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Artículos originales (todos) *** Original articles (all)

 

RESPIRATORY TRACT TUMORS

(Conceptos / Keywords: NSCLC; SCLC, Mesotheliomas; Tracheal tumors; Bronchial tumors; etc).

December 2012 - January 2013

 

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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]

- CASTELLANO -

TÍTULO / TITLE:Cribado de cancer de pulmon con tomografia computarizada de baja dosis despues del National Lung Screening Trial. El debate continua abierto.

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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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 o