUMA level and increase the SLUG and Bcl-2 level. PUMA silencing by  siRNA led to a significant decrease in TNF-alpha-induced apoptosis after treatment of TNF-alpha for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-alpha-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level. CONCLUSIONS: The findings suggested that TNF-alpha treatment promoted apoptosis via the NF-kappaB-dependent PUMA pathway. The anti-apoptotic role of TNF-alpha was via NF-kappaB-dependent SLUG and Bcl-2 pathway at a later time.

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[635]

TÍTULO / TITLE:  - Benefits of Rib Head Resection via Costotransverse Ligament Release Method for T3 Lung Cancer in the Paravertebral Space.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Nov 17.

AUTORES / AUTHORS:  - Chida M; Hayama M; Kobayashi S; Ishihama H; Oyaizu T; Minowa M; Matsumura Y

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Dokkyo Medical Uni versity, School of Medicine, Mibu, Tochigi, Japan.

RESUMEN / SUMMARY:  - Objective: Lung cancer located in the paravertebral region occasionally invades the rib head (T3) and not the spine (T4). In such cases, a costotransverse ligament release (CTLR) method may be useful for complete resection without performing a vertebrectomy.Methods: Eighteen patients with lung cancer underwent  chest wall resection between2001 and 2009 at our institutions. Of those, 7 who underwent chest wall removal with rib head resection via a CTLR method (group A)  and 11 without rib head resection(conventional distal rib resection, group B) were retrospectively analyzed.Results: Three patients in group A underwent induction chemoradiotherapy. All rib head resections were performed via a CTLR approach without postoperative complications. There were no deaths within 30 day  in group A and 1 in group B. The mean number of resected rib heads was 2.1 in group A, while 2.0 ribs were removed in group B. There was no significant difference for operation time between groups A and B(332+/-112 vs. 287 +/-114 mins, p = 0.449). Local recurrence was seen in 0 patients in group A and 3 in group B(p = 0.13). The median survival time was 1489 and 727 day, respectively, while 5-year survival rates were 0.48 and 0.41, respectively.Conclusion: A rib head resection via a CTLR method is an effective procedure for T3 lung cancer infiltrating the rib head.

 

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[636]

TÍTULO / TITLE:  - Ent-11alpha-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Jun;24(2):109-15. doi: 10.1007/s11670-012-0109-8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-012-0109-8

AUTORES / AUTHORS:  - Li L; Chen GG; Lu YN; Liu Y; Wu KF; Gong XL; Gou ZP; Li MY; Liang NC

INSTITUCIÓN / INSTITUTION:  - Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang 524023, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To examine the apoptotic effect of ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from  Pteris semipinnata L (PsL), in human lung cancer A549 cells. METHODS: A549 cells  were treated with 5F (0-80 mug/ml) for different time periods. Cytotoxicity was examined using a MTT method. Cell cycle was examined using propidium iodide staining. Apoptosis was examined using Hoechst 33258 staining, enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis. Expression of representative apoptosis-related proteins was evaluated by Western blot analysis. Reactive oxygen species (ROS) level was measured using standard protocols. Potential interaction of 5F with cisplatin was also examined. RESULTS: 5F inhibited the proliferation of A549 cells in a concentration- and time-dependent  manner. 5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase. Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis. The expression of p21 was increased. 5F exposure also increased Bax expression, release of cytochrome c and apoptosis inducing factor (AIF), and activation of caspase-3. 5F significantly sensitized the cells to cisplatin toxicity. Interestingly, treatment with 5F did  not increase ROS, but reduced ROS production induced by cisplatin. CONCLUSION: 5F could inhibit the proliferation of A549 cells by arresting the cells in G2 phase  and by inducing mitochondrial-mediated apoptosis.

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[637]

TÍTULO / TITLE:  - Intrapericardial bronchogenic cyst found incidentally during open heart surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Cardiovasc Thorac Ann. 2012 Dec;20(6):737-8. doi: 10.1177/0218492312449631.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0218492312449631

AUTORES / AUTHORS:  - Antoniou A; Filias V; Mourtzis N; Economidou S; Schortsanitis P; Panagiotou M

INSTITUCIÓN / INSTITUTION:  - mspanag@otenet.gr.

RESUMEN / SUMMARY:  - Bronchogenic cysts are embryological remnants occurring as developmental abnormalities of the primary foregut. The most common locations of these cysts are the mediastinum, lung parenchyma, and inferior pulmonary ligament. An intrapericardial location is an extremely rare finding. We describe the case of a 76-year-old man with aortic valve stenosis and coronary artery disease, in whom an intrapericardial bronchogenic cyst was found incidentally during the open heart procedure.

 

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[638]

TÍTULO / TITLE:  - Erlotinib : A Guide to Its Use in First-Line Treatment of Non-Small-Cell Lung Cancer with Epidermal Growth Factor-Activating Mutations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Diagn Ther. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s40291-013-0015-x

AUTORES / AUTHORS:  - Lyseng-Williamson KA

INSTITUCIÓN / INSTITUTION:  - Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, MDT@adis.com.

RESUMEN / SUMMARY:  - In the EU, the approved use of erlotinib (Tarceva(®)), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has recently been expanded to include first-line treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC) in patients with EGFR-activating mutations. In randomized, open-label, phase III clinical trials, oral erlotinib reduced the risk of progression, improved response rates, and was well tolerated relative to standard platinum-based doublet chemotherapy in Caucasian and Asian populations with advanced NSCLC with EGFR-activating mutations.

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[639]

TÍTULO / TITLE:  - Computed Tomography Guided Thoracoscopic Segmentectomy for Lung Cancer with Variant Bronchus.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2012 Dec 26.

AUTORES / AUTHORS:  - Akiba T; Morikawa T; Marushima H; Nakada T; Inagaki T; Ohki T

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan.

RESUMEN / SUMMARY:  - Lung segmentectomy with bronchial variation has rarely been reported. We report the case of a lung cancer patient with variant anatomy of the right upper lobe bronchus.Thoracoscopic posterior segmentectomy of the right upper lobe was performed. Variant bronchus and related blood vessels were confirmed preoperatively by three-dimensional multidetector computed tomography (3D-MDCT),  which facilitated visualization of the patient’s anatomy during surgery.

 

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[640]

TÍTULO / TITLE:  - Incidentally discovered malignant mesothelioma of the tunica vaginalis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Formos Med Assoc. 2013 Jan;112(1):57-8. doi: 10.1016/j.jfma.2011.08.024. Epub 2012 Jul 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jfma.2011.08.024

AUTORES / AUTHORS:  - Weng CH; Ho PY; Chen CK; Tsai WK

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan.

 

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[641]

TÍTULO / TITLE:  - Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncotarget. 2012 Nov;3(11):1428-38.

AUTORES / AUTHORS:  - Walsh KM; Amos CI; Wenzlaff AS; Gorlov IP; Sison JD; Wu X; Spitz MR; Hansen HM; Lu EY; Wei C; Zhang H; Chen W; Lloyd SM; Frazier ML; Bracci PM; Seldin MF; Wrensch MR; Schwartz AG; Wiencke JK

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.

RESUMEN / SUMMARY:  - Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic variation in nAChR genes influences lung cancer susceptibly  in African-Americans, and evaluated the association of these cancer susceptibility loci with smoking behavior. A total of 1308 African-Americans with lung cancer and 1241 African-American controls from three centers were genotyped  for 378 single nucleotide polymorphisms (SNPs) spanning the sixteen human nAChR genes. Associations between SNPs and the risk of lung cancer were estimated using logistic regression, adjusted for relevant covariates. Seven SNPs in three nAChR  genes were significantly associated with lung cancer at a strict Bonferroni-corrected level, including a novel association on chromosome 2 near the promoter of CHRNA1 (rs3755486: OR = 1.40, 95% CI = 1.18-1.67, P = 1.0 x 10-4). Association analysis of an additional 305 imputed SNPs on 2q31.1 supported this association. Publicly available expression data demonstrated that the rs3755486 risk allele correlates with increased CHRNA1 gene expression. Additional SNP associations were observed on 15q25.1 in genes previously associated with lung cancer, including a missense variant in CHRNA5 (rs16969968:  OR = 1.60, 95% CI = 1.27-2.01, P = 5.9 x 10-5). Risk alleles on 15q25.1 also correlated with an increased number of cigarettes smoked per day among the controls. These findings identify a novel lung cancer risk locus on 2q31.1 which  correlates with CHRNA1 expression and replicate previous associations on 15q25.1  in African-Americans.

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[642]

TÍTULO / TITLE:  - Impact of CHK2-small interfering RNA on CpG ODN7909-enhanced radiosensitivity in  lung cancer A549 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onco Targets Ther. 2012;5:425-31. doi: 10.2147/OTT.S38240. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S38240

AUTORES / AUTHORS:  - Chen W; Liu X; Qiao T; Yuan S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - OBJECTIVE: To investigate the impact of checkpoint kinase 2 (CHK2)-small interfering RNA (CHK2-siRNA) on the enhancement of radiosensitivity by CpG oligodeoxynucleotide (ODN) 7909 in lung cancer A549 cells. METHODS: The A549 cells were randomly divided into five groups: control, CpG, X-ray, CpG + X-ray, and CHK2-siRNA + CpG + X-ray. Cell colonization was observed using inverted microscopy. Cell cycle and apoptosis were analyzed by flow cytometry. CHK2 expression was detected by Western blot. CHK2-siRNA was adopted to silence the expression of CHK2. RESULTS: The level of CHK2 phosphorylation was higher in the  CpG + X-ray group than in the X-ray group. Increases in G(2)/mitotic (M) phase arrest and apoptosis and a decrease of cell survival rate in the CpG + X-ray group were statistically significant (P < 0.05) when compared with the CHK2-siRNA + CpG + X-ray group in which the expression of CHK2 was obviously inhibited. The  combination of CpG ODN7909 and X-ray irradiation was found to enhance the mitotic death of A549 cells. The sensitization enhancement ratio of mean death dose (D(0)) was 1.42 in the CpG + X-ray group, which was higher than that of the CHK2-siRNA + CpG + X-ray group, in which D(0) was 1.05. CONCLUSION: To a certain  extent, the impact of a combination of CpG ODN7909 and X-ray on G(2)/M phase arrest, apoptosis, and rate of cell survival was attenuated by CHK2-siRNA in human lung adenocarcinoma A549 cells, indicating that increased phosphorylation of CHK2 might be a radiosensitive pathway.

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[643]

TÍTULO / TITLE:  - The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Genet. 2013 Jan 9. pii: S2210-7762(12)00278-5. doi: 10.1016/j.cancergen.2012.12.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cancergen.2012.12.003

AUTORES / AUTHORS:  - Fiala O; Pesek M; Finek J; Benesova L; Belsanova B; Minarik M

INSTITUCIÓN / INSTITUTION:  - Department of Oncology and Radiotherapy, Medical School and Teaching Hospital Pilsen, Charles University Prague, Czech Republic. Electronic address: fiala.o@centrum.cz.

RESUMEN / SUMMARY:  - The role of KRAS mutations in molecular targeted therapy by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) has not been fully understood. The present investigation is aimed  at an elucidation of the role of specific KRAS mutation types in predicting outcomes of patients with advanced NSCLC receiving EGFR-TKI therapy. Initially, 448 NSCLC patients were tested for the presence of KRAS mutations, to obtain frequencies of specific KRAS mutation types. Subsequently, the clinical outcome of treatment was evaluated in a subgroup of 38 KRAS-positive patients receiving EGFR-TKI therapy. KRAS mutations were detected in 69 of 448 patients (15.4%), mostly in smokers (17.86% vs. 5.8%, P = 0.0048), and appeared more frequently in  adenocarcinomas than in squamous cell NSCLC or NSCLC that is not otherwise specified (21% vs. 6.99% vs. 4.4%, P = 0.0004). The most frequent type of KRAS mutation was G12C. The progression-free survival (PFS) was doubled in a group of  non-G12C patients compared with that of the G12C group (9.0 wk vs. 4.3 wk, P = 0.009). The overall survival (OS) was not significantly different between non-G12C and G12C groups (12.1 wk vs. 9.3 wk, P = 0.068). The G12C KRAS mutation  is a strong negative predictor for EGFR-TKI treatment, whereas other KRAS mutation types have not negatively predicted treatment efficacy compared with that for the wild-type KRAS genotype.

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[644]

TÍTULO / TITLE:  - Novel cytokines: IL-27, IL-29, IL-31 and IL-33. Can they be useful in clinical practice at the time diagnosis of lung cancer?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Oncol. 2012 Dec;34(4):348-53.

AUTORES / AUTHORS:  - Naumnik W; Naumnik B; Niewiarowska K; Ossolinska M; Chyczewska E

INSTITUCIÓN / INSTITUTION:  - Department of Pneumonology, Medical University of Bialystok, 15-540, Poland.

RESUMEN / SUMMARY:  - There are several antiproliferative and angiogenic factors, recently have been discovered (IL-27, IL-29, IL-31 and IL-33), but they have not been tested yet in  lung cancer patients. The aim of this pilot study was to assess the clinical usefulness of determination of IL-27, IL-29, IL-31 and IL-33 in advanced stages of lung cancer. Patients and Methods: The study included 45 patients (38 males; mean age 62 years; 45 with advanced NSCLC). Serum and BALF cytokine concentrations were evaluated by ELISA method before chemotherapy. The comparative groups consisted of patients with sarcoidosis (BBS, n = 15), hypersensivity pneumonitis (HP, n = 8) and healthy subjects (n = 15). Results: The serum IL-29 levels were higher in NSCLC patients than in the sarcoidosis group. However, serum IL-27, IL-31 and IL-33 did not differ markedly between: NSCLC, BBS, HP and the control group. Concentrations of IL-29 and IL-31 in BALF did not differ significantly between investigated groups. In all groups levels of IL-27 and IL-29 are significantly higher in serum than in BALF. Concentrations of IL-31 in BBS, HP and control groups tended to higher in BALF than in serum. These differences were significantly in NSCLC patients. Patients in stage IIIB of NSCLC had higher serum levels of IL-29 than these in stage IV. Lung cancer patients with partial remission (PR) after chemotherapy had significantly higher concentration of IL-27 in BALF than patients with SD. However, patients with SD had higher levels of IL-29 in BALF than patients with PD. A negative correlation  was found between serum IL-31 levels before therapy and time to progression of NSCLC. Conclusion: Determination of IL-27, IL-29 and IL-31 in serum and BALF can  be useful in clinical practice, but their practical significance needs further studies.

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[645]

TÍTULO / TITLE:  - In vitro inhibitory and pro-apoptotic effect of stellera chamaejasme L extract on human lung cancer cell line NCI-H157.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Tradit Chin Med. 2012 Sep;32(3):404-10.

AUTORES / AUTHORS:  - Liu X; Li Y; Yang Q; Chen Y; Weng X; Wang Y; Li N; Zhu X

INSTITUCIÓN / INSTITUTION:  - Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To investigate the inhibitory and pro-apoptotic effect of Stellera Chamaejasme L extract (ESC) in vitro. METHODS: ESC was first extracted with ethanol, and then washed using a polyamide column with 60% ethanol. ESC was then  decompressively recycled and vacuum dried at room temperature to obtain active fractions. Subsequently, the cytotoxic and apoptotic effects of ESC on NCI-H157 human lung cancer cells were determined. RESULTS: The results showed that ESC was rich in isomers of Chamaejasminor, neochamaejasmine and Sikokianin. ESC had significant cytotoxicity against NCI-H157 cells, with an IC50 of approximately 18.50 microg x mL(-). ESC caused significant increase in total apoptotic rate, the activity of caspase 3 and 8, CONCLUSION: The inhibitory effect of ESC on NCI-H157 tumor cells might partly be attributed to its apoptotic induction through activation of the Fas death receptor pathway.

 

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[646]

TÍTULO / TITLE:  - CC-Chemokine Ligand 18 Induces Epithelial to Mesenchymal Transition in Lung Cancer A549 Cells and Elevates the Invasive Potential.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53068. doi: 10.1371/journal.pone.0053068. Epub 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053068

AUTORES / AUTHORS:  - Ploenes T; Scholtes B; Krohn A; Burger M; Passlick B; Muller-Quernheim J; Zissel G

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, University, Medical Centre Freiburg, Freiburg, Germany.

RESUMEN / SUMMARY:  - Lung cancer is one of the leading causes of cancer related death worldwide with more than a million deaths per year. The poor prognosis is due to its high aggressiveness and its early metastasis. Although the exact mechanisms are still  unknown, the process of epithelial to mesenchymal transition (EMT) seems to be involved in these neoplastic processes. We already demonstrated that serum levels of CCL18, a primate specific chemokine, are highly elevated in patients with lung cancer and correlate with their survival time of patients with adenocarcinoma of  the lung. Therefore, we hypothesized that CCL18 may be directly involved in pathological processes of lung cancer, e.g. EMT. We investigated the effect of CCL18 on A549, an adenocarcinoma cell line of the lung, on EMT and other cell functions like proliferation, chemotaxis, invasion, chemoresistance and proliferation. Exposure of A549 lung cancer cells to CCL18 in various concentrations decreases the epithelial marker E-cadherin, whereas FSP-1, a marker of the mesenchymal phenotype increases. Accordingly, CCL18 induced the transcriptional EMT regulator SNAIL1 in a dose dependent fashion. In contrast, an increasing CCL18 concentration was associated with a decline of cell proliferation rate. In addition, CCL18 induced chemotaxis of these cells and increased their chemoresistance. Therefore, CCL18 may be an interesting therapeutic target for NSCLC.

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[647]

TÍTULO / TITLE:  - Occupational exposure to asbestos and lung cancer in men: evidence from a population-based case-control study in eight Canadian provinces.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 13;12(1):595.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-595

AUTORES / AUTHORS:  - Villeneuve PJ; Parent ME; Harris SA; Johnson KC

INSTITUCIÓN / INSTITUTION:  - Population Studies Division, Health Canada, Ottawa, Ontario, Canada. Paul.Villeneuve@hc-sc.gc.ca.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Asbestos is classified as a human carcinogen, and studies have consistently demonstrated that workplace exposure to it increases the risk of developing lung cancer. Few studies have evaluated risks in population-based settings where there is a greater variety in the types of occupations, and exposures. METHODS: This was a population based case-control study with 1,681 incident cases of lung cancer, and 2,053 controls recruited from 8 Canadian provinces between 1994 and 1997. Self-reported questionnaires were used to elicit a lifetime occupational history, including general tasks, and information for other risk factors. Occupational hygienists, who were blinded to case-control status, assigned asbestos exposures to each job on the basis of (i) concentration (low, medium, high), (ii) frequency (<5%, 5-30%, and >30% of the time in a normal work week), and (iii) reliability (possible, probable, definite). Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Those occupationally exposed to (i) low, and  (ii) medium or high concentrations of asbestos had ORs for lung cancer of 1.17 (95% CI=0.92 - 1.50) and 2.16 (95% CI=1.21-3.88), respectively, relative to those who were unexposed. Medium or high exposure to asbestos roughly doubled the risk  for lung cancer across all three smoking pack-year categories. The joint relationship between smoking and asbestos was consistent with a multiplicative risk model. CONCLUSIONS: Our findings provide further evidence that exposure to asbestos has contributed to an increased risk of lung cancer in Canadian workplaces, and suggests that nearly 3% of lung cancers among Canadian men are caused by occupational exposure to asbestos.

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[648]

TÍTULO / TITLE:  - Clinical impact of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in the evaluation of small cell carcinoma of the prostate.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rev Esp Med Nucl. Acceso gratuito al texto completo a partir de los 2 años de la fecha de publicación.

            ●● Enlace a la Editora de la Revista http://db.doyma.es/ 

            ●● Cita: Revista Española de Medicina Nuclear: <> Imagen Mol. 2012 Dec 4. pii: S2253-654X(12)00233-8. doi: 10.1016/j.remn.2012.10.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.remn.2012.10.005

AUTORES / AUTHORS:  - Sahiner I; Akkas BE; Ucmak Vural G

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Ankara Oncology Research and Training Hospital, Ankara, Turkey. Electronic address: ilginsahiner@yahoo.com.

RESUMEN / SUMMARY:  - Small cell carcinoma of prostate (PSCC) is an uncommon and aggressive type of prostate malignancy with limited data on the use of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the clinical management of this rare entity. In this report, clinical and imaging findings of  a patient with PSCC are presented. We aimed to discuss the role of PET/CT in the  evaluation of PSCC in combination with histopathological characteristics of tumor and emphasize the importance of PET/CT in the clinical management of PSCC.

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[649]

TÍTULO / TITLE:  - Endoscopic treatment of bronchial carcinoids in comparison to surgical resection: a retrospective study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2012 Jan;19(1):29-34. doi: 10.1097/LBR.0b013e3182446b52.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e3182446b52

AUTORES / AUTHORS:  - Neyman K; Sundset A; Naalsund A; Espinoza A; Solberg S; Kongerud J; Fosse E

INSTITUCIÓN / INSTITUTION:  - The Intervention Centre, Rikshospitalet, Sognsvannsveien 20, Oslo, Norway. kirill.neyman@gmail.com

RESUMEN / SUMMARY:  - BACKGROUND: Surgery is the gold standard of lung carcinoid treatment. However, bronchoscopic treatment may provide a complete cure in selected patients. The aim of the study was to review the results of laser treatment of bronchial carcinoids and to compare the outcome after laser resection against the outcome after surgical resection. METHODS: Seventy-three patients, 29 men and 44 women, median  age 53 years (range, 23 to 78 y), with bronchial carcinoids were treated by surgical resection (n=48) or endobronchial ablation (n=25). Bronchoscopic treatment was also performed in 5 of 48 surgical patients as a part of the surgical treatment strategy. RESULTS: Among 25 patients treated endoscopically, 16 were successfully treated with laser, whereas 9 were operated subsequently. One major complication was registered, as an inadvertent ventilation caused a nonfatal fire of the bronchoscope during Nd:YAG laser procedure. Forty-eight patients underwent surgical resection. Most of the patients underwent lobectomy and bilobectomy (30 and 5 patients, respectively). Four of the patients were dead by the end of the study, 1 was treated with laser, and 3 treated with surgical resection. The overall survival was 94.5% in the surgical group and 94.4% in the  group treated with endoscopic ablation (P=0.9). None of the 69 survivors had any  sign of recurrence on computed tomographic scans and bronchoscopy by the end of the study. CONCLUSIONS: This is a retrospective study and no randomization has been performed. However, the results add evidence to the view that transbronchial laser treatment may be offered as a safe, stand-alone procedure in the treatment  of typical carcinoid tumor in the central airways.

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[650]

TÍTULO / TITLE:  - Segmentation of biological target volumes on multi-tracer PET images based on information fusion for achieving dose painting in radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 1):545-52.

AUTORES / AUTHORS:  - Lelandais B; Gardin I; Mouchard L; Vera P; Ruan S

INSTITUCIÓN / INSTITUTION:  - University of Rouen, LITIS EA4108, QuantIF, 22 bd Gambetta, 76183 Rouen Cedex, France. benoit.lelandanis@univ-rouen.fr

RESUMEN / SUMMARY:  - Medical imaging plays an important role in radiotherapy. Dose painting consists in the application of a nonuniform dose prescription on a tumoral region, and is  based on an efficient segmentation of biological target volumes (BTV). It is derived from PET images, that highlight tumoral regions of enhanced glucose metabolism (FDG), cell proliferation (FLT) and hypoxia (FMiso). In this paper, a  framework based on Belief Function Theory is proposed for BTV segmentation and for creating 3D parametric images for dose painting. We propose to take advantage of neighboring voxels for BTV segmentation, and also multi-tracer PET images using information fusion to create parametric images. The performances of BTV segmentation was evaluated on an anthropomorphic phantom and compared with two other methods. Quantitative results show the good performances of our method. It  has been applied to data of five patients suffering from lung cancer. Parametric  images show promising results by highlighting areas where a high frequency or dose escalation could be planned.

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[651]

TÍTULO / TITLE:  - CK2 enzyme affinity against c-myc 424-434 substrate in human lung cancer tissue.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5233-6.

AUTORES / AUTHORS:  - Yaylim I; Ozkan NE; Isitmangil T; Isitmangil G; Turna A; Isbir T

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. ilhanyaylim@gmail.com

RESUMEN / SUMMARY:  - CK2 is a serine threonine kinase that participates in a variety of cellular processes with more than 300 defined substrates. This critical enzyme is known to be upregulated in cancers, but the role of this upregulation in carcinogenesis is not yet fully understood but c-myc, one of the defined CK2 substrates, is a well-known proto- oncogene that is normally essential in developmental process but is also involved in tumor development. We evaluated the optimal enzyme and substrate concentrations for CK2 activity in both neoplastic and non-neoplastic human lung tissues using the c-myc 424-434 peptide (EQKLISEEDL) as a substrate. The activities measured for the neoplastic tissue were 600-750 U/mg protein while those for the control tissue was in the range of 650-800 U/ mg. Km value for c-myc peptide was determined as 0.33 muM in non-neoplastic tissue and 0.18 muM in neoplastic tissue. In this study, we did not observe an increased activity in the neoplastic tissue when compared with the non-neoplastic lung tissue, but we recorded two times higher affinity for c-myc 424-434 in cancer tissue. Considering the metabolic position of c-myc 424-434, our results suggest that phosphorylation by CK2 may be important in dimerization and thus it might affect  the regulation of c-myc in cancer tissues.

 

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[652]

TÍTULO / TITLE:  - Malignant mesothelioma in Eastern Asia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):4849-53.

AUTORES / AUTHORS:  - Bianchi C; Bianchi T

INSTITUCIÓN / INSTITUTION:  - Center for Study of Environmental Cancer, Italian League Against Cancer, Hospital of Monfalcone, Monfalcone, Italy. legatumori1@interfree.it

RESUMEN / SUMMARY:  - Relatively low numbers of malignant mesotheliomas have been reported from Eastern Asia. In order to explore the causes of this fact, the available data on mesothelioma incidence/mortality in five countries (Japan, South Korea, Taiwan, Hong Kong, and Singapore) were reviewed. Data on the industrial histories of the  above countries were also examined. Mesothelioma incidence was low, despite a history of high shipbuilding and port activities, in which heavy exposure to asbestos generally has occurred. Underestimation of mesothelioma could partly explain the above discrepancy. Moreover, in some areas a sufficient latency period for mesothelioma development may have not yet elapsed, due to recent industrialization. However, other possibilities have to be considered. The cancer epidemiology in Eastern Asia differs deeply from that seen in Western countries,  an indication of differences in etiologic factors of cancer as well as in co-factors. In addition, the oncogenic spectrum of asbestos is wide, and not completely defined. In a very different milieu from that of Western countries, asbestos could preferentially hit targets other than serosal membranes.

 

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[653]

TÍTULO / TITLE:  - Bronchial deposits—another abnormal presentation of pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Cardiovasc Thorac Ann. 2012 Dec;20(6):754. doi: 10.1177/0218492312461925.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0218492312461925

AUTORES / AUTHORS:  - Khalil MW; Sharkey AJ; Loubani M

INSTITUCIÓN / INSTITUTION:  - wesam@doctor.com.

 

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[654]

TÍTULO / TITLE:  - EMP-1 promotes tumorigenesis of NSCLC through PI3K/AKT pathway.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Huazhong Univ Sci Technolog Med Sci. 2012 Dec;32(6):834-8. doi: 10.1007/s11596-012-1043-1. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11596-012-1043-1

AUTORES / AUTHORS:  - Lai S; Wang G; Cao X; Li Z; Hu J; Wang J

INSTITUCIÓN / INSTITUTION:  - Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, nancylailai@gmail.com.

RESUMEN / SUMMARY:  - This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and immunohistochemically detected to evaluate the correlation of EMP-1 expression to the clinical features of NSCLC. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling.  Moreover, tumor xenografts were established by subcutaneous injection of PC9 cell suspension (about 5x10(7)/mL in 100 muL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in NSCLC patients as compared with those with benign lung diseases. Over-expression  of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in  athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of NSCLC by activating PI3K/AKT pathway.

 

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[655]

TÍTULO / TITLE:  - Challenges of lung cancer management in a developing country.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Niger J Med. 2012 Apr-Jun;21(2):214-7.

AUTORES / AUTHORS:  - Ezemba N; Ekpe EE; Eze JC

INSTITUCIÓN / INSTITUTION:  - Division of Cardiothoracic Surgery, Department of Surgery, University of Nigeria  Teaching Hospital, Enugu. ndubueze.ezemba@unn.edu.ng

RESUMEN / SUMMARY:  - BACKGROUND: The investigation of pulmonary neoplasm in Nigeria is hampered by lack of investigative tools and religio-cultural beliefs that detest autopsy. However, recent publications seem to suggest an increasing incidence of this lesion in Nigeria. MATERIALS AND METHODS: A 30-month prospective study of all cases of lung cancer seen at a tertiary health institution in Nigeria was done to document the incidence and challenges of management in the region. RESULTS: Fifty one new cases of primary carcinoma of the lung were identified during the study period. The age ranged from 30-81 years, mean 56.6 +/- 21.6 years and male:female ratio of 2.4:1. The age-standardized incidence rate was 7.9 per 100.000 with a peak in the 60-69 year age group. In 42% of the males there was cigarette smoking history. Adenocarcinoma of the lung was the predominant histologic subtype, and treatment was largely palliative. CONCLUSION: The incidence of lung cancer in South East Nigeria is on the increase even in the absence of state-of-the-art diagnostic modalities. The high prevalence of cigarette smoking amongst the males is a call for the intensification of the preventive measures against tobacco use.

 

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[656]

TÍTULO / TITLE:  - Lentivirus-mediated shRNA interference targeting SLUG inhibits lung cancer growth and metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):4947-51.

AUTORES / AUTHORS:  - Wang YP; Wang MZ; Luo YR; Shen Y; Wei ZX

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. METHODS: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the  SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. RESULTS: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. CONCLUSION: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

 

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[657]

TÍTULO / TITLE:  - Synergistic effect of olaparib with combination of cisplatin on PTEN deficient lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0401

AUTORES / AUTHORS:  - Minami D; Takigawa N; Takeda H; Takata M; Ochi N; Ichihara E; Hisamoto A; Hotta K; Tanimoto M; Kiura K

INSTITUCIÓN / INSTITUTION:  - Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.

RESUMEN / SUMMARY:  - Poly (ADP-ribose) polymerase (PARP) enzyme plays a key role in the cellular machinery responsible for DNA damage repair. PTEN is a tumor-suppressor gene deactivating PI3K downstream of EGFR signaling. We hypothesize that PTEN deficient lung cancer cells suppressed DNA damage signaling and that the absence  of PTEN can sensitize these cells to a concurrent treatment of a DNA-damaging agent (cisplatin) and a PARP inhibitor (olaparib). To investigate the effect of olaparib and cisplatin on PTEN deficient lung tumors, two EGFR mutant (deletion in exon19) NSCLC cell lines, PC-9 (PTEN wild type) and H1650 (PTEN loss) were used. We transfected intact PTEN gene into H1650 cells (H1650(PTEN+)) and knocked down PTEN expression in the PC-9 cells (PC-9(PTEN-)) using shRNA. Combination of  cisplatin with olaparib showed a synergistic effect in vitro according to the combination index in H1650 cells. Restoration of PTEN in the H1650 cells decreased sensitivity to the combination. Ablation of PTEN in PC-9 cells increased sensitivity to olaparib and cisplatin. We also examined the effectiveness of cisplatin and olaparib in a xenograft model using H1650 and PC-9(PTEN-) cells. The combination of cisplatin with olaparib was more effective  than each agent individually. This effect was not observed in a xenograft model using H1650(PTEN+) and PC-9 cells. Mechanistic investigations revealed that PTEN-deficiency caused reductions in nuclear RAD51 and RPA focus formation, phosphorylated Chk1 and Mre11. Thus, genetic inactivation of PTEN led to suppression of DNA repair.

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[658]

TÍTULO / TITLE:  - Circulating tumor cells as lung cancer biomarkers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):631-4. doi: 10.3978/j.issn.2072-1439.2012.10.05.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.05

AUTORES / AUTHORS:  - Wong MP

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The University of Hong Kong, Hong Kong.

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[659]

TÍTULO / TITLE:  - Alveolar Type II Cells Possess the Capability of Initiating Lung Tumor Development.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e53817. doi: 10.1371/journal.pone.0053817. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053817

AUTORES / AUTHORS:  - Lin C; Song H; Huang C; Yao E; Gacayan R; Xu SM; Chuang PT

INSTITUCIÓN / INSTITUTION:  - Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.

RESUMEN / SUMMARY:  - Identifying cells of tumor origin is a fundamental question in tumor biology. Answers to this central question will not only advance our understanding of tumor initiation and progression but also have important therapeutic implications. In this study, we aimed to uncover the cells of origin of lung adenocarcinoma, a major subtype of non-small cell lung cancer. To this end, we developed new mouse  models of lung adenocarcinoma that enabled selective manipulation of gene activity in surfactant associated protein C (SPC)-expressing cells, including alveolar type II cells and bronchioalveolar stem cells (BASCs) that reside at the bronchioalveolar duct junction (BADJ). Our findings showed that activation of oncogenic Kras alone or in combination with the removal of the tumor suppressor p53 in SPC(+) cells resulted in development of alveolar tumors. Similarly, sustained EGF signaling in SPC(+) cells led to alveolar tumors. By contrast, BASCs failed to proliferate or produce tumors under these conditions. Importantly, in a mouse strain in which Kras/p53 activity was selectively altered in type II cells but not BASCs, alveolar tumors developed while BADJs retained normal architecture. These results confirm and extend previous findings and support a model in which lung adenocarcinoma can initiate in alveolar type II cells. Our results establish the foundation for elucidating the molecular mechanisms by which lung cancer initiates and progresses in a specific lung cell  type.

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[660]

TÍTULO / TITLE:  - Sorafenib combined with gemcitabine in EGFR-TKI-resistant human lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):68-72. Epub 2012 Oct 9.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.958

AUTORES / AUTHORS:  - Li J; Pan YY; Zhang Y

INSTITUCIÓN / INSTITUTION:  - Department of Geriatrics, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061;

RESUMEN / SUMMARY:  - Sorafenib is a multi-targeted agent and has been reported to have potent antitumor effects against various types of tumors, including human non-small cell lung cancer (NSCLC). In this study, we explored in vitro the antitumor effects of sorafenib alone and in combination with gemcitabine in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant human lung cancer cell lines and the related molecular mechanisms. The NSCLC cell lines A549 (mutant KRAS), H1666 (mutant BRAF) and H1975 (mutant EGFR-T790M) were treated with sorafenib and gemcitabine alone and in combination. The cytotoxicity was assessed by MTT assay, cell cycle distribution was analyzed by flow cytometry, and alterations in signaling pathways were analyzed by western blotting. We found that sorafenib exhibited dose-dependent growth inhibition in all three EGFR-TKI-resistant NSCLC cell lines. When sorafenib was combined with gemcitabine, synergistic activity was observed in the A549 and H1666 cells and antagonistic activity was observed in the H1975 cells. Sorafenib arrested the cell cycle at the G1 phase, whereas gemcitabine arrested the cell cycle at the S  phase. Sorafenib inhibited C-RAF and p-ERK in the A549 cells and B-RAF and p-ERK  in the H1666 and H1975 cells. The molecular mechanism of this synergism is that RAF/MEK/ERK which are activated by gemcitabine are efficiently suppressed by simultaneously administered sorafenib. By contrast, the mechanism of antagonism may be due to mutual interference with the cell cycle in the H1975 cells. In conclusion, we found that sorafenib exhibits antiproliferative effects in EGFR-TKI-resistant NSCLC cell lines and when combined with gemcitabine demonstrates synergistic activity in A549 and H1666 cells but antagonistic activity in H1975 cells.

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[661]

TÍTULO / TITLE:  - Multiscale in situ analysis of the role of dyskerin in lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Integr Biol (Camb). 2013 Jan 28;5(2):402-13. doi: 10.1039/c2ib20219k.

            ●● Enlace al texto completo (gratuito o de pago) 1039/c2ib20219k

AUTORES / AUTHORS:  - Fernandez-Garcia I; Marcos T; Munoz-Barrutia A; Serrano D; Pio R; Montuenga LM; Ortiz-de-Solorzano C

INSTITUCIÓN / INSTITUTION:  - Oncology Division, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, Pamplona, 31008, España. lmontuenga@unav.es.

RESUMEN / SUMMARY:  - Dyskerin is one of the three subunits of the telomerase ribonucleoprotein (RNP) complex. Very little is known about the role of dyskerin in the biology of the telomeres in cancer cells. In this study, we use a quantitative, multiscale 3D image-based in situ method and several molecular techniques to show that dyskerin is overexpressed in lung cancer cell lines. Furthermore, we show that dyskerin expression correlates with telomere length both at the cell population level - cells with higher dyskerin expression have short telomeres - and at the single cell level - the shortest telomeres of the cell are spatially associated with areas of concentration of dyskerin proteins. Using this in vitro model, we also show that exogenous increase in dyskerin expression confers resistance to telomere shortening caused by a telomerase inactivating drug. Finally, we show that resistance is achieved by the recovery of telomerase activity associated with dyskerin. In summary, using a novel multiscale image-based in situ method, we show that, in lung cancer cell lines, dyskerin responds to continuous telomere attrition by increasing the telomerase RNP activity, which in turn provides resistance to telomere shortening.

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[662]

TÍTULO / TITLE:  - Dual Inhibition of PI3K/Akt/mTOR Pathway and Role of Autophagy in Non-Small Cell  Lung Cancer Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberc Respir Dis (Seoul). 2012 Apr;72(4):343-51. doi: 10.4046/trd.2012.72.4.343. Epub 2012 Apr 30.

            ●● Enlace al texto completo (gratuito o de pago) 4046/trd.2012.72.4.343

AUTORES / AUTHORS:  - Jeong EH; Choi HS; Lee TG; Kim HR; Kim CH

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.

RESUMEN / SUMMARY:  - BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer  treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. METHODS: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. RESULTS: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. CONCLUSION: Taken together, our results suggest that the combination of temsirolimus and GSK690693  could be a novel strategy for lung cancer therapy. Inhibition of autophagy could  also be a promising method of enhancing the combination effect of these drugs.

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[663]

TÍTULO / TITLE:  - Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Daru. 2012 Oct 30;20(1):69. doi: 10.1186/2008-2231-20-69.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2008-2231-20-69

AUTORES / AUTHORS:  - Khaghanzadeh N; Mojtahedi Z; Ramezani M; Erfani N; Ghaderi A

INSTITUCIÓN / INSTITUTION:  - Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran. mojtahediz@sums.ac.ir.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers’ attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. METHODS: The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed. RESULTS: Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 +/- 5.3 muM and 52 +/- 1.97 muM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 muM and less concentrations of umbelliprenin, no suppressive effect was observed. CONCLUSIONS: We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

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[664]

TÍTULO / TITLE:  - Multipotent cancer stem cells derived from human malignant peritoneal mesothelioma promote tumorigenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52825. doi: 10.1371/journal.pone.0052825. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052825

AUTORES / AUTHORS:  - Varghese S; Whipple R; Martin SS; Alexander HR

INSTITUCIÓN / INSTITUTION:  - Division of General and Surgical Oncology, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

RESUMEN / SUMMARY:  - During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized  a CSC model for MPeM using stably expandable tumorigenic stem cells derived from  patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction  and the differentiating cells express lineage-specific markers such as TUBB3, an  early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARgamma and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived  from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression.

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[665]

TÍTULO / TITLE:  - Silencing of periostin inhibits nicotine-mediated tumor cell growth and epithelial-mesenchymal transition in lung cancer cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Report. 2013 Jan 9. doi: 10.3892/mmr.2013.1267.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1267

AUTORES / AUTHORS:  - Wu SQ; Lv YE; Lin BH; Luo LM; Lv SL; Bi AH; Jia YS

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang 310014, P.R. China.

RESUMEN / SUMMARY:  - Nicotine has been found to induce the proliferation of lung cancer cells through  tumor invasion and to confer resistance to apoptosis. Periostin is abnormally highly expressed in lung cancer and is correlated with angiogenesis, invasion and metastasis. Here, we investigated the roles of periostin in the lung cancer cell  proliferation, drug resistance, invasion and epithelial-mesenchymal transition (EMT) induced by nicotine. The periostin gene was silenced using small interfering RNA (siRNA) in A549 non-small cell lung cancer (NSCLC) cells. The cells were transfected with control or periostin siRNA plasmids. Periostin mRNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell proliferation was detected using the MTT assay and cell apoptosis  was detected by Annexin V-FITC and propidium iodide (PI) double staining. Tumor invasion was detected by the Boyden chamber invasion assay. Western blotting was  performed to detect the expression of the EMT marker Snail. Our results revealed  that stably periostin-silenced cells were acquired by G418 screening, and the periostin mRNA expression levels of which were decreased by nearly 80%. Periostin-silenced A549 cells exhibited reduced cell proliferation, elevated sensitivity to chemotherapy with cisplatin, decreased cell invasion and Snail expression (P<0.05). Nicotine upregulated the periostin protein levels in the A549 cells and this upregulation was not blocked by the generalized nicotinic acetylcholine receptor (nAChR) antagonist, hexamethonium. In conclusion, periostin is one of the targets regulated by nicotine in lung cancer cells and is involved in the cancer cell growth, drug resistance, invasion and EMT induced by  nicotine.

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[666]

TÍTULO / TITLE:  - Antimigratory Effects of the Methanol Extract from Momordica charantia on Human Lung Adenocarcinoma CL1 Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Evid Based Complement Alternat Med. 2012;2012:819632. doi: 10.1155/2012/819632. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/819632

AUTORES / AUTHORS:  - Hsu HY; Lin JH; Li CJ; Tsang SF; Tsai CH; Chyuan JH; Chiu SJ; Chuang SE

INSTITUCIÓN / INSTITUTION:  - Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan ; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.

RESUMEN / SUMMARY:  - Momordica charantia has been found to exhibit anticancer activity, in addition to its well-known therapeutic functions. We have demonstrated that the leaf extract  of Momordica charantia (MCME) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. In this study, a different  susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability, leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells. MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities. We  proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt, beta-catenin, and MMPs.

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[667]

TÍTULO / TITLE:  - Stat3 is a positive regulator of gap junctional intercellular communication in cultured, human lung carcinoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 18;12(1):605.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-605

AUTORES / AUTHORS:  - Geletu M; Arulanandam R; Greer S; Trotman-Grant A; Tomai E; Raptis L

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Neoplastic transformation of cultured cells by a number of  oncogenes such as src suppresses gap junctional, intercellular communication (GJIC); however, the role of Src and its effector Signal transducer and activator of transcription-3 (Stat3) upon GJIC in non small cell lung cancer (NSCLC) has not been defined. Immunohistochemical analysis revealed high Src activity in NSCLC biopsy samples compared to normal tissues. Here we explored the potential effect of Src and Stat3 upon GJIC, by assessing the levels of tyr418-phosphorylated Src and tyr705-phosphorylated Stat3, respectively, in a panel of NSCLC cell lines METHODS: Gap junctional communication was examined by electroporating the fluorescent dye Lucifer yellow into cells grown on a transparent electrode, followed by observation of the migration of the dye to the adjacent, non-electroporated cells under fluorescence illumination. RESULTS: An inverse relationship between Src activity levels and GJIC was noted; in five lines with high Src activity GJIC was absent, while two lines with extensive GJIC (QU-DB and SK-LuCi6) had low Src levels, similar to a non-transformed, immortalised lung epithelial cell line. Interestingly, examination of the mechanism indicated that Stat3 inhibition in any of the NSCLC lines expressing high endogenous Src activity levels, or in cells where Src was exogenously transduced, did not restore GJIC. On the contrary, Stat3 downregulation in immortalised lung epithelial cells or in the NSCLC lines displaying extensive GJIC actually suppressed junctional permeability. CONCLUSIONS: Our findings demonstrate that although Stat3 is generally growth promoting and in an activated form it can act as an oncogene, it is actually required for gap junctional communication both in nontransformed lung epithelial cells and in certain lung cancer lines that retain extensive GJIC.

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[668]

TÍTULO / TITLE:  - Radiotherapy for NSCLC: Review of conventional and new treatment techniques.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Public Health. 2012 Dec;5 Suppl 1:S45-9. doi: 10.1016/j.jiph.2012.09.002. Epub 2012 Nov 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jiph.2012.09.002

AUTORES / AUTHORS:  - Saadeddin A

INSTITUCIÓN / INSTITUTION:  - Riyadh Military Hospital, Riyadh, Saudi Arabia. Electronic address: dr.saadeddin@yahoo.com.

RESUMEN / SUMMARY:  - Radiotherapy is an essential modality in the management of lung cancer. It is used as a single modality or in combination with other modalities and aimed at cure or palliation. Recent advances in the simulation techniques or more precise  targeting of the tumor made radiotherapy more effective tool in the fight against lung cancer. Using PET scan and better gating for tumor motion are examples of these advances. This brief review will present summary of the role of radiotherapy in management of lung cancer.

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[669]

TÍTULO / TITLE:  - Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(11):e50253. doi: 10.1371/journal.pone.0050253. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050253

AUTORES / AUTHORS:  - Dalby AR; Emam I; Franke R

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Biosciences, University of Westminster, New Cavendish Street, London, United Kingdom. A.Dalby@Westminster.ac.uk

RESUMEN / SUMMARY:  - Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC) can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process.  The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If  there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

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[670]

TÍTULO / TITLE:  - RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Med. 2012 Aug;1(1):68-75. doi: 10.1002/cam4.13. Epub 2012 Jul 12.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cam4.13

AUTORES / AUTHORS:  - Sasaki H; Shimizu S; Tani Y; Maekawa M; Okuda K; Yokota K; Shitara M; Hikosaka Y; Moriyama S; Yano M; Fujii Y

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Immunology, and Surgery, Nagoya City University Graduate  School of Medical Sciences Nagoya, Japan.

RESUMEN / SUMMARY:  - RET encodes the tyrosine kinase receptor of growth factors belonging to the glial-derived neurotrophic factor family. Recently, RET gene rearrangements with  N-terminal of KIF5B gene were identified in lung adenocarcinomas from large-scale sequencing. We investigated RET mRNA expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/beta actin mRNA levels were not significantly different between lung cancer (6.359 +/- 15.268) and adjacent normal lung tissues (8.205 +/- 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/beta actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/beta actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 +/- 123.488) than in wild-type samples (5.9013 +/- 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions  and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors.

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[671]

TÍTULO / TITLE:  - Wnt5a Is Associated with Cigarette Smoke-Related Lung Carcinogenesis via Protein  Kinase C.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53012. doi: 10.1371/journal.pone.0053012. Epub 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053012

AUTORES / AUTHORS:  - Whang YM; Jo U; Sung JS; Ju HJ; Kim HK; Park KH; Lee JW; Koh IS; Kim YH

INSTITUCIÓN / INSTITUTION:  - Department of Oncology/Hematology and Brain Korea 21 Project for Biomedical Science, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a  and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate  (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of  Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.

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[672]

TÍTULO / TITLE:  - Treatment Monitoring Program for Implementation of Adherence to Second-Line Erlotinib for Advanced Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 9. pii: S1525-7304(12)00262-8. doi: 10.1016/j.cllc.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.007

AUTORES / AUTHORS:  - Gebbia V; Bellavia M; Banna GL; Russo P; Ferrau F; Tralongo P; Borsellino N

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Unit, La Maddalena Clinic for Cancer, University of Palermo, Palermo, Italy.

RESUMEN / SUMMARY:  - BACKGROUND: Adherence to erlotinib could be a determinant for clinical outcome and treatment toxicity in patients with advanced non-small-cell lung cancer (A-NSCLC). PATIENTS AND METHODS: In an observational study, the Basel Assessment  of Adherence Scale (BAAS), a visual analogue scale (VAS), pill counting, and missed appointment rate were used to evaluate adherence in a first cohort of patients who was prescribed erlotinib without a specifically designed management  strategy and in a second cohort of patients followed by an oral treatment monitoring program. RESULTS: Adherence > 95% by BAAS at 2 months of treatment in  the first and second cohorts was 72% and 84%, respectively (P = .042). Adherence  by pill counting was 78% and 87% in the first and second cohorts, respectively (P = .0021). Disease control rate (DCR) (complete response [CR] + partial response [PR] + stable disease [SD]) was significantly higher in all patients whose adherence by BAAS at 2 months was >/= 95% (P = .0266). DCR was higher in the second cohort compared with the first, being 63% (95% confidence interval [CI], 53%-72%) and 44% (95% CI, 30%-58%) in the second and the first cohort, respectively (P = .0368). A significant correlation between the number of adverse events and patient-reported adherence was observed (r = 0.105; P = .0001). CONCLUSION: Nonadherence may be related to poorer rates of response to erlotinib. Effective interventions to reduce nonadherence need to be implemented.

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[673]

TÍTULO / TITLE:  - Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Epigenetics. 2013 Jan 1;8(1):54-65. doi: 10.4161/epi.23078. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 4161/epi.23078

AUTORES / AUTHORS:  - Singh T; Prasad R; Katiyar SK

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology; University of Alabama at Birmingham; Birmingham, AL USA.

RESUMEN / SUMMARY:  - Non-small-cell lung cancer (NSCLC) represents approximately 80% of all types of lung cancer. Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia grandiflora, on NSCLC cells and the molecular mechanisms underlying these effects using in vitro and in vivo models. Treatment  of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 microM)  inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent manner. These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells. Concomitant treatment of cells with a proteasome inhibitor, MG132, prevented honokiol-induced degradation of class I HDACs, suggesting that honokiol reduced the levels of HDACs in NSCLC cells through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of NSCLC cells. Treatment of A549 and H1299 cells with honokiol resulted in an increase in G 1 phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent  kinases. Further, administration of honokiol by oral gavage significantly inhibited the growth of subcutaneous A549 and H1299 tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death and marked inhibition of class I HDACs proteins and HDAC activity in the tumor xenograft tissues. Together, our study provides new insights into the role of class I HDACs in the chemotherapeutic effects of honokiol on lung cancer cells.

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[674]

TÍTULO / TITLE:  - Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy in Resected Advanced Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 4. pii: S1525-7304(12)00260-4. doi: 10.1016/j.cllc.2012.10.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.008

AUTORES / AUTHORS:  - Sun HB; Ou W; Li Y; Fang Q; Qin J; Zhang L; Wang SY

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

RESUMEN / SUMMARY:  - INTRODUCTION: This study was to assess the association of epidermal growth factor receptor (EGFR) mutation status and efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Tumor samples (n = 150) from patients with IIIA-N2 NSCLC who either had  or had not received paclitaxel plus carboplatin or vinorelbine plus carboplatin doublet adjuvant chemotherapy were analyzed for EGFR mutations. The association of the presence of EGFR mutations and survival was assessed. RESULTS: Mutations were identified in 43 (28.7%) patients (n = 25 in the no chemotherapy [observation] arm and n = 18 in the chemotherapy arm). Patients with EGFR mutations had statistically significant improved disease-free survival (41 months [95% CI, 25.1-56.9 months] vs. 20 months [95% CI, 15.0-25.0 months]; 2P = .005) and overall survival (50 months [95% CI, 37.6-62.4 months] vs. 25 months [95% CI, 20.8-29.2 months]; 2P = .001), regardless of treatment. The patients with wild-type EGFR had greater overall survival with chemotherapy compared with no adjuvant therapy (hazard ratio [HR] 4.748 [95% CI, 2.844-7.928]; 2P < .001). In contrast, in patients with EGFR mutation in the observation group compared with the chemotherapy group had longer median disease-free survival (49 months [95% CI, 35.1-62.9 months] for the observation arm vs. 30 months [95% CI, 23.8-36.2 months] for the chemotherapy arm, 2P = .195) and overall survival (59 months [95% CI, 43.9-74.1 months] vs. 33 months [95% CI, 24.7-41.3 months]; 2P = .050). CONCLUSIONS: In this exploratory study, the status of EGFR mutations was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC. Further studies are required to confirm that a patient’s adjuvant treatment may be customized to their EGFR mutational status.

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[675]

TÍTULO / TITLE:  - Transducer of erbB2.1 is a potential cellular target of gefitinib in lung cancer  therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):373-377. Epub 2012 Oct 15.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.969

AUTORES / AUTHORS:  - Sun KK; Yang Y; Zhao L; Wang LL; Jiao Y

INSTITUCIÓN / INSTITUTION:  - Department of Gastrointestinal Surgery Division of Thoracic Surgery, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300; ; Key Laboratory of Radiation Biology, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.

RESUMEN / SUMMARY:  - Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines. Thorough understanding of the downstream cellular signaling of gefitinib will facilitate the discovery of biomarkers for predicting outcomes and monitoring anti-EGFR therapies, and provide information for key targets for therapeutic intervention. In this study,  we investigated the role of transducer of erbB2.1 (TOB1) in gefitinib therapy. Using the lung carcinoma cell lines A549 and NCI-H1975, the results suggested that gefitinib might mediate cell cycle arrest in lung cancer cells at least by targeting TOB1 expression. Gefitinib treatment caused cell cycle arrest predominantly at the G1 phase, which is associated with TOB1 nuclear translocation and its interaction with cyclin D1. We also showed that knockdown of TOB1 expression by RNAi rescued lung cancer cells from gefitinib-induced cell-proliferative arrest. These results suggest that TOB1 interaction with cyclin D1 and nuclear translocation is directly involved in the gefitinib-induced anti-proliferative cell cycle arrest.

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[676]

TÍTULO / TITLE:  - Early palliative care and metastatic non-small cell lung cancer: Potential mechanisms of prolonged survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chron Respir Dis. 2013;10(1):35-47. doi: 10.1177/1479972312471549.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1479972312471549

AUTORES / AUTHORS:  - Irwin KE; Greer JA; Khatib J; Temel JS; Pirl WF

INSTITUCIÓN / INSTITUTION:  - 1Massachusetts General Hospital Cancer Center, Boston, MA, USA.

RESUMEN / SUMMARY:  - Patients with advanced cancer experience a significant burden of physical symptoms and psychological distress at the end of life, and many elect to receive aggressive cancer-directed therapy. The goal of palliative care is to relieve suffering and promote quality of life (QOL) for patients and families. Traditionally, both the public and medical community have conceptualized the need for patients to make a choice between pursuing curative therapy or receiving palliative care. However, practice guidelines from the World Health Organization  and leadership from the oncology and palliative care communities advocate a different model of palliative care that is introduced from the point of diagnosis of life-threatening illness. Early palliative care has been shown to provide benefits in QOL, mood, and health care utilization. Additionally, preliminary research has suggested that in contrast to fears about palliative care hastening  death, referral to palliative care earlier in the course of illness may have the  potential to lengthen survival, particularly in patients with advanced nonsmall-cell lung cancer. This review summarizes the literature on potential survival benefits of palliative care and presents a model of how early integrated palliative care could potentially influence survival in patients with advanced cancer.

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[677]

TÍTULO / TITLE:  - Targeted therapies: Progress for KRAS mutant NSCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Clin Oncol. 2013 Feb;10(2):66. doi: 10.1038/nrclinonc.2012.233. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2012.233

AUTORES / AUTHORS:  - Hutchinson L

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[678]

TÍTULO / TITLE:  - A case of locally advanced breast cancer complicated by pulmonary tumor thrombotic microangiopathy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

            ●● Enlace a la Editora de la Revista http://cancerres.aacrjournals.org/ 

            ●● Cita: Cancer Research: <> Treat. 2012 Dec;44(4):267-70. doi: 10.4143/crt.2012.44.4.267. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4143/crt.2012.44.4.267

AUTORES / AUTHORS:  - Kim HJ; Kwak MH; Kong SY; Seong MW; Kang HS; Lee KS; Ro J

INSTITUCIÓN / INSTITUTION:  - Department of Cardiology, National Cancer Center, Goyang, Korea.

RESUMEN / SUMMARY:  - Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and  death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings.

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[679]

TÍTULO / TITLE:  - Years of sorafenib investigation in advanced non-small cell lung cancer: is there a ‘NExUS’ linking an unsuccessful treatment and a potentially active one?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):635-8. doi: 10.3978/j.issn.2072-1439.2012.10.06.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.06

AUTORES / AUTHORS:  - Metro G; Minotti V; Crino L

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, S. Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156 Perugia, Italy.

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[680]

TÍTULO / TITLE:  - Maintenance Treatment With Different Strategies in Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Dec 28. pii: S1525-7304(12)00264-1. doi: 10.1016/j.cllc.2012.10.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.010

AUTORES / AUTHORS:  - Cai H; Lin Y; Li W; Li X

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.

RESUMEN / SUMMARY:  - A meta-analysis of all relevant randomized controlled trials (RCTs) was performed to assess the role of maintenance therapy with either a continuation or a switch  strategy in the treatment of non-small-cell lung cancer and to investigate improvement in overall survival (OS) and progression-free survival (PFS). Depending on the tumor histologic type (squamous or nonsquamous), OS and PFS were also investigated. We used electronic databases to search for publications reporting RCTs comparing maintenance therapy and placebo or observation from January 1990 to March 2012. The primary endpoint of OS and the secondary endpoint of PFS were analyzed. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were derived. Eleven trials of 4790 patients were eligible for this analysis. A trend of improved OS was found in continuation maintenance therapy, despite a lack of statistical significance (HR 0.82; 95% CI, 0.66-1.01; P = .06). Improved OS with statistical significance was seen in switch maintenance therapy  (HR, 0.80; 95% CI, 0.72-0.90; P = .0002). PFS benefit was found with both continuation (HR, 0.54; 95% CI, 0.46-0.63; P < .00001) and switch maintenance therapy (HR, 0.64; 95% CI, 0.59-0.70; P < .00001). The squamous subgroup analysis demonstrated no statistically significant differences in either OS (HR, 0.91; 95% CI, 0.63-1.30; P = .60) or PFS (HR, 0.80; 95% CI, 0.58-1.10; P = .17), whereas the nonsquamous subgroup analysis revealed an improvement in both OS (HR, 0.78; 95% CI, 0.64-0.94; P = .009) and PFS (HR, 0.56; 95% CI, 0.50-0.63; P < .00001). Maintenance therapy was associated with higher drug-related grade 3 or greater toxic effects but without harming the patients’ quality of life. Maintenance therapy with either a continuation or a switch strategy significantly increased PFS but OS was significantly improved only with the switch strategy. Patients with a nonsquamous histologic subgroup seemed to be more suitable for maintenance therapy.

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[681]

TÍTULO / TITLE:  - New treatment trends in small cell carcinoma of the urinary bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J BUON. 2012 Oct-Dec;17(4):799-800.

AUTORES / AUTHORS:  - Sendur MA; Aksoy S; Yazici O; Akinci MB; Ozdemir NY; Zengin N

INSTITUCIÓN / INSTITUTION:  - Ankara Numune Education and Research Hospital, Department of Medi-cal Oncology, Ankara, Turkey.

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[682]

TÍTULO / TITLE:  - Review of the treatment of non-small cell lung cancer with gefitinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Med Insights Oncol. 2012;6:407-21. doi: 10.4137/CMO.S7340. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 4137/CMO.S7340

AUTORES / AUTHORS:  - Araki T; Yashima H; Shimizu K; Aomori T; Hashita T; Kaira K; Nakamura T; Yamamoto K

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan. ; Department of Pharmacy, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi 371-8511, Japan.

RESUMEN / SUMMARY:  - In the past decade, molecular-targeted drugs have been focused upon for the treatment of cancer. In 2002, gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor became available in Japan for the treatment of non-small cell lung cancer (NSCLC). Over 80% of selected patients, such as EGFR mutation-positive patients, respond to gefitinib treatment; however, most patients develop acquired resistance to gefitinib within a few years. Recently, many studies have been performed to determine precisely how to select patients who will respond to gefitinib, the best timing for its administration, and how to avoid the development of acquired resistance as well as adverse drug effects. This article reviews the use of gefitinib for the treatment of NSCLC from a pharmaceutical viewpoint.

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[683]

TÍTULO / TITLE:  - The efficacy of the inhalation of an aerosolized Group A streptococcal preparation in the treatment of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Dec;24(4):346-52. doi: 10.3978/j.issn.1000-9604.2012.10.08.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.10.08

AUTORES / AUTHORS:  - Liu J; Liu X; Cui F; Chen G; Guan Y; He J

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou  Medical College, Guangzhou, China; ; Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou, China;

RESUMEN / SUMMARY:  - OBJECTIVE: To observe the efficacy of the inhalation of an aerosolized group A streptococcal (GAS) preparation in treating orthotopic lung cancer in mouse models and assess the feasibility, safety, and effectiveness of this administration mode for lung cancer. METHODS: Lewis lung carcinoma (LLC) cell strains were administered via intrathoracic injection to establish orthotopic lung cancer mouse models. After the tumor-bearing models were successfully established, as confirmed by computed tomography, the mice were administered by inhalation with an aerosolized GAS preparation (GAS group) or aerosolized normal  saline (control group). The anti-tumor effect of the aerosolized GAS preparation  was evaluated histologically; meanwhile, the survival and quality of life were compared between these two groups. RESULTS: The aerosolized GAS preparation showed remarkably anti-tumor effect, causing the necrosis of the orthotopic lung  cancer cells in tumor-bearing mice. Furthermore, mice in the GAS group had significantly better quality of life and longer survival than those in control group. CONCLUSIONS: The inhalation of aerosolized GAS preparation may be a feasible, safe and effective solution for lung cancer.

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[684]

TÍTULO / TITLE:  - A dosimetric evaluation of VMAT for the treatment of non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Appl Clin Med Phys. 2012 Sep 1;14(1):4110. doi: 10.1120/jacmp.v14i1.4110.

AUTORES / AUTHORS:  - Merrow CE; Wang IZ; Podgorsak MB

INSTITUCIÓN / INSTITUTION:  - Roswell Park Cancer Institute. caitlin.doring@roswellpark.org.

RESUMEN / SUMMARY:  - The purpose of this study was to demonstrate the dosimetric potential of volumetric-modulated arc therapy (VMAT) for the treatment of patients with medically inoperable stage I/II non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT). Fourteen patients treated with 3D CRT with varying tumor locations, tumor sizes, and dose fractionation schemes were chosen for study. The prescription doses were 48 Gy in 4 fractions, 52.5 Gy in 5  fractions, 57.5 Gy in 5 fractions, and 60 Gy in 3 fractions for 2, 5, 1, and 6 patients, respectively. VMAT treatment plans with a mix of two to three full and  partial noncoplanar arcs with 5 degrees -25 degrees separations were retrospectively generated using Eclipse version 10.0. The 3D CRT and VMAT plans were then evaluated by comparing their target dose, critical structure dose, high dose spillage, and low dose spillage as defined according to RTOG 0813 and RTOG 0236 protocols. In the most dosimetrically improved case, VMAT was able to decrease the dose from 17.35 Gy to 1.54 Gy to the heart. The D2cm decreased in 11 of 14 cases when using VMAT. The three that worsened were still within the acceptance criteria. Of the 14 3D CRT plans, seven had a D2cm minor deviation, while only one of the 14 VMAT plans had a D2cm minor deviation. The R50% improved in 13 of the 14 VMAT cases. The one case that worsened was still within the acceptance criteria of the RTOG protocol. Of the 14 3D CRT plans, seven had an R50% deviation. Only one of the 14 VMAT plans had an R50% deviation, but it was still improved compared to the 3D CRT plan. In this cohort of patients, no evident dosimetric compromises resulted from planning SBRT treatments with VMAT relative to the 3D CRT treatment plans actually used in their treatment.

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[685]

TÍTULO / TITLE:  - Pleurectomy decortication in the treatment of the “trapped lung” in benign and malignant pleural effusions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Surg Clin. 2013 Feb;23(1):51-61, vi. doi: 10.1016/j.thorsurg.2012.10.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.thorsurg.2012.10.007

AUTORES / AUTHORS:  - Rathinam S; Waller DA

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Glenfield Hospital, University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK. srathinam@rcsed.ac.uk

RESUMEN / SUMMARY:  - Trapped lung is defined by the inability of the lung to expand and fill the thoracic cavity because of a restricting “peel.” This restriction may be secondary to a benign inflammatory or fibrotic cortex or to a malignant visceral  pleural tumor. This condition has a significant impact on the patient’s quality of life by causing dyspnea. This article discusses the role of surgery in relieving the trapped lung, including decortication in benign disease and pleurectomy in malignant disease. The surgical approaches of video-assisted thoracoscopy and thoracotomy are contrasted and the future potential for surgical trials in this condition is outlined.

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[686]

TÍTULO / TITLE:  - Anti-angiogenic treatments in advanced NSCLC: back to the drawing board.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):643-6. doi: 10.3978/j.issn.2072-1439.2012.10.11.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.11

AUTORES / AUTHORS:  - Bar J; Shiran I; Urban D; Agbarya A; Onn A

INSTITUCIÓN / INSTITUTION:  - Institute of Oncology Chaim Sheba Medical Center, Israel;

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[687]

TÍTULO / TITLE:  - Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e44591. doi: 10.1371/journal.pone.0044591. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0044591

AUTORES / AUTHORS:  - Bulk E; Yu J; Hascher A; Koschmieder S; Wiewrodt R; Krug U; Timmermann B; Marra A; Hillejan L; Wiebe K; Berdel WE; Schwab A; Muller-Tidow C

INSTITUCIÓN / INSTITUTION:  - Department of Medicine A - Hematology, Oncology, Pneumology, University of Muenster, Muenster, Germany.

RESUMEN / SUMMARY:  - Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we sequenced the entire coding region of EPHB6 in 80 non-small cell lung cancer patients and 3 tumor cell lines. Three potentially relevant mutations were identified in primary patient samples of NSCLC patients (3.8%). Two point mutations led to instable proteins. An in frame deletion mutation (del915-917) showed enhanced migration and accelerated wound healing in vitro. Furthermore, the del915-917 mutation increased the metastatic capability of NSCLC cells in an in vivo mouse model. Our results suggest that EPHB6 mutations promote metastasis in a subset of patients with non-small cell lung cancer.

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[688]

TÍTULO / TITLE:  - The Blocking of c-Met Signaling Induces Apoptosis through the Increase of p53 Protein in Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

            ●● Enlace a la Editora de la Revista http://cancerres.aacrjournals.org/ 

            ●● Cita: Cancer Research: <> Treat. 2012 Dec;44(4):251-61. doi: 10.4143/crt.2012.44.4.251. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4143/crt.2012.44.4.251

AUTORES / AUTHORS:  - Jung HY; Joo HJ; Park JK; Kim YH

INSTITUCIÓN / INSTITUTION:  - Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer. MATERIALS AND METHODS: The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry. RESULTS: SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein. CONCLUSION: Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity  to SU11274 in lung cancer.

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[689]

TÍTULO / TITLE:  - Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Dec;4(6):1010-1016. Epub 2012 Sep 28.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.730

AUTORES / AUTHORS:  - Hu Q; Li X; Su C; Chen X; Gao G; Zhang J; Zhao Y; Li J; Zhou C

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine;

RESUMEN / SUMMARY:  - One of the target genes of pemetrexed (PEM), thymidylate synthase (TS), has been  shown to have a close association with its efficacy. TS gene polymorphisms have been shown to be associated with the efficacy of antifolate treatment in enteron  tumors. The purpose of this study was to investigate the clinical significance of TS gene polymorphisms in patients with advanced NSCLC receiving PEM-based treatment. The variable nucleoid tandem repeat in the 5’-UTR region was amplified and detected using fluorescently labeled multiplex short tandem repeat polymerase chain reaction. The polymorphism in the 3’-UTR region of the TS gene was detected using the Taqman probe. Efficacy of PEM was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. None of the genotypes were associated with gender, smoking status and age. Disease control rate (DCR), objective response rate (ORR) and progression-free survival (PFS) were similar between patients harboring 2R and 3R alleles (PFS, p=0.518; DCR, p=0.631; ORR, p=0.541), as well as those with a 6-bp insertion and 6-bp deletion (PFS, p=0.776; DCR, p=0.626; ORR, p=0.330). To study the combined effect of TS polymorphisms, the study population was divided into three groups: 2R&6 del, 2R&6 ins and 3R&6 del. No significant differences were observed among the different groups according to DCR (p=0.517), ORR (p=0.611) and PFS (p=0.938). In conclusion, polymorphisms of the TS gene do not appear to be a prognostic marker for advanced NSCLC patients receiving PEM-based treatment.

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[690]

TÍTULO / TITLE:  - 3D lung tumor motion model extraction from 2D projection images of mega-voltage cone beam CT via optimal graph search.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 1):239-46.

AUTORES / AUTHORS:  - Chen M; Bai J; Zheng Y; Siochi RA

INSTITUCIÓN / INSTITUTION:  - Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA. mingqing-chen@uiowa.com

RESUMEN / SUMMARY:  - In this paper, we propose a novel method to convert segmentation of objects with  quasi-periodic motion in 2D rotational cone beam projection images into an optimal 3D multiple interrelated surface detection problem, which can be solved by a graph search framework. The method is tested on lung tumor segmentation in projection images of mega-voltage cone beam CT (MVCBCT). A 4D directed graph is constructed based on an initialized tumor mesh model, where the cost value for this graph is computed from the point location of a silhouette outline of projected tumor mesh in 2D projection images. The method was first evaluated on four different sized phantom inserts (all above 1.9 cm in diameter) with a predefined motion of 3.0 cm to mimic the imaging of lung tumors. A dice coefficient of 0.87 +/- 0.03 and a centroid error of 1.94 +/- 1.31 mm were obtained. Results based on 12 MVCBCT scans from 3 patients obtained 0.91 +/- 0.03 for dice coefficient and 1.83 +/- 1.31 mm for centroid error, compared with a difference between two sets of independent manual contours of 0.89 +/- 0.03 and 1.61 +/- 1.19 mm, respectively.

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[691]

TÍTULO / TITLE:  - Targeted therapies in small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):3-11. Epub 2012 Jul 6.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.791

AUTORES / AUTHORS:  - Lu HY; Wang XJ; Mao WM

INSTITUCIÓN / INSTITUTION:  - Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted drugs have less toxicity than chemotherapy drugs, but no targeted agents have been approved for use in the treatment of SCLC patients to date. Certain new targeted agents, including gefitinib, bevacizumab and Bcl-2 inhibitors, offer a promise of improved outcomes, however negative results are more commonly reported than positive. This review focuses on targeted therapies in SCLC.

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[692]

TÍTULO / TITLE:  - Targeting MDSCs enhance therapeutic vaccination responses against lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncoimmunology. 2012 Dec 1;1(9):1650-1651.

            ●● Enlace al texto completo (gratuito o de pago) 4161/onci.21970

AUTORES / AUTHORS:  - Srivastava MK; Dubinett S; Sharma S

INSTITUCIÓN / INSTITUTION:  - Department of Medicine; UCLA Lung Cancer Research Program; David Geffen School of Medicine; University of California at Los Angeles; Los Angeles, CA USA ; Molecular Gene Medicine Laboratory; Veterans Affairs Greater Los Angeles Healthcare System; Los Angeles, CA USA.

RESUMEN / SUMMARY:  - Myeloid-derived suppressor cells (MDSCs) are important regulators of immune responses. These cells suppress the cytotoxic activities of natural killer (NK)-cell and T-cell effectors and promote tumor growth. We demonstrated that depleting MDSCs improve therapeutic responses to vaccination in a murine model of lung cancer. This approach may prove beneficial against tumors in which MDSC exert prominent immunosuppressive effects.

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[693]

TÍTULO / TITLE:  - Lung adenocarcinoma in the era of targeted therapies: histological classification, sample prioritization, and predictive biomarkers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0983-z

AUTORES / AUTHORS:  - Conde E; Angulo B; Izquierdo E; Paz-Ares L; Belda-Iniesta C; Hidalgo M; Lopez-Rios F

INSTITUCIÓN / INSTITUTION:  - Laboratorio de Dianas Terapeuticas, Centro Integral Oncologico Clara Campal, Hospital Universitario Madrid Sanchinarro, Faculty of Medicine, Universidad San Pablo-CEU, Madrid, España.

RESUMEN / SUMMARY:  - The arrival of targeted therapies has presented both a conceptual and a practical challenge in the treatment of patients with advanced non-small cell lung carcinomas (NSCLCs). The relationship of these treatments with specific histologies and predictive biomarkers has made the handling of biopsies the key factor for success. In this study, we highlight the balance between precise histological diagnosis and the practice of conducting multiple predictive assays  simultaneously. This can only be achieved where there is a commitment to multidisciplinary working by the tumor board to ensure that a sensible protocol is applied. This proposal for prioritizing samples includes both recent technological advances and the some of the latest discoveries in the molecular classification of NSCLCs.

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[694]

TÍTULO / TITLE:  - ROS1-Targeted Therapy in Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Adv Hematol Oncol. 2012 Dec;10(12):827-8.

AUTORES / AUTHORS:  - Sequist LV

INSTITUCIÓN / INSTITUTION:  - Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts.

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[695]

TÍTULO / TITLE:  - Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J BUON. 2012 Oct-Dec;17(4):729-34.

AUTORES / AUTHORS:  - Wang H; Wu H; Cai K; Ju Q; Wang W

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, China.

RESUMEN / SUMMARY:  - Purpose: To investigate the prevalence of phosphatidylinositol 3-kinase (PIK3CA)  gene amplification in lung cancer, and to explore its prognostic value. Methods:  A total of 647 lung tumor samples from 290 patients were included in the study. The ratio of PIK3CA signals/centromere 3 signals in cancer cells was estimated by fluorescence in situ hybridization (FISH7rpar; analysis. Results: Both gains and  amplifications were significantly more frequent in squamous cell (gains: 19.4%; amplifications: 34.1%; p<0.0001) and large cell carcinoma (gains: 22.4%; amplifications: 20.4%; p<0.0001) compared with adenocarcinomas (gains 3.0%; amplifications: 4.0%). Conversely, adenocarcinomas displayed significantly more frequent deletions of the PIK3CA locus than the other two histologic types (p<0.0001). No clear correlation between PIK-3CA status and the pT stage, pN stage or the degree of tumor differentiation was found. Ki67 significantly increased with increasing of PIK3CA copy number: 47 tumors with a PIK-3CA deletion had a mean Ki67 of 16, while 103 tumors with PIK3CA amplification showed a mean Ki67 of 28 (p=0.004). Significant association between cell proliferation and PIK-3CA was found (p<0.05). However, no significant correlation was seen between patient survival and PIK3CA amplifications, deletions and gains. Conclusion: PIK3CA amplifications in large cell and squamous cell carcinomas were significantly higher compared with adenocarcinomas. The results suggest that PIK-3CA could be a promising target for selective lung cancer therapy.

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[696]

TÍTULO / TITLE:  - Dacomitinib, an emerging HER-targeted therapy for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):639-42. doi: 10.3978/j.issn.2072-1439.2012.10.09.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.09

AUTORES / AUTHORS:  - Carpenter RL; Lo HW

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Divisions of Surgical Sciences, Duke University School of  Medicine, Durham, NC 27710, USA.

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[697]

TÍTULO / TITLE:  - A 4D statistical shape model for automated segmentation of lungs with large tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 2):347-54.

AUTORES / AUTHORS:  - Wilms M; Ehrhardt J; Handels H

INSTITUCIÓN / INSTITUTION:  - Institute of Medical Informatics, University of Lubeck, Lubeck, Germany. wilms@imi.uni-luebeck.de

RESUMEN / SUMMARY:  - Segmentation of lungs with large tumors is a challenging and time-consuming task, especially for 4D CT data sets used in radiation therapy. Existing lung segmentation methods are ineffective in these cases, because they are either not  able to deal with large tumors and/or process every 3D image independently neglecting temporal information. In this paper, we present a approach for model-based 4D segmentation of lungs with large tumors in 4D CT data sets. In our approach, a 4D statistical shape model that accounts for inter- and intra-patient variability is fitted to the 4D image sequence, and the segmentation result is refined by a 4D graph-based optimal surface finding. The approach is evaluated using 10 4D CT data sets of lung tumor patients. The segmentation results are compared with a standard intensity-based approach and a 3D version of the presented model-based segmentation method. The intensity-based approach shows a better performance for normal lungs, however, fails in presence of large lung tumors. Although overall performance of 3D and 4D model-based segmentation is similar, the results indicate improved temporal coherence and improved robustness with respect to the segmentation parameters for the 4D model-based segmentation.

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[698]

TÍTULO / TITLE:  - A Clinical Review of Small-Cell Carcinoma of the Urinary Bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Genitourin Cancer. 2012 Dec 21. pii: S1558-7673(12)00235-2. doi: 10.1016/j.clgc.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clgc.2012.11.002

AUTORES / AUTHORS:  - Thota S; Kistangari G; Daw H; Spiro T

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Fairview Hospital, Cleveland Clinic Hospitals, Cleveland, OH. Electronic address: thotas@ccf.org.

RESUMEN / SUMMARY:  - Small-cell carcinoma of the urinary bladder is a rare and aggressive type of bladder cancer that has a poor prognosis. The incidence has been gradually increasing because of the aging population. Owing to its rarity there are no available treatment guidelines. Several retrospective studies and 1 prospective study have provided some insight into therapy for this disease. A multimodal approach that includes chemotherapy, local radiation therapy, and definitive surgery in resectable cases appears to be an optimal management approach.

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[699]

TÍTULO / TITLE:  - Statins use and female lung cancer risk in Taiwan.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Libyan J Med. 2012 Dec 27;7(0):1-3. doi: 10.3402/ljm.v7i0.20123.

AUTORES / AUTHORS:  - Lai SW; Liao KF; Lin CL; Sung FC; Cheng YH

INSTITUCIÓN / INSTITUTION:  - School of Medicine, China Medical University, Taichung, Taiwan; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.

RESUMEN / SUMMARY:  - In this present study, we found that the use of rosuvastatin with cumulative using duration >12 months could correlate with 2.8-fold increased risk of lung cancer in women. We did not have specific comments on these results. Further prospective clinical studies of statins use are needed to elucidate this issue.

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[700]

TÍTULO / TITLE:  - Thoracic abnormality detection with data adaptive structure estimation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 1):74-81.

AUTORES / AUTHORS:  - Song Y; Cai W; Zhou Y; Feng D

INSTITUCIÓN / INSTITUTION:  - Biomedical and Multimedia Information Technology Research Group, School of Information Technologies, University of Sydney, Australia.

RESUMEN / SUMMARY:  - Automatic detection of lung tumors and abnormal lymph nodes are useful in assisting lung cancer staging. This paper presents a novel detection method, by first identifying all abnormalities, then differentiating between lung tumors and abnormal lymph nodes based on their degree of overlap with the lung field and mediastinum. Regression-based appearance model and graph-based structure labeling are designed to estimate the actual lung field and mediastinum from the pathology-affected thoracic images adaptively. The proposed method is simple, effective and generalizable, and can be potentially applicable to other medical imaging domains as well. Promising results are demonstrated based on our evaluations on clinical PET-CT data sets from lung cancer patients.

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[701]

TÍTULO / TITLE:  - Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 28;12(1):624. doi: 10.1186/1471-2407-12-624.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-624

AUTORES / AUTHORS:  - Jala VR; Radde BN; Haribabu B; Klinge CM

INSTITUCIÓN / INSTITUTION:  - James Graham Brown Cancer Center, Department of Microbiology and Immunology, 505  South Hancock Street, Room 323, CTR Building, Louisville, KY 40202, USA. jvrao001@louisville.edu.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17beta-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant)  and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors alpha and beta (ERalpha and ERbeta), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. METHODS: The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western  blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. RESULTS: Analysis by real-time PCR and Western blotting revealed a significantly higher expression of  GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. CONCLUSION: The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression.

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[702]

TÍTULO / TITLE:  - Immunohistochemical expression of PAX5 and TdT by Merkel cell carcinoma and pulmonary small cell carcinoma: a potential diagnostic pitfall but useful discriminatory marker.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(2):142-7. Epub 2013 Jan 15.

AUTORES / AUTHORS:  - Kolhe R; Reid MD; Lee JR; Cohen C; Ramalingam P

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Georgia Health Sciences University Augusta, GA.

RESUMEN / SUMMARY:  - BACKGROUND: Merkel cell carcinoma is a high-grade neuroendocrine carcinoma of skin that is characterized by immature cells which, because of its striking morphologic similarity, may be confused with other small round blue cell tumors such as pulmonary small cell carcinoma or lymphoblastic leukemia/lymphoma. Immunohistochemistry is therefore paramount to ensuring accurate diagnostic distinction between these tumors. The aim of our study was to evaluate and compare the expression of PAX5 and Terminal deoxynucleotidyl transferase (TdT), in Merkel cell carcinoma and pulmonary small cell carcinoma. DESIGN: PAX5 and TdT immunohistochemical stains were performed on 27 Merkel cell carcinomas and 10 pulmonary small cell carcinomas. RESULTS: PAX5 was expressed in 24/27 (89%) Merkel cell carcinomas and 0/10 (0%) pulmonary small cell carcinomas. TdT was expressed in 21/27 (78%) Merkel cell carcinomas and 9/10 (90%) pulmonary small cell carcinomas. CONCLUSIONS: Our study confirms that PAX5 and TdT expression can be expressed in a high percentage of Merkel cell carcinomas and so when positive  are not diagnostic of lymphoblastic leukemia/lymphoma. When dealing with metastatic lesions, PAX5 negativity would favor a diagnosis of pulmonary small cell carcinoma over Merkel cell carcinoma. In addition, TTF-1 negative pulmonary  small cell carcinoma is to be differentiated from Merkel cell carcinoma.

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[703]

TÍTULO / TITLE:  - Comparison of different methods for detecting epidermal growth factor receptor mutations in peripheral blood and tumor tissue of non-small cell lung cancer as a predictor of response to gefitinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onco Targets Ther. 2012;5:439-47. doi: 10.2147/OTT.S37289. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S37289

AUTORES / AUTHORS:  - Xu F; Wu J; Xue C; Zhao Y; Jiang W; Lin L; Wu X; Lu Y; Bai H; Xu J; Zhu G; Zhang L

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Oncology in South China, Department of Medical Oncology,  Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of  China.

RESUMEN / SUMMARY:  - BACKGROUND: Previous studies have reported that epidermal growth factor receptor  (EGFR) mutation in tumor tissue and peripheral blood can predict the response to  EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC). However, the heterogeneity of the sample sources makes it difficult to evaluate the detecting methodologies. The goal of this study is to compare different methods for analyzing EGFR mutation in blood and tumor tissue. MATERIALS AND METHODS: Fifty-one advanced NSCLC patients treated with gefitinib were included in the study. The EGFR mutation status of each patients’ blood was analyzed by denaturing high-performance liquid chromatography (DHPLC), mutant-enriched liquidchip (ME-Liquidchip), and Scorpion Amplification Refractory Mutation System (Scorpion-ARMS) kits. EGFR mutation information in paired tumor samples detected  by Scorpion-ARMS served as a reference. Comparative analyses were performed on mutation status results obtained from different methods and on the association between the clinical outcome of TKI treatment and EGFR mutation status. RESULTS:  The response rate (RR) in the whole group was 33.3%. EGFR mutation rates were identified as 15.7%, 27.5%, and 29.4% by DHPLC, ME-Liquidchip, and Scorpion-ARMS  in blood, respectively. In 34 cases that had paired tumor samples, the mutation rate in tissue was 41.2%. The RRs of patients with mutation detected by different methods were 71.4% (tumor), 62.5% (blood, DHPLC), 50.0% (blood, ME-Liquidchip), and 66.7% (blood, Scorpion-ARMS). EGFR mutation detected by Scorpion-ARMS in blood and tumor tissues had better prediction of RR to EGFR-TKI (P = 0.002 and P  = 0.001) than mutation detected with DHPLC and ME-Liquidchip. CONCLUSION: Tumor tissue sample is the best source for EGFR mutation analysis in NSCLC patients. Peripheral blood samples may be used as an alternative source only in special conditions. Scorpion-ARMS, DHPLC, or ME-Liquidchip methods are all optional for detecting tumor EGFR mutation from blood.

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[704]

TÍTULO / TITLE:  - Improved PCR amplification for molecular analysis using DNA from long-term preserved formalin-fixed, paraffin-embedded lung cancer tissue specimens.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(1):76-9. Epub 2012 Nov 20.

AUTORES / AUTHORS:  - Taga M; Eguchi H; Shinohara T; Takahashi K; Ito R; Yasui W; Nakachi K; Kusunoki Y; Hamatani K

INSTITUCIÓN / INSTITUTION:  - Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. taga@rerf.or.jp

RESUMEN / SUMMARY:  - Archival tissue specimens are valuable resources of materials for molecular biological analyses in retrospective studies, especially for rare diseases or those associated with exposure to uncommon environmental events. Although successful amplification with PCR is essential for analysis of DNA extracted from archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens, we have often encountered problems with poor PCR amplification of target fragments. To overcome this, we examined whether heat treatment in alkaline solution could efficiently restore the PCR template activity of DNA that had already been extracted from FFPE lung cancer tissue specimens. The effect of the heat treatment was assessed  by PCR for the TP53 gene and other lung cancer-related gene loci. The heat treatment of DNA samples in borate buffer resulted in successful PCR amplification of DNA fragments ranging from 91 to 152 bp. This technique for restoration of template activity of DNA for PCR amplification is very simple and  economical, and requires no special apparatus, so it may be applicable for molecular analysis of DNA samples from FFPE tissue specimens at various laboratories.

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[705]

TÍTULO / TITLE:  - The epidemic status and risk factors of lung cancer in Xuanwei City, Yunnan Province, China.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Med. 2012 Dec;6(4):388-94. doi: 10.1007/s11684-012-0233-3. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11684-012-0233-3

AUTORES / AUTHORS:  - Xiao Y; Shao Y; Yu X; Zhou G

INSTITUCIÓN / INSTITUTION:  - Yunnan Center for Disease Control and Prevention, Kunming 650022, China. xyz6292@sina.com

RESUMEN / SUMMARY:  - Xuanwei City (formerly known as Xuanwei County) locates in the northeastern of Yunnan Province and is rich in coal, iron, copper and other mines, especially the smoky (bituminous) coal. Unfortunately, the lung cancer morbidity and mortality rates in this region are among China’s highest, with a clear upward trend from the mid-1970s to mid-2000s. In 2004-2005, the crude death rate of lung cancer was 91.3 per 100,000 in the whole Xuanwei City, while that for Laibin Town in this city was 241.14 per 100,000. The epidemiologic distribution (clustering patterns  by population, time, and space) of lung cancer in Xuanwei has some special features, e.g., high incidence in rural areas, high incidence in females, and an  early age peak in lung cancer deaths. The main factor that associates with a high rate of lung cancer incidence was found to be indoor air pollution caused by the  indoor burning of smoky coal. To a certain extent, genetic defects are also associated with the high incidence of lung cancer in Xuanwei. Taken together, lung cancer in this smoky coal combustion region is a unique model for environmental factor-related human cancer, and the current studies indicate that  abandoning the use of smoky coal is the key to diminish lung cancer morbidity and mortality.

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[706]

TÍTULO / TITLE:  - Data Analysis: Evaluation of nanoscale contrast agent enhanced CT scan to differentiate between benign and malignant lung cancer in mouse model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AMIA Annu Symp Proc. 2012;2012:27-35. Epub 2012 Nov 3.

AUTORES / AUTHORS:  - Bell RC; Rogith D; Johnson CW; Badea CT; Athreya KK; Espinosa G; Clark D; Ghafoori AP; Li Y; Kirsch DG; Annapragada A; Ghaghada K

INSTITUCIÓN / INSTITUTION:  - School of Biomedical Informatics, The University of Texas Health Sciences Center  at Houston, Houston, TX 77030 ; The Edward B. Singleton Department of Pediatric Radiology, Texas Children’s Hospital, Houston, TX 77030.

RESUMEN / SUMMARY:  - Proposed is a method for statistical analysis for a small sample size, repeated measure experiment with nesting factors. In the original experiment the Student t-test was used for analysis. Using the same data, we modeled the experiment into two groups of mice with benign and malignant primary lung tumors. 4 tumor nodules were selected from each mouse (N= 36). The dependent variables are the volume, diameter, and signal attenuation measured using computed tomography (CT). The measurements are made before injecting the contrast and at 0, 72, and 168 hours after injection. The contrast agent enhances tumor nodule volume and volume differences between benign and malignant tumor nodules measured across time (p <  0.05). The signal attenuation measured across time differentiates between benign  and malignant groups (p < 0.05). There is significant correlation between rate of change of volume and diameter of tumor. The advantages of this statistical method are discussed.

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[707]

TÍTULO / TITLE:  - What is the survival after surgery for localized malignant pleural mesothelioma?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs542

AUTORES / AUTHORS:  - Gelvez-Zapata SM; Gaffney D; Scarci M; Coonar AS

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Papworth Hospital NHS Foundation Trust, Papworth  Everard, Cambridge, UK.

RESUMEN / SUMMARY:  - A best evidence topic in thoracic surgery was written according to a structured protocol. This was with the purpose of assisting our management of patients with  localized malignant mesothelioma of the pleura (LMM). Although the terminology is used inconsistently, this variant has been formally defined by the WHO as a distinct entity defined as localized disease histologically identical to the diffuse form but without any evidence of pleural spread. Treatments for LMM include different combinations of surgery, chemotherapy and radiotherapy. There is an impression that LMM may have a better outcome than the commoner diffuse form of malignant mesothelioma that has been reported to have a survival between  8 and 14 months. In order to advise our patients on prognosis, we studied the duration of survival after surgical resection of LMM. A total of 150 papers were  found, of which 16 represented the best evidence to answer the question. The authors, journal, date, country of publication, study type, relevant outcomes and results of these papers are tabulated. It is difficult to combine the results of  these 16 papers because both treatments and results are reported differently. Some report median survival (range: 11.6-36 months) and others disease-free survival (range: 0 months to 11 years). Median survival to the longest follow-up  was 29 months when calculated by pooling data from informative papers using the Kaplan-Meier method. Our review suggests that survival in LMM is longer than that generally quoted for the more common diffuse form of malignant mesothelioma. Hence, aggressive treatment of LMM may be reasonable in appropriate patients.

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[708]

TÍTULO / TITLE:  - Pleural tuberculosis following lung cancer chemotherapy: a report of two cases proven pathologically by pleural biopsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 22;2013. pii: bcr2012008196. doi: 10.1136/bcr-2012-008196.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008196

AUTORES / AUTHORS:  - Madan K; Singh N; Das A; Behera D

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

RESUMEN / SUMMARY:  - Malignancy per se and cytotoxic chemotherapy given for its treatment both are recognised risk factors for the development of tuberculosis (TB). However, individual case descriptions of pleural tuberculosis (TB-PE) following chemotherapy for lung cancer (LC) have not been published previously. We herein report the first two cases of histopathologically proven TB-PE following LC chemotherapy. The first patient was a 38-year-old man with stage IV non-small cell LC (adenocarcinoma) who developed TB-PE following four cycles of chemotherapy (pemetrexed-cisplatin). The second patient was a 49-year-old man with extensive disease small cell LC who developed TB-PE after six cycles of chemotherapy (irinotecan-cisplatin). In both patients, diagnosis of TB-PE was established by demonstration of granulomatous inflammation, caseous necrosis and  positive stain for acid-fast bacilli in pleural biopsy specimens. Both cases responded to standard four-drug antitubercular therapy. These cases highlight the importance of carrying out an extensive evaluation for exudative pleural effusions in LC patients receiving chemotherapy, especially in countries with high TB prevalence. Attributing such pleural effusions to disease progression, without histopathological confirmation, may be associated with disastrous consequences.

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[709]

TÍTULO / TITLE:  - Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biomark. 2012 Jan 1;12(1):11-9. doi: 10.3233/CBM-2012-00280.

            ●● Enlace al texto completo (gratuito o de pago) 3233/CBM-2012-00280

AUTORES / AUTHORS:  - Tang X; Yin X; Xiang T; Li H; Li F; Chen L; Ren G

INSTITUCIÓN / INSTITUTION:  - Department of respiratory disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

RESUMEN / SUMMARY:  - Purpose: Protocadherin 10 (PCDH10), a homophilic cell adhesion member of the protocadherin family, plays important roles in calcium-dependent cell-cell adhesion and signal transduction. PCDH10 expression is downregulated in a number  of different malignances, predominantly through promoter methylation-driven silencing. This study was designed to investigate PCDH10 expression and promoter  methylation status in non-small cell lung cancer (NSCLC), and biological effects  of PCDH10 in lung cancer cells.Methods: The mRNA levels and promoter methylation  status of PCDH10 were examined by RT-PCR and methylation-specific PCR (MSP) in lung cancer cell lines as well as primary lung tissue samples, and the clinical correlation of PCDH10 promoter methylation in NSCLC was further analyzed. The effects of PCDH10 re-expression in lung cancer cell lines was determined by cell  proliferation, colony formation, and wound healing assays. Results: PCDH10 expression was downregulated or silenced in 4/8 lung cancer cell lines but could  be restored by treatment with 5-aza-2’-deoxycytidine and trichostatin A. PCDH10 was also downregulated in NSCLC tissues compared to their corresponding adjacent  tissues. Promoter methylation of PCDH10 was observed in 50% (20/40) of the NSCLC  tissues but not in tumor-adjacent or normal tissues, and PCDH10 promoter methylation was statistically related to smoking. Ectopic expression of PCDH10 in silenced cells can reduce lung cancer cell proliferation and migration. Conclusion: PCDH10 is frequently downregulated by promoter methylation and may serve as a tumor suppressor gene (TSG) in NSCLC.

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[710]

TÍTULO / TITLE:  - Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Biochim Biophys Sin (Shanghai). 2013 Feb;45(2):115-22. doi: 10.1093/abbs/gms113.

            ●● Enlace al texto completo (gratuito o de pago) 1093/abbs/gms113

AUTORES / AUTHORS:  - Li S; Tian H; Yue W; Li L; Gao C; Si L; Li W; Hu W; Qi L; Lu M

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan 250012, China.

RESUMEN / SUMMARY:  - Metastasis-associated protein 1 (MTA1) high expression has been detected in a wide variety of human aggressive tumors and plays important roles in the malignant biological behaviors such as invasion, metastasis, and angiogenesis. However, the specific roles and mechanisms of MTA1 protein in regulating the malignant behaviors of non-small-cell lung cancer (NSCLC) cells still remain unclear. To elucidate the detailed functions of MTA1 protein, we down-regulated the MTA1 protein expression in NSCLC cell line by RNA interference (RNAi) in vitro, and found that down-regulation of MTA1 protein significantly inhibited the migration and invasion potentials of 95D cells. Further research revealed that down-regulation of MTA1 protein significantly decreased the activity of matrix metalloproteinase-9, which could be the mechanism responsible for the inhibition  of 95D cells migration and invasion. In addition, the tube formation assay demonstrated that the number of complete tubes induced by the conditioned medium  of MTA1-siRNA 95D cells was significantly smaller than that of 95D cells. These findings demonstrate that MTA1 protein plays important roles in regulating the migration, invasion, and angiogenesis potentials of 95D cells, suggesting that MTA1 protein down-regulation by RNAi might be a novel therapeutic approach to inhibit the progression of NSCLC.

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[711]

TÍTULO / TITLE:  - Integrative Proteomics and Tissue Microarray Profiling Indicate the Association between Overexpressed Serum Proteins and Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51748. doi: 10.1371/journal.pone.0051748. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051748

AUTORES / AUTHORS:  - Liu Y; Luo X; Hu H; Wang R; Sun Y; Zeng R; Chen H

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, China.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC) can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA) and Multiple reaction monitoring (MRM) assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum  proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG) and Leucine-rich alpha-2-glycoprotein (LRG1), two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.

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[712]

TÍTULO / TITLE:  - Using the Theory of Coevolution to predict protein- interactions in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer. 2012 Dec 14. doi: 10.5732/cjc.012.10100.

            ●● Enlace al texto completo (gratuito o de pago) 5732/cjc.012.10100

AUTORES / AUTHORS:  - Zhang M; Chan M; Tu W; He L; Lee C; He M

INSTITUCIÓN / INSTITUTION:  - Life Sciences School, Sun Yat-sen University, Guangzhou, Guangdong 510275, P.R. China lsshem@mail.sysu.edu.cn.

RESUMEN / SUMMARY:  - Systems biology has become an effective approach for understanding the molecular  mechanisms underlying the development of lung cancer. In this study, sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from NCBI databases. The Theory of Coevolution was then used to construct a protein-protein interaction (PPI) network of NSCLC. Adopting the reverse thinking approach, we analyzed the NSCLC proteins one at a time. Fifteen key proteins were identified and categorized into a special protein family F(K), which included CCND1, CDH1, CDKN2A, CSCL12, EGF, EGFR, FAS, FRAP1, MGMT, PARK2, PTEN, CACNA2D2, TUBB, SMARCA2, and WNT7A. Seven key nodes of the sub-network were identified, which included PARK2, WNT7A, SMARCA2, FRAP1, CDKN2A, CCND1, and EGFR. The PPI predictions of EGFR-EGF, PARK2-FAS, PTEN-FAS, and CACNA2D2-CDH1 were confirmed experimentally by retrieving BioGRID and Pubmed databases. We proposed that the proteins, which included PARK2, WNT7A, SMARCA2, FRAP1, CDKN2A, CCND1, and EGFR, could serve as potential diagnostic molecular markers for NSCLC. In accordance with the developmental mode of lung cancer established by Minna et al., we assumed that the occurrence and development of lung cancer was linked not only to gene loss in the 3p region (WNT7A, 3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1), 6q25.2-q27 (PARK2),  and 11q13 (CCND1). Lastly, it might lead to the invasion or metastasis of lung cancer.

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[713]

TÍTULO / TITLE:  - Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco-  and suppressor gene changes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Jan 5;13(1):8.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-8

AUTORES / AUTHORS:  - Ninomiya H; Kato M; Sanada M; Takeuchi K; Inamura K; Motoi N; Nagano H; Nomura K; Sakao Y; Okumura S; Mano H; Ogawa S; Ishikawa Y

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for  specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients. METHODS: To gain insights into etiology and carcinogenic mechanisms we conducted analyses  to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling. RESULTS: Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1),  7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion. CONCLUSION: Global genomic comparison with SNP  arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and  suppressor genes despite a similar overall aberration frequency, suggesting very  strong oncogenic potency of ALK activation by gene fusion.

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[714]

TÍTULO / TITLE:  - Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54193. doi: 10.1371/journal.pone.0054193. Epub 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054193

AUTORES / AUTHORS:  - Barr MP; Gray SG; Hoffmann AC; Hilger RA; Thomale J; O’Flaherty JD; Fennell DA; Richard D; O’Leary JJ; O’Byrne KJ

INSTITUCIÓN / INSTITUTION:  - Thoracic Oncology, Institute of Molecular Medicine, Trinity Centre for Health Sciences St. James’s Hospital & Trinity College Dublin, Dublin, Ireland.

RESUMEN / SUMMARY:  - INTRODUCTION: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. METHODS: An isogenic model of cisplatin resistance was generated in a  panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and beta-catenin. Cisplatin-DNA adduct formation, DNA damage (gammaH2AX) and cellular platinum uptake (ICP-MS) was also assessed. RESULTS: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response  to cisplatin, increased resistance to cisplatin-induced cell death, accumulation  of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and beta-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased gammaH2AX foci were observed compared to parental cell lines. CONCLUSION: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer.

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[715]

TÍTULO / TITLE:  - Five new studies find potential genetic and epigenic drug targets for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ONS Connect. 2012 Dec;27(12):20.

AUTORES / AUTHORS:  - McBride D

INSTITUCIÓN / INSTITUTION:  - Kaiser Permanente Oakland Medical Center, CA, USA.

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[716]

TÍTULO / TITLE:  - The National Lung Cancer Gene Library Alliance of China was launched.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):552. doi: 10.3978/j.issn.2072-1439.2012.11.04.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.11.04

AUTORES / AUTHORS:  - Zou S

INSTITUCIÓN / INSTITUTION:  - Editorial office, Journal of Thoracic Disease, Guangzhou 510120, China.

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[717]

TÍTULO / TITLE:  - Comparative modeling and docking studies of p16ink4/Cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Theor Biol Med Model. 2013 Jan 1;10(1):1.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1742-4682-10-1

AUTORES / AUTHORS:  - E Zahra SN; Khattak NA; Mir A

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying  comparative modeling and molecular docking studies. RESULTS: YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated  overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional  interactor E2F1. CONCLUSION: This research may provide a basis for understanding  biological insights of P16-INK4 and RB1 proteins which will be helpful in future  to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely to be provide  a gateway for developing computer aided drug designing.

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[718]

TÍTULO / TITLE:  - Cancer genes in lung cancer: racial disparities: are there any?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Cancer. 2012 Jul;3(7-8):467-80. doi: 10.1177/1947601912465177.

            ●● Enlace al texto completo (gratuito o de pago) 1177_1947601912465177 [pii

            ●● Enlace al texto completo (gratuito o de pago) 1177/1947601912465177

AUTORES / AUTHORS:  - El-Telbany A; Ma PC

INSTITUCIÓN / INSTITUTION:  - Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA ; Case Western Reserve University School of  Medicine, Cleveland, OH, USA.

RESUMEN / SUMMARY:  - Cancer is now known as a disease of genomic alterations. Mutational analysis and  genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent “oncogenic drivers” in the processes of tumorigenesis and progression. In this review, we will highlight the key driver oncogenic gene mutations and fusions identified in lung cancer. The review will summarize and report the available demographic and clinicopathological data as well as molecular details behind various lung cancer gene alterations in the context of race. We hope to shed some light into the disparities in the incidence of various genetic mutations among lung cancer patients of different racial backgrounds. As molecularly targeted therapy continues to advance in lung cancer, racial differences in specific genetic/genomic alterations can have an important  impact in the choices of therapeutics and in our understanding of the drug sensitivity/resistance profile. The most relevant genes in lung cancer described  in this review include the following: EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1. Commonly identified genetic/genomic alterations such as missense or nonsense mutations, small insertions or deletions, alternative splicing, and chromosomal fusion rearrangements were discussed. Relevance in current targeted therapeutic drugs was mentioned when appropriate. We also highlighted various targeted therapeutics that are currently under clinical development, such as the  MET inhibitors and antibodies. With the advent of next-generation sequencing, the landscape of genomic alterations in lung cancer is expected to be much transformed and detailed in upcoming years. These genomic landscape differences in the context of racial disparities should be emphasized both in tumorigenesis and in drug sensitivity/resistance. It is hoped that such effort will help to diminish racial disparities in lung cancer outcome in the future.

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[719]

TÍTULO / TITLE:  - Evaluation of 4D dose to a moving target with Monte Carlo dose calculation in stereotactic body radiotherapy for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiol Phys Technol. 2013 Jan;6(1):233-40. doi: 10.1007/s12194-012-0193-y. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12194-012-0193-y

AUTORES / AUTHORS:  - Matsugi K; Nakamura M; Miyabe Y; Yamauchi C; Matsuo Y; Mizowaki T; Hiraoka M

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology Division, Shiga Medical Center for Adults, 5-4-30 Moriyama, Moriyama, 524-8524, Japan, matsugi.kiyotomo@gmail.com.

RESUMEN / SUMMARY:  - We evaluated the four-dimensional (4D) dose to a moving target by a Monte Carlo dose calculation algorithm in stereotactic body radiation therapy (SBRT) planning based on the isocenter dose prescription. 4D computed tomography scans were performed for 12 consecutive patients who had 14 tumors. The gross tumor volume (GTV) and internal target volume (ITV) were contoured manually, and the planning  target volume (PTV) was defined as the ITV with a 5-mm margin. The beam apertures were shaped into the PTV plus a 5-mm leaf margin. The prescription dose was 48 Gy in 4 fractions at the isocenter. The GTV dose was calculated by accumulation of respiratory-phase dose distributions that were mapped to a reference images, whereas the ITV and PTV doses were calculated with the respiration-averaged images. The doses to 99 % (D(99)) of the GTV, ITV, and PTV were 90.2, 89.3, and 82.0 %, respectively. The mean difference between the PTV D(99) and GTV D(99) was -9.1 % (range -13.4 to -4.0 %), and that between the ITV and GTV was -1.1 % (range -5.5 to 1.9 %). The mean homogeneity index (HI) for the GTV, ITV, and PTV  was 1.14, 1.15, and 1.26, respectively. Significant differences were observed in  the D(99) and HI between the PTV and GTV, whereas no significant difference was seen between the ITV and GTV. When SBRT planning is performed based on the isocenter dose prescription with a 5-mm PTV margin and a 5-mm leaf margin, the ITV dose provides a good approximation of the GTV dose.

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[720]

TÍTULO / TITLE:  - Expressions of Osteopontin (OPN), alphanubeta3 and Pim-1 Associated with Poor Prognosis in Non-small Cell Lung Cancer (NSCLC).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Jun;24(2):103-8. doi: 10.1007/s11670-012-0103-1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-012-0103-1

AUTORES / AUTHORS:  - Jin Y; Tong DY; Tang LY; Chen JN; Zhou J; Feng ZY; Shao CK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To examine the expressions of osteopontin (OPN), (alpha) (nu) (beta) (3) and Pim-1 in non-small cell lung cancer (NSCLC), and investigate their potential pathogenic roles in the development of NSCLC. METHODS: Immunohistochemistry was used to examine the expressions of OPN, (alpha) (nu) (beta) (3) and Pim-1 in cohort (136 cases) of NSCLC samples and their adjacent normal lung tissue specimens. Statistical analysis was performed to evaluate the  relationships among expressions of OPN, (alpha) (nu) (beta) (3) and Pim-1 and their associations with patients clinico- pathological parameters. RESULTS: The expressions of OPN and Pim-1 were predominantly observed in cytoplasm. The expression of (alpha) (nu) (beta) (3) was mostly detected in cytoplasm and/or membrane. In NSCLC samples, the positive rates of OPN, (alpha) (nu) (beta) (3) and Pim-1 expressions were 68.4% (93/136), 77.2% (105/136) and 57.4% (78/136), respectively. In normal lung tissues, in contrast, the positive rates of OPN, (alpha) (nu) (beta) (3) and Pim-1 were 24.0% (12/50), 26.0% (13/50) and 16.0% (8/50), respectively. There were significant differences of the positive expression rates of OPN, (alpha) (nu) (beta) (3) and Pim-1 between NSCLCs samples and normal lung tissues (P<0.01). In addition, the positive expression of OPN, (alpha) (nu) (beta) (3) and Pim-1 in NSCLCs samples was significantly associated  with increased pathological grade, lymph node metastasis and advanced clinical stage (P<0.01), and they were independent of other clinicopathological parameters (P>0.05). Furthermore, a significantly positive correlation between the expression of OPN and (alpha) (nu) (beta) (3) (r=0.38, P<0.01), OPN and Pim-1 (r=0.37, P<0.01), or (alpha) (nu) (beta) (3) and Pim-1 (r=0.20, P<0.05) was evaluated in our NSCLC cohort. CONCLUSION: OPN, (alpha) (nu) (beta) (3) and Pim-1 proteins are frequently overexpressed in NSCLC, and they may play important roles in the development and/or progression of NSCLC.

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[721]

TÍTULO / TITLE:  - Is there a survival advantage of incomplete resection of non-small-cell lung cancer that is found to be unresectable at thoracotomy?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs428

AUTORES / AUTHORS:  - Dall K; Ford C; Fisher R; Dunning J

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK.

RESUMEN / SUMMARY:  - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: in patients with non-small-cell lung cancer that is found to be unresectable at thoracotomy, is incomplete resection superior for achieving survival advantage? Altogether more than 400 papers were found using the reported search, of which nine represented the best evidence to answer  the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers  were tabulated. In total, data from an estimated 1083 patients were analysed. Three-year survival rates varied from 0 to 22% in incomplete resection and from 0 to 10% in exploratory thoracotomy. Median survival ranged from 6.5 to 19.1 months in incomplete resection and from 5.3 to 17 months in exploratory thoracotomy. The majority of studies (8/9) found survival in incomplete resection to be superior.  However, only 3/9 studies presented statistical analysis of results. The largest  of these found superior postoperative survival in incomplete resection (including residual nodal disease), one study showed a significant survival difference for R1 but not R2 resection and another with small patient numbers (n = 29) found no  significant difference. We conclude that the best evidence suggests that there may be a survival advantage from incomplete resection of non-small-cell lung cancer when there is microscopic (R1) or nodal residual disease, but not when macroscopic residual (R2) disease remains.

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[722]

TÍTULO / TITLE:  - Development and Validation of the Quality-of-Life Assessment System for Lung Cancer Based on Traditional Chinese Medicine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Evid Based Complement Alternat Med. 2012;2012:945910. doi: 10.1155/2012/945910. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/945910

AUTORES / AUTHORS:  - Wan C; You S; Quan P; Song Y; Liu T; Lu J; Zheng P

INSTITUCIÓN / INSTITUTION:  - School of Humanities and Management and Research Center on Quality of Life and Applied Psychology, Guangdong Medical College, Dongguan 523808, China.

RESUMEN / SUMMARY:  - Traditional Chinese Medicine (TCM) has many unique features. Thequality-of-life (QoL) instrument for lung cancer based on Traditional Chinese Medicine (QLASTCM-Lu) was the first self-reported instrument specifically developed to assess the quality of life from the perspective of TCM. Structured group methods  and theory in developmental rating scale were employed to establish a general and a specific module, respectively. Quantitative and qualitative data from 240 lung  cancer patients were collected to assess the psychometric properties. The three identified scales of the QLASTCM-Lu (correspondence between man and universe, unity of the body and spirit, and lung cancer specific module) and the total score demonstrated excellent psychometric properties. Test-retest reliability of  all domains ranged from 0.93 to 0.96, and internal consistency alpha ranged from  0.86 to 0.93. Correlation and factor analysis demonstrated good construct validity. Significant differences in the QLASTCM-Lu scales and total score were found among groups differing in TCM syndrome, supporting the clinical sensitivity of the QLASTCM-Lu. Statistically significant changes were found for each scale and the total score. Responsiveness of the QLASTCM-Lu was greater than that of QLQ-LC43. The QLASTCM-Lu is a psychometrically sound and clinically sensitive measure of quality of life for lung cancer patients, which can be applied to both TCM therapy and Western medicine therapy.

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[723]

TÍTULO / TITLE:  - Stereotactic ablative radiotherapy for non-small cell lung cancer: rationale and  outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Compr Canc Netw. 2012 Dec 1;10(12):1514-20.

AUTORES / AUTHORS:  - Iyengar P; Timmerman RD

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, USA.

RESUMEN / SUMMARY:  - Stereotactic ablative radiotherapy (SABR), also known in older reports as stereotactic body radiation therapy, represents an evolving and expanding radiation treatment option for many forms of local malignancy, from primary tumors to metastatic and recurrent disease. It involves the precise delivery of higher doses of external-beam radiation per treatment over a shortened treatment  course compared with traditional regimens. SABR has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and is becoming a more viable option for surgical candidates with early-stage primary NSCLCs who prefer noninvasive modalities of treatment. Although SABR is being used for the treatment of primary and metastatic disease in many sites of the body, such as the central nervous system, liver, pancreas, spine metastases, and isolated nodal disease in the mediastinum and abdomen, this article focuses on treatment of NSCLC in the thorax. Specifically, this review provides the rationale, evidence, and indications for treating early-stage lung cancers with SABR.

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[724]

TÍTULO / TITLE:  - Addition of a MEK Inhibitor Improves Survival in KRAS-Mutant NSCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Jan;3(1):OF23. doi: 10.1158/2159-8290.CD-RW2012-221. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2012-221

RESUMEN / SUMMARY:  - Selumetinib plus docetaxel provides clinical benefit to patients with KRAS-mutant NSCLC.

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[725]

TÍTULO / TITLE:  - Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53087. doi: 10.1371/journal.pone.0053087. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053087

AUTORES / AUTHORS:  - Attoub S; Arafat K; Gelaude A; Al Sultan MA; Bracke M; Collin P; Takahashi T; Adrian TE; De Wever O

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology & Therapeutics, Faculty of Medicine & Health Sciences, U. A. E. University, Al-Ain, United Arab Emirates.

RESUMEN / SUMMARY:  - A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24  h were between 1.7 and 2.5 microM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 microM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.

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[726]

TÍTULO / TITLE:  - Specific organ metastases and survival in small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):617-620. Epub 2012 Jul 9.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.792

AUTORES / AUTHORS:  - Nakazawa K; Kurishima K; Tamura T; Kagohashi K; Ishikawa H; Satoh H; Hizawa N

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Mito, Ibaraki 305-8575;

RESUMEN / SUMMARY:  - The aim of our retrospective study was to evaluate the clinicopathological features associated with distant metastasis from small cell lung cancer (SCLC). We reviewed patients diagnosed with SCLC metastasis at the time of presentation between 1999 and 2010. Among the consecutive 251 SCLC patients diagnosed, 152 (60.6%) patients had distant metastasis, of which 20.3, 18.3, 15.5, 10.0 and 6.0% of patients had liver, bone, brain, lung and adrenal gland metastasis, respectively. In a multivariate analysis using Cox’s proportional hazards model,  we identified that liver, bone and brain metastasis as well as the presence of pleural and/or pericardial fluids were unfavorable prognostic factors. However, lung, adrenal gland and extrathoracic lymph node metastasis were not statistically significant prognostic factors. With regard to the treatment of SCLC patients, particularly those with liver, bone and brain metastasis or pleural and/or pericardial fluids, we should take the metastasizing organs into consideration.

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[727]

TÍTULO / TITLE:  - Improving lung cancer survival; time to move on.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Pulm Med. 2012 Dec 13;12:77. doi: 10.1186/1471-2466-12-77.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2466-12-77

AUTORES / AUTHORS:  - Heuvers ME; Hegmans JP; Stricker BH; Aerts JG

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Diseases and Tuberculosis, Erasmus Medical University Center, Rotterdam, The Netherlands. m.heuvers@erasmusmc.nl

RESUMEN / SUMMARY:  - BACKGROUND: During the past decades, numerous efforts have been made to decrease  the death rate among lung cancer patients. Nonetheless, the improvement in long-term survival has been limited and lung cancer is still a devastating disease. DISCUSSION: With this article we would like to point out that survival of lung cancer could be strongly improved by controlling two pivotal prognostic factors: stage and treatment. This is corresponding with recent reports that show a decrease in lung cancer mortality by screening programs. In addition, modulation of the patient’s immune system by immunotherapy either as monotherapy  or combined with conventional cancer treatments offers the prospect of tailoring  treatments much more precisely and has also been shown to lead to a better response to treatment and overall survival of non-small cell lung cancer patients. SUMMARY: Since only small improvements in survival can be expected in advanced disease with the use of conventional therapies, more research should be  focused on lung cancer screening programs and patient tailored immunotherapy with or without conventional therapies. If these approaches are clinically combined in a standard multidisciplinary policy we might be able to advance the survival of patients with lung cancer.

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[728]

TÍTULO / TITLE:  - MnSOD promotes tumor invasion via upregulation of FoxM1-MMP2 axis and related with poor survival and relapse in Lung Adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0527

AUTORES / AUTHORS:  - Chen PM; Wu YH; Li MC; Cheng YW; Chen CY; Lee H

INSTITUCIÓN / INSTITUTION:  - Chung Shan Medical University.

RESUMEN / SUMMARY:  - Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme responsible for the elimination of superoxide radical. The role of MnSOD in tumor progression in  different human cancers is still controversial. In the present study, MnSOD expression in lung cancer cells was explored by knockdown or overexpression using transfection of a small hairpin RNA or an expression vector, respectively, to determine whether MnSOD expression mediates lung cancer cell invasion, and oncogenic potential by increasing FoxM1 and MMP2 expression. Western blotting showed that FoxM1 and MMP2 expression was dependent on MnSOD expression, suggesting that FoxM1 could be upregulated by MnSOD. Three FoxM1 promoters were constructed to verify this activation of FoxM1 by MnSOD and to determine the transcription factors responsible. Luciferase reporter and chromatin immunoprecipitation assays indicated that MnSOD overexpression in lung cancer cells promoted binding of E2F1 and Sp1 to their putative FoxM1 promoter binding sites and activated FoxM1 reporter activity. MnSOD also enhanced the potential for cell invasion, and anchorage-independent colony growth on soft-agar plates, again via upregulation of FoxM1 and MMP2 expression. In lung cancer patients, evaluation of MnSOD expression in lung tumors by immunohistochemistry indicated a positive correlation between FoxM1 and MMP2 mRNA expressions. Kaplan-Meier and Cox regression analysis revealed a poorer overall survival (OS) and relapse free  survival (RFS) in patients with MnSOD-positive tumors than with MnSOD-negative tumors. We conclude that MnSOD may promote tumor aggressiveness via upregulation  of the FoxM1-MMP2 axis, and that MnSOD expression can independently predict survival and relapse in resected lung adenocarcinoma patients.

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[729]

TÍTULO / TITLE:  - Palliative Care: An Approach for All Internists Comment on “Early Palliative Care in Advanced Lung Cancer: A Qualitative Study”

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Intern Med. 2013 Jan 28:1-2. doi: 10.1001/jamainternmed.2013.1888.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamainternmed.2013.1888

AUTORES / AUTHORS:  - Smith AK

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[730]

TÍTULO / TITLE:  - Statistical classification of multivariate flow cytometry data analyzed by manual gating: Stem, progenitor, and epithelial marker expression in nonsmall cell lung  cancer and normal lung.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cytometry A. 2013 Jan;83(1):150-60. doi: 10.1002/cyto.a.22240. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cyto.a.22240

AUTORES / AUTHORS:  - Normolle DP; Donnenberg VS; Donnenberg AD

INSTITUCIÓN / INSTITUTION:  - Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213; University of Pittsburgh Cancer Institute.

RESUMEN / SUMMARY:  - The use of supervised classification to extract markers from primary flow cytometry data is an emerging field that has made significant progress, spurred by the growing complexity of multidimensional flow cytometry. Whether the markers are extracted without supervision or by conventional gate and region methods, the number of candidate variables identified is typically larger than the number of specimens (p > n) and many variables are highly intercorrelated. Thus, comparison across groups or treatments to determine which markers are significant is challenging. Here, we utilized a data set in which 86 variables were created by conventional manual analysis of individual listmode data files, and compared the  application of five multivariate classification methods to discern subtle differences between the stem/progenitor content of 35 nonsmall cell lung cancer and adjacent normal lung specimens. The methods compared include elastic-net, lasso, random forest, diagonal linear discriminant analysis, and best single variable (best-1). We described a broadly applicable methodology consisting of: 1) variable transformation and standardization; 2) visualization and assessment of correlation between variables; 3) selection of significant variables and modeling; and 4) characterization of the quality and stability of the model. The  analysis yielded both validating results (tumors are aneuploid and have higher light scatter properties than normal lung), as well as leads that require followup: Cytokeratin+ CD133+ progenitors are present in normal lung but reduced  in lung cancer; diploid (or pseudo-diploid) CD117+CD44+ cells are more prevalent  in tumor. We anticipate that the methods described here will be broadly applicable to a variety of multidimensional cytometry problems. © 2012 International Society for Advancement of Cytometry.

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[731]

TÍTULO / TITLE:  - The roles of epidermal growth factor receptor (EGFR) inhibitors in the management of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Public Health. 2012 Dec;5 Suppl 1:S50-60. doi: 10.1016/j.jiph.2012.09.004. Epub 2012 Nov 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jiph.2012.09.004

AUTORES / AUTHORS:  - Al Olayan A; Al Hussaini H; Rahman Jazieh A

INSTITUCIÓN / INSTITUTION:  - King Abdulaziz Medical City for National Guard - King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Electronic address: alolayanas@ngha.med.sa.

RESUMEN / SUMMARY:  - Targeting epidermal growth factor receptor (EGFR) is an important treatment option for non-small cell lung cancer (NSCLC). These targeted therapies have been studied extensively in NSCLC in first line and subsequent lines, including maintenance in empiric fashion or in patients with tumors harboring the EGFR mutations. In this manuscript, we will review in details the evolutions of these  targeted therapy in the management of NSCLC.

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[732]

TÍTULO / TITLE:  - Non-local means resolution enhancement of lung 4D-CT data.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 1):214-22.

AUTORES / AUTHORS:  - Zhang Y; Wu G; Yap PT; Feng Q; Lian J; Chen W; Shen D

INSTITUCIÓN / INSTITUTION:  - School of Biomedical Engineering, Southern Medical University, Guang Zhou, China.

RESUMEN / SUMMARY:  - Image resolution in 4D-CT is a crucial bottleneck that needs to be overcome for improved dose planning in radiotherapy for lung cancer. In this paper, we propose a novel patch-based algorithm to enhance the image quality of 4D-CT data. Our premise is that anatomical information missing in one phase can be recovered from complementary information embedded in other phases. We employ a patch-based mechanism to propagate information across phases for reconstruction of intermediate slices in the axial direction, where resolution is normally the lowest. Specifically, structurally-matching and spatially-nearby patches are combined for reconstruction of each patch. For greater sensitivity to anatomical  nuances, we further employ a quad-tree technique to adaptively partition each slice of the image in each phase for more fine-grained refinement. Our evaluation based on a public 4D-CT lung data indicates that our algorithm gives very promising results with significantly enhanced image structures.

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[733]

TÍTULO / TITLE:  - Effect of endostar combined with cisplatin on expression of VEGF and Sema3A of Lewis lung cancer rats.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Trop Med. 2013 Jan;6(1):57-60. doi: 10.1016/S1995-7645(12)60201-6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1995-7645(12)60201-6

AUTORES / AUTHORS:  - Feng P; Zhang ZL; Zhang ZH; Zhang XL; Xiang F; Tang JH; Xiang BL

INSTITUCIÓN / INSTITUTION:  - Master of Respiratory Medicine, Hebei Northern College, Zhangjiakou 075000, Hebei, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate the therapeutic effect of endostar (ED) combined with cisplatin(DDP) on model of C57BL/6 rats, and to further investigate the inhibiting mechanism of endostar from tumor angiogenesis. METHODS: Lewis lung cancer cells were inoculated in C57BL/6 mouse, then the mouse were randomized into control group (group A), ED (group B), DDP (group C) and ED/DDP (group D). They were treated according to the plan. And the expressions of VEGF and Sema3A were evaluated by immunhistochemisty. RESULTS: The weight of tumor increased in group A and B. It was decreased in group C and D. The tumor volume was increased  in all the 4 groups. The VEGF expression of group D was obviously lower than the  other group 3, but the Sema3A expressed of group D was significantly strengthener than the other group 3. The VEGF expression of group B and group D were obviously low especially in the 4th-8th days. Pearson correlated analysis showed that the expression VEGF and Sema3A were negatively correlated (r=-0.72, P<0.05). CONCLUSIONS: ED combined with DDP could control the tumor growth effectively, and avoid weight loss. ED could reduce VEGF expression, and enhance Sema3A expression. Tumor vessel presents transient normalization. It is easy for DDP perfusion, and to kill tumor cells.

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[734]

TÍTULO / TITLE:  - Heterogeneity of the EGFR mutation status between the primary tumor and metastatic lymph node and the sensitivity to EGFR tyrosine kinase inhibitor in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-012-0241-x

AUTORES / AUTHORS:  - Shimizu K; Yukawa T; Hirami Y; Okita R; Saisho S; Maeda A; Yasuda K; Nakata M

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima,  Kurashiki, Okayama, 701-0192, Japan, kshimizu@med.kawasaki-m.ac.jp.

RESUMEN / SUMMARY:  - The purpose of this study was to clarify the distribution of epidermal growth factor receptor (EGFR) mutations between primary tumors (PT) and metastatic lymph node (MLN) in patients with resected non-small cell lung cancer (NSCLC) and to identify a better predictive marker of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective review of the data of 70 lung  cancer patients with lymph node metastasis who underwent surgical resection. Analysis to detect EGFR mutations was performed by a peptide nucleic acid-locked  nucleic acid polymerase chain reaction clamp method. EGFR mutations were detected in 15.7 % of both the PT and MLN and in 14.3 % of the PT only. The response rate  to EGFR-TKI tended to be higher in patients with EGFR mutations in the MLN, as all patients with EGFR mutations in the MLN showed disease control to treatment with EGFR-TKI. Our results demonstrated that the EGFR mutation status of MLN is a predictive marker of the response to EGFR-TKI therapy in patients with recurrent  NSCLC after surgical resection.

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[735]

TÍTULO / TITLE:  - Assessment of the feeding arteries by three-dimensional computed tomography angiography prior to multi-arterial infusion chemotherapy for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):363-367. Epub 2012 Oct 26.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1000

AUTORES / AUTHORS:  - Ye XD; Yuan Z; Ye JD; Xiao XS

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong  University, Shanghai 200030;

RESUMEN / SUMMARY:  - The aim of this study was to evaluate the efficacy of multi-detector row helical  computed tomography (MDCT) angiography in the detection of feeding arteries prior to multi-arterial infusion for lung cancer. A total of 59 consecutive patients (44 males and 15 females; age range, 27-86 years; median age, 62 years) with non-small cell lung cancer underwent MDCT angiography of the thorax prior to multi-arterial infusion for lung cancer. Findings on CT angiograms, including CT  scans, maximum intensity projections and three-dimensional volume-rendered images, were used to evaluate the depiction of bronchial and non-bronchial systemic arteries. The results of detecting the feeding arteries for lung cancer  by MDCT angiography and conventional angiography were compared. Among the 59 patients treated with multi-arterial infusion chemotherapy, a total of 80 feeding arteries (62 bronchial feeding arteries and 18 non-bronchial systemic arteries) were detected by conventional angiography and/or MDCT angiography. In 56 (70%) feeding arteries (including 44 bronchial feeding arteries and 12 non-bronchial systemic arteries) for lung cancers, concordant findings were observed with the two modalities. In 23 (29%) cases, MDCT angiography could not be used to define feeding arteries, but was used to identify the ostia of these feeding arteries. In one (1/80, 1.3%) case, the CT-defined feeding artery was not selectively catheterized. MDCT angiography of the chest is able to provide an overview for successful catheterization in multi-arterial infusion chemotherapy for lung cancer.

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[736]

TÍTULO / TITLE:  - The impact of cardiovascular comorbidities on the outcome of surgery for non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs489

AUTORES / AUTHORS:  - Takenaka T; Katsura M; Shikada Y; Tsukamoto S; Takeo S

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.

RESUMEN / SUMMARY:  - OBJECTIVESThe presence of cardiovascular comorbidity in non-small-cell lung cancer (NSCLC) patients increases with age. Therefore, the influence of cardiovascular comorbidity in NSCLC patients on their short- or long-term prognosis remains controversial. This study evaluated the possible risk factors related to the short-term and long-term survivals in NSCLC patients with cardiovascular comorbidity.METHODSOne thousand one hundred and sixty-two consecutive patients with NSCLC who had undergone a surgical resection between 1984 and 2010 were enrolled in this study. A total of 360 (31%) patients with cardiovascular comorbidities were analysed to identify the risk factors for postoperative complications and prognostic factors.RESULTSThe patients with cardiovascular comorbidity included 301 with hypertension, 28 with coronary artery disease, 35 with peripheral vascular disease, 23 with arrhythmia and 11 with abdominal aortic aneurysm. Eighty-three patients exhibited more than one type of comorbidity. The postoperative cardiovascular morbidity rates were 3.6% in the cardiovascular comorbidity patients and 3.3% among patients without cardiovascular comorbidity (P = 0.73). No correlation was observed between preoperative cardiovascular comorbidity and postoperative pulmonary complications (P = 0.52). The operative mortality rates were 1.0% for the cardiovascular comorbidity patients and 0.8% for the other patients (P = 0.51). No difference in the postoperative outcomes was observed between the patients with and without cardiovascular comorbidity. The 5-year survival rates were 62.5% in comparison with 65.4% among patients without cardiovascular comorbidity (P = 0.48).CONCLUSIONSPatients with cardiovascular comorbidity were not found to be at increased risk of mortality and morbidity following surgery for NSCLC. In addition, cardiovascular comorbidity did not influence the long-term outcomes of  patients after a pulmonary resection for NSCLC.

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[737]

TÍTULO / TITLE:  - Febrile complications after endobronchial ultrasound-guided transbronchial needle aspiration for intra-pulmonary mass lesions of lung cancer—a series of 3 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respir Investig. 2012 Dec;50(4):162-5. doi: 10.1016/j.resinv.2012.08.006. Epub 2012 Sep 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.resinv.2012.08.006

AUTORES / AUTHORS:  - Oguri T; Imai N; Imaizumi K; Elshazley M; Hashimoto I; Hashimoto N; Hasegawa Y

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Nagoya Graduate School of Medicine, Nagoya, Japan.

RESUMEN / SUMMARY:  - Recent case reports have shown that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions is sometimes accompanied by severe infectious complications. Here, we report 3 cases with refractory febrile complications following EBUS-TBNA for intra-pulmonary large mass lesion of lung cancer (squamous cell carcinoma, n=2; adenocarcinoma, n=1). After the EBUS-TBNA, all cases showed prolonged fever and systemic inflammation despite receiving a sufficient dose of broad-spectrum antibiotics. The presence of a low-density area inside the masses upon CT examination, suggesting necrosis, may be a predictive sign of febrile complications associated with EBUS-TBNA.

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[738]

TÍTULO / TITLE:  - Anti-angiogenic agents in Non-Small-Cell Lung Cancer (NSCLC): a perspective on the MONET1 (Motesanib NSCLC Efficacy and Tolerability) study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):558-61. doi: 10.3978/j.issn.2072-1439.2012.10.02.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.10.02

AUTORES / AUTHORS:  - Das M; Wakelee H

INSTITUCIÓN / INSTITUTION:  - VA Palo Alto Health Care System, Palo Alto, CA, USA;

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[739]

TÍTULO / TITLE:  - Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: revisiting exploratory thoracotomies and incomplete resections.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs512

AUTORES / AUTHORS:  - Foucault C; Mordant P; Grand B; Achour K; Arame A; Dujon A; Barthes FL; Riquet M

INSTITUCIÓN / INSTITUTION:  - Department of General Thoracic Surgery, Georges Pompidou European Hospital, Paris Descartes University, Paris, France.

RESUMEN / SUMMARY:  - OBJECTIVESOnly patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations.METHODSA total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections.RESULTSET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The  frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1  extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade.CONCLUSIONSET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.

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[740]

TÍTULO / TITLE:  - A case of lambert-eaton myasthenic syndrome with small-cell lung cancer and transient increase in anti-acetylcholine-receptor-binding antibody titer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurol. 2012 Dec;8(4):305-7. doi: 10.3988/jcn.2012.8.4.305. Epub 2012 Dec  21.

            ●● Enlace al texto completo (gratuito o de pago) 3988/jcn.2012.8.4.305

AUTORES / AUTHORS:  - Lee JH; Shin HY; Kim SM; Sunwoo IN

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Yonsei University College of Medicine, Seoul, Korea. ; Department of Neurology, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The titers of antibodies against voltage-gated calcium channels are frequently increased in LEMS, but only rarely is titer of anti-acetylcholine-receptor-binding antibodies (AChR-abs) increased. CASE REPORT: A 57-year-old male was admitted to our hospital due to dry mouth and eyes and progressive proximal limb weakness of 2 months duration. The results of a repetitive nerve stimulation test disclosed all criteria for the electrophysiological LEMS pattern, and the patient’s AChR-abs titer was 0.587 nmol/L. At a follow-up performed 5 years after successful treatment of SCLC and LEMS, his AChR-abs titer had decreased to 0.001 nmol/L. CONCLUSIONS: We suggest that this was a case of transient pseudopositivity of AChR-abs in SCLC with LEMS.

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[741]

TÍTULO / TITLE:  - Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52753. doi: 10.1371/journal.pone.0052753. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052753

AUTORES / AUTHORS:  - Barbone D; Cheung P; Battula S; Busacca S; Gray SG; Longley DB; Bueno R; Sugarbaker DJ; Fennell DA; Broaddus VC

INSTITUCIÓN / INSTITUTION:  - Lung Biology Center, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.

RESUMEN / SUMMARY:  - When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein,  Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

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[742]

TÍTULO / TITLE:  - Expression and function of Annexin II in lung cancer tissue.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Trop Med. 2013 Feb;6(2):150-2. doi: 10.1016/S1995-7645(13)60012-7.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1995-7645(13)60012-7

AUTORES / AUTHORS:  - Cui JW; Wang YL

INSTITUCIÓN / INSTITUTION:  - First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To explore the expression of Annexin II and its relationship with the  cell differentiation, proliferation in lung cancer. METHODS: RT-PCR and Western blot assays were used to detect the expression of Annexin II in lung cancer tissues and cell lines. RESULTS: Annexin II was significantly up-regulated in lung cancer tissues, and in lung cancer cell lines, Annexin II had higher mRNA and protein expressions. CONCLUSIONS: Annexin II is up-regulated in lung cancer,  suggesting that the Annexin II has a potential value in the human lung cancer.

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[743]

TÍTULO / TITLE:  - Differential expression of hypoxia-inducible factor 1alpha in non-small cell lung cancer and small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clinics (Sao Paulo). 2012 Dec;67(12):1373-8.

AUTORES / AUTHORS:  - Karetsi E; Ioannou MG; Kerenidi T; Minas M; Molyvdas PA; Gourgoulianis KI; Paraskeva E

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Medical School, University of Thessaly, Larissa, Greece.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1alpha and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1alpha expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1alpha nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression (Fisher’s exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1alpha differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

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[744]

TÍTULO / TITLE:  - The significance of MAGED4 expression in non-small cell lung cancer as analyzed by real-time fluorescence quantitative PCR.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):733-738. Epub 2012 Jul 4.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.786

AUTORES / AUTHORS:  - Ma QY; Pang LW; Chen ZM; Zhu YJ; Chen G; Chen J

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Huashan Hospital Affiliated to Fudan University,  Shanghai 200040, P.R. China.

RESUMEN / SUMMARY:  - The aim of this study was to detect differences in the expression levels of melanoma-associated antigen D4 (MAGED4) mRNA between non-small cell lung cancer (NSCLC) tissues and normal tissues, and to compare differences in the expression  levels of MAGED4 in tumor patients. Patients were grouped according to age, gender, smoking history, tumor size, pathological classification, degree of lung  cancer cell differentiation and presence of lymph node metastasis. The expression levels of MAGED4 were detected using real-time fluorescence quantitative PCR. MAGED4 expression was higher in squamous cell carcinomas compared to adenocarcinomas (P<0.05), in poorly differentiated tissues compared to well-differentiated tissues (P<0.05), and in patients with lymph node metastasis  compared to patients without lymph node metastasis (P<0.05). MAGED4 may be used as a specific antigen for NSCLC to influence the improvement of diagnosis, prognosis and immunological therapy outcomes in lung cancer patients.

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[745]

TÍTULO / TITLE:  - PTEN expression in non small cell lung carcinoma based on digitized image analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J BUON. 2012 Oct-Dec;17(4):719-23.

AUTORES / AUTHORS:  - Panagiotou I; Tsiambas E; Lazaris AC; Kavantzas N; Konstantinou M; Kalkandi P; Ragkos V; Metaxas GE; Roukas DK; Vilaras G; Patsouris E

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, 401 GA Hospital of Athens, Athens, Greece.

RESUMEN / SUMMARY:  - Purpose: HER2 depended signalling pathway is dereg-ulated in a subset of non small cell lung carcinoma (NSCLC). The tumor suppressor gene PTEN (10q21) regulates the HER2/PI3K/Akt signalling pathway. Our aim was to evaluate PTEN protein expression in NSCLC based on a quantitative analysis method correlating also the results with clinicopathological parameters. Methods: Protein expression was determined by immunohistochemistry (IHC) in 61 paraffin-embedded cases of patients with NSCLC. Digital image analysis (staining intensity levels) was performed in the corresponding immunostained slides. Results: Loss of PTEN expression was observed in 24 (39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%) cases. Multivariate analysis determined that PTEN overexpression was associated with lower risk to develop metastases (p=0.05). Conclusion: PTEN deregulation is a relatively frequent genetic event in NSCLC, associated with progressive metastatic process in those patients. Because of binding to the ErbB2 receptor, trastuzumab stabilizes and activates PTEN gene, and loss of its expression negatively affects the response rates in such patients.

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[746]

TÍTULO / TITLE:  - Human Papillomavirus Up-Regulates MMP-2 and MMP-9 Expression and Activity by Inducing Interleukin-8 in Lung Adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54423. doi: 10.1371/journal.pone.0054423. Epub 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054423

AUTORES / AUTHORS:  - Shiau MY; Fan LC; Yang SC; Tsao CH; Lee H; Cheng YW; Lai LC; Chang YH

INSTITUCIÓN / INSTITUTION:  - Hungkuang University, Taichung, Taiwan, Republic of China.

RESUMEN / SUMMARY:  - Human papillomavirus (HPV) infection is associated with non-smoking female lung cancer. Our previous report demonstrated that HPV 16 promotes lung tumor cell progression by up-regulating interleukin-17 (IL-17). IL-17 and its downstream signaling mediator, interleukin-8 (IL-8), have been implicated to modulate a variety of pro-angiogenic factors and play important roles in tumor angiogenesis  and metastasis. Accordingly, we hypothesized that HPV infection may potentiate tumorigenic and metastatic characteristics of the infected cells through IL-8. The goal of the present study was to determine whether HPV infection in lung adenocarcinoma cells can promote the expression of IL-8 and metalloproteinases (MMPs) to make the transformed cells equipped with angiogenic and metastatic characteristics. The expression of IL-8 and MMPs in HPV 16 E6-transfected H1299 cells was analyzed to examine the hypothesis. HPV 16 E6 up-regulates pro-angiogenic MMP-2 and MMP-9 through inducing IL-8 expression in lung cancer cells. The results indicate that, in addition to cell proliferation-related machinery, HPV infection promotes the expression and activities of angiogenic and metastatic molecules in lung adenocarcinoma cells. The cytokines induced by HPV infection may work together to confer the malignant and tumorigenic potentials on the infected cells by promoting machineries of growth, angiogenic and metastatic  characteristics.

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[747]

TÍTULO / TITLE:  - Decrease of PDSS2 expression, a novel tumor suppressor, in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Epidemiol. 2013 Jan 9. pii: S1877-7821(12)00162-2. doi: 10.1016/j.canep.2012.12.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canep.2012.12.004

AUTORES / AUTHORS:  - Chen P; Yu J; Knecht J; Chen Q

INSTITUCIÓN / INSTITUTION:  - Department of Genetic and Molecular Biology, Xi’an Jiaotong University School of  Medicine, Xi’an 710061, China; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Cancer Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA; Program in Integrative Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.

RESUMEN / SUMMARY:  - Background: Prenyl diphosphate synthase subunit 2 (PDSS2) gene has recently been  reported as a potential tumor suppressor. The association of PDSS2 and non-small  cell lung cancer (NSCLC) has not been known. Methods: To investigate its association with NSCLC, we examined the expression level of PDSS2 in 28 paired clinical samples of non-small cell lung cancer tissues and surrounding normal tissues. Results: PDSS2 was constitutionally expressed in normal lung tissues regardless of sex, race and smoking history. An overall decreased PDSS2 expression was found in the tumor tissues compared to surrounding normal tissues. Decrease in PDSS2 expression was more severe in poorly and poor-to-moderately differentiated lung cancers, while the decrease was not significant in moderately to well-differentiated tumors. Moreover, the expression of PDSS2 decreased more in higher pathological stage, and in patients with lymph node metastasis. The decrease in PDSS2 expression in tumor tissues was not related to sex or histological type of NSCLC, but was related to smoking history. No correlation has been found between PDSS2 and the clinical factors of EGRF, Ki-67 and p53. Conclusion: Taken together, decreased expression of PDSS2 in NSCLC was evident. This is an initial report for the expression of PDSS2 in relation to different factors in lung cancer. Loss of PDSS2 could serve as a potential biomarker in NSCLC development. The role of PDSS2 as a tumor suppressor, and the mechanism of  its potential anti-tumor action in NSCLC warrant further investigation.

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[748]

TÍTULO / TITLE:  - ADH IB Expression, but Not ADH III, Is Decreased in Human Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52995. doi: 10.1371/journal.pone.0052995. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052995

AUTORES / AUTHORS:  - Mutka SC; Green LH; Verderber EL; Richards JP; Looker DL; Chlipala EA; Rosenthal GJ

INSTITUCIÓN / INSTITUTION:  - N30 Pharmaceuticals, Inc., Boulder, Colorado, United States of America.

RESUMEN / SUMMARY:  - Endogenous S-nitrosothiols, including S-nitrosoglutathione (GSNO), mediate nitric oxide (NO)-based signaling, inflammatory responses, and smooth muscle function. Reduced GSNO levels have been implicated in several respiratory diseases, and inhibition of GSNO reductase, (GSNOR) the primary enzyme that metabolizes GSNO, represents a novel approach to treating inflammatory lung diseases. Recently, an  association between decreased GSNOR expression and human lung cancer risk was proposed in part based on immunohistochemical staining using a polyclonal GSNOR antibody. GSNOR is an isozyme of the alcohol dehydrogenase (ADH) family, and we demonstrate that the antibody used in those studies cross reacts substantially with other ADH proteins and may not be an appropriate reagent. We evaluated human lung cancer tissue arrays using monoclonal antibodies highly specific for human GSNOR with minimal cross reactivity to other ADH proteins. We verified the presence of GSNOR in >/=85% of specimens examined, and extensive analysis of these samples demonstrated no difference in GSNOR protein expression between cancerous and normal lung tissues. Additionally, GSNOR and other ADH mRNA levels  were evaluated quantitatively in lung cancer cDNA arrays by qPCR. Consistent with our immunohistochemical findings, GSNOR mRNA levels were not changed in lung cancer tissues, however the expression levels of other ADH genes were decreased.  ADH IB mRNA levels were reduced (>10-fold) in 65% of the lung cancer cDNA specimens. We conclude that the previously reported results showed an incorrect association of GSNOR and human lung cancer risk, and a decrease in ADH IB, rather than GSNOR, correlates with human lung cancer.

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[749]

TÍTULO / TITLE:  - Pulmonary tumor thrombotic microangiopathy showing aggressive course after transurethral resection of urinary bladder: an autopsy case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Mol Morphol. 2012 Dec;45(4):238-42. doi: 10.1007/s00795-012-0586-3. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00795-012-0586-3

AUTORES / AUTHORS:  - Hirano H; Ichibori H; Kizaki T; Matsumoto T; Ohka Z; Mori T; Okamoto M; Ogasawara D; Kamemura K; Yoshikawa R; Itagaki T; Matsuda Y; Sano H

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine, Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, Japan. hihirano@toneyama.go.jp

RESUMEN / SUMMARY:  - A 77-year-old man developed pulmonary tumor thrombotic microangiopathy (PTTM) 2 days after undergoing transurethral resection for urothelial carcinoma (G3) of the urinary bladder and died of respiratory failure 6 days later. Histological findings demonstrated marked intimal fibrocellular proliferation, fibrin thrombi, and both cancer cells and fibrin thrombi in the arteries of the lungs, findings consistent with PTTM. Prominent stenosis in arteries smaller than 300 mum was also seen. The Ki-67 labeling index of primary and metastasized cancer cells was  62.4 % and 70.2 %, respectively. The membranes of metastasized cancer cells expressed E-cadherin, similar to membranes in the urinary bladder. An aggressive  PTTM course is affected by intimal fibrocellular proliferation and the high cell  proliferation of cancer cells. Furthermore, prominent stenosis in small arteries  and membranous staining of E-cadherin of metastasized cells suggest that cancer cells formed clusters by maintaining adhesion molecules and migrated into the arteries of the lungs, where they easily caused damage to the endothelium of small arteries, in contrast to dispersed cancer cells.

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[750]

TÍTULO / TITLE:  - Feasibility of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine  for completely resected non-small-cell lung cancer: a retrospective study in Japan.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respir Investig. 2012 Dec;50(4):157-61. doi: 10.1016/j.resinv.2012.09.002. Epub 2012 Oct 27.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.resinv.2012.09.002

AUTORES / AUTHORS:  - Kenmotsu H; Ohde Y; Shukuya T; Eida H; Akamatsu H; Ono A; Nakamura Y; Tsuya A; Kaira K; Naito T; Murakami H; Takahashi T; Maniwa T; Isaka M; Endo M; Kondo H; Yamamoto N

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, Shizuoka 411-8777, Japan. h.kenmotsu@scchr.jp

RESUMEN / SUMMARY:  - BACKGROUND: The efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy, such as the combination of CDDP and vinorelbine (VNR), has been established for surgically resected non-small-cell lung cancer (NSCLC). However,  the optimal treatment schedule and dosage for CDDP and VNR are unknown. We evaluated patient compliance with and the safety of adjuvant chemotherapy of CDDP at 80 mg/m(2) administered on day 1 plus VNR at 25 mg/m(2) administered on days 1 and 8, every 3 weeks. METHODS: Medical records of 100 surgically resected NSCLC patients, treated with a combination of CDDP and VNR at the Shizuoka Cancer Center between February 2006 and October 2011, were retrospectively reviewed. RESULTS: Eighty-three (83%) patients completed the planned 4 cycles of CDDP plus  VNR and 59 (59%) received the planned doses. Sixty-eight percent of the patients  experienced a decreased neutrophil count (grade ¾ toxicity); 1%, a decreased platelet count; and 4%, febrile neutropenia. No treatment-related deaths were noted in this study. Univariate analysis of the factors influencing patient compliance with this adjuvant chemotherapy showed that neither patient characteristics nor surgical procedure was significantly associated. CONCLUSIONS: Our results indicated that adjuvant chemotherapy with CDDP at 80 mg/m(2) administered on day 1 plus VNR at 25 mg/m(2) administered on days 1 and 8, every  3 weeks, was feasible for surgically resected NSCLC cases.

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[751]

TÍTULO / TITLE:  - True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e49689. doi: 10.1371/journal.pone.0049689. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0049689

AUTORES / AUTHORS:  - Brunelli M; Bria E; Nottegar A; Cingarlini S; Simionato F; Calio A; Eccher A; Parolini C; Iannucci A; Gilioli E; Pedron S; Massari F; Tortora G; Borze I; Knuutila S; Gobbo S; Santo A; Tondulli L; Calabro F; Martignoni G; Chilosi M

INSTITUCIÓN / INSTITUTION:  - ISH Molecular Lab, Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy. matteo.brunelli@univr.it

RESUMEN / SUMMARY:  - Squamous lung carcinoma lacks specific “ad hoc” therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed >/=8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with >/=8 signals maintained  a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed >/=8 fluorescent signals at FISH evidencing a 3q/3 ratio  >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We  concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2)  a case results truly “amplified for chromosome 3q” when showing >/=8 fluorescent  3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

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[752]

TÍTULO / TITLE:  - Prognostic Significance of Weight Gain During Definitive Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2012 Dec 20. pii: S1525-7304(12)00263-X. doi: 10.1016/j.cllc.2012.10.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.10.009

AUTORES / AUTHORS:  - Sher DJ; Gielda BT; Liptay MJ; Warren WH; Batus M; Fidler MJ; Garg S; Bonomi P

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Rush University Medical Center, Chicago, IL. Electronic address: david_sher@rush.edu.

RESUMEN / SUMMARY:  - BACKGROUND: The successful treatment of locally advanced non-small-cell lung cancer (NSCLC) with chemoradiotherapy (CRT) is still compromised by poor locoregional and distant control rates. Given the morbidity associated with treatment, it is critical to determine clinical prognostic factors to risk stratify patients before and after aggressive therapy. This study aimed to discern the prognostic value of weight gain during CRT in patients with locally advanced NSCLC. PATIENTS AND METHODS: This was a retrospective analysis of 92 patients treated with definitive split-course CRT between 2004 and 2010 at Rush University Medical Center. Weight gain was defined as a weight change greater than the highest quartile of change between the start and finish of CRT (4.5 lb). Overall survival (OS), locoregional progression-free survival (PFS), and distant  metastasis-free survival (DMFS) were determined using Kaplan-Meier analysis, and  the cumulative incidences of locoregional and distant recurrence were calculated. Cox regression (multivariate analysis) was used to determine independent predictors of OS. RESULTS: With a median follow-up of 50 months for surviving patients, the median, 3- and 5-year OS probabilities were 25 months, 37%, and 29%, respectively. The 3-year cumulative risks of locoregional and distant metastases were 51% and 64%. Patients who experienced weight gain were significantly more likely to survive (3-year OS, 55% vs. 31%; P = .04) and prolonged DMFS resulted. Weight gain was the only significant predictor of survival on multivariate analysis. CONCLUSIONS: Weight gain during split-course CRT was associated with superior OS and DMFS. The presence of weight gain may have utility in risk stratification after CRT as well as in identifying novel treatment approaches for patients with locally advanced NSCLC.

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[753]

TÍTULO / TITLE:  - Planning target volume assessment in lung tumors during 3D conformal radiotherapy by means of an aSi electronic portal imaging device in cine mode.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0984-y

AUTORES / AUTHORS:  - Caivano R; Clemente S; Fiorentino A; Chiumento C; Pedicini P; Califano G; Cozzolino M; Fusco V

INSTITUCIÓN / INSTITUTION:  - Radiotherapy Department, I.R.C.C.S.-C.R.O.B., Via Padre Pio 1, Rionero in Vulture, Pz, 85028, Italy, rocchina.caivano@gmail.com.

RESUMEN / SUMMARY:  - PURPOSE: The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). METHODS: Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID  was used in cine mode acquisition: acquired images were used to the aim. RESULTS  AND CONCLUSIONS: Treatment monitoring with an EPID in cine mode is shown to be a  clinically feasible and useful tool.

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[754]

TÍTULO / TITLE:  - Primary lung carcinoid, a rare cause of paraparesis: report of a case and review  of the literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Nov;4(Suppl 1):49-55. doi: 10.3978/j.issn.2072-1439.2012.s005.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.s005

AUTORES / AUTHORS:  - Visouli AN; Darwiche K; Kourtoglou GI; Zarogoulidis P; Mpakas A; Machairiotis N; Stylianaki A; Christofis C; Katsikogiannis N; Tsakiridis K; Courcoutsakis N; Zarogoulidis K

INSTITUCIÓN / INSTITUTION:  - Cardiothoracic Department, St Luke’s Hospital, Panorama, Thessaloniki, Greece;

RESUMEN / SUMMARY:  - Carcinoids are neuroendocrine tumors mainly involving the gastrointestinal tract, lungs and bronchi. They were considered benign with slow growth, but they can be  malignant in a substantial percentage of patients (metastasizing to liver, bones, skin, etc). Endocrine activity results in carcinoid syndrome. Proximal myopathy has been reported in 7% of patients with carcinoid syndrome. Bronchopulmonary and thymic carcinoids producing adrenocorticotropic hormone can cause Cushing’s syndrome, a main feature of which is myopathy. There are a few reports of carcinoids associated with paraneoplastic neurological syndromes, including neuropathy. We hereby present an extremely rare case of a primary lung carcinoid  presented with paraparesis due to polyneuropathy, and review the relevant literature. To the best of our knowledge there is no similar previous report. Complete resolution of paraparesis after excision of the lung carcinoid suggests  paraneoplastic neurological syndrome.

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[755]

TÍTULO / TITLE:  - Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Dec;4(6):1032-1034. Epub 2012 Sep 27.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.725

AUTORES / AUTHORS:  - Bettio D; Cariboni U; Venci A; Valente M; Spaggiari P; Alloisio M

INSTITUCIÓN / INSTITUTION:  - Cytogenetic and Medical Genetic Laboratory, Operative Unit of Clinical Investigations;

RESUMEN / SUMMARY:  - The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal. Following pneumonectomy, cytogenetic analysis successfully performed on spontaneous metaphases obtained by the direct method from samples of the three lung lobes showed the presence of three clonal cell populations, each progressively having increased karyotype complexity. Fluorescence in situ hybridization (FISH), performed using ALK (2p23) break probe and ALK/EML4 t(2;2);inv(2) fusion probe, showed a normal pattern for all specimens. Histological evaluation confirmed the presence of AC in the superior right lobe and classified the GGO lesion as BAC and the normal tissue of the middle lobe as  AAH. To the best of our knowledge, this is the first case in which the cytogenetic study of spontaneous metaphases showed a clear clonal relationship among AC, BAC and AAH present simultaneously in different lobes of the same lung. This case appears to indicate that the entire lung was somehow predisposed to a neoplastic transformation starting with a diffuse AAH characterized by high proliferative activity. Moreover, the 5q13 region involved in the translocation shared by BAC and AC contains at least 4 genes encoding important regulators of the cell cycle that may be considered new molecular markers of lung cancer.

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[756]

TÍTULO / TITLE:  - Syndrome of inappropriate anti-diuretic hormone in non-small cell lung carcinoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ecancermedicalscience. 2012;6:279. doi: 10.3332/ecancer.2012.279. Epub 2012 Nov 14.

            ●● Enlace al texto completo (gratuito o de pago) 3332/ecancer.2012.279

AUTORES / AUTHORS:  - McDonald P; Lane C; Rojas GE; Masood A

INSTITUCIÓN / INSTITUTION:  - School of Medicine, Wayne State University, Detroit, MI 48201, USA.

RESUMEN / SUMMARY:  - Paraneoplastic syndrome (PNS) related to lung cancer is very common. However, the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is rare in non-small cell lung cancer (NSCLC). We are reporting the case of a 58-year-old female presenting with dyspnea, cough, weight loss, digital clubbing, and one week of haemoptysis. CT showed a mediastinal mass completely encasing her superior vena cava, causing significant narrowing of the trachea and right mainstem bronchus. Bronchoscopy and biopsy identified a non-resectable NSCLC. Palliative radiation therapy was initiated. The day after her first radiation treatment, the patient developed asymptomatic hyponatremia, confirmed to be SIADH by laboratory evaluation. NSCLC-associated SIADH has been reported only thrice over the past two decades and never following radiation therapy with clinical improvement. The patient was discharged home on fluid restriction after her respiratory status improved to continue outpatient radiation and chemotherapy. SIADH in the setting of NSCLC is discussed.

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[757]

TÍTULO / TITLE:  - Small cell carcinoma of the ovary of hypercalcemic type: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol Med. 2012;2012:461873. doi: 10.1155/2012/461873. Epub 2012 Dec 30.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/461873

AUTORES / AUTHORS:  - Zaied S; Gharbi O; Zayene A; Rjiba R; Hadhri R; Hadded A; Hochlef M; Ben Fatma L; Ben Ahmed S

INSTITUCIÓN / INSTITUTION:  - Department of Oncological Medicine, CHU Farhat Hached, 4000 Sousse, Tunisia.

RESUMEN / SUMMARY:  - Introduction. The small cell carcinoma of hypercalcemic type of ovary is a very aggressive tumor. It is associated with two-thirds of cases with hypercalcemia most often asymptomatic. It occurs mostly for young women. The treatment combines surgery, chemotherapy, and radiotherapy. Case Presentation. We report a case of small cell carcinoma of the ovary hypercalcemic type in a young Tunisian woman aged 25 years after a severe abdominal pain syndrome and a large ovarian mass discovered in scanner; a laparotomy was performed by radical surgery. The pathological examination of the specimen confirmed the diagnosis. The radiological assessment performed after surgery showed a continuing evolution. Palliative chemotherapy was established, and the patient had died two months after diagnosis. Conclusion. The hypercalcemic small cell carcinoma of the ovary  is a rare disease of poor prognosis.

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[758]

TÍTULO / TITLE:  - A case of paraneoplastic limbic encephalitis associated with small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberc Respir Dis (Seoul). 2012 Nov;73(5):273-7. doi: 10.4046/trd.2012.73.5.273.  Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 4046/trd.2012.73.5.273

AUTORES / AUTHORS:  - Ryu JY; Lee SH; Lee EJ; Min KH; Hur GY; Lee SY; Kim JH; Lee SY; Shin C; Shim JJ; In KH; Kang KH; Yoo SH

INSTITUCIÓN / INSTITUTION:  - Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to  be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic  resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and  neurologic symptoms gradually improved.

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[759]

TÍTULO / TITLE:  - Breast metastasis from a pulmonary adenocarcinoma: Case report and review of the  literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):328-332. Epub 2012 Oct 25.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.995

AUTORES / AUTHORS:  - Sanguinetti A; Puma F; Lucchini R; Santoprete S; Cirocchi R; Corsi A; Triola R; Avenia N

INSTITUCIÓN / INSTITUTION:  - Endocrine Surgical Unit.

RESUMEN / SUMMARY:  - Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4-1.3% has been reported in the literature. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, diagnosed concomitantly with the primary tumor. A 43-year-old female presented with dyspnea and a dry cough of 3 weeks’ duration. A subsequent chest radiograph  revealed a massive pleural effusion. Additionally, on physical examination, a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent bronchoscopy, simple right mastectomy and medical thoracoscopy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Histologically, both the primary and metastatic anatomic sites demonstrated a micropapillary component, which has recently been recognized as an important prognostic factor. Although the patient received chemotherapy, she succumbed to her condition within 8 months. Accurate differentiation of metastasis from primary carcinoma is very important as the treatment and prognosis of the two differ significantly.

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[760]

TÍTULO / TITLE:  - Limb necrosis in a lung cancer case presenting with widespread thrombosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Report Vasc Med. 2012;2012:172952. doi: 10.1155/2012/172952. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/172952

AUTORES / AUTHORS:  - Erdis E; Karahan O

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Hatay Antakya State Hospital, 31040 Hatay, Turkey.

RESUMEN / SUMMARY:  - The malignancies are commonly associated with enhanced thrombotic vascular events. The thrombotic events are also increased in lung cancer subtypes. Even, the systemic mortal thrombotic disorders were reported in the literature. We report a case of a nonsmall-cell carcinoma patient who progressed with widespread thrombosis.

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[761]

TÍTULO / TITLE:  - Skull destruction from intracranial metastasis arising from pulmonary squamous cell carcinoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Case Rep. 2013 Jan 24;7(1):28.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-7-28

AUTORES / AUTHORS:  - Kader I; Strong M; George M

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Squamous cell carcinoma of the lung represents 30% of all non-small cell lung carcinomas. It arises from dysplasia of squamous epithelium of the bronchi and is strongly associated with cigarette smoking. Squamous cell carcinoma of the lung is known to produce metastases in the brain parenchyma. CASE PRESENTATION: We present the case of an 80-year-old indigenous Australian man with an unusual presentation of metastatic carcinoma of the lung. The case demonstrated a squamous cell carcinoma of the lung with an intracranial metastatic lesion destroying the parietal bone and extending into the extracranial soft tissue. A visible deformity as a result of the metastasis was evident on physical examination and computed tomography demonstrated extensive bone destruction. CONCLUSION: The authors were unable to find a case of this occurring from a squamous cell carcinoma of the lung anywhere in the world literature. The case report demonstrates an unusual disease presentation with a rare intracranial metastasis invading through the skull.

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[762]

TÍTULO / TITLE:  - An unusual case of pulmonary adenocarcinoma with multiple and extraordinary metastases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Jun;9(2):93-8. doi: 10.5812/iranjradiol.7733. Epub 2012 Jun 30.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.7733

AUTORES / AUTHORS:  - Haghighatkhah HR; Sanei Taheri M; Kharrazi SM; Ghazanfari Amlashi D; Haddadi M; Pourabdollah M

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is not uncommon. Hereby, we report a case of pulmonary adenocarcinoma  with multiple muscular, cutaneous, pancreatic and peritoneal metastases. Actually, all these features occurring in one patient makes it an extraordinary case. A rare anatomic variation, double inferior vena cava (IVCs), was another rare manifestation in this case.

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[763]

TÍTULO / TITLE:  - Isolated solitary intramedullary spinal cord metastasis presenting as the first manifestation of small-cell lung cancer: report of a rare case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Report Neurol Med. 2012;2012:617280. doi: 10.1155/2012/617280. Epub 2012 Dec 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/617280

AUTORES / AUTHORS:  - Duransoy YK; Mete M; Selcuki M; Isisag A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Faculty of Medicine, Celal Bayar University, 45040 Manisa, Turkey.

RESUMEN / SUMMARY:  - Background. Intramedullary spinal cord metastases presenting as the first manifestation of malignancies are extremely rare lesions. Case Description. The authors report a 74-year-old woman who presented with an isolated intramedullary  spinal cord metastasis which presents as first manifestation of malignancy without central nervous system and/or other organ involvement. She went under surgery, and after histopathological evaluation, primary focus was determined in  lung in positron emission tomography. She is still alive after 9 months since the first diagnosis of primary focus. Conclusion. In patients with solitary intramedullary lesion in the spinal magnetic resonance imaging, whole-body investigation might help for diagnosis of primary focus and approach to treatment.

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[764]

TÍTULO / TITLE:  - Role of adjuvant chemotherapy after pneumonectomy for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1349-1353. Epub 2012 Sep 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.892

AUTORES / AUTHORS:  - Wang M; Zhao J; Su YJ; Zhao XL; Wang CL

INSTITUCIÓN / INSTITUTION:  - Department of Lung Cancer, Cancer Institute and Hospital, Tianjin Medical University, Key Laboratory of Cancer Prevention and Therapy Tianjin; ; Tianjin Diagnosis and Treatment Center of Lung Cancer;

RESUMEN / SUMMARY:  - Adjuvant chemotherapy is used as an alternative treatment for non-small cell lung cancer (NSCLC); however, the efficiency of post-pneumonectomy adjuvant chemotherapy in NSCLC has not been clarified. In the present study, patients who  benefited from adjuvant chemotherapy with TP/NP/GP were identified. A total of 217 patients who underwent pneumonectomy were identified in this study. Of these, 87 underwent pneumonectomy combined with adjuvant chemotherapy (TP/NP/GP regimen) and 130 underwent pneumonectomy only in the initial management. The primary endpoint of the present study was overall survival. Actuarial survival analysis was conducted using the Kaplan-Meier method. Postoperative adjuvant chemotherapy  significantly improved the survival rate of patients who underwent left pneumonectomy and in patients with a preoperative forced expiratory volume in 1 sec (FEV1) greater than or equal to 21. Age had no effect on the survival rate of patients with or without postoperative adjuvant therapy. Post-pneumonectomy adjuvant chemotherapy is an efficient therapy in NSCLC for patients with preoperative FEV1 greater than or equal to 21 or who received left pneumonectomy.

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[765]

TÍTULO / TITLE:  - EGFR mutation testing in non-small cell lung cancer (NSCLC).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Public Health. 2012 Dec;5 Suppl 1:S31-4. doi: 10.1016/j.jiph.2012.09.008. Epub 2012 Nov 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jiph.2012.09.008

AUTORES / AUTHORS:  - Al Dayel F

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital  and Research Centre, Riyadh, Saudi Arabia. Electronic address: dayelf@kfshrc.edu.sa.

RESUMEN / SUMMARY:  - Lung carcinoma is subdivided into small cell carcinoma and non-small cell carcinoma (NSCLC). NSCLC is heterogeneous group of carcinomas and accounts for 70-80% of lung cancer. NSCLC is further divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with non-small cell lung cancer (NSCLC). These mutations involve exons 18, 19, 20 and 21. Patients harboring these mutations in their tumors show good response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this manuscript is to provide an overview of EGFR mutations in NSCLC as well as to briefly discuss sample requirements and testing guidelines for EGFR mutation.

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[766]

TÍTULO / TITLE:  - Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nanobiotechnology. 2012 Dec 18;10(1):46.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-3155-10-46

AUTORES / AUTHORS:  - Akbarzadeh A; Samiei M; Joo SW; Anzaby M; Hanifehpour Y; Nasrabadi HT; Davaran S

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The aim of present study was to develop the novel methods for chemical and physical modification of superparamagnetic iron oxide nanoparticles (SPIONs) with polymers via covalent bonding entrapment. These modified SPIONs were used for encapsulation of anticancer drug doxorubicin. METHOD: At first approach silane—grafted magnetic nanoparticles was prepared and used as a template for polymerization of the N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) via radical polymerization. This temperature/pH-sensitive  copolymer was used for preparation of DOX—loaded magnetic nanocomposites. At second approach Vinyltriethoxysilane-grafted magnetic nanoparticles were used as  a template to polymerize PNIPAAm-MAA in 1, 4 dioxan and methylene-bis-acrylamide  (BIS) was used as a cross-linking agent. Chemical composition and magnetic properties of Dox—loaded magnetic hydrogel nanocomposites were analyzed by FT-IR, XRD, and VSM. RESULTS: The results demonstrate the feasibility of drug encapsulation of the magnetic nanoparticles with NIPAAm—MAA copolymer via covalent bonding. The key factors for the successful prepardtion of magnetic nanocomposites were the structure of copolymer (linear or cross-linked), concentration of copolymer and concentration of drug. The influence of pH and temperature on the release profile of doxorubicin was examined. The in vitro cytotoxicity test (MTT assay) of both magnetic DOx—loaded nanoparticles was examined. The in vitro tests showed that these systems are no toxicity and are biocompatible. CONCLUSION: IC50 of DOx—loaded Fe3O4 nanoparticles on A549 lung cancer cell line showed that systems could be useful in treatment of lung cancer.

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[767]

TÍTULO / TITLE:  - Prognostic factors before and after recurrence of resected non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Respir Investig. 2012 Dec;50(4):151-6. doi: 10.1016/j.resinv.2012.08.007. Epub 2012 Oct 3.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.resinv.2012.08.007

AUTORES / AUTHORS:  - Baba T; Uramoto H; Takenaka M; Chikaishi Y; Oka S; Shigematsu Y; Hanagiri T; Tanaka F

INSTITUCIÓN / INSTITUTION:  - Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807-8555, Japan.  t-baba@med.uoeh-u.ac.jp

RESUMEN / SUMMARY:  - BACKGROUND: The post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between  surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited. METHODS: From a group of 775 NSCLC patients who consecutively underwent curative surgery, 133 patients showing recurrence were retrospectively  analyzed. RESULTS: Recurrence was most often seen in smokers and patients with advanced stage disease. In patients experiencing relapse, the 1- and 2-year recurrence rates were 58% and 84%, respectively. A multivariate analysis showed that patients who underwent limited surgery, had non-adenocarcinoma disease, or had metastatic lymph node involvement showed early recurrence (p-values: <0.01, 0.04, and 0.04, respectively). Among all relapsed patients, the 2-year overall survival rate after recurrence was 37%. A multivariate analysis demonstrated that patients with lymph node metastasis at the time of surgery and patients who experienced early recurrence were significantly more likely to have a shorter survival time after recurrence (hazard ratio, 1.73; p=0.03; hazard ratio, 2.56; p<0.001, respectively). CONCLUSIONS: Patients who are node-positive, show non-adenocarcinoma disease, and/or undergo limited surgery should receive careful follow-up during the first year after surgery for NSCLC. The present data provide additional information about postoperative recurrence in NSCLC patients.

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[768]

TÍTULO / TITLE:  - Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2012;2:208. doi: 10.3389/fonc.2012.00208. Epub 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00208

AUTORES / AUTHORS:  - Cuaron J; Dunphy M; Rimner A

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center New York, NY, USA.

RESUMEN / SUMMARY:  - The integral role of positron-emission tomography (PET) using the glucose analog  tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early  detection of recurrence. Here, we review the current literature on these aspects  of PET in the management of NSCLC. FDG-PET, particularly integrated (18)F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. (18)F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results  can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. (18)F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on (18)F-FDG-PET scan when CT criteria for malignant involvement are not met. (18)F-FDG-PET scans have  widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. (18)F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. (18)F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3-6 months, using (18)F-FDG-PET to evaluate equivocal CT findings. As high (18)F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, (18)F-FDG-PET-positive findings require pathological confirmation in most cases.  There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable (18)F-FDG-PET response  appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.

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[769]

TÍTULO / TITLE:  - Early Palliative Care in Advanced Lung Cancer: A Qualitative Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Intern Med. 2013 Jan 28:1-8. doi: 10.1001/jamainternmed.2013.1874.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamainternmed.2013.1874

AUTORES / AUTHORS:  - Yoong J; Park ER; Greer JA; Jackson VA; Gallagher ER; Pirl WF; Back AL; Temel JS

RESUMEN / SUMMARY:  - BACKGROUND Early ambulatory palliative care (PC) is an emerging practice, and its key elements have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial that demonstrated improved quality of life, mood, and survival in patients with newly diagnosed metastatic non-small cell lung cancer who received early PC integrated with standard oncologic care vs standard oncologic care alone. Our objectives were to (1) identify key elements of early PC clinic visits, (2) explore the timing of key elements, and (3) compare the content of PC and oncologic visit notes at the critical time points of clinical deterioration and radiographic disease progression. METHODS We randomly selected 20 patients who received early PC and survived within 4 periods: less than 3 months (n = 5), 3 to 6 months (n = 5), 6 to 12 months (n = 5), and 12 to 24 months (n = 5). We performed content analysis on PC and oncologic visit notes from the electronic health records of these patients. RESULTS Addressing symptoms and coping were the most prevalent components of the  PC clinic visits. Initial visits focused on building relationships and rapport with patients and their families and on illness understanding, including prognostic awareness. Discussions about resuscitation preferences and hospice predominantly occurred during later visits. Comparing PC and oncologic care visits around critical time points, both included discussions about symptoms and  illness status; however, PC visits emphasized psychosocial elements, such as coping, whereas oncologic care visits focused on cancer treatment and management  of medical complications. CONCLUSIONS Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a responsive and time-sensitive model. During critical clinical time points, PC and oncologic care visits have distinct features that suggest a key role for PC involvement and enable oncologists to focus on cancer treatment and managing medical complications.

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[770]

TÍTULO / TITLE:  - The role of primary care as part of the multidisciplinary team (MDT) in the management of lung cancer: the “Dream MDT” report - new guidance from the UK Lung Cancer Coalition.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Prim Care Respir J. 2013 Jan 29. pii: pcrj-2012-11-0172. doi: 10.4104/pcrj.2013.00007.

            ●● Enlace al texto completo (gratuito o de pago) 4104/pcrj.2013.00007

AUTORES / AUTHORS:  - Bellamy D; Peake M; Williams A

INSTITUCIÓN / INSTITUTION:  - Retired general practitioner in Bournemouth; member of the UK Lung Cancer Coalition.

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[771]

TÍTULO / TITLE:  - Genome-wide association study identifies a novel susceptibility locus at 12q23.1  for lung squamous cell carcinoma in han chinese.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS Genet. 2013 Jan;9(1):e1003190. doi: 10.1371/journal.pgen.1003190. Epub 2013  Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pgen.1003190

AUTORES / AUTHORS:  - Dong J; Jin G; Wu C; Guo H; Zhou B; Lv J; Lu D; Shi Y; Shu Y; Xu L; Chu M; Wang C; Zhang R; Dai J; Jiang Y; Yu D; Ma H; Zhao X; Yin Z; Yang L; Li Z; Deng Q; Cao S; Qin Z; Gong J; Sun C; Wang J; Wu W; Zhou G; Chen H; Guan P; Chen Y; Liu X; Liu L; Xu P; Han B; Bai C; Zhao Y; Zhang H; Yan Y; Liu J; Amos CI; Chen F; Tan W; Jin L; Wu T; Hu Z; Lin D; Shen H

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key  Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

RESUMEN / SUMMARY:  - Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was  significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19x10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P  = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.

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[772]

TÍTULO / TITLE:  - Factors Influencing a Specific Pathologic Diagnosis of Non-Small-Cell Lung Carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Lung Cancer. 2013 Jan 4. pii: S1525-7304(12)00255-0. doi: 10.1016/j.cllc.2012.11.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.004

AUTORES / AUTHORS:  - Sulpher JA; Owen SP; Hon H; Tobros K; Shepherd FA; Sabri E; Gomes M; Sekhon H; Liu G; Canil CM; Wheatley-Price P

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Department of Medicine, The Ottawa Hospital Cancer  Centre, University of Ottawa, Ottawa, Ontario, Canada.

RESUMEN / SUMMARY:  - INTRODUCTION: Historically, a non-small-cell lung carcinoma diagnosis, without pathologic subclassification, provided sufficient information to guide therapy. Evidence now demonstrates that pathologic subtype classification is central in selecting optimal treatment. This review aimed to identify factors associated with a specific pathologic diagnosis. METHODS: All nonoperative cases of non-small-cell lung carcinoma (NSCLC) referred to the medical oncology divisions  of the Ottawa Hospital Cancer Centre (2008) and Princess Margaret Hospital, Toronto (2007-2010) were identified. The charts were reviewed for demographics, diagnostic methods, and final diagnosis. Logistic regression was performed to identify variables associated with a specific diagnosis. RESULTS: Of 739 patient  records analyzed, 377 (51%) were men, 299 (40%) were aged over 70 years, and 510  (69%) had an Eastern Cooperative Oncology Group performance status of 0-2. Three  hundred and eighty five (52%) of patients were diagnosed in a tertiary academic center. The lung primary was sampled in 503 (68%) of patients. Computed tomography-guided biopsy (n = 370, 50%) and bronchoscopy (n = 179, 24%) were the  most common techniques. Four hundred and seventy seven (65%) of biopsies were cytologic specimens alone, and immunohistochemistry was performed in 337 (46%) of cases. The most common diagnoses were adenocarcinoma (n = 338, 46%), NSCLC not otherwise specified (n = 254, 34%), and squamous cell carcinoma (n = 115, 16%). Overall, 456 (62%) of patients received a specific pathologic diagnosis. Factors  significantly associated with attaining a specific pathologic diagnosis were diagnosis outside an academic center (adjusted odds ratios [OR] 2.1 [95% CI, 1.41-3.14]; P = .0003), histologic laboratory samples (adjusted OR 1.58 [95% CI,  1.003-2.49]; P = .049), and immunohistochemical testing (adjusted OR 1.82 [95% CI, 1.25-2.70], P = .0021). CONCLUSIONS: A significant minority of patients with  NSCLC do not receive a specific pathologic diagnosis. In an era of individualized medicine, this may potentially impact optimal clinical management.

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[773]

TÍTULO / TITLE:  - The peripheral immune response and lung cancer prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncoimmunology. 2012 Nov 1;1(8):1414-1416.

            ●● Enlace al texto completo (gratuito o de pago) 4161/onci.21096

AUTORES / AUTHORS:  - Showe MK; Kossenkov AV; Showe LC

INSTITUCIÓN / INSTITUTION:  - The Wistar Institute; Philadelphia, PA USA.

RESUMEN / SUMMARY:  - Attempts to refine and improve outcome predictions using tumor gene expression have been recently reported. We show that peripheral blood mononuclear cell (PBMC)-associated gene signatures can predict outcome in non-small cell lung carcinoma patients independent of demographic data or TNM staging, and that this  information may persist after tumor resection.

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[774]

TÍTULO / TITLE:  - Prognostic value of LIPC in non-small cell lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Cycle. 2013 Jan 23;12(4).

AUTORES / AUTHORS:  - Galluzzi L; Goubar A; Olaussen KA; Vitale I; Senovilla L; Michels J; Robin A; Dorvault N; Besse B; Validire P; Fouret P; Behrens C; Wistuba II; Soria JC; Kroemer G

INSTITUCIÓN / INSTITUTION:  - Institut Gustave Roussy (IGR); Villejuif, France; Universite Paris Descartes/Paris V; Sorbonne Paris Cite; Paris, France.

RESUMEN / SUMMARY:  - Non-small cell lung carcinoma (NSCLC) is the most common form of lung cancer and  is associated with a high mortality rate worldwide. The majority of individuals bearing NSCLC are treated with surgery plus adjuvant cisplatin, an initially effective therapeutic regimen that, however, is unable to prevent relapse within  5 y after tumor resection in an elevated proportion of patients. The factors that predict the clinical course of NSCLC and its sensitivity to therapy remain largely obscure. One notable exception is provided by pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. PDXK has recently been shown to be required for optimal cisplatin responses in vitro and in vivo and to constitute a bona fide prognostic marker in the NSCLC setting. Together with PDXK, 84 additional factors were identified that influence the response of NSCLC cells to cisplatin in vitro including the hepatic lipase LIPC. Here, we report that the intratumoral levels of LIPC, as assessed by immunohistochemistry  in two independent cohorts of NSCLC patients, positively correlate with disease outcome. In one out of two cohorts studied, the overall survival of NSCLC patients bearing LIPC (high) lesions was unaffected, if not slightly worsened, by cisplatin-based adjuvant therapy. Conversely, the overall survival of patients with LIPC (low) lesions was prolonged by post-operative cisplatin. Pending validation in appropriate clinical series, these results suggest that LIPC (low)  NSCLC patients would be those who mainly benefit from adjuvant cisplatin therapy. Thus, the expression levels of LIPC appear to have an independent prognostic value (and perhaps a predictive potential) in the setting of NSCLC. If these findings were confirmed by additional studies, LIPC expression levels might allow not only for NSCLC patient stratification, but also for the implementation of personalized therapeutic approaches.

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[775]

TÍTULO / TITLE:  - Achaete-Scute Complex Homolog-1 Promotes DNA Repair in the Lung Carcinogenesis through Matrix Metalloproteinase-7 and O(6)-Methylguanine-DNA Methyltransferase.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52832. doi: 10.1371/journal.pone.0052832. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052832

AUTORES / AUTHORS:  - Wang XY; Jensen-Taubman SM; Keefe KM; Yang D; Linnoila RI

INSTITUCIÓN / INSTITUTION:  - Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

RESUMEN / SUMMARY:  - Lung cancer is the leading cause of cancer-related deaths in the world. Achaete-scute complex homolog-1 (Ascl1) is a member of the basic helix-loop-helix (bHLH) transcription factor family that has multiple functions in the normal and  neoplastic lung such as the regulation of neuroendocrine differentiation, prevention of apoptosis and promotion of tumor-initiating cells. We now show that Ascl1 directly regulates matrix metalloproteinase-7 (MMP-7) and O(6)-methylguanine-DNA methyltransferase (MGMT). Loss- and gain-of-function experiments in human bronchial epithelial and lung carcinoma cell lines revealed  that Ascl1, MMP-7 and MGMT are able to protect cells from the tobacco-specific nitrosamine NNK-induced DNA damage and the alkylating agent cisplatin-induced apoptosis. We also examined the role of Ascl1 in NNK-induced lung tumorigenesis in vivo. Using transgenic mice which constitutively expressed human Ascl1 in airway lining cells, we found that there was a delay in lung tumorigenesis. We conclude that Ascl1 potentially enhances DNA repair through activation of MMP-7 and MGMT which may impact lung carcinogenesis and chemoresistance. The study has  uncovered a novel and unexpected function of Ascl1 which will contribute to better understanding of lung carcinogenesis and the broad implications of transcription factors in tobacco-related carcinogenesis.

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[776]

TÍTULO / TITLE:  - beta-Cryptoxanthin Restores Nicotine-Reduced Lung SIRT1 to Normal Levels and Inhibits Nicotine-Promoted Lung Tumorigenesis and Emphysema in A/J Mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Prev Res (Phila). 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0368

AUTORES / AUTHORS:  - Iskandar AR; Liu C; Smith DE; Hu KQ; Choi SW; Ausman LM; Wang XD

INSTITUCIÓN / INSTITUTION:  - 1Nutrition and Cancer Biology Lab, Jean-Mayer USDA HNRCA at Tufts University, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University.

RESUMEN / SUMMARY:  - Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent.  Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied by significant reductions in survival probability and lung Sirtuin 1 (SIRT1) expression, which has been proposed as a tumor suppressor. The decreased level of SIRT1 was associated with  increased levels of AKT phosphorylation and interleukin (il)-6 mRNA but decreased tumor suppressor p53 and retinoic acid receptor (RAR)-beta mRNA levels in the lungs. Using this mouse model, we then determined whether beta-cryptoxanthin (BCX), a xanthophyll that is strongly associated with a reduced risk of lung cancer in several cohort studies, can inhibit nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses was associated with reductions of the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed expression of lung SIRT1, p53, and RAR-beta to that of the control group, increased survival probability; and decreased the levels of lung il-6 mRNA and phosphorylation of AKT. The present study indicates that BCX is a preventive agent against emphysema and lung cancer with SIRT1 as a potential target. In addition, our study establishes a relevant animal lung cancer model for studying tumor growth within  emphysematous microenvironments.

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[777]

TÍTULO / TITLE:  - Urotensin II contributes to the formation of lung adenocarcinoma inflammatory microenvironment through the NF-kappaB pathway in tumor-bearing nude mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1259-1263. Epub 2012 Sep 21.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.932

AUTORES / AUTHORS:  - Zhou CH; Wan YY; Chu XH; Song Z; Xing SH; Wu YQ; Yin XX

INSTITUCIÓN / INSTITUTION:  - School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004;

RESUMEN / SUMMARY:  - Urotensin II (UII), a somatostatin-like cyclic peptide, was originally isolated from the fish urophysis. Our previous study showed that UII stimulates the proliferation of A549 lung adenocarcinoma cells and promotes tumor growth in a nude mouse xenograft model, suggesting that UII may contribute to the pathogenesis of lung adenocarcinoma. In this study, the underlying mechanism for  UII to promote lung adenocarcinoma growth was explored by observing the effect of UII on the tumor inflammatory microenvironment in tumor-bearing nude mice. Immunohistochemical analysis showed that UII promoted the infiltration of CD68(+) tumor-associated macrophages (TAMs) in the tumor micro-environment. Enzyme-linked immunosorbent assay (ELISA) demonstrated that UII promoted the release of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9). Western blot analysis showed that UII promoted the activation of nuclear factor-kappaB (NF-kappaB). These findings suggest that the  enhanced levels of IL-6, TNF-alpha and MMP-9 in the tumor microenvironment, which likely resulted from increased activation of NF-kappaB induced by UII, may be one of the important mechanisms by which UII promotes lung adenocarcinoma growth. These findings imply that antagonists of UII or urotensin II-receptor (UT-R) have potential for the prevention and treatment of lung adenocarcinoma.

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[778]

TÍTULO / TITLE:  - Low-dose gamma-radiation inhibits benzo[a]pyrene-induced lung adenoma development in a/j mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dose Response. 2012 Dec;10(4):516-26. doi: 10.2203/dose-response.12-040.Bruce. Epub 2012 Nov 22.

            ●● Enlace al texto completo (gratuito o de pago) 2203/dose-response.12-040.Bruce

AUTORES / AUTHORS:  - Bruce VR; Belinsky SA; Gott K; Liu Y; March T; Scott B; Wilder J

INSTITUCIÓN / INSTITUTION:  - University of New Mexico, Biomedical Sciences Graduate Program, Health Sciences Center, and Lovelace Respiratory Research Institute, Respiratory Immunology Program, Albuquerque, NM.

RESUMEN / SUMMARY:  - Low-dose ionizing radiation (LDR) may lead to suppression of smoking-related lung cancer. We examined the effects of a known cigarette smoke carcinogen Benzo[a]pyrene (B[a]P) alone or in combination with fractionated low-dose gamma radiation (60 - 600 mGy total dose) on the induction of lung neoplasms in the A/J mouse. Our results show that 600 mGy of gamma radiation delivered in six biweekly fractions of 100 mGy starting 1 month after B[a]P injection significantly inhibits the development of lung adenomas per animal induced by B[a]P. Our data also indicated that the six biweekly doses suppressed the occurrence of spontaneous hyperplastic foci in the lung, although this suppression failed to reach statistical significance when analyzed as average foci per lung possibly related to the small sample sizes used for the control and test groups.

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[779]

TÍTULO / TITLE:  - Second Complete Remission of Relapsed Stage IV Non-Small Cell Lung Cancer Following Retreatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tuberc Respir Dis (Seoul). 2012 Apr;72(4):381-5. doi: 10.4046/trd.2012.72.4.381.  Epub 2012 Apr 30.

            ●● Enlace al texto completo (gratuito o de pago) 4046/trd.2012.72.4.381

AUTORES / AUTHORS:  - Yoo SJ; Lee JE; Jung SY; Park DI; Park MR; Park HS; Jung SS; Kim JO; Kim SY

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Chungnam National University Hospital & Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Korea.

RESUMEN / SUMMARY:  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now, they have received each regimen, continuously, and the CR state has been maintained.

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[780]

TÍTULO / TITLE:  - Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e53449. doi: 10.1371/journal.pone.0053449. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053449

AUTORES / AUTHORS:  - Ma X; Yao Y; Yuan D; Liu H; Wang S; Zhou C; Song Y

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

RESUMEN / SUMMARY:  - BACKGROUND: Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE. METHODS AND MATERIALS: Lewis lung carcinoma (LLC) cell line expressing  enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose  of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel  density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining. RESULTS: The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups. CONCLUSION: Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.

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[781]

TÍTULO / TITLE:  - Residential segregation and lung cancer mortality in the United States.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Surg. 2013 Jan 1;148(1):37-42. doi: 10.1001/jamasurgery.2013.408.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamasurgery.2013.408

AUTORES / AUTHORS:  - Hayanga AJ; Zeliadt SB; Backhus LM

RESUMEN / SUMMARY:  - OBJECTIVE To examine the relationship between race and lung cancer mortality and  the effect of residential segregation in the United States. DESIGN A retrospective, population-based study using data obtained from the 2009 Area Resource File and Surveillance, Epidemiology and End Results program. SETTING Each county in the United States. PATIENTS Black and white populations per US county. MAIN OUTCOME MEASURES A generalized linear model with a Poisson distribution and log link was used to examine the association between residential segregation and lung cancer mortality from 2003 to 2007 for black and white populations. Our primary independent variable was the racial index of dissimilarity. The index is a demographic measure that assesses the evenness with which whites and blacks are distributed across census tracts within each county.  The score ranges from 0 to 100 in increasing degrees of residential segregation.  RESULTS The overall lung cancer mortality rate was higher for blacks than whites  (58.9% vs 52.4% per 100 000 population). Each additional level of segregation was associated with a 0.5% increase in lung cancer mortality for blacks (P &lt; .001) and an associated decrease in mortality for whites (P = .002). Adjusted lung cancer mortality rates among blacks were 52.4% and 62.9% per 100 000 population in counties with the least (&lt;40% segregation) and the highest levels of segregation (>/=60% segregation), respectively. In contrast, the adjusted lung cancer mortality rates for whites decreased with increasing levels of segregation. CONCLUSION Lung cancer mortality is higher in blacks and highest in  blacks living in the most segregated counties, regardless of socioeconomic status.

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[782]

TÍTULO / TITLE:  - Pushing the envelope of disparity research to find modifiable factors: comment on “residential segregation and lung cancer mortality in the United States”.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Surg. 2013 Jan 1;148(1):42-3. doi: 10.1001/jamasurgery.2013.405.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamasurgery.2013.405

AUTORES / AUTHORS:  - Chang DC

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[783]

TÍTULO / TITLE:  - Diagnosis of lung cancer: a bronchoscopist’s perspective.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2012 Jan;19(1):12-8. doi: 10.1097/LBR.0b013e3182425b5d.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e3182425b5d

AUTORES / AUTHORS:  - Griffin JP; Zaman MK; Niell HB; Tolley EA; Cole FH Jr; Weiman DS

INSTITUCIÓN / INSTITUTION:  - Pulmonary/Critical Care Section, Memphis Veterans Affairs Medical Center, Memphis, TN 38163, USA. jpgriffin@uthsc.edu

RESUMEN / SUMMARY:  - BACKGROUND: Guidelines recommend multiple types of cytologic and tissue samplings in the diagnosis of lung cancer by bronchoscopy, but differences of opinion exist as to the relative value of bronchial brushings and endobronchial or transbronchial biopsies. Our objective was to determine concordance of these procedures by a test of symmetry in a historical cohort referred to the pulmonary diagnostic laboratory. METHODS: From 1988 to 2001, patients with pathologic confirmation of primary lung cancer were examined by standard bronchoscopic techniques of that period. An electronic medical record system was used, with statistical analysis of symmetry between brushings and biopsies establishing the  diagnosis. RESULTS: Of 968 patients, 98% had bronchoscopy for 624 central and 322 peripheral suspect lesions. Bronchial brushings from 915 patients confirmed pulmonary malignancy in 811 (89%) patients. Endobronchial or transbronchial biopsies from 739 patients showed lung cancer in 603 (82%) cases. Bronchial washings in 16 patients and transthoracic needle biopsies in 30 patients established diagnosis. Transbronchial needle aspiration of mediastinal nodes identified metastases in 94 patients. Only 14 patients required a surgical procedure for diagnosis, but 188 received surgical excision as primary treatment. Statistical evaluation used only patients with both bronchial brushings and endobronchial or transbronchial biopsies. Analysis by a test of symmetry showed a significant difference (P<0.0001). CONCLUSIONS: Positive, suspicious, and negative specimens were consistent, with bronchial brushings being more sensitive with a lower false-negative rate than endobronchial or transbronchial biopsies. Multiple techniques are recommended for bronchoscopic confirmation of lung cancer, but bronchial brushings should be collected initially, as technical or patient limitations might preclude diagnostic tissue biopsies.

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[784]

TÍTULO / TITLE:  - Fine needle aspiration diagnosis of pulmonary hamartoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cytol. 2012 Oct;29(4):250-1. doi: 10.4103/0970-9371.103944.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0970-9371.103944

AUTORES / AUTHORS:  - Handa U; Mundi I; Saini V

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Government Medical College and Hospital, Chandigarh, India.

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[785]

TÍTULO / TITLE:  - Mesothelioma - Update on Diagnostic Strategies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Pulm Med. 2012 Nov;19(6):282-288.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CPM.0b013e318272ce61

AUTORES / AUTHORS:  - Rosario CM; Lin X; Kamp DW

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Pulmonary & Critical Care Medicine, Jesse Brown VA Medical Center and Northwestern University Feinberg School of Medicine,  240 E. Huron, McGaw M-330, Chicago, IL 60611.

RESUMEN / SUMMARY:  - Malignant pleural mesothelioma (MPM) can be a challenging diagnosis for clinicians to make as it is often difficult to distinguish from benign asbestos pleural effusions and metastatic carcinomas. In this review, we present a case of MPM and discuss clinical manifestations, traditional diagnostic techniques, and the role of cytopathologic immunostains and serum biomarkers in the diagnosis of  MPM.

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[786]

TÍTULO / TITLE:  - How Have We Diagnosed Early-Stage Lung Cancer without Radiographic Screening? A Contemporary Single-Center Experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52313. doi: 10.1371/journal.pone.0052313. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052313

AUTORES / AUTHORS:  - Taiwo EO; Yorio JT; Yan J; Gerber DE

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America ; Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of  America.

RESUMEN / SUMMARY:  - BACKGROUND: The National Lung Screening Trial (NLST), which demonstrated a reduction in lung cancer mortality, may result in widespread computed tomography  (CT)-based screening of select populations. How early-stage lung cancer has been  diagnosed without screening, and what proportion of these cases would be captured by a screening program modeled on the NLST, is not currently known. We therefore  evaluated current patterns of early-stage lung cancer presentation. METHODOLOGY/PRINCIPAL FINDINGS: We performed a single-institution retrospective analysis of patients diagnosed with stage I-II non-small cell lung cancer (NSCLC) from 2000-2009. Associations between patient and imaging characteristics were assessed using univariate and multivariate analyses. A total of 412 patients met  criteria for analysis. Among those with available reason for initial imaging, the reason was symptoms in 51%, follow-up of other conditions in 43%, and screening in 6%. Reason for imaging was associated with race (P<0.001), insurance type (P = 0.005), and disease stage (P<0.001). Type of initial imaging was associated with  reason for imaging (P<0.001), year (chest x-ray 67% in 2000-2004 vs. 49% in 2005-2009; P<0.001), and disease stage (P = 0.005). Among patients with available quantified smoking history, 48% were age 55-74 years and smoked 30-plus pack-years, therefore meeting NLST entry criteria. CONCLUSIONS/SIGNIFICANCE: Symptoms remain a dominant but declining reason for detection of early-stage NSCLC. The proportion of cases detected initially by CT scan without antecedent chest x-ray has increased considerably. Because as few as half of cases meet NLST eligibility criteria, clinicians should remain aware of the diverse circumstances of early-stage lung cancer presentation to expedite therapy.

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[787]

TÍTULO / TITLE:  - Molecular dissection of AKT activation in lung cancer cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0558

AUTORES / AUTHORS:  - Guo Y; Du J; Kwiatkowski DJ

INSTITUCIÓN / INSTITUTION:  - Brigham and Women’s Hospital and Harvard Medical School.

RESUMEN / SUMMARY:  - AKT is a critical signaling node downstream of PI3K, which is often activated in  cancer. We analyzed the state of activation of AKT in 80 human non-small cell lung cancer cell lines under serum starvation conditions. We identified 13 lines  which showed persistent AKT activation in the absence of serum. In 12 of the 13 lines, AKT activation could be attributed to loss of PTEN, activating mutation in EGFR or PIK3CA, or amplification of ERBB2. HCC2429 was the only cell line that had no alterations in those genes, but had high phospho-AKT(Ser473) levels under  serum starvation conditions. However, the activation of AKT in HCC2429 was PI3K-  and mTORC2- dependent based upon use of specific inhibitors. Kinome tyrosine phosphorylation profiling showed that both Notch and SRC were highly activated in this cell line. Despite the activation of Notch, AKT activation and cell survival were not affected by Notch inhibitors DAPT or Compound E. In contrast, SRC inhibitors PP2 and dasatinib both significantly decreased pAKT(Ser473) levels and reduced cell survival by inducing apoptosis. Further, a combination of SRC and mTOR inhibition synergistically blocked activation of AKT and induced apoptosis.  Over-expression of SRC has been identified previously in human lung cancers, and  these results suggest that a combination of SRC and mTOR inhibitors may have unique therapeutic benefit for a subset of lung cancers with these molecular features.

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[788]

TÍTULO / TITLE:  - High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cytopathol. 2012 Dec 5. doi: 10.1002/cncy.21260.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21260

AUTORES / AUTHORS:  - Sun PL; Jin Y; Kim H; Lee CT; Jheon S; Chung JH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea; Department  of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Activating mutations in the epidermal growth factor receptor (EGFR) in non-small cell lung carcinoma (NSCLC) are associated significantly with responsiveness to EGFR tyrosine kinase inhibitors. The objective of this study was to investigate the suitability of cytologic specimens for assessing EGFR mutations in lung adenocarcinomas. METHODS: Sixty paired histologic and cytologic specimens of lung adenocarcinoma were collected. Exons 18 through 21 of the EGFR  gene were amplified using polymerase chain reaction, and the mutation status of each sample was analyzed by pyrosequencing. A comparison of EGFR mutation status  between histologic specimens and cytologic specimens was performed. RESULTS: The  overall EGFR mutation concordance rate between histologic specimens and corresponding cytologic specimens was 91.7%. No significant difference was observed in the concordance rate between cytologic specimens from primary lesions and specimens from metastatic lesions (P = .63). The following parameters were correlated with the most reliable EGFR mutation results using the pyrosequencing  method (100% concordance with the corresponding histologic specimens) in cytologic samples: a DNA concentration >25 ng/muL, content of >30 tumor cells, or a tumor percentage >30%. CONCLUSIONS: In this study, routinely prepared cytologic specimens were reliable sources for assessing EGFR mutation status. The authors concluded that cytologic specimens from metastatic lesions and primary tumors are suitable for the successful assessment of EGFR mutation status. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.

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[789]

TÍTULO / TITLE:  - Image-guided percutaneous transthoracic biopsy in lung cancer - Emphasis on CT-guided technique.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Public Health. 2012 Dec;5 Suppl 1:S22-30. doi: 10.1016/j.jiph.2012.09.001. Epub 2012 Nov 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jiph.2012.09.001

AUTORES / AUTHORS:  - Khankan AA; Al-Muaikeel M

INSTITUCIÓN / INSTITUTION:  - Department of Medical Imaging, King Abdulaziz Medical City, Riyadh, Saudi Arabia. Electronic address: Khankan@ngha.med.sa.

RESUMEN / SUMMARY:  - Image-guided percutaneous transthoracic core biopsy especially with CT guidance is playing an increasing role in the diagnosis and management of lung cancer. The recent advances in the specific chemotherapy and novel targeted therapy and the increasing need for specific diagnosis of tumor histopathologic subtypes have direct impact on the radiologists performing lung biopsy and important implications for the biopsy technique. Close cooperation between radiologists and referring physicians with understanding of the technical aspects of the biopsy procedure can help clinicians make appropriate referrals for this procedure and understand the significance and limitations of the results. Additionally, the appropriate management of complications can limit morbidity related to the biopsy procedure.

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[790]

TÍTULO / TITLE:  - CLPTM1L Is Overexpressed in Lung Cancer and Associated with Apoptosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52598. doi: 10.1371/journal.pone.0052598. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052598

AUTORES / AUTHORS:  - Ni Z; Tao K; Chen G; Chen Q; Tang J; Luo X; Yin P; Tang J; Wang X

INSTITUCIÓN / INSTITUTION:  - Central Lab, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - CLPTM1L is believed to be associated with lung cancer. However, there is little information regarding its expression and function. Here using immunohistochemistry, we found that CLPTM1L expression was markedly increased in  lung cancer tissues relative to normal tissues, especially in lung adenocarcinoma. CLPTM1L expression was not found to be associated with stages, smoking status, lymph node metastasis, or T lymphocyte infiltration but with differentiation stage. We found CLPTM1L to be enriched in the mitochondrial compared with plasma membrane protein extracts. CLPTM1L-EGFP transfection showed  that the molecule product was expressed in cytoplasm and indicated the mitochondrial localization stained with mitochondrial marker MitoTracker. CLPTM1L transferred lung cancer cell line 95-D showed no growth inhibition or cell apoptosis, but it did show inhibited sensitivity to cis-diamminedichloroplatinum(II) (cisplatin, CDDP). Knockdown of CLPTM1L by RNAi  did not interfere with cell proliferation but it did increase cell sensitivity to CDDP and activation of caspase-9 and caspase-3/7. These data indicate CLPTM1L is  a mitochondria protein and that it may be associated with anti-apoptotic mechanism which affects drug-resistance in turn.

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[791]

TÍTULO / TITLE:  - Impact of the 7th TNM staging lung cancer in surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Infect Public Health. 2012 Dec;5 Suppl 1:S41-4. doi: 10.1016/j.jiph.2012.09.010. Epub 2012 Nov 6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jiph.2012.09.010

AUTORES / AUTHORS:  - Bamousa A; Alkattan K

INSTITUCIÓN / INSTITUTION:  - Riyadh Military Hospital, Riyadh, Saudi Arabia. Electronic address: ahbamousa@yahoo.com.

RESUMEN / SUMMARY:  - Accurate staging of lung cancer is very critical to determine the proper management approach of each patient and to address prognosis issues. In this manuscript, we will discuss the impact of the most recent staging categories (7th TNM staging) on the management of non-small cell lung cancer.

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[792]

TÍTULO / TITLE:  - Advances in lung cancer surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Carcinog. 2012;11:21. doi: 10.4103/1477-3163.105341. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1477-3163.105341

AUTORES / AUTHORS:  - Hennon MW; Yendamuri S

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Roswell Park Cancer Institute, NY, USA ; Department of Surgery, State University of New York, Buffalo, NY, USA.

RESUMEN / SUMMARY:  - The last few years have witnessed an explosion of the use of minimally invasive techniques for the detection, diagnosis, and treatment of all stages of lung Cancer. The use of these techniques has improved the risk-benefit ratio of surgery and has made it more acceptable to patients considering lung surgery. They have also facilitated the delivery of multi-modality therapy to patients with advanced lung cancer. This review article summarizes current surgical techniques that represent the “cutting edge” of thoracic surgery for lung cancer.

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[793]

TÍTULO / TITLE:  - Anti-Lung-Cancer Activity and Liposome-Based Delivery Systems of beta-Elemene.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Evid Based Complement Alternat Med. 2012;2012:259523. doi: 10.1155/2012/259523. Epub 2012 Nov 28.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/259523

AUTORES / AUTHORS:  - Chen M; Zhang J; Yu S; Wang S; Zhang Z; Chen J; Xiao J; Wang Y

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.

RESUMEN / SUMMARY:  - In the past decade, beta-elemene played an important role in enhancing the effects of many anticancer drugs and was widely used in the treatment of different kinds of malignancies and in reducing the side effects of chemotherapy. Further study showed that it is also a promising anti-lung cancer drug. However,  the clinical application of beta-elemene was limited by its hydrophobic property, poor stability, and low bioavailability. With the development of new excipients and novel technologies, plenty of novel formulations of beta-elemene have improved dramatically, which provide a positive perspective in terms of clinical  application for beta-elemene. Liposome as a drug delivery system shows great advantages over traditional formulations for beta-elemene. In this paper, we summarize the advanced progress being made in anti-lung cancer activity and the new liposomes delivery systems of beta-elemene. This advancement is expected to improve the level of pharmacy research and provide a stronger scientific foundation for further study on beta-elemene.

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[794]

TÍTULO / TITLE:  - Histologic and molecular characterization of lung cancer with tissue obtained by  electromagnetic navigation bronchoscopy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2013 Jan;20(1):10-5. doi: 10.1097/LBR.0b013e31828197e9.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e31828197e9

AUTORES / AUTHORS:  - Ha D; Choi H; Almeida FA; Arrossi A; Brainard J; Cicenia J; Farver C; Gildea T; Machuzak MS; Mazzone P

INSTITUCIÓN / INSTITUTION:  - *Department of Internal Medicine daggerRespiratory Institute double daggerPathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.

RESUMEN / SUMMARY:  - BACKGROUND: : Electromagnetic navigation bronchoscopy (ENB) is a catheter-based adjunct to standard bronchoscopic techniques for the sampling of lung lesions. We sought to evaluate the adequacy of ENB-obtained samples for histologic subtyping  of lung cancer, epidermal growth factor receptor (EGFR) mutations, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocations. METHODS: : We retrospectively analyzed consecutive patients who underwent ENB for the diagnosis of lung lesions between 2008 and 2011. In those proven to be a primary lung cancer by ENB, tissue adequacy for histologic subtyping was recorded. Accuracy was determined by comparison with resected specimens when available. Tissue adequacy for EGFR mutation and/or EML4-ALK analyses was also reviewed. RESULTS: : Sixty-five ENB cases resulted in a diagnosis of lung cancer. Tissues obtained were adequate for histologic subtyping in all 65 cases. Forty-three (66.2%) were diagnosed with adenocarcinoma, 19 (29.2%) with squamous cell carcinoma, 3 (4.6%) with small cell carcinoma. In 51 cases (78.5%), subtyping was performed by morphology alone, whereas 11 (21.5%) required immunohistochemical staining. Sixteen of 65 tumors underwent surgical resection. Concordance of histologic subtyping between ENB and surgical specimens was 87.5% (14 tumors). ENB-obtained samples from 15 patients with adenocarcinoma  were sent for EGFR mutation analysis, of which 14 (93.3%) were adequate. Samples  from 2 patients were evaluated for EML4-ALK gene rearrangements, both of which were adequate for analysis. CONCLUSIONS: : ENB is effective at obtaining tissue samples adequate for histologic subtyping, EGFR mutation, and EML4-ALK translocation analysis.

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[795]

TÍTULO / TITLE:  - Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):625-630. Epub 2012 Jul 20.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.815

AUTORES / AUTHORS:  - Shigematsu Y; Hanagiri T; Shiota H; Kuroda K; Baba T; Ichiki Y; Yasuda M; Uramoto H; Takenoyama M; Yasumoto K; Tanaka F

INSTITUCIÓN / INSTITUTION:  - Second Department of Surgery, School of Medicine, University of Occupational and  Environmental Health, Kitakyushu, Yahatanishi 807-8555, Japan.

RESUMEN / SUMMARY:  - It is not easy to induce cytotoxic T lymphocytes (CTLs) against cancer in in vitro culture. Regulatory T cells (Tregs) are considered to play a pivotal role in tumor immune escape. In this study, we analyzed the distribution of Tregs among tumor-infiltrating lymphocytes (TILs), regional lymph node lymphocytes (RLNLs) and peripheral blood lymphocytes (PBLs) in patients with lung cancer, and analyzed the effect of Tregs on the induction of CTLs in vitro. A total of 84 patients with non-small cell lung cancer underwent surgery between January 2003 and December 2004. The TILs, RLNLs and PBLs from these patients were subjected to a comparison analysis. The proportion of CD4(+)CD25(+)Foxp3(+) cells in these lymphocytes was determined by flow cytometry. The effects of Tregs on the induction of CTLs was analyzed by the depletion of Tregs in mixed lymphocyte-tumor cell culture (MLTC). The average proportions of Tregs in the TILs, RLNLs and PBLs were 10.4+/-9.5, 4.4+/-2.4 and 2.8+/-2.1%, respectively. The proportion of Tregs in the RLNLs was significantly higher than that in the PBLs (P<0.001); furthermore, TILs contained a larger number of Tregs than RLNLs (P=0.034). These Tregs substantially suppressed the induction of CTLs against autologous tumor cells. The depletion of Tregs in the MLTC resulted in the successful induction of CTLs. Tregs were found at a higher frequency in the TILs  and RLNLs than in the PBLs in lung cancer patients. Since Tregs inhibited the induction of CTLs, the depletion of Tregs may represent a new therapeutic strategy for lung cancer patients.

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[796]

TÍTULO / TITLE:  - Two Panels of Plasma MicroRNAs as Non-Invasive Biomarkers for Prediction of Recurrence in Resectable NSCLC.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54596. doi: 10.1371/journal.pone.0054596. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054596

AUTORES / AUTHORS:  - Sanfiorenzo C; Ilie MI; Belaid A; Barlesi F; Mouroux J; Marquette CH; Brest P; Hofman P

INSTITUCIÓN / INSTITUTION:  - Institute for Research on Cancer and Ageing in Nice IRCAN, INSERM U1081 - CNRS UMR 7284, Team 3, Nice, France ; University Hospital Center of Nice, Pasteur Hospital, Department of Pneumology, Nice, France ; University of Nice Sophia Antipolis, Faculty of Medicine, Team 3, Nice, France.

RESUMEN / SUMMARY:  - The diagnosis of non-small cell lung carcinoma (NSCLC) at an early stage, as well as better prediction of outcome remains clinically challenging due to the lack of specific and robust non-invasive markers. The discovery of microRNAs (miRNAs), particularly those found in the bloodstream, has opened up new perspectives for tumor diagnosis and prognosis. The aim of our study was to determine whether expression profiles of specific miRNAs in plasma could accurately discriminate between NSCLC patients and controls, and whether they are able to predict the prognosis of resectable NSCLC patients. We therefore evaluated a series of seventeen NSCLC-related miRNAs by quantitative real-time (qRT)-PCR in plasma from 52 patients with I-IIIA stages NSCLC, 10 patients with chronic obstructive pulmonary disease (COPD) and 20-age, sex and smoking status-matched healthy individuals. We identified an eleven-plasma miRNA panel that could distinguish NSCLC patients from healthy subjects (AUC = 0.879). A six-plasma miRNA panel was  able to discriminate between NSCLC patients and COPD patients (AUC = 0.944). Furthermore, we identified a three-miRNA plasma signature (high miR-155-5p, high  miR-223-3p, and low miR-126-3p) that significantly associated with a higher risk  for progression in adenocarcinoma patients. In addition, a three-miRNA plasma panel (high miR-20a-5p, low miR-152-3p, and low miR-199a-5p) significantly predicted survival of squamous cell carcinoma patients. In conclusion, we identified two plasma miRNA expression profiles that may be useful for predicting the outcome of patients with resectable NSCLC.

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[797]

TÍTULO / TITLE:  - 2-[18 F]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) findings of chronic expanding intrapericardial hematoma: a potential interpretive pitfall that mimics a malignant tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cardiothorac Surg. 2013 Jan 17;8:13. doi: 10.1186/1749-8090-8-13.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1749-8090-8-13

AUTORES / AUTHORS:  - Tokue H; Tokue A; Okauchi K; Tsushima Y

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic and Interventional Radiology, Gunma University Hospital, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. tokue@s2.dion.ne.jp.

RESUMEN / SUMMARY:  - ABSTRACT: A 77-year-old man who had undergone mitral valve replacement 5 years previously presented with an intrapericardial mass. Computed tomography and magnetic resonance imaging showed that the mass lesion contained hematoma components. Positron-emission tomography (PET) with 2-[18 F] fluoro-2-deoxy-d-glucose (FDG) revealed uptake in the peripheral rim of the mass. These findings suggested the presence of hematoma associated with a malignant lesion. Surgical resection was performed, and the histological diagnosis was chronic expanding intrapericardial hematoma without neoplastic changes. Chronic expanding intrapericardial hematoma is a rare disease but should be considered when an expanding mass is found in a patient after cardiac surgery. The FDG-PET findings of chronic expanding hematomas, including FDG uptake in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential  interpretive pitfall that mimics a malignant tumor.

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[798]

TÍTULO / TITLE:  - Lung cancer with scattered consolidation: detection of new independent radiological category of peripheral lung cancer on thin-section computed tomography.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interact Cardiovasc Thorac Surg. 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs520

AUTORES / AUTHORS:  - Matsunaga T; Suzuki K; Hattori A; Fukui M; Kitamura Y; Miyasaka Y; Takamochi K; Oh S

INSTITUCIÓN / INSTITUTION:  - Division of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.

RESUMEN / SUMMARY:  - OBJECTIVESGround glass opacity (GGO) on thin-section computed tomography (CT) has been reported to be a favourable prognostic marker in lung cancer, and the size or area of GGO is commonly used for preoperative evaluation. However, it can sometimes be difficult to evaluate the status of GGO.METHODSA retrospective study was conducted on 572 consecutive patients with resected lung cancer of clinical stage IA between 2004 and 2011. All patients underwent preoperative CT and their  radiological findings were reviewed. The areas of consolidation and GGO were evaluated for all lung cancers. Lung cancers were divided into three categories on the basis of the status of GGO: GGO, part solid and pure solid. Lung cancers in which it was difficult to measure GGO were selected and their clinicopathological features were investigated.RESULTSSeventy-one (12.4%) patients had lung cancer in whom it was difficult to measure GGO. In all these cases, consolidation and GGO were not easily measured because of their scattered  distribution. In this cohort, nodal metastases were not observed at all. The frequency of other pathological factors, such as lymphatic and/or vascular invasion, was significantly lower (P < 0.0001).CONCLUSIONSThis new category of lung cancer with scattered consolidation on thin-section CT scan tended to be pathologically less invasive. When lung cancer has GGO and is difficult to measure because of a scattered distribution, its prognosis could be favourable regardless of the area of GGO. This new category could be useful for the preoperative evaluation of lung cancer.

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[799]

TÍTULO / TITLE:  - Pulmonary adenocarcinoma with osseous metastasis and secondary paresis in a blue  and gold macaw (Ara ararauna).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Zoo Wildl Med. 2012 Dec;43(4):909-13.

AUTORES / AUTHORS:  - Fredholm DV; Carpenter JW; Shumacher LL; Moon RS

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Sciences College of Veterinary Medicine, Kansas State University, Manhattan, 66506, USA. dfredholm@ufl.edu

RESUMEN / SUMMARY:  - A 16-yr-old female blue and gold macaw (Ara ararauna) was presented with an acute history of lethargy, inappetance, ataxia, and paralysis. The bird had rapidly progressed from a normal state to complete inability to perch or ambulate within  a 48-hr period. Neurologic examination revealed bilateral hind limb paresis with  upper motor neuron signs present in both legs and the vent. Radiographs identified multiple nodular soft-tissue opacities within the cranial coelomic cavity and a single nodule superimposed with the thoracic spine. The bird was euthanized and submitted for necropsy, which revealed a primary pulmonary adenocarcinoma with multiple sites of osseous metastasis, including the vertebrae, and subsequent spinal cord compression. This is the first report of pulmonary adenocarcinoma in this species, although reports of similar tumors in other psittacines have been published. This report, along with others previously  published, suggests that vertebral metastasis of primary pulmonary tumors may be  more common in psittacine species than previously recognized and, as such, should be considered as a differential diagnosis in psittacine birds exhibiting signs of neurologic dysfunction attributed to a spinal cord lesion.

 

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[800]

TÍTULO / TITLE:  - The Inconclusive Evidence on CT Screening for Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virtual Mentor. 2012 Nov 1;14(11):861-7. doi: 10.1001/virtualmentor.2012.14.11.jdsc1-1211.

            ●● Enlace al texto completo (gratuito o de pago) 1001/virtualmentor.2012.14.11.jdsc1-1211

AUTORES / AUTHORS:  - Gierada DS; Kotner LM Jr

INSTITUCIÓN / INSTITUTION:  - Professor of radiology in the Cardiothoracic Imaging Section of the Mallinckrodt  Institute of Radiology at Washington University School of Medicine in Saint Louis, Missouri.

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[801]

TÍTULO / TITLE:  - Measurements of tumor size using CT and PET compared to histopathological size in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Interv Radiol. 2012 Jan 9. doi: 10.5152.dir.2013.053.

            ●● Enlace al texto completo (gratuito o de pago) 5152.dir.2013.053

AUTORES / AUTHORS:  - Aydin F; Dertsiz L; Budak ES; Yildiz A; Ozbilim G; Gungor F

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Akdeniz University School of Medicine, Antalya, Turkey.

RESUMEN / SUMMARY:  - PURPOSE: In this study, we aimed to compare the tumor sizes determined by maximum morphological computed tomography (CT) and functional positron emission tomography (PET) with the histopathological size to determine which method provides the best correlation with the histopathological size in lung carcinoma patients.MATERIALS AND METHODS: Forty lung carcinoma patients (39 males, one female) diagnosed histopathologically from surgical resection materials were included in this retrospective study. The mean age (+/-standard deviation, SD) of the patients was 67.8+/-10.3 years with a range of 44 to 81 years. The PET scans  were performed within the same week as the CT scan. In the CT scans, the morphological tumor sizes were measured three-dimensionally by the longest transaxial section in the parenchymal and mediastinal screening window. The functional tumor sizes were also measured three-dimensionally in the PET scans. These two measurement values were compared with the histopathological size using  Bland-Altman plotting. Bland-Altman plotting was also performed to define the 95% limits of agreement, which was presented as the bias +/-1.96 SD. RESULTS: The histopathological sizes were measured in a range of 1.2 to 7.5 cm. The maximum measurement of the tumors on the CT scans showed a lower concordance (mean difference, -0.30) than that obtained from PET, and the SD was found to be larger than the PET (1.96 SD was 3.50 for CT and 2.50 for PET). CONCLUSION: The PET measurements of tumor size were more compatible with the histopathological sizes  than the CT measurements in patients with non-small cell lung cancer.

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[802]

TÍTULO / TITLE:  - Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cytogenet. 2012 Dec 3;5(1):44.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1755-8166-5-44

AUTORES / AUTHORS:  - Dai Z; Kelly JC; Meloni-Ehrig A; Slovak ML; Boles D; Christacos NC; Bryke CR; Schonberg SA; Otani-Rosa J; Pan Q; Ho AK; Sanders HR; Zhang ZJ; Jones D; Mowrey PN

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific  tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK. RESULTS: In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on  formalin fixed paraffin-embedded tissue to determine the incidence of ALK rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal  patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5’ end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3’ end of the ALK signal. Two patients showed a deletion of the 3’ ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions  by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR mutation (T790M) was detected. Two KRAS mutations were detected among 24 ALK-rearranged samples tested. CONCLUSIONS: In a large unselected series, the frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR mutations were seen.

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[803]

TÍTULO / TITLE:  - Primary pulmonary synovial sarcoma in pregnancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Obstet Gynecol. 2012;2012:326031. doi: 10.1155/2012/326031. Epub 2012 Nov 7.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/326031

AUTORES / AUTHORS:  - Bunch K; Deering SH

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA  98431, USA.

RESUMEN / SUMMARY:  - Background. Primary pulmonary synovial sarcoma is a rare malignancy with a poor prognosis. Surgical resection and postoperative management of these tumors has not been previously described in pregnancy. Case. A 38-year-old pregnant woman was admitted for evaluation of a right thoracic mass found on chest radiography at 26 weeks of gestation. A computed tomography-guided biopsy was subsequently completed and demonstrated a high-grade neoplasm. A right pneumonectomy was performed at 28 weeks of gestation due to pulmonary decompensation, and pathological examination revealed a pulmonary synovial sarcoma. The patient developed a postpartum pulmonary embolism and expired 6 weeks after delivery. Conclusion. Aggressive intervention for pulmonary malignancies during pregnancy may be necessary. Complete tumor resection is the most important prognostic factor in primary pulmonary synovial sarcoma.

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[804]

TÍTULO / TITLE:  - Electromagnetic tracking navigation to guide radiofrequency ablation of a lung tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2012 Oct;19(4):323-7. doi: 10.1097/LBR.0b013e31827157c9.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e31827157c9

AUTORES / AUTHORS:  - Amalou H; Wood BJ

INSTITUCIÓN / INSTITUTION:  - Center for Interventional Oncology, NIH Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

RESUMEN / SUMMARY:  - Radiofrequency ablation (RFA) may be an option for patients with lung tumors who  have unresectable disease and are not suitable for available palliative modalities. RFA electrode positioning may take several attempts, necessitating multiple imaging acquisitions or continuous use of computed tomography. Electromagnetic tracking uses miniature sensors integrated with RFA equipment to  guide tools in real time, while referencing to preprocedure imaging. This technology was demonstrated successfully during a lung tumor ablation, and this was more accurate at targeting the tumor compared with traditional freehand needle insertion. It is possible, although speculative and anecdotal, that more accuracy could prevent unnecessary repositioning punctures and decrease radiation exposure. Electromagnetic tracking has theoretical potential to benefit minimally invasive interventions.

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[805]

TÍTULO / TITLE:  - The optimal use of radiotherapy in small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Compr Canc Netw. 2013 Jan 1;11(1):107-14.

AUTORES / AUTHORS:  - Shultz DB; Grecula JC; Hayman J; Diehn M; Loo BW Jr

INSTITUCIÓN / INSTITUTION:  - From the aDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, California; bDepartment of Radiation Oncology, Wexner Medical Center at the Ohio State University, James Cancer Hospital, Columbus, Ohio; cDepartment of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan; dStanford Cancer Institute, Stanford, California; and eInstitute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, California.

RESUMEN / SUMMARY:  - Small cell lung cancer is an aggressive malignancy that is highly responsive to radiation therapy (RT), which has an important role in all stages of disease. For locally advanced, limited-stage disease, the standard of care is chemotherapy with concurrent radiation, which should be started early. The optimal radiation dose and field design remain to be determined. Randomized trials are currently being conducted to determine if dose intensification will improve outcomes, whereas consensus on elective nodal irradiation is evolving. Current studies are  evaluating the potential benefit of consolidative thoracic RT in the management of patients with extensive-stage disease that has responded favorably to chemotherapy. Finally, prophylactic cranial irradiation improves survival in both limited- and extensive-stage disease that has responded to initial therapy.

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[806]

TÍTULO / TITLE:  - Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2012 Dec 27;7:222. doi: 10.1186/1748-717X-7-222.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-7-222

AUTORES / AUTHORS:  - Chang HJ; Ko HL; Lee CY; Wu RH; Yeh YW; Jiang JS; Kao SJ; Chi KH

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Therapy and Oncology, Shin-Kong Wu Ho-Su Memorial Hospital, 95, Wen-Chang Road, Shih-Lin, Taipei City, Taiwan. M006565@ms.skh.org.tw.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. METHODS: Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8-16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45-72 Gy). The median estimated biological effective dose at 10 Gy (BED10) was 71.8 Gy (range, 65.3-119.0 Gy), and that at 3 Gy (BED3) was 123.8 Gy  (range, 112.5-233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm3 (range: 2.5-178.1 cm3). RESULTS: The median follow-up period was 25.8 months (range, 3.0-60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2  months versus >50 months (not reached) in the patients without EPD (p < 0.001). Those patients with smaller GTV (<==27.9 cm3) had a better survival than those with larger GTV (>27.9 cm3): >40 months versus 12.85 months (p = 0.047). The patients with <==2 lesions had a median survival >40 months, whereas those with >==3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed >==grade 3 radiation pneumonitis. CONCLUSION: Using Tomotherapy in hypofractionation may be effective for selected  primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than lesion number in predicting survival.

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[807]

TÍTULO / TITLE:  - Necrotizing Sarcoid Granulomatosis Mimicking Lung Malignancy: MDCT, PET-CT and Pathologic Findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Mar;9(1):37-41. doi: 10.5812/iranjradiol.6572. Epub 2012 Mar  25.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.6572

AUTORES / AUTHORS:  - Sahin H; Ceylan N; Bayraktaroglu S; Tasbakan S; Veral A; Savas R

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Faculty of Medicine, Ege University, Izmir, Turkey.

RESUMEN / SUMMARY:  - Necrotizing sarcoid granulomatosis (NSG) is a rare disease which is classified in the spectrum of pulmonary angiitis and granulomatosis. It is a variant of sarcoidosis and differs from it histologically. Diagnosis is based on the pathological features, but radiology may help in the differential diagnosis. It is characterized by alveolar infiltrates or parenchymal nodules in multidetector  computed tomography (MDCT). We report a case of a 50-year-old man with the diagnosis of NSG mimicking lung malignancy. Radiological and pathological findings and also the destructive course of the disease will be discussed.

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[808]

TÍTULO / TITLE:  - Surgical management of malignant pleural mesothelioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Surg Clin. 2013 Feb;23(1):73-87, vi. doi: 10.1016/j.thorsurg.2012.10.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.thorsurg.2012.10.002

AUTORES / AUTHORS:  - Yanagawa J; Rusch V

INSTITUCIÓN / INSTITUTION:  - Thoracic Surgery Service, Department of Surgery, Memorial Sloan-Kettering Cancer  Center, 1275 York Avenue, New York, NY 10065, USA.

RESUMEN / SUMMARY:  - The uniquely diffuse nature of malignant pleural mesothelioma (MPM) makes it difficult to diagnose, stage, and treat. In addition, it is a relatively uncommon disease, making adequate prospective trials difficult to perform and leading to several controversies regarding the best management of MPM. Perhaps the greatest  area of dispute is whether extrapleural pneumonectomy or pleurectomy/decortication is the most appropriate curative operation for patients who are physiologically candidates for both. Although median survival remains poor, important strides have been made in the treatment of MPM, mainly in the form of multimodality therapeutic regimens.

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[809]

TÍTULO / TITLE:  - Surgical management of malignant pleural effusions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Surg Clin. 2013 Feb;23(1):43-9, vi. doi: 10.1016/j.thorsurg.2012.10.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.thorsurg.2012.10.001

AUTORES / AUTHORS:  - Murthy SC; Rice TW

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute,  Cleveland Clinic, 9500 Euclid Avenue/Desk J4-1, Cleveland, OH 44195, USA. murthys1@ccf.org

RESUMEN / SUMMARY:  - The two reasonable options for surgical management of malignant pleural effusions are tunneled pleural catheters and video-assisted thoracic surgery with talc pleurodesis. Successful palliation demands balancing the patient’s wishes, performance status, and prognosis with the ability to obtain full lung expansion  and control fluid production. There is no ideal procedure; surgical treatment must be individualized.

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[810]

TÍTULO / TITLE:  - The CXCL12/CXCR4 autocrine loop increases the metastatic potential of non-small cell lung cancer in vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):277-282. Epub 2012 Oct 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.960

AUTORES / AUTHORS:  - Dai X; Mao Z; Huang J; Xie S; Zhang H

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

RESUMEN / SUMMARY:  - The CXCL12/CXCR4 endocrine axis has been demonstrated to play a pivotal role in organ-specific metastasis of many different types of tumors, but the precise role of the CXCL12/CXCR4 autocrine loop remains poorly understood. In this study, we constructed a functional CXCL12/CXCR4 autocrine loop in A549 cells using a gene transfection technique to evaluate its effect on the metastasis of non-small cell lung cancer (NSCLC). Our results demonstrated that the CXCL12/CXCR4 autocrine loop significantly promoted the motility, proliferation and invasiveness of the A549 cells, suggesting a key role of the CXCL12/CXCR4 autocrine loop in NSCLC metastasis. In addition, these findings suggest that targeted therapies directed  against CXCR4 should consider the CXCL12 expression status of the NSCLC to be treated, since tumors with autocrine overexpression of CXCL12 may be more suitable for the application of chemokine-based anti-cancer therapies.

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[811]

TÍTULO / TITLE:  - EGFR-directed monoclonal antibodies in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-012-0244-7

AUTORES / AUTHORS:  - Pirker R

INSTITUCIÓN / INSTITUTION:  - Department of Medicine I, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria, robert.pirker@meduniwien.ac.at.

RESUMEN / SUMMARY:  - Several monoclonal antibodies directed against the epidermal growth factor receptor (EGFR) have been evaluated in patients with non-small cell lung cancer (NSCLC). Cetuximab, a chimeric monoclonal antibody, has been studied in combination with first-line chemotherapy in phase II and two phase III trials in  patients with advanced NSCLC. The phase III FLEX trial demonstrated an increase in survival for cisplatin/vinorelbine plus cetuximab compared to chemotherapy alone in patients with advanced EGFR-expressing NSCLC. Cetuximab added to carboplatin/paclitaxel failed to improve progression-free survival in the BMS099  phase III trial. However, a meta-analysis of four randomized trials confirmed a significant survival benefit for platinum-based chemotherapy plus cetuximab compared to chemotherapy alone. High EGFR expression of tumor cells was then shown to predict the benefit of cetuximab, whereas KRAS mutations and EGFR fluorescent in situ hybridization analysis were without predictive value. Matuzumab and panitumumab have also been studied in phase II trials. Necitumumab, a fully human monoclonal antibody, is currently evaluated in combination with chemotherapy in two phase III trials in patients with advanced NSCLC. Cetuximab is also studied in combination with chemoradiotherapy in patients with locally advanced NSCLC.

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[812]

TÍTULO / TITLE:  - A study of circulating anti-CD25 antibodies in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0980-2

AUTORES / AUTHORS:  - Ye L; Li X; Sun S; Guan S; Wang M; Guan X; Lee KH; Wei J; Liu B

INSTITUCIÓN / INSTITUTION:  - Departments of Pulmonary Oncology and Pathology, The Third Affiliated Hospital of Harbin Medical University, Harbin, 150040, People’s Republic of China.

RESUMEN / SUMMARY:  - PURPOSE: Tumors can trigger specific immune response to tumor-associated antigens but the precise mechanism remains unclear. Since regulatory T-lymphocytes (Treg)  play a crucial role in controlling autoimmune responses, the present work was undertaken to test whether dysfunction of Treg cells could be involved in developing autoimmunity in patients with lung cancer. METHODS: In this study, we  developed an in-house enzyme-linked immunosorbent assay to test circulating anti-CD25 autoantibodies among 272 patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender and smoking history. RESULTS: Mann-Whitney U test showed that the anti-CD25 IgG level was significantly higher in patients with NSCLC than control subjects (Z = -7.48, P < 0.001) while the anti-CD25 IgA level was not significantly changed in the patient group as compared with the control group (Z = -1.34, P = 0.181). Spearman correlation analysis failed to reveal a significant correlation between the levels of anti-CD25 IgG and IgA either in patients with NSCLC (r = -0.034, P = 0.578) or in control subjects (r = 0.055, P = 0.429). ROC analysis showed an AUC  of 0.70 for anti-CD25 IgG, in which NSCLC at stage III had the highest AUC (0.75). The sensitivity against a specificity of >90 % was 35.0 % for anti-CD25 IgG assay with an inter-assay deviation of 9.4 %, and 4.0 % for anti-CD25 IgA assay with an inter-assay deviation of 13.0 %. CONCLUSIONS: Circulating anti-CD25 IgG antibody may be a useful biomarker for prognosis of lung cancer.

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[813]

TÍTULO / TITLE:  - Dexamethasone Reduces Sensitivity to Cisplatin by Blunting p53-Dependent Cellular Senescence in Non-Small Cell Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51821. doi: 10.1371/journal.pone.0051821. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051821

AUTORES / AUTHORS:  - Ge H; Ni S; Wang X; Xu N; Liu Y; Wang X; Wang L; Song D; Song Y; Bai C

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China ; Department of Respiratory Medicine, The Affiliated Hospital of Nantong University, Nantong, China.

RESUMEN / SUMMARY:  - INTRODUCTION: Dexamethasone (DEX) co-treatment has proved beneficial in NSCLC patients, improving clinical symptoms by the reduction of side effects after chemotherapy. However, recent studies have shown that DEX could render cancer cells more insensitive to cytotoxic drug therapy, but it is not known whether DEX co-treatment could influence therapy-induced senescence (TIS), and unknown whether it is in a p53-dependent or p53-independent manner. METHODS: We examined  in different human NSCLC cell lines and detected cellular senescence after cisplatin (DDP) treatment in the presence or absence of DEX. The in vivo effect of the combination of DEX and DDP was assessed by tumor growth experiments using  human lung cancer cell lines growing as xenograft tumors in nude mice. RESULTS: Co-treatment with DEX during chemotherapy in NSCLC resulted in increased tumor cell viability and inhibition of TIS compared with DDP treated group. DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1), the lower cellular secretory program and down-regulation of NF-kappaB and its signaling cascade. DEX also significantly reduced DDP sensitivity in vivo. CONCLUSIONS: Our results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced  cellular senescence after chemotherapy in NSCLC, which may, at least in part, in  a p53-dependent manner. These data therefore raise concerns about the widespread  combined use of gluocorticoids (GCs) with antineoplastic drugs in the clinical management of cancer patients.

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[814]

TÍTULO / TITLE:  - Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Thorac Dis. 2012 Dec;4(6):569-76. doi: 10.3978/j.issn.2072-1439.2012.08.18.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.08.18

AUTORES / AUTHORS:  - Zarogoulidis P; Kerenidi T; Huang H; Kontakiotis T; Tremma O; Porpodis K; Kalianos A; Rapti A; Foroulis C; Zissimopoulos A; Courcoutsakis N; Zarogoulidis K

INSTITUCIÓN / INSTITUTION:  - Pulmonary Department, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;

RESUMEN / SUMMARY:  - BACKGROUND: Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. METHODS: Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. RESULTS: There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). CONCLUSIONS: The significance for each lung function test is different among the  stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

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[815]

TÍTULO / TITLE:  - Bronchoscopic staging of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ther Adv Respir Dis. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1753465812468041

AUTORES / AUTHORS:  - Hanna WC; Yasufuku K

INSTITUCIÓN / INSTITUTION:  - Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, ON, Canada.

RESUMEN / SUMMARY:  - Advances in bronchoscopy have contributed valuable tools to the diagnosis and staging of lung cancer. Detection of lesions at the premalignant microscopic stage has become possible with autofluorescence bronchoscopy and narrow band imaging. Bronchoscopy also allows for sampling of visible intra-bronchial lesions and for transbronchial needle aspiration of lesions in pulmonary parenchyma. With endobronchial ultrasound guidance, real-time evaluation and biopsy of mediastinal and pulmonary lesions can be achieved, enabling accurate clinical and pathological T-staging and N-staging without the need for surgery. In combination with advanced imaging techniques, Navigational bronchoscopy allows for the targeting and biopsy of the most peripheral lesions that are located in the smallest airways. For patients in whom tumor genetics are important, bronchoscopic-guided transbronchial biopsy can provide sufficient material for molecular analysis. As minimally invasive technology continues to evolve and improve, bronchoscopic techniques are poised to continue to be essential for the  diagnosis and staging of lung cancer.

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[816]

TÍTULO / TITLE:  - Gastroesphageal variceal hemorrhage induced by metastatic liver tumor of lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol. 2012 Sep;5(3):644-50. doi: 10.1159/000345956. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345956

AUTORES / AUTHORS:  - Honda T; Kobayashi H; Saiki M; Sogami Y; Miyashita Y; Inase N

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, Yamanashi Prefectural Central Hospital, Kofu, Japan.

RESUMEN / SUMMARY:  - Gastroesophageal variceal hemorrhage is a lethal complication of portal hypertension. Liver cirrhosis is often the principal cause of the portal hypertensive state. Malignant tumors coexist with portal hypertension in some cases. Non-small-cell lung cancer (NSCLC) is likely to become metastatic. Liver is a frequent site of cancer metastasis, but diffuse hepatic sinusoidal metastasis is uncommon as a metastatic form of NSCLC. This report describes a patient with gastroesophageal variceal hemorrhage owing to a metastatic liver tumor of NSCLC. The patient, a male smoker with stage IV NSCLC, was free of any hepatitis viral infection and had no alcohol addiction. Liver dysfunction and liver disease had never been pointed out in his medical history. His tumor harbored an L858R epidermal growth factor receptor mutation. Gefitinib was initiated but had to be ceased because of interstitial lung disease. Sequential steroid therapy was effective and bevacizumab-containing chemotherapy was commenced. Both chemotherapy regimens produced favorable effects against the metastatic liver tumor, eliciting atrophic change regardless of the chemotherapy-free interval. One day the patient was admitted to our hospital because of black stool and hypotension. Upper gastrointestinal endoscopy revealed a beaded appearance of the gastroesophageal varix with bloody gastric contents. The portal hypertension might have been caused by changes in portal vein hemodynamics induced by the conformational changes underlying the favorable response of the liver tumor to molecular targeted chemotherapy and notable regression.

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[817]

TÍTULO / TITLE:  - Enteric adenocarcinoma lung: a rare presentation in an Omani woman.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 25;2013. pii: bcr2012007667. doi: 10.1136/bcr-2012-007667.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007667

AUTORES / AUTHORS:  - Qureshi A; Furrukh M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Sultan Qaboos University Hospital, Muscat, Oman.

RESUMEN / SUMMARY:  - Pulmonary adenocarcinoma is a common neoplasm, yet the one with enteric or intestinal differentiation poses a diagnostic challenge to pathologists as it shares a common immunohistochemical profile with metastatic colorectal carcinoma. We report a case of a 61-year-old woman. She was on surveillance when incidentally she was discovered to have multiple bilateral lung nodules on imaging; the largest was surgically removed for histological examination. Morphology was consistent with a moderately differentiated adenocarcinoma .The tumour cells were positive for cytokeratin (CK) 7, CDX2, CK20 and were negative for thyroid transcription factor 1. The morphology and immune histochemical profile raised the differential diagnosis of a metastatic colorectal carcinoma and a primary lung adenocarcinoma with enteric differentiation. On the basis of morphology and CK7 positivity we established the diagnosis of enteric-type adenocarcinoma of primary lung origin. She has completed planned courses of palliative chemotherapy and remains on surveillance.

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[818]

TÍTULO / TITLE:  - Synchronous Colonic Masses as Initial Presentation of Metastatic Lung Cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Gastrointest Cancer. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12029-012-9462-6

AUTORES / AUTHORS:  - Baber J; Diedrich W; Agrawal S

INSTITUCIÓN / INSTITUTION:  - Dayton VA Medical Center, Wright State University-Boonshoft School of Medicine, Dayton, OH, USA, jbaber@loyola.edu.

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[819]

TÍTULO / TITLE:  - Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2012 Dec 20;3:e449. doi: 10.1038/cddis.2012.186.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.186

AUTORES / AUTHORS:  - Paul I; Chacko AD; Stasik I; Busacca S; Crawford N; McCoy F; McTavish N; Wilson B; Barr M; O’Byrne KJ; Longley DB; Fennell DA

INSTITUCIÓN / INSTITUTION:  - Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland, UK.

RESUMEN / SUMMARY:  - Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial  and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells,  caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired  during cisplatin resistance, can be bypassed by death receptor agonism.

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[820]

TÍTULO / TITLE:  - Metastatic common bile duct cancer from pulmonary adenocarcinoma presenting as obstructive jaundice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Korean J Gastroenterol. 2013 Jan 25;61(1):50-3.

AUTORES / AUTHORS:  - Cha IH; Kim JN; Kim YS; Ryu SH; Moon JS; Lee HK

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology, Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, 85 Jeo-dong 2-ga, Jung-gu, Seoul 100-032, Korea.

RESUMEN / SUMMARY:  - We report an extremely rare case of metastatic common bile duct cancer from pulmonary adenocarcinoma presenting as obstructive jaundice. The patient was a 76-year-old male, who presented with generalized weakness and right upper quadrant pain. Plain chest X-ray noted multiple small nodules in both lung fields. Abdominal computed tomography scan showed a stricture of the mid common bile duct along with ductal wall enhancement. Endoscopic retrograde cholangiography revealed a concentric, abrupt narrowing of the mid-common bile duct suggestive of primary bile duct cancer. However, pathology comfirmed metastatic common bile duct cancer arising from pulmonary adenocarcinoma with immunohistochemical study with thyroid transcriptional factor-1 (TTF-1). (Korean  J Gastroenterol 2013;61:50-53).

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[821]

TÍTULO / TITLE:  - A Novel Muscarinic Antagonist R2HBJJ Inhibits Non-Small Cell Lung Cancer Cell Growth and Arrests the Cell Cycle in G0/G1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e53170. doi: 10.1371/journal.pone.0053170. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053170

AUTORES / AUTHORS:  - Hua N; Wei X; Liu X; Ma X; He X; Zhuo R; Zhao Z; Wang L; Yan H; Zhong B; Zheng J

INSTITUCIÓN / INSTITUTION:  - Beijing Institute of Pharmacology and Toxicology, Beijing, China.

RESUMEN / SUMMARY:  - Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to  depress the growth of small cell lung cancers (SCLCs). In this study we intended  to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC) cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and  37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

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[822]

TÍTULO / TITLE:  - Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1183-1186. Epub 2012 Sep 5.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.893

AUTORES / AUTHORS:  - Birau A; Ceausu RA; Cimpean AM; Gaje P; Raica M; Olariu T

INSTITUCIÓN / INSTITUTION:  - Department of Intensive Care, ‘Vasile Goldis’ Western University of Arad, Arad, Arad 310396;

RESUMEN / SUMMARY:  - Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis appears to be a promising target for lung cancer therapy; however, the clinical significance of vascular changes are not completely understood. The aim of this study was to evaluate the types and morphology of blood vessels in various lung carcinomas. Using double immunostaining, we investigated 39 biopsies from patients admitted with various histological types of lung carcinoma. Tumor blood vessels were quantified separately for CD34/smooth muscle actin and described as either immature, intermediate or mature. Double immunostaining evaluation of the type of blood vessels in lung carcinomas revealed a marked heterogeneity. The immature and intermediate type of vessels were more common in adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) of the lung. Small cell lung carcinomas revealed a significant correlation between pathological and immature types of blood vessels. Therefore, quantifying the types of tumor vessels in lung carcinomas may be an important element to improve  the results of anti-vascular therapy.

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[823]

TÍTULO / TITLE:  - Endobronchial miRNAs as Biomarkers in Lung Cancer Chemoprevention.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Prev Res (Phila). 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0382

AUTORES / AUTHORS:  - Mascaux C; Feser WJ; Lewis MT; Baron AE; Coldren CD; Merrick DT; Kennedy TC; Eckelberger JI; Rozeboom LM; Franklin WA; Minna JD; Bunn PA; Miller YE; Keith RL; Hirsch FR

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations:Department of Medicine, Division of Medical Oncology; Departments of 2Biostatistics and Informatics and 3Pathology; 4Division of Pulmonary Sciences and Critical Care Medicine, Colorado School of Public Health and University of Colorado School of Medicine, Aurora;Denver Veterans Affairs Medical Center, Denver, Colorado; 6Genome and Sciences Resource, Vanderbilt University Medical Center, Nashville, Tennessee; and 7Hamon Center of Therapeutic Oncology Research, Departments of Internal Medicine and Pharmacology, University  of Texas Southwestern Medical Center, Texas.

RESUMEN / SUMMARY:  - Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analog) with placebo in high-risk subjects showed improvement in bronchial histology in former, but not current, smokers. This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoint and predictive biomarkers  to incorporate into chemoprevention trials.Matched bronchial biopsies were obtained at baseline and at 6-month follow-up from 125 high-risk individuals who  completed the trial: 31/29 and 37/28 current/former smokers in the iloprost and placebo arm, respectively. We analyzed the expression of 14 selected miRNAs by Real Time PCR in 496 biopsies.The expression of seven miRNAs was significantly correlated with histology at baseline. The expression of miR-34c was inversely correlated with histology at baseline (P < 0.0001) and with change in histology at follow-up (P = 0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was upregulated at baseline (P < 0.0001) and downregulated after treatment with iloprost (P = 0.0023). No miRNA at baseline reliably predicted a response to iloprost.No biomarker predictive of response to iloprost was found. MiR-34c was inversely correlated with baseline histology and with histology changes. Mir-34c changes at follow-up could be used as a quantitative biomarker that parallels histologic response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies. Cancer Prev Res; 1-9. ©2012 AACR.

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[824]

TÍTULO / TITLE:  - Mesothelioma as a rapidly developing Giant Abdominal Cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2012 Dec 20;10(1):277.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-10-277

AUTORES / AUTHORS:  - Vyas D; Pihl K; Kavuturu S; Vyas A

RESUMEN / SUMMARY:  - ABSTRACT: The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing  massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM). We describe a BCM arising in the retroperitoneal tissue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month  time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium), family history, social (alcohol, smoking) or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.

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[825]

TÍTULO / TITLE:  - Modern staging of small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Compr Canc Netw. 2013 Jan 1;11(1):99-104.

AUTORES / AUTHORS:  - Kalemkerian GP; Gadgeel SM

INSTITUCIÓN / INSTITUTION:  - From the aDivision of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, and bDeptartment of Hematology and Oncology, Wayne State University/Karmanos Cancer Institute, Detroit, Michigan.

RESUMEN / SUMMARY:  - For many years, small cell lung cancer (SCLC) has been staged using the Veterans  Affairs classification system, which includes only 2 stages: limited (primary tumor and regional lymph nodes within a tolerable radiation field) and extensive  (anything beyond limited stage). The TNM staging system used for non-small cell lung cancer is also prognostic for SCLC and should be integrated into the classification scheme for patients with SCLC. The staging workup for SCLC has traditionally included contrast-enhanced CT scans of the chest and abdomen, bone  scan, and MRI or CT scan of the brain. Recent data suggest that PET can improve both staging accuracy and treatment planning in patients with SCLC, although further prospective studies are needed to fully define its role.

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[826]

TÍTULO / TITLE:  - Opposite role of Kindlin-1 and Kindlin-2 in lung cancers.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(11):e50313. doi: 10.1371/journal.pone.0050313. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050313

AUTORES / AUTHORS:  - Zhan J; Zhu X; Guo Y; Wang Y; Wang Y; Qiang G; Niu M; Hu J; Du J; Li Z; Cui J; Ma B; Fang W; Zhang H

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education of Beijing, Beijing, People’s Republic of China.

RESUMEN / SUMMARY:  - Lung cancer is highly heterogenous and is composed of various subtypes that are in diverse differential stages. The newly identified integrin-interacting proteins Kindlin-1 and Kindlin-2 are the activators of transmembrane receptor integrins that play important roles in cancer progression. In this report we present the expression profiles of Kindlin-1 and Kindlin-2 in lung cancers using  patient specimens and established their correlation with lung cancer progression. We found that Kindlin-1 was expressed in epithelia-derived non-small-cell lung cancer, especially in squamous cell lung cancer but expressed at low levels in poorly differentiated large cell lung cancer. However, Kindlin-2 was highly expressed in large cell lung cancer. Both Kindlin-1 and Kindlin-2 were found not  expressed or expressed at very low levels in neuroendocrine-derived small cell lung cancer. Importantly, the Kindlin-1 expression level was positively correlated with the differentiation of squamous cell lung cancer. Surprisingly, we found that the very homologous Kindlin family proteins, Kindlin-1 and Kindlin-2, displayed counteracting functional roles in lung cancer cells. Ectopic expression of Kindlin-1 in non-small-cell lung cancer cells inhibited in vitro cell migration and in vivo tumor growth, while Kindlin-2 promoted these functions. Mechanistically, Kindlin-1 prohibited epithelail to mesenchymal transition in non-small-cell lung cancer cells, while Kindlin-2 enhanced epithelail to mesenchymal transition in these cells. Taken together, we demonstrated that Kindlin-1 and Kindlin-2 differentially regulate lung cancer cell progression. Further, the expression levels of Kindlin-1 might be potentially used as a marker for lung cancer differentiation and targeting Kindlin-2 might block the invasive growth of large cell lung cancer.

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[827]

TÍTULO / TITLE:  - Small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Natl Compr Canc Netw. 2013 Jan 1;11(1):78-98.

AUTORES / AUTHORS:  - Kalemkerian GP; Akerley W; Bogner P; Borghaei H; Chow LQ; Downey RJ; Gandhi L; Ganti AK; Govindan R; Grecula JC; Hayman J; Heist RS; Horn L; Jahan T; Koczywas M; Loo BW Jr; Merritt RE; Moran CA; Niell HB; O’Malley J; Patel JD; Ready N; Rudin CM; Williams CC Jr; Gregory K; Hughes M

RESUMEN / SUMMARY:  - Neuroendocrine tumors account for approximately 20% of lung cancers; most ( approximately 15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most  cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

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[828]

TÍTULO / TITLE:  - Gallbladder Metastasis of Non-small Cell Lung Cancer Presenting as Acute Cholecystitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Sep;24(3):249-52. doi: 10.1007/s11670-012-0249-x.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-012-0249-x

AUTORES / AUTHORS:  - Jeong YS; Han HS; Lim SN; Kim MJ; Han JH; Kang MH; Ryu DH; Lee OJ; Lee KH; Kim ST

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine.

RESUMEN / SUMMARY:  - Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ,  metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and  abdomen showed a cavitary mass in the right lower lobe of the lung and irregular  wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a  moderately-differentiated squamous cell carcinoma displaying the same morphology  as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.

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[829]

TÍTULO / TITLE:  - Management of benign and malignant pleural effusions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Thorac Surg Clin. 2013 Feb;23(1):ix. doi: 10.1016/j.thorsurg.2012.11.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.thorsurg.2012.11.001

AUTORES / AUTHORS:  - Choong CK

INSTITUCIÓN / INSTITUTION:  - Department of Surgery (MMC), The Knox Hospital, Monash University, 262 Mountain Highway, Wantirna 3152, Melbourne, Victoria, Australia. cliffchoong@hotmail.com

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[830]

TÍTULO / TITLE:  - Role of NEDD9 in invasion and metastasis of lung adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Nov;4(5):795-800. Epub 2012 Sep 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.693

AUTORES / AUTHORS:  - Chang JX; Gao F; Zhao GQ; Zhang GJ

INSTITUCIÓN / INSTITUTION:  - Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University;

RESUMEN / SUMMARY:  - Treatment failure for lung adenocarcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate the invasion- and metastasis-related gene, neural precursor cell expressed, developmentally downregulated 9 (NEDD9), in lung adenocarcinoma tissues and cell lines. The expression of NEDD9 was analyzed by the SP method of  immunohistochemistry for 60 formalin-fixed and paraffin-embedded (FFPE) lung adenocarcinoma tissues in which 32 cases were metastastic and 28 were without metastases. NEDD9 mRNA expression and protein levels were quantified by fluorescence quantitative reverse transcription-polymerase chain reaction (FQ-PCR) and western blotting in the highly invasive lung adenocarcinoma cell lines A549 and 95D as well as in SPC-A-1 cells with low invasive potential. The immunostaining scores revealed a statistically significant difference between metastatic and non-metastatic lung adenocarcinomas (p<0.001). FQ-PCR and western  blotting demonstrated that NEDD9 expression was higher in A549 and 95D compared to SPC-A-1 cells (P=0.003). Our results provide evidence that NEDD9 is upregulated in metastatic lung adenocarcinoma and in highly invasive lung adenocarcinoma cell lines, suggesting its potential involvement in regulating cell migration and invasion.

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[831]

TÍTULO / TITLE:  - Isolated renal metastasis from squamous cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Multidiscip Respir Med. 2013 Jan 16;8(1):2.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2049-6958-8-2

AUTORES / AUTHORS:  - Jun C; Gai L; Zhiqiang C; Ting Y; Shuang L; Jiyuan Y

RESUMEN / SUMMARY:  - ABSTRACT: Renal metastasis from non-small cell lung cancer is rather uncommon. The mechanism underlying the occurrence of metastasis in this site is still not well understood. We report a case of a 53-year-old Chinese woman who had moderately differentiated squamous cell carcinoma of the lung. After a ten months post-surgery interval of disease free survival, computed tomography (CT) scan found that left renal parenchymal was occupied by a mass, confirmed by kidney biopsy to be a metastasis from squamous cell lung carcinoma. Based on this case,  we are warned to be cautious in diagnosis and treatment when renal lesion are detected.

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[832]

TÍTULO / TITLE:  - Analysis of factors influencing skip lymphatic metastasis in pN(2) non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Dec;24(4):340-5. doi: 10.3978/j.issn.1000-9604.2012.10.06.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.10.06

AUTORES / AUTHORS:  - Li GL; Zhu Y; Zheng W; Guo CH; Chen C

INSTITUCIÓN / INSTITUTION:  - Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou  350001, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported, the risk factors for skip lymphatic metastasis are still controversy and debatable. This study investigated, by multivariate logistic regression analysis, the clinical features of skip metastasis to mediastinal lymph nodes (N(2)) in non-small cell lung cancer (NSCLC) patients. METHODS: We collected the clinicopathological data of 256 pN(2)-NSCLC patients who underwent lobectomy plus systemic lymph node dissection in Fujian Medical University Union Hospital. The cases in the present  study were divided into two groups: skip metastasis (N(2) skip+) and non- skip metastasis (N(2) skip-). A retrospective analysis of clinical pathological features of two groups was performed. To determine an independent factor, multivariate logistic regression analysis was used to identify possible risk factors. RESULTS: A total of 256 pN(2)-NSCLC patients were recruited. The analysis results showed that gender, pathologic types, surgery, pleural involvement, smoking history, age, tumor stages, and differentiation were not statistical significant factors impacting on skip metastasis in pN(2)-NSCLC (P>0.05), whereas tumor size was an independent factor for skip metastasis (P=0.02). CONCLUSIONS: The rate of skip lymphatic metastasis increases in pN(2)-NSCLC patients, in accompany with an increased tumor size.

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[833]

TÍTULO / TITLE:  - Pleomorphic rhabdomyosarcoma with pulmonary tumour embolism.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2012 Nov 30;2012. pii: bcr2012007163. doi: 10.1136/bcr-2012-007163.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007163

AUTORES / AUTHORS:  - Abdulaziz S; Geddawy M; Al Efraij K; Jamil MG

INSTITUCIÓN / INSTITUTION:  - Department of Adult Critical Care Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. dr-salman@hotmail.com

RESUMEN / SUMMARY:  - Pulmonary tumour embolism is a known complication of cancer disease. To date, pleomorphic rhabdomyosarcoma has been described once with this entity. We report  a case of pulmonary tumour embolism diagnosed in the operation room after cardiac arrest of a 30-year-old male patient who had surgical amputation of his right upper limb due to recurrent sarcoma, mandating urgent and successful embolectomy.

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[834]

TÍTULO / TITLE:  - Phosphoproteomics and lung cancer research.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Sep 26;13(10):12287-314. doi: 10.3390/ijms131012287.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms131012287

AUTORES / AUTHORS:  - Lopez E; Cho WC

INSTITUCIÓN / INSTITUTION:  - Hospital Universitario Nino Jesus, Department of Oncohematology of Children, Madrid 28009, España. williamcscho@gmail.com.

RESUMEN / SUMMARY:  - Massive evidence suggests that genetic abnormalities contribute to the development of lung cancer. These molecular abnormalities may serve as diagnostic, prognostic and predictive biomarkers for this deadly disease. It is imperative to search these biomarkers in different tumorigenesis pathways so as to provide the most appropriate therapy for each individual patient with lung malignancy. Phosphoproteomics is a promising technology for the identification of biomarkers and novel therapeutic targets for cancer. Thousands of proteins interact via physical and chemical association. Moreover, some proteins can covalently modify other proteins post-translationally. These post-translational modifications ultimately give rise to the emergent functions of cells in sequence, space and time. Phosphoproteomics clinical researches imply the comprehensive analysis of the proteins that are expressed in cells or tissues and can be employed at different stages. In addition, understanding the functions of  phosphorylated proteins requires the study of proteomes as linked systems rather  than collections of individual protein molecules. In fact, proteomics approaches  coupled with affinity chromatography strategies followed by mass spectrometry have been used to elucidate relevant biological questions. This article will discuss the relevant clues of post-translational modifications, phosphorylated proteins, and useful proteomics approaches to identify molecular cancer signatures. The recent progress in phosphoproteomics research in lung cancer will be also discussed.

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[835]

TÍTULO / TITLE:  - Fucoidan from seaweed Fucus vesiculosus inhibits migration and invasion of human  lung cancer cell via PI3K-Akt-mTOR pathways.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(11):e50624. doi: 10.1371/journal.pone.0050624. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050624

AUTORES / AUTHORS:  - Lee H; Kim JS; Kim E

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Recently there has been an increased interest in the pharmacologically active natural products associated with remedies of various kinds of diseases, including cancer. Fucoidan is a polysaccharide derived from brown seaweeds and has long been used as an ingredient in some dietary supplement products. Although fucoidan has been known to have anti-cancer activity, the anti-metastatic effects and its detailed mechanism of actions have been poorly understood. Therefore, the aims of this study were to demonstrate the anti-metastatic functions of fucoidan and its mechanism of action using A549, a highly metastatic human lung cancer cell line. METHODS AND PRINCIPAL FINDINGS: Fucoidan inhibits the growth of A549 cells at the concentration of 400 microg/ml. Fucoidan treatment of non-toxic dose (0-200 microg/ml) exhibits a concentration-dependent inhibitory effect on the invasion and migration of the cancer cell via decreasing its MMP-2 activity. To know the mechanism of these inhibitory effects, Western blotting was performed. Fucoidan treatment down-regulates extracellular signal-related kinase 1 and 2 (ERK1/2) and phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathways. Furthermore, fucoidan decreases the cytosolic and nuclear levels of Nuclear Factor-kappa B (p65). CONCLUSIONS/SIGNIFICANCE: The present study suggests that fucoidan exhibits anti-metastatic effect on A549 lung cancer cells via the down-regulation of ERK1/2 and Akt-mTOR as well as NF-kB signaling pathways. Hence, fucoidan can be considered as a potential therapeutic  reagent against the metastasis of invasive human lung cancer cells.

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[836]

TÍTULO / TITLE:  - CDA-2, a Urinary Preparation, Inhibits Lung Cancer Development through the Suppression of NF-kappaB Activation in Myeloid Cell.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52117. doi: 10.1371/journal.pone.0052117. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052117

AUTORES / AUTHORS:  - Wang X; Jiang CM; Wan HY; Wu JL; Quan WQ; Bals R; Wu KY; Li D

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy, Putuo People’s Hospital, Shanghai, China.

RESUMEN / SUMMARY:  - CDA-2 (cell differentiation agent 2), a urinary preparation, has potent anti- proliferative and pro-apoptotic properties in cancer cells. However, the mechanisms of tumor inhibitory action of CDA-2 are far from clear, and especially there was no report on lung cancer. Here we demonstrate that CDA-2 and its main component phenylacetylglutamine (PG) reduce the metastatic lung tumor growth, and increases survival time after inoculation with Lewis lung carcinoma (LLC) cells in a dose-dependent manner in C57BL6 mice. Proliferative program analysis in cancer cells revealed a fundamental impact of CDA-2 and PG on proliferation and apoptosis, including Bcl-2, Bcl-XL, cIAP1, Survivin, PCNA, Ki-67 proteins and TUNEL assays. CDA-2 and PG significantly reduced NF-kappaB DNA-binding activity in lung cancer cells and in alveolar macrophages of tumor bearing mice and especially decreased the release of inflammatory factors including TNFalpha, IL-6, and KC. Furthermore, CDA-2 and PG decrease the expressions of TLR2, TLR6, and CD14, but not TLR1, TLR3, TLR4, and TLR9 in bone-marrow-derived macrophages (BMDM) of mice stimulated by LLC-conditioned medium (LLC-CM). Over-expressing TLR2 in BMDM prevented CDA-2 and PG from inhibiting NF-kappaB activation, as well as induction of TNFalpha and IL-6. TLR2:TLR6 complexes mediate the effect of NF-kappaB inactivation by CDA-2. In conclusion, CDA-2 potently inhibits lung tumor development by reduction of the inflammation in lung through suppression of NF-kappaB activation in myeloid cells, associating with modulation of TLR2 signaling.

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[837]

TÍTULO / TITLE:  - Advances in bronchoscopy for lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Carcinog. 2012;11:19. doi: 10.4103/1477-3163.105337. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1477-3163.105337

AUTORES / AUTHORS:  - Dhillon SS; Dexter EU

INSTITUCIÓN / INSTITUTION:  - Department of Medicine Pulmonary Medicine and Thoracic Oncology, Roswell Park Cancer Institute, New York, USA ; Department of Medicine, State University of New York at Buffalo, New York, USA.

RESUMEN / SUMMARY:  - Bronchoscopic techniques have seen significant advances in the last decade. The development and refinement of different types of endobronchial ultrasound and navigation systems have led to improved diagnostic yield and lung cancer staging  capabilities. The complication rate of these minimally invasive procedures is extremely low as compared to traditional transthoracic needle biopsy and surgical sampling. These advances augment the safe array of methods utilized in the work up and management algorithms of lung cancer.

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[838]

TÍTULO / TITLE:  - Metachronous Malignant Mesothelioma and Pulmonary Adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Turk Patoloji Derg. 2013;29(1):83-86. doi: 10.5146/tjpath.2013.01156.

            ●● Enlace al texto completo (gratuito o de pago) 5146/tjpath.2013.01156

AUTORES / AUTHORS:  - Ozbudak IH; Ozbudak O; Arslan G; Erdogan A; Ozbilim G

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Akdeniz University, Faculty of Medicine, ANTALYA, TURKEY.

RESUMEN / SUMMARY:  - The prevalence of multiple primary malignant neoplasms in a single patient is reported in a wide variation. The co-existence of malignant mesothelioma and pulmonary carcinoma is a rare entity. Herein, we reported a 60-year-old man who was a retired employee and heavy smoker. He had a suspicious history of asbestos  exposure. He complained of chest pain and computerized tomography revealed a mass in the lower lobe of left lung. The patient underwent a left lower lobectomy and  was diagnosed as pulmonary adenocarcinoma. During follow-up two years after surgery, the patient complained of dyspnea and chest computerized tomography scan revealed right pleural effusion and diffuse pleural thickening. For the differential diagnosis, the patient underwent wedge biopsy from the right lower lobe and was diagnosed as epithelial diffuse malignant mesothelioma. The development of malignant pleural mesothelioma and lung carcinoma could be associated with asbestos exposure. However, a history of asbestos exposure is not required for the diagnosis. The influence of effective anticancer therapies that  improve the survival rates and increase the population ages could be related to the occurrence of a second malignancy.

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[839]

TÍTULO / TITLE:  - Small cell carcinoma of the prostate after high-dose-rate brachytherapy for low-risk prostatic adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):53-56. Epub 2012 Oct 25.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.998

AUTORES / AUTHORS:  - Komiya A; Yasuda K; Nozaki T; Fujiuchi Y; Hayashi SI; Fuse H

INSTITUCIÓN / INSTITUTION:  - Departments of Urology and.

RESUMEN / SUMMARY:  - In the present study, we describe an 80-year-old patient who developed prostatic  small cell carcinoma (SCC) following high-dose-rate brachytherapy (HDR-BT) for low-risk prostatic adenocarcinoma. The patient received one implant of Ir-192 and 7 fractions of 6.5 Gy within 3.5 days, for a total prescribed dose of 45.5 Gy. A  total of 27 months after HDR-BT, the patient complained of difficulty in urinating. His serum prostate-specific antigen (PSA) levels were 3.2 ng/ml. Systemic examination revealed an enlargement of the prostate, urethral stenosis,  pelvic lymph node swelling and multiple lung and bone lesions. His serum neuron-specific enolase (NSE) levels were elevated to 120 ng/ml. A prostate needle biopsy was performed for pathological examination. Histologically, there were tumor cells with hyperchromatic nuclei and scant cytoplasm showing a solid or trabecular growth pattern. Immunohistochemically, they were positive for AE1/AE3, CD56 and synaptophysin, and negative for PSA, PAP and CD57. These findings are consistent with SCC of the prostate. A review of the prostate needle biopsy specimen prior to HDR-BT did not reveal any tumor cells positive for chromogranin A, nor synaptophysin. The final diagnosis was SCC of the prostate with local progression, with lung, lymph node and bone metastases. Three cycles of etoposide/cisplatin (EP) were administered. A greater than 50% decrease in the serum NSE levels was observed. However, there was no objective response. Due to the deterioration of the patient’s general condition, EP was discontinued. One month later, his serum NSE showed a rapid increase to 210 ng/ml with aggressive local progression and the patient succumbed to the disease 5.5 months after the start of EP therapy.

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[840]

TÍTULO / TITLE:  - Interaction between lung cancer cell and myofibroblast influenced by cyclic tensile strain.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lab Chip. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1039/c2lc41050h

AUTORES / AUTHORS:  - Huang JW; Pan HJ; Yao WY; Tsao YW; Liao WY; Wu CW; Tung YC; Lee CH

INSTITUCIÓN / INSTITUTION:  - Department of Mechanical and Mechatronic Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan.

RESUMEN / SUMMARY:  - Using a cell culture chip with a deformable substrate driven by a hydraulic force, we investigated the motility of cancer cells affected by myofibroblasts undergoing cyclic tensile strain (CTS). CTS reduced both the expression of alpha-smooth muscle actin in the myofibroblast and the ability of the myofibroblast to accelerate cancer cell migration. However, with the treatment of a pro-inflammatory factor interleukin-1beta on the myofibroblasts, the effects of CTS on the myofibroblast were diminished. This result suggests an antagonism between mechanical and chemical stimulations on mediating cancer metastasis by the stromal myofibroblast.

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[841]

TÍTULO / TITLE:  - CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2013 Jan 15;14(1):1713-27. doi: 10.3390/ijms14011713.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14011713

AUTORES / AUTHORS:  - Cavallaro S

INSTITUCIÓN / INSTITUTION:  - Functional Genomics Center, Institute of Neurological Sciences, Italian National  Research Council, Via Paolo Gaifami, 18, Catania 95125, Italy. sebastiano.cavallaro@cnr.it.

RESUMEN / SUMMARY:  - Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of  brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC) and the pharmacological tools that may be used to interfere with this signaling axis.

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[842]

TÍTULO / TITLE:  - Solitary metastasectomy in non-small cell lung cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J BUON. 2012 Oct-Dec;17(4):712-8.

AUTORES / AUTHORS:  - Karagkiouzis G; Koulaxouzidis G; Tomos P; Spartalis ED; Konstantinou F; Charpidou A; Syrigos KN

INSTITUCIÓN / INSTITUTION:  - 2nd Department of General Thoracic Surgery, “Sotiria” Hospital of Chest Diseases, Athens, Greece.

RESUMEN / SUMMARY:  - Purpose: Stage IV disease at initial presentation ac-counts for approximately 41% of newly diagnosed cases with non-small cell lung cancer (NSCLC). Although the majority of these patients have disseminated metastatic disease at diagnosis, a small percentage of them are found to have a solitary site of extrathoracic metastasis. In addition, patients who have received surgical or multimodality treatment with curative intent may experience metachronous solitary distant recurrences during the natural course of their disease. Our aim was to review the possible role of surgical resection in the management of NSCLC with solitary hematogenous metastasis. Methods: We performed electronic literature search of PubMed, EMBASE and the Cochrane Library for articles in English using a number of key words. Results: All identified studies reported survival benefit for patients operated for their single metastatic lesion. Patients with metachronous disease had slightly better prognosis than those with synchronous metastatic lesions. We  found no prospective randomized trials comparing surgical and non-surgical treatment modalities for NSCLC with solitary hematogenous metastasis. Conclusions: Available evidence supports the presumption that in highly selected  patients with isolated synchronous or metachronous hematogenous metastasis surgical resection as part of an aggressive approach positively affects patients’ survival. Factors that are in favor of a satisfactory outcome include control of  primary site, confirmed solitary metastatic disease, good performance status (PS), metachronous lesions and longer disease-free interval (DFI). Prospective randomized trials are necessary to provide stronger evidence. Finally, it is worth investigating the biology of these tumors presenting with single-site distant metastasis.

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[843]

TÍTULO / TITLE:  - Angiogenesis and mast cell density in invasive pulmonary adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Ther. 2012 Oct;8(4):537-41. doi: 10.4103/0973-1482.106530.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0973-1482.106530

AUTORES / AUTHORS:  - Ullah E; Nagi AH; Lail RA

INSTITUCIÓN / INSTITUTION:  - Department of Morbid Anatomy and -Histopathology, University of Health Sciences,  -Khayaban-e-Jamia, Lahore, Pakistan.

RESUMEN / SUMMARY:  - Introduction: Angiogenesis and mast cells affect the behavior of pulmonary adenocarcinoma. Measuring the angiogenesis and mast cell density (MCD) and their  effect on survival of the patients may be helpful to guide the use of cancer chemotherapeutic agents which target tumor angiogenesis and mast cells. Materials and Methods: It was a descriptive study, conducted at Gulab Devi Chest Hospital and University of Health Sciences Lahore. It included 23 newly diagnosed, adult patients of invasive pulmonary adenocarcinoma. Clinical history was obtained and  biopsy specimen was processed. Angiogenesis was determined by immunohistochemical staining with CD34. Mast cells were counted in toluidine blue stained sections. Patients were followed-up till death. Results: Mean age of the patients was 54.83 +/- 2.799 years. Majority (60.9%) were males. Only 39.1% patients were smokers. Morphologically, large proportions of tumors (73.9%) were nonmucinous and moderately or poorly differentiated. Majority (69.6%) of patients presented at advanced stage (Tumor-Node-Metastasis staging (TNM )III and IV). Mean microvascular density (MVD) was 13.04 +/- 1.12 and mean MCD was 3.26 +/- 0.36 per high power field (HPF). High MVD was associated with poor differentiation and advanced stage and correlated with poor survival (P = 0.0001). High MCD was associated with high grade but not with the advance stage of disease. However, high MCD correlated with poor survival (P = 0.047). Moreover, MCD was positively  correlated with angiogenesis (r = 0.727, P = 0.0001). Treatment did not affect the survival significantly (P = 0.069). Conclusion: High angiogenesis and MCD predict poor survival and are positively correlated with each other and with the  histological grades in pulmonary adenocarcinoma. High angiogenesis is also associated with advance TNM stage of disease.

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TÍTULO / TITLE:  - Lung cancer in “true tracheal bronchus”: a rare coincidence.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Bronchology Interv Pulmonol. 2012 Oct;19(4):340-2. doi: 10.1097/LBR.0b013e31826ba8f2.

            ●● Enlace al texto completo (gratuito o de pago) 1097/LBR.0b013e31826ba8f2

AUTORES / AUTHORS:  - Sindhwani G; Rawat J; Gupta M; Chandra S

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Medicine, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India. girish.sindhwani75@gmail.com

RESUMEN / SUMMARY:  - Tracheal bronchus is a rare congenital anomaly (incidence ranging from 0.1% to 2%) of bronchial tree in which an aberrant bronchus originates in trachea anywhere above carina, but usually within 2 cm of carina. Cancer within the bronchial anomaly is further uncommon. A subtype of tracheal bronchus, known as “true tracheal bronchus” or “pig bronchus” is a condition in which right upper lobe (RUL) bronchus is absent and the RUL is ventilated by the aberrant tracheal  bronchus. We present a case of true tracheal bronchus with malignancy of the affected RUL. To the best of our knowledge, in world literature, this is the second case of true tracheal bronchus affected by lung cancer.

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