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

Connective and Soft Tissue Tumors.

February - March 2013


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TÍTULO / TITLE:  - Outcome Prediction in Primary Resected Retroperitoneal Soft Tissue Sarcoma: Histology-Specific Overall Survival and Disease-Free Survival Nomograms Built on  Major Sarcoma Center Data Sets.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.3747

AUTORES / AUTHORS:  - Gronchi A; Miceli R; Shurell E; Eilber FC; Eilber FR; Anaya DA; Kattan MW; Honore C; Lev DC; Colombo C; Bonvalot S; Mariani L; Pollock RE

INSTITUCIÓN / INSTITUTION:  - Alessandro Gronchi, Rosalba Miceli, Chiara Colombo, and Luigi Mariani, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Elizabeth Shurell, Fritz C. Eilber, and Frederick R. Eilber, University of California at Los Angeles, Los Angeles, CA; Daniel A. Anaya, Baylor College of Medicine; Dina C. Lev and Raphael E. Pollock, Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX; Michael W. Kattan, Cleveland Clinic Foundation, Cleveland, OH; and Charles Honore and Sylvie Bonvalot, Institute Gustave Roussy, Villejuif, France.

RESUMEN / SUMMARY:  - PURPOSEIntegration of numerous prognostic variables not included in the conventional staging of retroperitoneal soft tissue sarcomas (RPS) is essential in providing effective treatment. The purpose of this study was to build a specific nomogram for predicting postoperative overall survival (OS) and disease-free survival (DFS) in patients with primary RPS. PATIENTS AND METHODSData registered in three institutional prospective sarcoma databases were  used. We included patients with primary localized RPS resected between 1999 and 2009. Univariate (Kaplan and Meier plots) and multivariate (Cox model) analyses were carried out. The a priori chosen prognostic covariates were age, tumor size, grade, histologic subtype, multifocality, quality of surgery, and radiation therapy. External validation was performed by applying the nomograms to the patients of an external cohort. The model’s discriminative ability was estimated  by means of the bootstrap-corrected Harrell C statistic.ResultsIn all, 523 patients were identified at the three institutions (developing set). At a median  follow-up of 45 months (interquartile range, 22 to 72 months), 171 deaths were recorded. Five- and 7-year OS rates were 56.8% (95% CI, 51.4% to 62.6%) and 46.7% (95% CI, 39.9% to 54.6%. Two hundred twenty-one patients had disease recurrence.  Five- and 7-year DFS rates were 39.4% (95% CI, 34.5% to 45.0%) and 35.7% (95% CI, 30.3% to 42.1%). The validation set consisted of 135 patients who were identified at the fourth institution for external validation. The bootstrap-corrected Harrell C statistics for OS and DFS were 0.74 and 0.71 in the developing set and  0.68 and 0.69 in the validating set. CONCLUSIONThese nomograms accurately predict OS and DFS. They should be used for patient counseling in clinical practice and stratification in clinical trials.




TÍTULO / TITLE:  - High-Grade KIT-Negative Sarcoma of the Small Bowel in a Patient With Chronic Myeloid Leukemia Receiving Long-Term Tyrosine Kinase Inhibitors.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.7989

AUTORES / AUTHORS:  - Martz J; Jain S; Vahdat LT; Qin L; Mosquera JM; Antonescu CR; Popa EC

INSTITUCIÓN / INSTITUTION:  - Ludwig-Maximilians Universitat Munich, Munich, Germany.




TÍTULO / TITLE:  - Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial.

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

REVISTA / JOURNAL:  - Lancet Oncol. 2013 Mar 8. pii: S1470-2045(13)70049-4. doi: 10.1016/S1470-2045(13)70049-4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(13)70049-4

AUTORES / AUTHORS:  - Schwartz GK; Tap WD; Qin LX; Livingston MB; Undevia SD; Chmielowski B; Agulnik M; Schuetze SM; Reed DR; Okuno SH; Ludwig JA; Keedy V; Rietschel P; Kraft AS; Adkins D; Van Tine BA; Brockstein B; Yim V; Bitas C; Abdullah A; Antonescu CR; Condy M; Dickson MA; Vasudeva SD; Ho AL; Doyle LA; Chen HX; Maki RG

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: schwartg@mskcc.org.

RESUMEN / SUMMARY:  - BACKGROUND: Preclinical studies have shown synergistic antitumour activity by inhibition of insulin-like growth factor-1 receptor (IGF-1R) and mTOR. The expression of IGF-1R seems to be crucial for this effect. We investigated the safety and efficacy of the combination of the IGF-1R antibody cixutumumab and the mTOR inhibitor temsirolimus in patients with chemotherapy-refractory bone and soft-tissue sarcomas according to IGF-1R expression by immunohistochemistry. METHODS: We undertook a multicentre, open-label, phase 2 study in 19 cancer centres in the USA. Patients aged at least 16 years with a histologically confirmed diagnosis of bone or soft-tissue sarcoma were allocated on the basis of IGF-1R expression by immunohistochemistry to one of three treatment groups: IGF-1R-positive soft-tissue sarcoma (group A), IGF-1R-positive bone sarcomas (group B), or IGF-1R-negative bone and soft-tissue sarcoma (group C). Patients received weekly treatment with cixutumumab (6 mg/kg, intravenous) and temsirolimus (25 mg, intravenous flat dose) in 6-week cycles. A Simon optimal two-stage design was used for every arm. The primary endpoint was progression-free survival (PFS) at 12 weeks by intention-to-treat analysis in the first 54 patients assigned to every treatment arm. Although patients still remain on treatment, this trial has completed enrolment and this represents the final analysis. This study is registered with ClinicalTrials.gov, number NCT01016015. FINDINGS: Between Nov 18, 2009, and April 11, 2012, 388 patients were screened for IGF-1R expression and 54 were assigned to each arm. 17 of 54 patients in the  IGF-1R-positive soft-tissue sarcoma group (31%; one-sided 95% CI lower bound 21%; two-sided 90% CI 21-43), 19 of 54 in IGF-1R-positive bone sarcoma group (35%; one-sided 95% CI lower bound 24%; two-sided 90% CI 24-47), and 21 of 54 in the IGF-1R-negative group (39%, one-sided 95% CI lower bound 28%; two-sided 90% CI 28-51) were progression free at 12 weeks. On April 6, 2011, the protocol was amended to include three additional patients in the IGF-1R-positive soft-tissue sarcoma group (total of 57 patients) and nine more in the IGF-1R-negative group (total of 63 patients). There were 2546 adverse events reported during the study, 214 (8%) of which were grade 3-4. The most common grade 3-4 toxicities in the 174 treated patients were anaemia in 16 (9%) patients, hyperglycaemia in 18 (10%), hypophosphataemia in 16 (9%), lymphopenia in 25 (14%), oral mucositis in 19 (11%), and thrombocytopenia in 19 (11%). INTERPRETATION: The combination of cixutumumab and temsirolimus shows clinical activity in patients with sarcoma and forms a basis for future trials. However, IGF-1R expression by immunohistochemistry is not predictive of clinical outcome after treatment with this combination. FUNDING: National Cancer Institute and CycleforSurvival Fund, Memorial Sloan-Kettering Cancer Center.




TÍTULO / TITLE:  - Adult Ewing Sarcoma: Survival and Local Control Outcomes in 36 Patients With Metastatic Disease.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827de65e

AUTORES / AUTHORS:  - Ahmed SK; Robinson SI; Okuno SH; Rose PS; Issa Laack NN

INSTITUCIÓN / INSTITUTION:  - *Mayo Medical School Divisions of daggerOncology double daggerOrthopedic Surgery  section signRadiation Oncology, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - OBJECTIVES:: To assess the clinical features and outcomes in adult patients with  metastatic Ewing sarcoma (ES). METHODS:: The records of 36 ES patients with metastatic disease >/=18 years seen from 1977 to 2007 at the Mayo Clinic were studied retrospectively. Factors relevant to prognosis, survival, and local control (LC) were analyzed. RESULTS:: The 4-year overall survival (OS) and event-free survival (EFS) rates were 20% and 11%, respectively. Patients treated  from 1993 to 2007 had significantly improved outcomes compared with those treated from 1977 to 1992: 4-year OS and EFS of 31% and 16%, respectively, versus 0% (P=0.01). Primary tumor (P=0.005 and 0.04) and metastatic sites (P=0.05) were independent EFS prognostic factors. Four patients (11%) received surgery, 18 (50%) radiation therapy (RT), 4 (11%) surgery+radiation therapy (S+RT), and 10 (28%) received no LC. The 4-year EFS rates were 0% for surgery, 21% for RT, 0% for S+RT, and 0% for no LC (P=0.0001). OS in patients who received vincristine, doxorubicin, and cyclophosphamide alternating with ifosphamide and etoposide (VDC/IE) chemotherapy was improved (P=0.04). Relapses were documented in 18 patients (excluding patients who received no LC). In total, 44% of patients had all of their metastatic site(s) treated. Patients who received treatment to all extrapulmonary metastases had significantly improved outcomes compared with those who did not receive treatment to all sites: 4-year OS and EFS of 33% and 11%, respectively, versus 0% (P=0.04 and 0.02). CONCLUSIONS:: Our results suggest outcomes for adult patients with metastatic ES are similar to pediatric cohorts in the modern era. VDC/IE chemotherapy and treatment to all metastatic lesions is associated with improved outcomes.




TÍTULO / TITLE:  - Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study.

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

REVISTA / JOURNAL:  - Ann Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds659

AUTORES / AUTHORS:  - Samuels BL; Chawla S; Patel S; von Mehren M; Hamm J; Kaiser PE; Schuetze S; Li J; Aymes A; Demetri GD

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Kootenai Cancer Center, Post Falls.

RESUMEN / SUMMARY:  - BackgroundThis expanded access program (EAP) was designed to provide trabectedin  access for patients with incurable soft tissue sarcoma (STS) following progression of disease with standard therapy. The outcomes of trial participants  accrued over approximately 5 years are reported.Patients and methodsAdult patients with advanced STS of multiple histologies, including leiomyosarcoma and  liposarcoma (L-sarcomas), following relapse or disease progression following standard-of-care chemotherapy, were enrolled. Trabectedin treatment cycles (1.5 mg/m(2), intravenously over 24 h) were repeated q21 days. Objective response, overall survival (OS), and safety were evaluated.ResultsOf 1895 patients enrolled, 807 (43%) had evaluable objective response data, with stable disease reported in 343 (43%) as best response. L-sarcoma patients exhibited longer, OS compared with other histologies [16.2 months (95% confidence interval (CI) 14.1-19.5) versus 8.4 months (95% CI 7.1-10.7)], and a slightly higher objective  response rate [6.9% (95% CI 4.8-9.6) versus 4.0% (95% CI 2.1-6.8)]. The median treatment duration was 70 days representing a median of three treatment cycles; 30% of patients received >/=6 cycles. Safety and tolerability in this EAP were consistent with prior clinical trial data.ConclusionResults of this EAP are consistent with previous reports of trabectedin, demonstrating disease control despite a low incidence of objective responses in advanced STS patients after failure of standard chemotherapy.ClinicalTrials.govNCT00210665.




TÍTULO / TITLE:  - Clinical and Genetic Analysis of a Korean Patient with X-linked Chondrodysplasia  Punctata: Identification of a Novel Splicing Mutation in the ARSE Gene.

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

REVISTA / JOURNAL:  - Ann Clin Lab Sci. 2013 Winter;43(1):70-5.

AUTORES / AUTHORS:  - Jeon GW; Kwon MJ; Lee SJ; Sin JB; Ki CS

INSTITUCIÓN / INSTITUTION:  - Ph.D. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, Republic of Korea, 135-710. Tel.: +82-2-3410-2709; fax: +82-2-3410-2719; e-mail:  changski@skku.edu.

RESUMEN / SUMMARY:  - X-linked recessive chondrodysplasia punctata (CDPX1) is a rare congenital disorder of bone and cartilage development, characterized by punctate calcification in areas of endochondral bone formation, leading to stippled epiphyses, severe nasal and midfacial hypoplasia, short stature, and brachytelephalangy. CDPX1 is caused by mutations in the arylsulfatase E (ARSE) gene located on chromosome Xp22.3. Although most affected males have milder symptoms, some have significant medical problems including respiratory compromise and cervical spinal stenosis due to dysplastic vertebrae. Herein, we present the  case of a male infant with the characteristic features of CDPX1 and severe spinal cord compression. Direct sequencing analysis revealed a novel variation (c.430G>A) in the ARSE gene that was thought to be a missense mutation (p.Gly144Arg), but proved to be a novel splicing mutation (r.[430g>a; 430_431ins430+1_430+21) adding seven amino acids between p.Ile143 and p.Gly144 (p.Ile143_Gly-144insSerMetTyrValPheLysSer). This report expands the spectrum of mutations of the ARSE gene and, to the best of our knowledge, is the first clinically and genetically confirmed case of CDPX1 with severe spinal cord compression in Korea.




TÍTULO / TITLE:  - Correction for Whitehouse et al., Neighbor of Brca1 gene (Nbr1) functions as a negative regulator of postnatal osteoblastic bone formation and p38 MAPK activity.

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

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4428. doi: 10.1073/pnas.1300714110. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1300714110




TÍTULO / TITLE:  - Locoregional Recurrence After Preoperative Radiation Therapy for Retroperitoneal  Sarcoma: Adverse Impact of Multifocal Disease and Potential Implications of Dose  Escalation.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2868-y

AUTORES / AUTHORS:  - McBride SM; Raut CP; Lapidus M; Devlin PM; Marcus KJ; Bertagnolli M; George S; Baldini EH

INSTITUCIÓN / INSTITUTION:  - Harvard Radiation Oncology Program, Boston, MA, USA, smmcbride@partners.org.

RESUMEN / SUMMARY:  - BACKGROUND: Locoregional recurrence (LRR) rates following preoperative radiation  therapy (RT) and radical resection for retroperitoneal sarcoma (RPS) are high. Targeted radiation dose escalation has been proposed as a means to decrease LRR,  but is applicable only if LRRs are confined to within the RT field. We analyzed predictors for LRR and examined LRR locations to determine the potential benefit  of dose escalation. METHODS: For 33 patients treated with preoperative RT and radical resection, we determined high-risk tumor volumes appropriate for boost and identified the number of recurrences within this volume. Clinical and pathologic variables predictive of overall survival (OS), freedom from progression (FFP), LRR, and distant recurrence (DR) were evaluated. RESULTS: Median follow-up was 32.9 months. At 1 and 3 years, OS was 87 and 64 %, FFP rates were 71 and 45 %, cumulative incidences of LRR were 19 and 37 %, and of DR were 13 and 21 %. On multivariate analysis, multifocal disease was a significant predictor of increased incidence of LRR. At first relapse, 6 patients had isolated LR, 2 isolated RR, 6 isolated DR, 1 synchronous LR and RR, and 1 synchronous LR, RR, and DR. Ultimately, 4 patients (25 % of those who recurred) had isolated in-field recurrences within the hypothetical high-risk dose-painting boost volumes and that thus might have been prevented with dose-escalation. CONCLUSION: Following preoperative RT and resection, LRR rates are high and associated with multifocal disease. Preoperative dose escalation to high-risk tumor volumes may perhaps benefit only a limited subset of patients, and therefore strategies are needed to select appropriate patients for consideration  of this approach.




TÍTULO / TITLE:  - IQGAP1 suppresses TbetaRII-mediated myofibroblastic activation and metastatic growth in liver.

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

REVISTA / JOURNAL:  - J Clin Invest. 2013 Mar 1;123(3):1138-56. doi: 10.1172/JCI63836. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1172/JCI63836

AUTORES / AUTHORS:  - Liu C; Billadeau DD; Abdelhakim H; Leof E; Kaibuchi K; Bernabeu C; Bloom GS; Yang L; Boardman L; Shah VH; Kang N

RESUMEN / SUMMARY:  - In the tumor microenvironment, TGF-beta induces transdifferentiation of quiescent pericytes and related stromal cells into myofibroblasts that promote tumor growth and metastasis. The mechanisms governing myofibroblastic activation remain poorly understood, and its role in the tumor microenvironment has not been explored. Here, we demonstrate that IQ motif containing GTPase activating protein 1 (IQGAP1) binds to TGF-beta receptor II (TbetaRII) and suppresses TbetaRII-mediated signaling in pericytes to prevent myofibroblastic differentiation in the tumor microenvironment. We found that TGF-beta1 recruited  IQGAP1 to TbetaRII in hepatic stellate cells (HSCs), the resident liver pericytes. Iqgap1 knockdown inhibited the targeting of the E3 ubiquitin ligase SMAD ubiquitination regulatory factor 1 (SMURF1) to the plasma membrane and TbetaRII ubiquitination and degradation. Thus, Iqgap1 knockdown stabilized TbetaRII and potentiated TGF-beta1 transdifferentiation of pericytes into myofibroblasts in vitro. Iqgap1 deficiency in HSCs promoted myofibroblast activation, tumor implantation, and metastatic growth in mice via upregulation of paracrine signaling molecules. Additionally, we found that IQGAP1 expression was  downregulated in myofibroblasts associated with human colorectal liver metastases. Taken together, our studies demonstrate that IQGAP1 in the tumor microenvironment suppresses TbetaRII and TGF-beta dependent myofibroblastic differentiation to constrain tumor growth.




TÍTULO / TITLE:  - Magnetic Resonance Imaging-Guided Focused Ultrasound Treatment of Symptomatic Uterine Fibroids: Impact of Technology Advancement on Ablation Volumes in 115 Patients.

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

REVISTA / JOURNAL:  - Invest Radiol. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e3182806904

AUTORES / AUTHORS:  - Trumm CG; Stahl R; Clevert DA; Herzog P; Mindjuk I; Kornprobst S; Schwarz C; Hoffmann RT; Reiser MF; Matzko M

INSTITUCIÓN / INSTITUTION:  - From the *Department of Clinical Radiology, Klinikum der Ludwig-Maximilians-Universitat Munchen-Grosshadern, Munchen; daggerDepartment of  Diagnostic and Interventional Radiology, Klinikum Dachau, Dachau; and double daggerDepartment and Policlinics of Diagnostic Radiology, Universitatsklinikum Carl Gustav Carus Dresden, Dresden, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)-guided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. MATERIALS AND METHODS: This is a retrospective analysis of 115 women (mean age, 42 years; range, 27-54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean +/- SD total volume and number of treated fibroids (per patient) were  89 +/- 94 cm and 2.2 +/- 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. RESULTS: Magnetic resonance imaging-guided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% +/- 15% (range, 38%-100%). Mean applied energy level was 5400 +/- 1200 J, and mean number of sonications was 74 +/- 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. CONCLUSIONS: With technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio  can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials.




TÍTULO / TITLE:  - Uterine leiomyoma: available medical treatments and new possible therapeutic options.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):921-34. doi: 10.1210/jc.2012-3237. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3237

AUTORES / AUTHORS:  - Islam MS; Protic O; Giannubilo SR; Toti P; Tranquilli AL; Petraglia F; Castellucci M; Ciarmela P

INSTITUCIÓN / INSTITUTION:  - PhD, Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020 Ancona, Italy. p.ciarmela@univpm.it.

RESUMEN / SUMMARY:  - Context: Uterine leiomyomas (fibroids or myomas) are benign tumors of the uterus  and are clinically apparent in up to 25% of reproductive-age women. Heavy or abnormal uterine bleeding, pelvic pain or pressure, infertility, and recurrent pregnancy loss are generally associated with leiomyoma. Although surgical and radiological therapies are frequently used for the management of this tumor, medical therapies are considered the first-line treatment of leiomyoma. Evidence  Acquisition and Synthesis: A review was conducted of electronic and print data comprising both original and review articles on pathophysiology and medical treatments of uterine leiomyoma retrieved from the PubMed or Google Scholar database up to June 2012. These resources were integrated with the authors’ knowledge of the field. Conclusion: To date, several pathogenetic factors such as genetic factors, epigenetic factors, estrogens, progesterone, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in leiomyoma development and growth. On the basis of current hypotheses, several  medical therapies have been investigated. GnRH agonist has been approved by US Food and Drug Administration for reducing fibroid volume and related symptoms. In addition, the FDA also approved an intrauterine device, levonorgestrel-releasing  intrauterine system (Mirena), for additional use to treat heavy menstrual bleeding in intrauterine device users only. Currently, mifepristone, asoprisnil,  ulipristal acetate, and epigallocatechin gallate have been shown to be effective  for fibroid regression and symptomatic improvement which are all in clinical trial. In addition, some synthetic and natural compounds as well as growth factor inhibitors are now under laboratory investigation, and they could serve as future therapeutic options.




TÍTULO / TITLE:  - Clinical Outcomes of Adult Patients With Relapsed Ewing Sarcoma: A 30-Year Single-Institution Experience.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318281d6ab

AUTORES / AUTHORS:  - Robinson SI; Ahmed SK; Okuno SH; Arndt CA; Rose PS; Laack NN

INSTITUCIÓN / INSTITUTION:  - Divisions of *Medical Oncology double daggerPediatric Hematology and Oncology section signOrthopedic Oncology Departments of paragraph signRadiation Oncology parallelOrthopedic Surgery daggerMayo Medical School, College of Medicine, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - OBJECTIVES:: We aimed to determine the prognostic factors that influence the outcome of adult patients who have disease relapse after treatment for localized  Ewing sarcoma. METHODS:: We retrospectively searched for the records of patients  aged 18 years and older with localized Ewing sarcoma at Mayo Clinic, Rochester, Minnesota, from 1977 to 2007, who had disease relapse after initial treatment. Patient records were reviewed to analyze factors affecting survival. RESULTS:: A  total of 49 patients were identified. The 5-year postrelapse survival rate was 30%. Significant factors affecting the 5-year postrelapse survival rate included  site of initial relapse (local vs. distant, 55% vs. 22%, P=0.045); time to relapse (<2 vs. >/=2 y from original diagnosis, 12% vs. 50%, P=0.003); and second remission with complete surgical resection versus definitive radiotherapy to the  recurrent disease (48% vs. 13%, P<0.001). None of these factors were significant  on multivariate modeling. CONCLUSIONS:: Adult patients with Ewing sarcoma who have disease relapse after primary treatment of localized disease will continue to have recurrences regardless of the modality of salvage therapy. Those that have relapse locally or >2 years after the initial diagnosis and are able to achieve a second remission with definitive surgical or radiation therapy have better survival than those who have disease relapse distantly or before the 2-year time point.




TÍTULO / TITLE:  - Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread—results of a large prospective trial.

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

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds650

AUTORES / AUTHORS:  - Andreou D; Boldt H; Werner M; Hamann C; Pink D; Tunn PU

INSTITUCIÓN / INSTITUTION:  - Department of Orthopedic Oncology, Sarcoma Center Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin.

RESUMEN / SUMMARY:  - BackgroundThe role of sentinel lymph node biopsy (SLNB) in soft tissue sarcoma patients has yet to be determined. We sought to evaluate the role of SLNB in the  treatment of patients with clear cell sarcoma (CCS), synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdomyosarcoma (RMS).Patients and methodsSixty-two consecutive patients without history of regional lymphatic spread or evidence of  distant metastases underwent SLNB.ResultsPositive sentinel nodes were identified  in 2 out of 42 patients with SS and in 6 out of 12 patients with CCS. Only two CCS patients had further metastatic nodes in regional dissection. Both of these patients, along with another CCS patient, developed distant metastases and ultimately died of disease. The remaining three CCS patients are disease-free in  follow-up. One patient with SS and another with ES developed regional lymph node  metastases following a negative SLNB, while a further patient with RMS developed  distant metastases followed by a local recurrence with regional metastases shortly after.ConclusionsSLNB is an important diagnostic tool for patients with CCS, who appear to have a high rate of clinically occult regional lymph node metastases at diagnosis. For SS patients, SLNB appears to be of very little relevance.




TÍTULO / TITLE:  - Neoadjuvant and adjuvant chemotherapy with high-dose ifosfamide, doxorubicin, cisplatin and high-dose methotrexate in non-metastatic osteosarcoma of the extremities: a phase II trial in Japan.

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

REVISTA / JOURNAL:  - J Chemother. 2013 Feb;25(1):41-8. doi: 10.1179/1973947812Y.0000000055.

            ●● Enlace al texto completo (gratuito o de pago) 1179/1973947812Y.0000000055

AUTORES / AUTHORS:  - Kudawara I; Aoki Y; Ueda T; Araki N; Naka N; Nakanishi H; Matsumine A; Ieguchi M; Mori S; Myoui A; Kuratsu S; Hashimoto N; Yoshikawa H

INSTITUCIÓN / INSTITUTION:  - Osaka National Hospital, Osaka, Japan. kudawara@onh.go.jp

RESUMEN / SUMMARY:  - From 1997 to 2003, 40 patients (all <40 years of age) with non-metastatic osteosarcoma of the extremities were treated with OOS-D and definitive surgery. Two cycles of doxorubicin 90 mg/m(2) plus cisplatin 120 mg/m(2) and ifosfamide 15 g/m(2) were given as neoadjuvant chemotherapy, and two cycles of doxorubicin/cisplatin and ifosfamide, and two cycles of high-dose methotrexate (10-12 g/m(2)) were given post-operatively. All patients underwent limb salvage surgeries, and 66% showed good response to neoadjuvant chemotherapy. With a median follow-up period of 117 months, 31 of the evaluable 40 patients were continuously disease-free, 7 were currently alive with no evidence of disease, and 2 died of disease. There was no local recurrence. The 5-year event-free and overall survival rates were 83 and 98%, respectively. The 10-year event-free and  overall survival rates were 80 and 95%, respectively. The major form of toxicity  was haematological one.




TÍTULO / TITLE:  - High-throughput tyrosine kinase activity profiling identifies FAK as a candidate  therapeutic target in Ewing sarcoma.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1944

AUTORES / AUTHORS:  - Crompton BD; Carlton AL; Thorner AR; Christie AL; Du J; Calicchio ML; Rivera MN; Fleming MD; Kohl NE; Kung AL; Stegmaier K

INSTITUCIÓN / INSTITUTION:  - Pediatric Oncology, Dana-Farber Cancer Institute.

RESUMEN / SUMMARY:  - Limited progress has been made in the treatment of advanced-stage pediatric solid tumors despite the accelerated pace of cancer discovery over the last decade. Tyrosine kinase inhibition is one tractable therapeutic modality for treating human malignancy. However, little is known about the kinases critical to the development or maintenance of many pediatric solid tumors, such as Ewing sarcoma. Utilizing a fluorescent, bead-based technology to profile activated tyrosine kinases, we identified focal adhesion kinase (FAK, PTK2) as a candidate target in Ewing sarcoma. FAK is a tyrosine kinase critical for cellular adhesion, growth, and survival. As such, it is a compelling target for cancer-based therapy. In this study, we have demonstrated that FAK is highly phosphorylated in primary Ewing sarcoma tumor samples and that downregulation of FAK by shRNA and treatment with a FAK-selective kinase inhibitor, PF-562271, impaired growth and colony formation in Ewing sarcoma cell lines. Moreover, treatment of Ewing sarcoma cell  lines with PF-562271 induced apoptosis and led to downregulation of AKT/mTOR and  CAS activity. Finally, we demonstrated that small-molecule inhibition of FAK attenuated Ewing sarcoma tumor growth in vivo. With FAK inhibitors currently in early-phase clinical trials for adult malignancies, these findings may bear immediate relevance to patients with Ewing sarcoma.




TÍTULO / TITLE:  - Advanced soft-tissue sarcoma in elderly patients: patterns of care and survival.

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

REVISTA / JOURNAL:  - Ann Oncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt059

AUTORES / AUTHORS:  - Garbay D; Maki RG; Blay JY; Isambert N; Piperno Neumann S; Blay C; Zanardi E; Boudou-Rouquette P; Bozec L; Duffaud F; Bertucci F; Italiano A

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Institut Bergonie, Bordeaux, France.

RESUMEN / SUMMARY:  - BackgroundThere are no data regarding the management of advanced soft-tissue sarcoma (STS) in elderly patients.Patients and methodsWe retrospectively reviewed the charts of patients >/=75 years old diagnosed with metastatic or unresectable  STS between 1991 and 2011 in 11 French and American centers.ResultsThe study included 361 patients. Of these, 223 patients (62%) received systemic therapy, whereas 123 patients (34%) were managed with best supportive care (BSC) only. Patients who received BSC were more likely to be >/=80 years, with performance status (PS) >/= 2, Charlson comorbidity score >/= 10, and metastatic disease. The median progression-free survival of patients treated with systemic therapy was 4  months (95% CI: 2.9-5.1). Thirty-six patients (16%) stopped chemotherapy because  of toxicity. Median overall survival (OS) of patients managed with specific therapy was 10.9 months (95% CI: 8.3-13.5) versus 5.3 months (95% CI: 3.6-7.1) for patients managed with BSC (P = 0.001). On multivariate analysis, age >/= 80 years, PS >/= 2, and number of metastatic sites were the only independent factors associated with OS.ConclusionA high proportion of elderly patients with advanced  STS were denied chemotherapy. Further efforts are needed to define better the optimal care for fit and unfit elderly patients with STS.




TÍTULO / TITLE:  - Denosumab Treatment of Metastatic Giant-Cell Tumor of Bone in a 10-Year-Old Girl.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.46.4255

AUTORES / AUTHORS:  - Karras NA; Polgreen LE; Ogilvie C; Manivel JC; Skubitz KM; Lipsitz E

INSTITUCIÓN / INSTITUTION:  - City of Hope National Medical Center, Duarte, CA.




TÍTULO / TITLE:  - Immunosenescence is associated with presence of Kaposi’s sarcoma in antiretroviral treated human immunodeficiency virus infection.

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

REVISTA / JOURNAL:  - AIDS. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1097/QAD.0b013e3283601144

AUTORES / AUTHORS:  - Unemori PA; Leslie KS; Hunt PW; Sinclair E; Epling L; Mitsuyasu R; Effros RB; Dock J; Dollard SG; Deeks SG; Martin JN; Maurer TS

INSTITUCIÓN / INSTITUTION:  - aDermatology, University of California, San Francisco, San Francisco, CA, United  States bInternal Medicine, University of California, San Francisco, San Francisco, CA, United States cCenter for AIDS Research Core Immunology Lab, University of California, San Francisco, San Francisco, CA, United States dDepartment of Pathology & Laboratory Medicine, David Geffen School of Medicine,  University of California, Los Angeles, CA, United States eCenters for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, Georgia, USA fDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States.

RESUMEN / SUMMARY:  - OBJECTIVE:: Some antiretroviral-treated HIV-infected patients develop Kaposi’s sarcoma (KS) despite long-term suppression of HIV replication. These KS lesions are consistent with KS observed in the elderly uninfected population (“classical  KS”). We investigated potential mechanisms for this phenomenon, focusing on measures of immune activation and T cell senescence. DESIGN:: We compared markers of immunosenescence, naive T cells, activation, and inflammation in CD4+ and CD8+ T cells from antiretroviral-treated subjects with new onset KS (“cases”, n = 19)  and from treated subjects without KS (“controls”, n = 47). RESULTS:: There was increased frequency of CD4+ and CD8+ T cells with an immunosenescence phenotype (CD57+ and CD28-) in cases vs. controls (CD4+T cells: CD57+ 7.4% vs. 3.7%, p = 0.025; CD28- 9.1% vs. 4.8%, p = 0.025; CD8+ T cells: CD57+ 41.5% vs. 27.7%, p = 0.003; CD28- 60.5% vs. 51.3%, p = 0.041). Cases had lower proportions of naive T  cells (CD27+CD28+CD45RA+) in CD4+ (23.0% vs. 32.2%, p = 0.023) and CD8+ (11.3% vs. 20.7%, p < 0.001) T cell compartments. CCR5 was more highly expressed in CD4+ (16.3% vs. 11.0%, p = 0.025), and CD8+ (43.1% vs. 28.3%, p < 0.001) T cell compartments in cases vs. controls. There was no difference in telomere length or telomerase activity in PBMCs, or in T cell expression of activation markers (HLADR+CD38+). CONCLUSIONS:: Among antiretroviral-treated subjects, increased frequencies of T cells with an immunosenescence phenotype and lower frequencies of naive T cells were associated with presence of KS among effectively treated subjects. These data suggest that certain immunologic perturbations-including those associated with aging-might be causally associated with development of KS.




TÍTULO / TITLE:  - Anti-KIT monoclonal antibody inhibits imatinib-resistant gastrointestinal stromal tumor growth.

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

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3501-6. doi: 10.1073/pnas.1222893110. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1222893110

AUTORES / AUTHORS:  - Edris B; Willingham SB; Weiskopf K; Volkmer AK; Volkmer JP; Muhlenberg T; Montgomery KD; Contreras-Trujillo H; Czechowicz A; Fletcher JA; West RB; Weissman IL; van de Rijn M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Stanford University Medical Center, Stanford, CA 94305.

RESUMEN / SUMMARY:  - Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract and arises from the interstitial cells of Cajal. It is characterized by expression of the receptor tyrosine kinase CD117 (KIT). In 70-80% of GIST cases, oncogenic mutations in KIT are present, leading to constitutive activation of the receptor, which drives the proliferation of these  tumors. Treatment of GIST with imatinib, a small-molecule tyrosine kinase inhibitor, inhibits KIT-mediated signaling and initially results in disease control in 70-85% of patients with KIT-positive GIST. However, the vast majority  of patients eventually develop resistance to imatinib treatment, leading to disease progression and posing a significant challenge in the clinical management of these tumors. Here, we show that an anti-KIT monoclonal antibody (mAb), SR1, is able to slow the growth of three human GIST cell lines in vitro. Importantly,  these reductions in cell growth were equivalent between imatinib-resistant and imatinib-sensitive GIST cell lines. Treatment of GIST cell lines with SR1 reduces cell-surface KIT expression, suggesting that mAb-induced KIT down-regulation may  be a mechanism by which SR1 inhibits GIST growth. Furthermore, we also show that  SR1 treatment enhances phagocytosis of GIST cells by macrophages, indicating that treatment with SR1 may enhance immune cell-mediated tumor clearance. Finally, using two xenotransplantation models of imatinib-sensitive and imatinib-resistant GIST, we demonstrate that SR1 is able to strongly inhibit tumor growth in vivo. These results suggest that treatment with mAbs targeting KIT may represent an alternative, or complementary, approach for treating GIST.




TÍTULO / TITLE:  - Kaposi’s Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes.

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

REVISTA / JOURNAL:  - J Virol. 2013 Apr;87(8):4417-31. doi: 10.1128/JVI.03282-12. Epub 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03282-12

AUTORES / AUTHORS:  - Singh VV; Kerur N; Bottero V; Dutta S; Chakraborty S; Ansari MA; Paudel N; Chikoti L; Chandran B

INSTITUCIÓN / INSTITUTION:  - H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and  Science, North Chicago, Illinois, USA.

RESUMEN / SUMMARY:  - Kaposi’s sarcoma-associated herpesvirus (KSHV) infections of endothelial and B cells are etiologically linked with Kaposi’s sarcoma (KS) and primary effusion B-cell lymphoma (PEL), respectively. KS endothelial and PEL B cells carry multiple copies of the nuclear episomal latent KSHV genome and secrete a variety  of inflammatory cytokines, including interleukin-1beta (IL-1beta) and IL-18. The  maturation of IL-1beta and IL-18 depends upon active caspase-1, which is regulated by a multiprotein inflammasome complex induced by sensing of danger signals. During primary KSHV infection of endothelial cells, acting as a nuclear  pattern recognition receptor, gamma interferon-inducible protein 16 (IFI16) colocalized with the KSHV genome in the nuclei and interacted with ASC and procaspase-1 to form a functional inflammasome (Kerur N et al., Cell Host Microbe 9:363-375, 2011). Here, we demonstrate that endothelial telomerase-immortalized human umbilical cells (TIVE) supporting KSHV stable latency (TIVE-LTC cells) and  PEL (cavity-based B-cell lymphoma 1 [BCBL-1]) cells show evidence of inflammasome activation, such as the activation of caspase-1 and cleavage of pro-IL-1beta and  pro-IL-18. Interaction of ASC with IFI16 but not with AIM2 or NOD-like receptor P3 (NLRP3) was detected. The KSHV latency-associated viral FLIP (vFLIP) gene induced the expression of IL-1beta, IL-18, and caspase-1 mRNAs in an NF-kappaB-dependent manner. IFI16 and cleaved IL-1beta were detected in the exosomes released from BCBL-1 cells. Exosomal release could be a KSHV-mediated strategy to subvert IL-1beta functions. In fluorescent in situ hybridization analyses, IFI16 colocalized with multiple copies of the KSHV genome in BCBL-1 cells. IFI16 colocalization with ASC was also detected in lung PEL sections from  patients. Taken together, these findings demonstrated the constant sensing of the latent KSHV genome by IFI16-mediated innate defense and unraveled a potential mechanism of inflammation induction associated with KS and PEL lesions.




TÍTULO / TITLE:  - A dose-finding study of temsirolimus and liposomal doxorubicin for patients with  recurrent and refractory bone and soft tissue sarcoma.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 5. doi: 10.1002/ijc.28083.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28083

AUTORES / AUTHORS:  - Thornton KA; Chen AR; Trucco MM; Shah P; Wilky BA; Gul N; Carrera-Haro MA; Ferreira MF; Shafique U; Powell JD; Meyer CF; Loeb DM

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.

RESUMEN / SUMMARY:  - There are few effective therapies for high-risk sarcomas. Initial chemosensitivity is often followed by relapse. In vitro, mammalian target of rapamycin (mTOR) inhibition potentiates the efficacy of chemotherapy on resistant sarcoma cells. Although sarcoma trials using mTOR inhibitors have been disappointing, these drugs were used as maintenance. We conducted a Phase I/II clinical trial to test the ability of temsirolimus to potentiate the cytotoxic effect of liposomal doxorubicin and present here the dose-finding portion of this study. Adult and pediatric patients with recurrent or refractory sarcomas were treated with increasing doses of liposomal doxorubicin and temsirolimus using a continual reassessment method for escalation, targeting a dose-limiting toxicity  rate of 20%. Blood samples were drawn before and after the first dose of temsirolimus in Cycles 1 and 2 for pharmacokinetic analysis. The maximally tolerated dose combination was liposomal doxorubicin 30 mg/m2 monthly with temsirolimus 20 mg/m2 weekly. Hematologic toxicity was common but manageable. Dose-limiting toxicities were primarily renal. Concurrent administration of liposomal doxorubicin resulted in increased exposure to sirolimus, the active metabolite of temsirolimus. Thus, the combination of liposomal doxorubicin and temsirolimus is safe for heavily pretreated sarcoma patients. Co-administration with liposomal doxorubicin did not alter temsirolimus pharmacokinetics, but increased exposure to its active metabolite.




TÍTULO / TITLE:  - Lenograstim in preventing chemotherapy-induced febrile neutropenia in patients with soft tissue sarcoma.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Feb;33(2):679-84.

AUTORES / AUTHORS:  - Badalamenti G; Incorvaia L; Provenzano S; Bronte G; Leto G; Fulfaro F; Maltese G

INSTITUCIÓN / INSTITUTION:  - Department of Surgical and Oncological Sciences, Via del Vespro 129, 90127 Palermo, Italy. giuseppe.badalamenti@unipa.it

RESUMEN / SUMMARY:  - BACKGROUND: Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in chemotherapeutic regimens for soft tissue sarcoma. Prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN). The correct timing of G-CSF administration should be considered in order to optimize the prophylactic treatment. PATIENTS AND METHODS: Patients (>/=18 years old) affected by soft tissue sarcoma and treated with epirubicin and ifosfamide, underwent prophylactic treatment with G-CSF (lenograstim at 263 mug) from day 5 to day 9. The proportion of patients experiencing FN and G4 neutropenia was considered. RESULTS: A total of 36 patients receiving three cycles of chemotherapy with epirubicin plus ifosfamide were treated. None developed FN; G4 neutropenia was reported in 17% of patients.  No treatment delay or dose reduction was required, no antibiotic therapy was administered and no hospitalization occurred. CONCLUSION: Five-day lenograstim treatment is efficient as prophylaxis of FN for soft tissue sarcoma chemotherapy  regimens and allows maintenance of chemotherapy dose intensity.




TÍTULO / TITLE:  - JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic  differentiation of rhabdomyosarcoma cells.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Feb 25. doi: 10.1038/onc.2013.46.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.46

AUTORES / AUTHORS:  - Walters ZS; Villarejo-Balcells B; Olmos D; Buist TW; Missiaglia E; Allen R; Al-Lazikani B; Garrett MD; Blagg J; Shipley J

INSTITUCIÓN / INSTITUTION:  - Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.

RESUMEN / SUMMARY:  - Rhabdomyosarcomas (RMS) are the most frequent soft-tissue sarcoma in children and characteristically show features of developing skeletal muscle. The alveolar subtype is frequently associated with a PAX3-FOXO1 fusion protein that is known to contribute to the undifferentiated myogenic phenotype of RMS cells. Histone methylation of lysine residues controls developmental processes in both normal and malignant cell contexts. Here we show that JARID2, which encodes a protein known to recruit various complexes with histone-methylating activity to their target genes, is significantly overexpressed in RMS with PAX3-FOXO1 compared with the fusion gene-negative RMS (t-test; P<0.0001). Multivariate analyses showed that higher JARID2 levels are also associated with metastases at diagnosis, independent of fusion gene status and RMS subtype (n=120; P=0.039). JARID2 levels were altered by silencing or overexpressing PAX3-FOXO1 in RMS cell lines with and without the fusion gene, respectively. Consistent with this, we demonstrated that JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein. Silencing JARID2 resulted in reduced cell proliferation coupled with myogenic differentiation, including increased expression of Myogenin (MYOG) and Myosin Light Chain (MYL1) in RMS cell lines representative of both the alveolar and embryonal subtypes. Induced myogenic differentiation was associated with a decrease in JARID2 levels and this phenotype could be rescued by overexpressing JARID2. Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that  the interaction of JARID2 at these promoters is dependent on EED, a core component of the polycomb repressive complex 2 (PRC2). Therefore, JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS. JARID2 and other components of PRC2 may  represent novel therapeutic targets for treating RMS patients.Oncogene advance online publication, 25 February 2013; doi:10.1038/onc.2013.46.




TÍTULO / TITLE:  - The effect of high-intensity focused ultrasound treatment on immune function in patients with uterine fibroids.

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

REVISTA / JOURNAL:  - Int J Hyperthermia. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02656736.2013.775672

AUTORES / AUTHORS:  - Wang X; Qin J; Chen J; Wang L; Chen W; Tang L

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynaecology, First Affiliated Hospital, Chongqing Medical University , Chongqing .

RESUMEN / SUMMARY:  - Abstract Purpose: The aim of this study was to investigate the effect of high-intensity focused ultrasound (HIFU) on immune function in patients with uterine fibroids, in a randomised comparison to conventional myomectomy. Methods: The patients were assigned (1:1) to the HIFU group or the myomectomy (MY) group.  Venous blood samples were collected 24 h before and 24 h and 72 h after operation. The percentages of CD4+ and CD8+ T cells and natural killer (NK) cells were quantified by flow cytometry (FCM). Serum levels of interleukin-2 (IL-2), IL-6 and IL-10 were determined using enzyme-linked immunosorbent assay. Results:  HIFU was associated with early ambulation, fewer post-operative complications, and shorter hospital stay (p < 0.001). The percentages of CD4+ and CD8+ T cells and NK cells in the HIFU group were not significantly altered after treatment compared with before treatment. In contrast, the numbers of these cells in the MY group decreased significantly 24 h after conventional myomectomy (p < 0.001). The CD4+/CD8+ T cell ratios were also decreased significantly 24 h and 72 h after conventional myomectomy (p < 0.001). Serum levels of IL-6 and IL-10 increased after treatment in both groups. Peak IL-6 and IL-10 levels were significantly lower in the HIFU group than in the MY group (p < 0.001). In contrast, IL-2 level decreased significantly in the MY group compared to the HIFU group at 24 h post-operation (p < 0.001). Conclusions: Short-term post-operative immune function is better preserved after HIFU treatment. Better preserved immune function may reflect a reduction in tissue trauma after HIFU treatment and contribute to reduced post-operative complications.




TÍTULO / TITLE:  - Sustained Autocrine Induction and Impaired Negative Feedback of Osteoclastogenesis in CD14(+) Cells of Giant Cell Tumor of Bone.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Apr;182(4):1357-66. doi: 10.1016/j.ajpath.2012.12.021. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.12.021

AUTORES / AUTHORS:  - Avnet S; Salerno M; Zini N; Alberghini M; Gibellini D; Baldini N

INSTITUCIÓN / INSTITUTION:  - Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address: sofia.avnet@ior.it.

RESUMEN / SUMMARY:  - Giant cell tumor (GCT) of bone is a histologically benign osteolytic tumor featuring prominent osteoclast-like giant cells, mononuclear osteoclast precursors, and spindle-shaped stromal cells (SCs). Thus far, most studies have identified SCs as truly transformed elements that are responsible for sustained giant cell formation via receptor activator of NF-kappaB ligand (RANKL) paracrine induction. However, we have previously shown that SCs are hyperplastic, rather than neoplastic, and able to induce giant cell formation similar to that of normal mesenchymal SCs; we hypothesized that other cell subsets of GCTs might be  primarily relevant for the pathogenesis. In this study, we show that the nonproliferating CD14(+) cells of GCTs, exhibiting typical monoblast lineage features, secrete high amounts of RANKL, thereby activating a RANKL/RANK autocrine loop that determines sustained giant cell formation. Moreover, these cells also lack adequate negative feedback control of the RANKL signaling pathway, as determined by endogenous interferon beta. These data demonstrate that CD14(+) cells of GCTs are abnormally stimulated to limitless differentiation into multinucleated giant cells and provide useful suggestions for the development of  novel therapies.




TÍTULO / TITLE:  - The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi’s sarcoma (KS) in a cohort of HIV-infected men.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 19;108(5):1173-7. doi: 10.1038/bjc.2013.75. Epub 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.75

AUTORES / AUTHORS:  - Luu HN; Amirian ES; Scheurer ME

INSTITUCIÓN / INSTITUTION:  - 1] Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA [2] Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, the University of Texas Health Science Center-Houston, Houston, TX 77030, USA.

RESUMEN / SUMMARY:  - Background:Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and  HAART use on the risk of KS development in an on-going US cohort of HIV-infected  men.Methods:Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS).Results:We identified 530 incident KS cases with a total follow-up time of 26 594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio - HR=0.56, 95% CI: 0.35-0.90, P=0.02 and HR=0.27, 95% CI: 0.16-0.48, P<0.0001, respectively). There was no evidence of multiplicative interaction between current smoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97-4.73, Pinteraction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35-0.92, P=0.02).Conclusion:The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.




TÍTULO / TITLE:  - Screening for Potential Targets for Therapy in Mesenchymal, Clear Cell, and Dedifferentiated Chondrosarcoma Reveals Bcl-2 Family Members and TGFbeta as Potential Targets.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Apr;182(4):1347-56. doi: 10.1016/j.ajpath.2012.12.036. Epub 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.12.036

AUTORES / AUTHORS:  - van Oosterwijk JG; Meijer D; van Ruler MA; van den Akker BE; Oosting J; Krenacs T; Picci P; Flanagan AM; Liegl-Atzwanger B; Leithner A; Athanasou N; Daugaard S; Hogendoorn PC; Bovee JV

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

RESUMEN / SUMMARY:  - The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We constructed tissue microarrays containing 42 dedifferentiated, 23 clear cell, and 23 mesenchymal chondrosarcomas and performed immunohistochemistry to study the expression of growth plate-signaling molecules and molecules shown to be involved in conventional chondrosarcoma. We observed high expression of SOX-9 and FGFR-3, as  well as aberrant cellular localization of heparan sulfate proteoglycans, in all subtypes. TGFbeta signaling through p-SMAD2 and PAI-1 was highly active in all chondrosarcoma subtypes, which suggests that TGFbeta inhibitors as a possible therapeutic strategy in rare chondrosarcoma subtypes. As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play an important role in chemoresistance, suggesting a promising role for targeting Bcl-2 family members in chondrosarcoma treatment, irrespective of the subtype.




TÍTULO / TITLE:  - Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 5;108(4):836-47. doi: 10.1038/bjc.2012.579.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.579

AUTORES / AUTHORS:  - Fujiwara-Okada Y; Matsumoto Y; Fukushi J; Setsu N; Matsuura S; Kamura S; Fujiwara T; Iida K; Hatano M; Nabeshima A; Yamada H; Ono M; Oda Y; Iwamoto Y

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - Background:Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear.Methods:Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical  prognosis was also investigated by immunohistochemistry.Results:Proliferation of  OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin  D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of  YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1  was significantly related to the poorer overall survival in OS patients.Conclusion:Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.




TÍTULO / TITLE:  - Somatic mutations of the mitochondrial genome in Chinese patients with Ewing sarcoma.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 31. pii: S0046-8177(12)00426-1. doi: 10.1016/j.humpath.2012.11.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.11.004

AUTORES / AUTHORS:  - Yu M; Wan Y; Zou Q

INSTITUCIÓN / INSTITUTION:  - Ontario Cancer Institute/Princess Margaret Hospital, University Health Network and University of Toronto, Toronto, M5G 2M9 Ontario, Canada. Electronic address:  manyu@uhnres.utoronto.ca.

RESUMEN / SUMMARY:  - Somatic mutations in mitochondrial DNA (mtDNA) have been long proposed to drive initiation and progression of human malignancies. Our previous study revealed a high prevalence of somatic mutations in the D-loop region of mtDNA in Ewing sarcoma (EWS). However, it is unclear whether somatic mutations also occur in the coding regions of mtDNA in EWS. To test this possibility, in the present study, we sequenced the whole mitochondrial genome from 20 cases of EWS specimens and their corresponding peripheral blood samples. We identified a total of 6 somatic  mutations in the mtDNA coding regions in our EWS series, and 5 of them were missense or frame-shift mutations that have the potential to directly influence proper mitochondrial function. In combination with our earlier observations on the D-loop fragment, 70% (14/20) of EWS tissues appeared to harbor somatic mtDNA  mutations. Among the identified 25 somatic mutations, 19 (76%) were located in the D-loop control region, 1 (4%) was in the sequence of the tRNA(Val) gene, 1 (4%) was in the mitochondrial ATP synthase subunit 6 gene, and 4 (16%) occurred in genes encoding components of the mitochondrial respiratory complexes. In addition, patients carrying somatic mtDNA mutations did not show significant association with their clinicopathologic characteristics. Together, these findings suggest that somatic mtDNA mutations occur in both protein coding and noncoding regions of mtDNA, which may play critical roles in the pathogenesis of  EWS and should be further explored for its possible use as a novel marker for monitoring EWS occurrence and advancement.




TÍTULO / TITLE:  - Regulation of viral and cellular gene expression by Kaposi’s sarcoma associated herpesvirus (KSHV) PAN RNA.

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

REVISTA / JOURNAL:  - J Virol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03111-12

AUTORES / AUTHORS:  - Rossetto CC; Tarrant-Elorza M; Verma S; Purushothaman P; Pari GS

INSTITUCIÓN / INSTITUTION:  - The University of Nevada, Reno, Department of Microbiology & Immunology, School of Medicine, Reno NV 89557.

RESUMEN / SUMMARY:  - Kaposi’s sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi’s sarcoma and body cavity lymphoma. In cell culture, KSHV results in a latent infection and lytic reactivation is usually induced with the expression of the K-Rta or by treatment with TPA and/or n-butyrate. Lytic infection is marked by the activation of the entire viral genomic transcription cascade and the production of infectious virus. KSHV infected cells express a highly abundant long noncoding transcript referred to as polyadenylated nuclear RNA (PAN RNA). PAN RNA interacts with specific demethylases and physically binds to the KSHV genome to mediate activation of viral gene expression. A recombinant BACmid lacking the PAN RNA locus fails to express K-Rta and does not produce virus. We now show that the lack of PAN RNA expression results in the failure of the initiation of the entire KSHV transcription program. In addition to previous findings of an interaction with demethylases, we show that PAN RNA binds to protein components of the polycomb repression complex 2 (PRC2). RNA Seq analysis using cell lines that express PAN RNA show that transcription involving the expression of proteins involved in cell cycle, immune response and inflammation is disregulated. Expression of PAN RNA in various cell types results in an enhanced growth phenotype, higher cell densities and increased survival compared to control cells. Also, PAN RNA expression mediates a decrease in the production of inflammatory cytokines. These data support a role for PAN RNA as a major global regulator of viral and cellular gene expression.




TÍTULO / TITLE:  - Osteosarcoma of the pelvis: a monoinstitutional experience in patients younger than 41 years.

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

REVISTA / JOURNAL:  - Tumori. 2012 Nov;98(6):702-8. doi: 10.1700/1217.13492.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1217.13492

AUTORES / AUTHORS:  - Ferrari S; Palmerini E; Fabbri N; Staals E; Ferrari C; Alberghini M; Picci P

INSTITUCIÓN / INSTITUTION:  - Sezione di Chemioterapia, Istituto Ortopedico Rizzoli, Via Pupilli 1, Bologna, Italy. stefano.ferrari@ior.it

RESUMEN / SUMMARY:  - AIMS AND BACKGROUND: Information is scarce on systemic treatment of pelvic osteosarcoma because most chemotherapy protocols for osteosarcoma include patients with extremity tumors and aged up to 30-40 years. METHODS: Data on patients <41 years of age with high-grade pelvic osteosarcoma were prospectively  collected. Patients received two chemotherapy protocols consisting of methotrexate, cisplatin, doxorubicin (MAP) and standard-dose or high-dose ifosfamide. RESULTS: Forty patients between 11 and 36 years were included. The most frequent histological subtype was osteoblastic followed by chondroblastic (37.5%). Complete surgical remission was achieved in 65% of patients. Eighteen patients had MAP/standard-dose ifosfamide, 22 MAP/high-dose ifosfamide. Primary chemotherapy was given to 25 patients and 6 (24%) of them had a good histological response. Median follow-up was 32 months (range, 4-134). Five-year overall survival was 27.5%: 33% in localized and 0 in metastatic patients ( P = 0.02); 45% in patients with complete surgical remission and 0 for patients without complete surgical remission (P = 0.001). Local recurrence rate was 46%. In patients with complete surgical remission, 5-year overall survival was 32% with MAP/standard-dose ifosfamide and 59% with MAP/high-dose ifosfamide regimen (P = 0.3). CONCLUSIONS: Local control is the major issue in the treatment of pelvic osteosarcoma. Poor pathological response and high incidence of chondroblastic variant indicate different characteristics between pelvic and extremity osteosarcoma. Chemotherapy with MAP and high-dose ifosfamide might be beneficial  in patients with pelvic osteosarcoma and warrants further investigation.





TÍTULO / TITLE:Autologe Stammzellentransplantation bei erwachsenen Patienten mit Sarkomen der Ewing Familie - eine Einzelzentrum-Analyse.

TÍTULO / TITLE:  - Autologous stem cell transplantation in adults with metastatic sarcoma of the Ewing family: a single centre experience.

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

REVISTA / JOURNAL:  - Wien Klin Wochenschr. 2013 Mar;125(5-6):129-133. Epub 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00508-013-0328-0

AUTORES / AUTHORS:  - Lamm W; Rabitsch W; Kostler WJ; Kalhs P; Ubl P; Brodowicz T

INSTITUCIÓN / INSTITUTION:  - Sarcoma Program, Clinical Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

RESUMEN / SUMMARY:  - BACKGROUND: Adults with metastatic Ewing family sarcomas (ES) after being treated with standard therapy for localised disease have limited treatment options with curative intent. The aim of this retrospective single centre study was to evaluate the efficacy of autologous stem cell transplantation (ASCT) in this patient population. METHODS: We report on seven consecutive patients with ES. Four patients with initial localised disease developed distant metastases after being treated with initial standard pre-operative chemotherapy followed by surgery and subsequent standard post-operative chemotherapy. Three patients with  initial metastatic disease were pre-treated with standard polychemotherapy. All patients received high-dose chemotherapy (HDCT) followed by ASCT for metastatic disease. RESULTS: For patients with initial metastatic disease, partial remission (PR) was achieved in three patients prior to HDCT. Type of response subsequent to ASCT was complete response (CR) in four patientswith initial localised disease and CR in two patients with initial metastatic disease. No patient died within the first 100 days after HDCT. Side effects were rare and manageable. CONCLUSION: This retrospective analysis suggests that ASCT may be considered in patients with metastatic ES, previously treated with standard therapy.




TÍTULO / TITLE:  - Kaposi Sarcoma-Associated Herpesvirus Induces Rapid Release of Angiopoietin-2 from Endothelial Cells.

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

REVISTA / JOURNAL:  - J Virol. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03303-12

AUTORES / AUTHORS:  - Ye FC; Zhou FC; Nithianantham S; Chandran B; Yu X; Weinberg A; Gao SJ

INSTITUCIÓN / INSTITUTION:  - Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106.

RESUMEN / SUMMARY:  - Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the pro-angiogenic and pro-inflammatory cytokine angiopoietin-2 (Ang-2). Here we report that KSHV induces rapid release of Ang-2 that is pre-synthesized and stored in the Weibel-Palade bodies (WPB) of endothelial cells upon binding to its integrins receptors. Blocking viral binding to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine kinase receptors signaling pathways, leading to tyrosine phosphorylation of focal adhesion kinase (FAK), the tyrosine kinase Src, and the Calalpha2 subunit of L-type calcium channel to trigger rapid calcium (Ca2+) influx. Pre-treatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV induced Ca2+ influx and Ang-2 release. Inhibition of Ca2+ mobilization with  calcium channel blockers also inhibits Ang-2 release. Thus, the interaction between KSHV and its integrins receptors plays a key role in regulating rapid Ang-2 release from endothelial cells. This finding highlights a novel mechanism of viral induction of angiogenesis and inflammation, which might play important roles in the early event of KS tumor development.




TÍTULO / TITLE:  - Downregulation of phosphatidylethanolamine binding protein 1 associates with clinical risk factors in gastrointestinal stromal tumors, but not with activation of the RAF-1-MEK-ETV1 pathway.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 31. pii: S0304-3835(13)00090-6. doi: 10.1016/j.canlet.2013.01.044.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.044

AUTORES / AUTHORS:  - Schoppmann SF; Beer A; Nirtl N; Ba-Ssalamah A; Brodowicz T; Streubel B; Birner P

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Medical University of Vienna, Austria.

RESUMEN / SUMMARY:  - Aim of this study was to investigate phosphatidylethanolamine binding protein 1 (PEBP1) in GIST and its relations with MEK1/2 activation and ETV1 by immunohistochemistry. Loss of PEBP1 was found in 22/161 (13.7%) GIST, was associated with clinical risk factors and with a trend towards shorter disease free survival, but not with pMEK1/2 and ETV1 expression. So downregulation of PEBP1 does not activate the Ras-Raf-1-MEK1/2-ERK1/2 pathway by phosphorylation of MEK1/2 and does not influence ETV1 expression in GIST. Loss of PEBP1 associates with clinical risk factors, but since no significant influence on survival was found, further studies are required.




TÍTULO / TITLE:  - Systemic mastocytosis.

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

REVISTA / JOURNAL:  - Blood. 2013 Feb 14;121(7):1071.

AUTORES / AUTHORS:  - Bouvier S; Arnaud A

INSTITUCIÓN / INSTITUTION:  - Centre Hospitalier Universitaire de Nimes.




TÍTULO / TITLE:  - Ovarian tissue cryopreserved for fertility preservation from patients with Ewing  or other sarcomas appear to have no tumour cell contamination.

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

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Feb 26. pii: S0959-8049(13)00106-8. doi: 10.1016/j.ejca.2013.01.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.032

AUTORES / AUTHORS:  - Greve T; Wielenga VT; Grauslund M; Sorensen N; Christiansen DB; Rosendahl M; Yding Andersen C

INSTITUCIÓN / INSTITUTION:  - Laboratory of Reproductive Biology, Rigshospitalet - Copenhagen University Hospital, Denmark. Electronic address: tinegreve@gmail.com.

RESUMEN / SUMMARY:  - AIM: The chemotherapy required to treat patients with sarcoma may as a side-effect induce infertility in girls and young women. If these patients have ovarian cortical tissue cryopreserved prior to chemotherapy, they may, if necessary, have the tissue transplanted and restore their fertility. The aim of this study was to evaluate the risk of residual cancer cells in the ovarian cortex intended for transplantation. PATIENTS AND METHODS: Ovarian tissue stored  for fertility preservation from 16 surviving patients diagnosed with sarcoma (nine with Ewing sarcomas, four with osteosarcomas, two with synovial sarcomas and one with chondrosarcoma) was evaluated for the presence of malignant cells by histology and by transplantation to immunodeficient mice for 20weeks. A fraction  of the tissue from patients with Ewing sarcoma was also evaluated for the presence of the molecular marker EWS-FLI1 by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The transplant itself and selected murine organs were analysed for the presence of malignant cells by histology. RESULTS: All the mice accommodated the human tissue for 20weeks of transplantation period  with none of the mice developing any sign of cancer. In no instance were any cancer cells detected by histology or RT-qPCR. CONCLUSION: Ovarian tissue from patients with sarcoma appears to be without metastatic malignant cells in numbers that allow detection. Although the actual pieces of ovarian tissue used for transplantation remain unchecked, the current data indicate that the procedure is safe at least in patients that survive the sarcoma disease.




TÍTULO / TITLE:  - Malignant inflammatory myofibroblastic tumor of the prostate.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Apr 1;31(10):e144-7. doi: 10.1200/JCO.2012.44.4851. Epub 2013  Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.4851

AUTORES / AUTHORS:  - Liu C; Zhao X; Zhao Z; Lu P; Jin F; Li G

INSTITUCIÓN / INSTITUTION:  - Department of Breast Surgery, General Surgery, First Hospital of China Medical University, Shenyang, China 110001; zhongguoyida2011@163.com.




TÍTULO / TITLE:  - Mullerian Carcinosarcoma Arising From Intestinal Endometriosis.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.1600

AUTORES / AUTHORS:  - Agito MD; Rehmus EH; Powell AT

INSTITUCIÓN / INSTITUTION:  - Akron General Medical Center, Akron, OH.




TÍTULO / TITLE:  - Anorectal gastrointestinal stromal tumors: a retrospective multicenter analysis of 15 cases emphasizing their high local recurrence rate and the need for standardized therapeutic approach.

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

REVISTA / JOURNAL:  - Int J Colorectal Dis. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00384-013-1655-3

AUTORES / AUTHORS:  - Agaimy A; Vassos N; Markl B; Meidenbauer N; Kohler J; Spatz J; Hohenberger W; Haller F; Croner RS; Schneider-Stock R; Matzel K

INSTITUCIÓN / INSTITUTION:  - Institute of Pathology, University Hospital Erlangen, Krankenhausstrasse 8-10, 91054, Erlangen, Germany, abbas.agaimy@uk-erlangen.de.

RESUMEN / SUMMARY:  - PURPOSE: This study aims to report our multicenter experience with diagnosis, management, and prognosis of anorectal gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: We retrospectively reviewed cases treated and/or followed up at our institutions in the period 2000-2011. RESULTS: Fifteen patients were identified (eight men and seven women; mean age, 55 years). Presenting symptoms were rectal/perirectal (eight), rectovaginal space (four), or retrovesical/prostatic (three) mass. Primary surgical treatment was local excision (six), deep anterior resection (eight), and palliative diagnostic excision (one). Tumor mean size was 4.8 cm. All but two cases were high risk (Miettinen and Lasota, Semin Diagn Pathol 23:70-83, 2006). R0 resection was achieved in 46 % of cases: one of six local excisions vs. five of seven deep anterior resection (16 vs. 71 %, respectively). All three cases who received total mesorectal excision had R0. Non-R0 status was mainly due to opening of tumor capsule at surgery (Rx). Seven of 14 patients (50 %) developed >/=1 pelvic  local recurrences at a mean period of 48.4 months (mean follow-up, 61.6 months).  Only two patients developed distant metastasis (adrenal, liver, and peritoneal).  Recurrences developed after Rx (three), R1 (two), and unknown R-status (two). Successful mutational analysis in 13 patients revealed KIT mutations in all (10 exon 11, 2 exon 9, and 1 exon 13). CONCLUSION: Our results confirm the high local recurrence rate of anorectal GISTs (50 %) which correlates with the common practice of suboptimal oncological primary tumor resection (Rx or R1 = 7/13). This uncommon subset of GISTs needs more standardized oncological surgical approach to minimize the propensity for local disease recurrence.




TÍTULO / TITLE:  - Osteoid Osteoma: MR-guided Focused Ultrasound for Entirely Noninvasive Treatment.

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

REVISTA / JOURNAL:  - Radiology. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13120873

AUTORES / AUTHORS:  - Napoli A; Mastantuono M; Marincola BC; Anzidei M; Zaccagna F; Moreschini O; Passariello R; Catalano C

INSTITUCIÓN / INSTITUTION:  - Department of Radiological, Oncological and Anatomo-pathological Sciences and Department of Orthopedics and Traumatology, Policlinico Umberto I-Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.

RESUMEN / SUMMARY:  - Purpose:To determine the preliminary feasibility, safety, and clinical efficacy of magnetic resonance (MR)-guided focused ultrasound for the treatment of painful osteoid osteoma.Materials and Methods:This prospective institutional review board-approved study involved six consecutive patients (five males and one female; mean age, 21 years) with a diagnosis of osteoid osteoma based on clinical and imaging findings. All patients underwent MR-guided focused ultrasound ablation after providing informed consent. Lesions located in the vertebral body  were excluded. The number of sonications and the energy deposition were recorded. Treatment success was determined at 1, 3, and 6 months after treatment. A visual  analog scale (VAS) score for pain was used to assess changes in symptoms. MR imaging features of osteoid osteoma (edema, hyperemia, and nidus vascularization) were considered at baseline and at imaging follow-up.Results:Treatment was performed with a mean of 4 sonications +/-1.8 (standard deviation), with a mean energy deposition of 866 J +/- 211. No treatment- or anesthesia-related complications occurred. The pre- and posttreatment mean VAS scores significantly  differed (7.9 +/-1.4 and 0.0 +/- 0.0, respectively). At imaging, the edema and hyperemia associated with osteoid osteoma gradually disappeared in all lesions. However, nidus vascularization still persisted after treatment in four of six patients.Conclusion:This limited series demonstrated that MR-guided focused ultrasound treatment of osteoid osteoma can be performed safely with a high rate  of success and without apparent treatment-related morbidity.© RSNA, 2013.




TÍTULO / TITLE:  - Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Feb 15;73(4):1298-307. doi: 10.1158/0008-5472.CAN-12-2086. Epub  2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2086

AUTORES / AUTHORS:  - Zhang K; Chu K; Wu X; Gao H; Wang J; Yuan YC; Loera S; Ho K; Wang Y; Chow W; Un F; Chu P; Yen Y

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, CA 91010, USA.

RESUMEN / SUMMARY:  - Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first comparatively examined the amplification and expression of FRS2  with CDK4 and MDM2 in dedifferentiated liposarcoma (DDLS) and undifferentiated high-grade pleomorphic sarcoma (UHGPS). Amplification and expression of the three genes were identified in 90% to 100% (9-11 of 11) of DDLS, whereas that of FRS2,  CDK4, and MDM2 were observed in 55% (41 of 75), 48% (36 of 75), and 44% (33/75) of clinically diagnosed UHGPS, suggesting that these “UHGPS” may represent DDLS despite lacking histologic evidence of lipoblasts. Immunohistochemical analysis of phosphorylated FRS2 protein indicated that the FGFR/FRS2 signaling axis was generally activated in about 75% of FRS2-positive high-grade liposarcomas. Moreover, we found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872. Importantly, the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of FU-DDLS-1 and LiSa-2 cells with a concomitant suppression of FGFR signal transduction. Attenuation of FRS2 protein in FU-DDLS-1 and LiSa-2  cell lines decreased the phosphorylated extracellular signal-regulated kinase ½ and AKT and repressed cell proliferation. These findings indicate that analysis of FRS2 in combination with CDK4 and MDM2 will more accurately characterize pathologic features of high-grade liposarcomas. Activated FGFR/FRS2 signaling may play a functional role in the development of high-grade liposarcomas, therefore,  serve as a potential therapeutic target.




TÍTULO / TITLE:  - Virilizing sclerosing-stromal tumor of the ovary in a young woman with McCune Albright syndrome: clinical, pathological, and immunohistochemical studies.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb;98(2):E314-20. doi: 10.1210/jc.2012-3551. Epub  2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3551

AUTORES / AUTHORS:  - Boussaid K; Meduri G; Maiza JC; Gennero I; Escourrou G; Bros A; Leguevaque P; Bennet A; Caron P

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Metabolic Diseases, Centre Hospitalier Universitaire Rangueil-Larrey, 24 Chemin de Pourvouville, TSA 30030, 31059 Toulouse Cedex 9, France.

RESUMEN / SUMMARY:  - CONTEXT: McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, cafe-au-lait skin pigmentations, and gonadotropin-independent sexual precocious puberty, resulting from a somatic postzygotic activating mutation of the GNAS1 gene. SETTING: We report a virilizing sclerosing-stromal tumor of the ovary in a young female with MAS. PATIENT: She presented polyostotic fibrous dysplasia of the left upper and lower limbs and a cafe-au-lait skin spot in the posterior area of the neck. She had a history of precocious puberty, diagnosed at the age of 6 years and treated with cyproterone acetate until the age of 10 years; then she developed central puberty with severe oligomenorrhea. At the age  of 23 years, she was hospitalized for a virilization syndrome including hirsutism, acne, deepening of the voice, amenorrhea, and clitoromegaly. Serum levels of T were dramatically increased (1293 ng/dl; normal range, 10-80). The abdominal computed tomography scan revealed a solid mass located on the left ovary. INTERVENTION: An ovariectomy was performed, and histological examination revealed a sclerosing-stromal tumor with pseudolobular pattern. RESULTS: Immunohistochemical studies revealed that the tumor cells expressed all steroidogenic enzymes involved in androgen synthesis. Molecular analysis revealed that ovarian tumor cells harbored the Arg 201 activating mutation in the GNAS1 gene. After surgery, T levels returned to normal, the patient retrieved a normal  gonadal function, and she was able to become pregnant. CONCLUSION: This observation extends the clinical spectrum of ovarian pathology of women with MAS. However, the mechanisms causing this ovarian tumor remain unclear, even if the gsp oncogene has been implicated in the pathogenesis of some gonadal tumors.




TÍTULO / TITLE:  - Gene Expression Patterns of Insulin-Like Growth Factor 2 in Human Uterine Fibroid Tissues: A Genetic Study with Clinical Correlations.

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

REVISTA / JOURNAL:  - Gynecol Obstet Invest. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000347017

AUTORES / AUTHORS:  - Csatlos E; Rigo Jr J; Laky M; Joo JG

INSTITUCIÓN / INSTITUTION:  - First Department of Gynecology and Obstetrics, Semmelweis University, Budapest, Hungary.

RESUMEN / SUMMARY:  - Background/Aims: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. Methods: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. Results: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. Conclusion: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.




TÍTULO / TITLE:  - Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies upon the HMGA2-IGF2BP2 pathway.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3947

AUTORES / AUTHORS:  - Li Z; Zhang Y; Ramanujan K; Ma Y; Kirsch DG; Glass DJ

INSTITUCIÓN / INSTITUTION:  - Muscle Diseases, Novartis Institutes of Biomedical Research.

RESUMEN / SUMMARY:  - Embryonic rhabdomyosarcoma (ERMS) is the most common soft-tissue tumor in children. Here we report the identification of the minor groove DNA binding factor HMGA2 as a driver of ERMS development. HMGA2 was highly expressed in normal myoblasts and ERMS cells, where its expression was essential to maintain cell proliferation, survival in vitro and tumor outgrowth in vivo. Mechanistic investigations revealed that upregulation of the IGF mRNA binding protein IGF2BP2 was critical for HMGA2 action. In particular, IGF2BP2 was essential for mRNA and  protein stability of NRAS, a frequently mutated gene in ERMS. shRNA-mediated attenuation of NRAS or pharmacological inhibition of the MEK/ERK effector pathway demonstrated that NRAS and NRAS-mediated signaling was required for tumor maintenance. Taken together, these findings implicate the HMGA2-IGFBP2-NRAS signaling pathway as a critical oncogenic driver in ERMS.




TÍTULO / TITLE:  - mTOR Inhibitors Block Kaposi Sarcoma Growth by Inhibiting Essential Autocrine Growth Factors and Tumor Angiogenesis.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Apr 1;73(7):2235-46. doi: 10.1158/0008-5472.CAN-12-1851. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1851

AUTORES / AUTHORS:  - Roy D; Sin SH; Lucas A; Venkataramanan R; Wang L; Eason A; Chavakula V; Hilton IB; Tamburro KM; Damania B; Dittmer DP

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Curriculum in Genetics and Molecular Biology; Department of Microbiology and Immunology; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.

RESUMEN / SUMMARY:  - Kaposi sarcoma originates from endothelial cells and it is one of the most overt  angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma-associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin. Cancer Res; 73(7); 2235-46. ©2012 AACR.




TÍTULO / TITLE:  - Kaposi’s sarcoma: a reversible cause of ARDS in HIV-infected patient.

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

REVISTA / JOURNAL:  - Intensive Care Med. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00134-013-2891-2

AUTORES / AUTHORS:  - Repesse X; Au SM; Charron C; Vieillard-Baron A

INSTITUCIÓN / INSTITUTION:  - Assistance Publique-Hopitaux de Paris, Boulogne-Billancourt, 92100, France, xavier.repesse@apr.aphp.fr.




TÍTULO / TITLE:  - Immune reconstitution inflammatory syndrome associated with kaposi sarcoma: higher incidence and mortality in Africa than in the UK.

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

REVISTA / JOURNAL:  - AIDS. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/QAD.0b013e328360a5a1

AUTORES / AUTHORS:  - Letang E; Lewis JJ; Bower M; Mosam A; Borok M; Campbell TB; Naniche D; Newsom-Davis T; Shaik F; Fiorillo S; Miro JM; Schellenberg D; Easterbrook PJ

INSTITUCIÓN / INSTITUTION:  - aBarcelona Centre for International Health Research (CRESIB, Hospital Clinic-Universitat de Barcelona), Barcelona, España bCentro de Investigacao em Saude de Manhica (CISM), Manhica, Maputo province, Mozambique cDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSH&TM), London, UK dDepartment of Oncology, Chelsea and Westminster Hospital, London, UK. eDepartment of Infectious Diseases, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa fDepartment of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe gDivision of Infectious Diseases, Department of Medicine, University of Colorado  Denver, Aurora, USA hInfectious Diseases Service, Hospital Clinic / IDIBAPS, Universitat de Barcelona, Barcelona, España iDepartment of Disease Control, London School of Hygiene and Tropical Medicine (LSH&TM), London, UK. jHIV Department, World Health Organisation, Geneva, Switzerland.

RESUMEN / SUMMARY:  - OBJECTIVES:: Assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral (ART)-naive HIV-infected patients with KS initiating  ART in both well-resourced and limited-resourced settings. DESIGN:: Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with KS  from Sub-Saharan Africa (SSA) and one from the UK. METHODS:: KS-IRIS case definition was standardised across sites. Cox regression and Kaplan-Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and KS-associated mortality. RESULTS:: Fifty-eight of 417 (13.9%) eligible subjects experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (p = 0.001). ART alone as initial KS treatment (HR 2.97); T1 KS-stage (HR 2.96); and plasma HIV-1 RNA >5 log10 copies/ml (HR 2.14) independently predicted KS-IRIS at baseline. Detectable plasma KS-associated Herpes Virus (KSHV) DNA additionally predicted KS-IRIS among the 254 patients with KSHV DNA assessed (HR 2.98). Nineteen KS-IRIS patients died, all in SSA. KS-mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (HR 19.24), lack of chemotherapy (HR 2.35), pre-ART CD4 < 200 cells/mul (HR 2.04) and detectable baseline KSHV DNA (HR 2.12). CONCLUSIONS:: KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced KS disease and lower chemotherapy availability. KS-IRIS is a major contributor to KS-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of KS, and advocate on access to systemic chemotherapy in Africa.




TÍTULO / TITLE:  - Somatic mitochondrial DNA mutations in Chinese patients with osteosarcoma.

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

REVISTA / JOURNAL:  - Int J Exp Pathol. 2013 Feb 27. doi: 10.1111/iep.12015.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iep.12015

AUTORES / AUTHORS:  - Yu M; Wan Y; Zou Q

INSTITUCIÓN / INSTITUTION:  - Ontario Cancer Institute/Princess Margaret Hospital, University Health Network and University of Toronto, Toronto, ON, Canada.

RESUMEN / SUMMARY:  - Somatic mutations in mitochondrial DNA (mtDNA) have been long proposed to drive the pathogenesis and progression of human malignancies. Previous investigations have revealed a high frequency of somatic mutations in the D-loop control region  of mtDNA in osteosarcoma. However, little is known with regard to whether or not  somatic mutations also occur in the coding regions of mtDNA in osteosarcoma. To test this possibility, in the present study we screened somatic mutations over the full-length mitochondrial genome of 31 osteosarcoma tumour tissue samples, and corresponding peripheral blood samples from the same cohort of patients. We detected a sum of 11 somatic mutations in the mtDNA coding regions in our series. Nine of them were missense or frameshift mutations that have the potential to hamper mitochondrial respiratory function. In combination with our earlier observations on the D-loop fragment, 71.0% (22/31) of patients with osteosarcoma  carried at least one somatic mtDNA mutation, and a total of 40 somatic mutations  were identified. Amongst them, 29 (72.5%) were located in the D-loop region, two  (5%) were in the sequences of the tRNA genes, two (5%) were in the mitochondrial  ATP synthase subunit 6 gene and seven (17.5%) occurred in genes encoding components of the mitochondrial respiratory complexes. In addition, somatic mtDNA mutation was not closely associated with the clinicopathological characteristics  of osteosarcoma. Together, these findings suggest that somatic mutations are highly prevalent events in both coding and non-coding regions of mtDNA in osteosarcoma. Some missense and frameshift mutations are putatively harmful to proper mitochondrial activity and might play vital roles in osteosarcoma carcinogenesis.




TÍTULO / TITLE:  - Pediatric case report on magnetic resonance imaging/transrectal ultrasound-fusion biopsy of rhabdomyosarcoma of the bladder/prostate: a new tool to reduce therapy-associated morbidity?

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

REVISTA / JOURNAL:  - Urology. 2013 Feb;81(2):417-20. doi: 10.1016/j.urology.2012.10.043.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.10.043

AUTORES / AUTHORS:  - Kuru TH; Roethke MC; Nyarangi-Dix J; Okouoyo S; Stockklausner C; Schenk JP; Debus J; Roth W; Teber D; Pahernik S; Schlemmer HP; Hohenfellner M; Hadaschik BA

INSTITUCIÓN / INSTITUTION:  - Department of Urology, UniversityHospital Heidelberg, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Rhabdomyosarcomas are the most common soft tissue sarcomas in children. Here we present management of an 18-month-old boy with metastatic rhabdomyosarcoma of the bladder/prostate. After radiochemotherapy, high-spatial-resolution 3-Tesla multiparametric magnetic resonance imaging (MRI) showed regressive systemic disease but a residual mass at the right seminal vesicle. For histologic re-evaluation, 3-dimensional-controlled stereotactic MRI/transrectal ultrasound (TRUS)-fusion biopsy specimens were taken. Because histologic analysis showed nonvital tissue, a decision could be made against adjuvant radical cystoprostatectomy. Advanced 3-Tesla imaging and MRI/TRUS-fusion biopsies in children are feasible and represent an effective tool to examine suspicious pelvic lesions. Depending on histology, this can lead to a significant reduction  of therapy-associated morbidity.




TÍTULO / TITLE:  - Incidence and relative survival of chordomas: The standardized mortality ratio and the impact of chordomas on a population.

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

REVISTA / JOURNAL:  - Cancer. 2013 Mar 15. doi: 10.1002/cncr.28032.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.28032

AUTORES / AUTHORS:  - Smoll NR; Gautschi OP; Radovanovic I; Schaller K; Weber DC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Geneva University Medical Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland. nrsmoll@me.com.

RESUMEN / SUMMARY:  - BACKGROUND: Chordomas are rare bone tumors arising from remnants of the embryonic notochord. METHODS: Data for this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (1973-2009) to calculate the incidence, relative survival (RS), and standardized  mortality ratio (SMR) of patients diagnosed with intracranial and extracranial chordomas and to assess the effects of age and sex on this disease. RESULTS: The  overall incidence of extracranial and intracranial chordomas was 8.4 per 10 million population. The median overall survival of patients with chordoma patients was 7.7 years. The median survival was 7.7 years for male patients and 7.8 years for female patients. Younger patients (aged <40 years) survived longer  compared with older patients (10-year RS, 68% vs 43%). The estimated age-standardized 5-year, 10-year, and 20-year RS rates was 72%, 48%, and 31%, respectively. The SMR in the overall cohort was 4.6 (95% confidence interval, 4.22-5.0) or 21.0 (95% confidence interval, 16.6-27.2) in young adult patients and 3.0 (95% confidence interval, 2.6-3.4) in elderly patients. CONCLUSIONS: The  elderly had a more aggressive form of this disease; and, other than the incidence, sex did not influence outcome in this disease. The study of chordomas  presents a good case for the contribution that the SMR can have on measuring the  impact of a disease on a population of patients. Although the younger population  has better survival rates, the impact (SMR) in the younger age groups is much higher than in older populations. 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.




TÍTULO / TITLE:  - Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells.

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

REVISTA / JOURNAL:  - J Cell Biochem. 2013 Mar 13. doi: 10.1002/jcb.24535.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24535

AUTORES / AUTHORS:  - Lopez-Herradon A; Portal-Nunez S; Garcia-Martin A; Lozano D; Perez-Martinez FC; Cena V; Esbrit P

INSTITUCIÓN / INSTITUTION:  - Laboratorio de Metabolismo Mineral y Oseo, Instituto de Investigacion Sanitaria (IIS)-Fundacion Jimenez Diaz and Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RETICEF), Madrid, España.

RESUMEN / SUMMARY:  - Recent in vivo findings suggest that the bone sparing capacity of parathyroid hormone-related protein (PTHrP) in diabetic mice might be due at least in part through targeting a suppressed Wnt/beta-catenin pathway in osteoblasts. We here aimed to examine the inhibitory action of a high glucose environment on specific  components of the canonical Wnt pathway, and the putative compensatory effects of PTHrP, in osteoblastic cell cultures. Mouse osteoblastic MC3T3-E1 cells and primary cultures of fetal mouse calvaria were exposed to normal (5.5 mM) or high  (25 mM) D-glucose (HG), with or without PTHrP (1-36) or PTHrP (107-139) for different times. In some experiments, MC3T3-E1 cells were incubated with the Wnt  pathway activators Wnt3a and LiCl, or were transfected with plasmids encoding either a mutated beta-catenin that cannot be targeted for degradation or a human  PTHrP (-36/+139) cDNA, or the corresponding empty plasmid, in the presence or absence of HG. The gene expression of Wnt3a and low density receptor-like proteins (LRP)-5 and 6, as well as beta-catenin protein stabilization and beta-catenin-dependent transcription activity were evaluated. Oxidative stress status under HG condition was also assessed. The present data demonstrate that HG can target different components of the canonical Wnt pathway, while beta-catenin  degradation appears to be a key event leading to inhibition of Wnt/beta-catenin signalling in mouse osteoblastic cells. Both PTHrP peptides tested were able to counteract this deleterious action of HG. These in vitro findings also provide new clues to understand the underlying mechanisms whereby PTHrP can increase bone formation. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.




TÍTULO / TITLE:  - Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt065

AUTORES / AUTHORS:  - Li Y; Zhang J; Zhang L; Si M; Yin H; Li J

INSTITUCIÓN / INSTITUTION:  - Department of Orthopedics and.

RESUMEN / SUMMARY:  - Notch signaling pathway plays critical roles in human cancers, including osteosarcoma, suggesting that the discovery of specific agents targeting Notch would be extremely valuable for osteosarcoma. Our previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of osteosarcoma cells by triggering cell cycle arrest and apoptosis in vitro. However, the underlying mechanism is still unclear. In this study, we found that DATS suppressed cell survival, wound-healing capacity, invasion and angiogenesis in osteosarcoma cells. These effects were associated with decreased expression of Notch-1 and its downstream genes, such as vascular endothelial growth factor and matrix metalloproteinases, as well as increased expression of a panel of tumor-suppressive microRNAs (miRNAs), including miR-34a, miR-143, miR-145 and miR-200b/c that are typically lost in osteosarcoma. We also found that reexpression of miR-34a and miR-200b by transfection led to reduced expression of Notch-1, resulting in the inhibition of osteosarcoma cell proliferation, invasion and angiogenesis. These results clearly suggest that DATS inhibited osteosarcoma  growth and aggressiveness via a novel mechanism targeting a Notch-miRNA regulatory circuit. Our data provide the first evidence that the downregulation of Notch-1 and reexpression of miRNAs by DATS may be an effective approach for the treatment of osteosarcoma.




TÍTULO / TITLE:  - Metastasizing “benign” cutaneous fibrous histiocytoma: a clinicopathologic analysis of 16 cases.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Apr;37(4):484-95. doi: 10.1097/PAS.0b013e31827070d4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e31827070d4

AUTORES / AUTHORS:  - Doyle LA; Fletcher CD

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

RESUMEN / SUMMARY:  - Cutaneous fibrous histiocytoma (FH) is considered a benign tumor; however, certain types of FH have been shown to have a tendency for local recurrence, and  there are rare reported cases of metastasis. In this study, 16 cases of morphologically benign FH with locoregional or distant metastasis were identified in consult files. Pathologic features of primary, recurrent, and metastatic tumors, as well as clinical outcome, were evaluated. Nine were male and 7 were female patients; mean age was 42 years (range, 3 to 68 y). Primary tumors arose on the leg in 5 patients, buttock in 1, trunk in 3, shoulder in 3, neck in 2, and finger in 1. The primary site in 1 case was unknown. Fifteen primary tumors available for review involved the dermis; 6 extended into the superficial subcutis. Tumor size ranged from 1 to 5 cm (median 3.2 cm). Histologically, primary tumors showed characteristic features of FH, being composed in most cases of a polymorphous population of bland spindle and histiocytoid cells in a mixed storiform and fascicular growth pattern with admixed foam cells, multinucleate cells, and inflammatory cells in varying proportions. Histologic variants included 11 cellular (2 with mixed atypical and cellular features), 2 aneurysmal, 1 atypical, and 1 epithelioid type. All tumors showed entrapment of hyalinized collagen bundles. Mitotic activity ranged from <1 to 13/10 HPF. Focal necrosis was seen in 1 primary tumor. Ten patients had local tumor recurrence; 4 patients  had multiple local recurrences. Time to first recurrence ranged from 6 weeks to 13 years. The local recurrences of 1 tumor showed increased cytologic atypia, but recurrences were otherwise morphologically similar to primary tumors. Metastases  occurred 0 to 180 months after diagnosis (median 17 mo) and involved the lungs (12 patients), lymph nodes (8), soft tissues (6), and liver (1). Five patients developed multiple satellite nodules in the region of the primary tumor. Metastases were morphologically similar to the primary tumors. So far, 6 patients died of disease, with a median time to death of 64 months (range, 10 to 168 mo).  Four patients are alive with metastatic disease. Two patients are disease free at last follow-up, and 1 patient died of unrelated disease. Metastasis of morphologically benign cutaneous FH is an extremely rare but clinically aggressive event. Primary tumors tend to be large and cellular, but aggressive behavior cannot be predicted on morphologic grounds alone; however, early or frequent local recurrence may warrant closer clinical follow-up.




TÍTULO / TITLE:  - Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Mar 5. pii: S0360-3016(13)00128-4. doi: 10.1016/j.ijrobp.2013.01.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.01.032

AUTORES / AUTHORS:  - Bahig H; Roberge D; Bosch W; Levin W; Petersen I; Haddock M; Freeman C; Delaney TF; Abrams RA; Indelicato DJ; Baldini EH; Hitchcock Y; Kirsch DG; Kozak KR; Wolfson A; Wang D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology Centre Hospitalier de l’Universite de Montreal,  Montreal, QC, Canada.

RESUMEN / SUMMARY:  - PURPOSE: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). METHODS AND MATERIALS: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin)  were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. RESULTS: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm3 (7-413 cm3), 280 cm3 and 360 cm3. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm3 (24-565 cm3) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm3 (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm3, respectively. There were 3 large tumors with >30 cm3 of SE not included in the CTV3cm volume. CONCLUSION: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of  the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE.




TÍTULO / TITLE:  - Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation.

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

REVISTA / JOURNAL:  - Eur J Pharmacol. 2013 Mar 13;706(1-3):41-47. doi: 10.1016/j.ejphar.2013.02.042.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2013.02.042

AUTORES / AUTHORS:  - Fernandez JM; Molinuevo MS; Sedlinsky C; Schurman L; Cortizo AM; McCarthy AD

INSTITUCIÓN / INSTITUTION:  - Laboratorio de Investigacion en Osteopatias y Metabolismo Mineral, Facultad de Ciencias Exactas, Universidad Nacional de La Plata. 47 y 115, (1900) La Plata, Argentina.

RESUMEN / SUMMARY:  - Accumulation of advanced glycation endproducts (AGEs) in bone tissue occurs in ageing and in Diabetes mellitus, and is partly responsible for the increased risk of low-stress bone fractures observed in these conditions. In this study we evaluated whether the anti-osteoporotic agent strontium ranelate can prevent the  deleterious effects of AGEs on bone cells, and possible mechanisms of action involved. Using mouse MC3T3E1 osteoblastic cells in culture we evaluated the effects of 0.1mM strontium ranelate and/or 100mug/ml AGEs-modified bovine serum albumin (AGEs-BSA) on cell proliferation, osteogenic differentiation and pro-inflammatory cytokine production. We found that AGEs-BSA alone decreased osteoblastic proliferation and differentiation (P<0.01) while increasing IL-1beta and TNFalpha production (P<0.01). On its own, strontium ranelate induced opposite effects: an increase in osteoblast proliferation and differentiation (P<0.01) and a decrease in cytokine secretion (P<0.01). Additionally, strontium ranelate prevented the inhibitory and pro-inflammatory actions of AGEs-BSA on osteoblastic cells (P<0.01). These effects of strontium ranelate were blocked by co-incubation with either the MAPK inhibitor PD98059, or the calcium channel blocker nifedipine. We also evaluated by Western blotting the activation status of ERK (a MAPK) and b-catenin. Activation of both signaling pathways was decreased by AGEs  treatment, and this inhibitory effect was prevented if AGEs were co-incubated with strontium ranelate (P<0.01). On its own, strontium ranelate increased both pERK and activated b-catenin levels. In conclusion, this study demonstrates that  strontium ranelate can prevent the deleterious in vitro actions of AGEs on osteoblastic cells in culture by mechanisms that involve calcium channel, MAPK and b-catenin activation.




TÍTULO / TITLE:  - Zoledronic acid negatively affects the expansion of in vitro activated human NK cells and their cytolytic interactions with Ewing sarcoma cells.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar 19. doi: 10.3892/or.2013.2350.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2350

AUTORES / AUTHORS:  - Mueller SK; Altvater B; Chen C; Kailayangiri S; Ahlmann M; Dirksen U; Juergens H; Rossig C

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany.

RESUMEN / SUMMARY:  - Disseminated Ewing sarcoma remains a fatal disease despite advanced multimodal treatment regimens. Immunotherapies as well as novel drugs and biologicals are currently being explored to eliminate minimal residual disease after conventional therapy thereby rescuing patients at a high risk for relapse. Insights into the interactions between novel therapies provide the basis for the development of effective combination strategies. We investigated the effects of the aminobisphosphonate zoledronic acid (ZA) on the in vitro expansion of human natural killer (NK) cells and their cytolytic activity against Ewing sarcoma cells. ZA significantly impaired the in vitro expansion of activated NK cells from both healthy donors and Ewing sarcoma patients in a dose-dependent manner. Expression of differentiation markers and activating receptors was unaffected by  the drug. Activated NK cells from both healthy donors and patients had potent degranulation responses to Ewing sarcoma cells. In the presence of ZA at concentrations reflecting pharmaceutical serum levels, the in vitro antitumor activity of NK cells from Ewing sarcoma patients was significantly impaired. We conclude that ZA can impede in vitro NK cell expansion and cytolytic NK cell responses to Ewing sarcoma. These observations raise caution against the combination of adoptive NK cell transfer with ZA maintenance therapy in Ewing sarcoma. Future studies aim to identify potentiating interactions of novel drugs  with cellular therapies.




TÍTULO / TITLE:  - Expression of microRNA-30c and its target genes in human osteoblastic cells by nano-bioglass ceramic-treatment.

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

REVISTA / JOURNAL:  - Int J Biol Macromol. 2013 May;56:181-5. doi: 10.1016/j.ijbiomac.2013.02.017. Epub 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijbiomac.2013.02.017

AUTORES / AUTHORS:  - Moorthi A; Vimalraj S; Avani C; He Z; Partridge NC; Selvamurugan N

INSTITUCIÓN / INSTITUTION:  - Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.

RESUMEN / SUMMARY:  - Osteoblast differentiation is tightly regulated by post transcriptional regulators such as microRNAs (miRNAs). Several bioactive materials including nano-bioglass ceramic particles (nBGC) influence differentiation of the osteoblasts, but the molecular mechanisms of nBGC-stimulation of osteoblast differentiation via miRNAs are not yet determined. In this study, we identified that nBGC-treatment stimulated miR-30c expression in human osteoblastic cells (MG63). The bioinformatics tools identified its regulatory network, molecular function, biological processes and its target genes involved in negative regulation of osteoblast differentiation. TGIF2 and HDAC4 were found to be its putative target genes and their expression was down regulated by nBGC-treatment in MG63 cells. Thus, this study advances our understanding of nBGC action on bone cells and supports utilization of nBGC in bone tissue engineering.




TÍTULO / TITLE:  - Long-lasting Clinical Benefit of Sunitinib Malate in the Treatment of a Case of Heavily Pre-treated Metastatic Liposarcoma.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):1061-3.

AUTORES / AUTHORS:  - Porzio R; Bella MA; Rossi G; Ardizzoni A

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy. rosa.porzio@libero.it.

RESUMEN / SUMMARY:  - BACKGROUND: Soft tissue sarcomas are a heterogeneous group of malignant neoplasms including several distinct entities with different cell differentiation and clinical prognosis, but which are often treated as a single disease. Case Report: We report the case of a male patient, heavily treated for a metastatic well-differentiated liposarcoma occurring in the left lateral neck. He received radiotherapy and different lines of standard chemotherapy with local progression  and lung metastasis. In November 2009, on the basis of a phase II study demonstrating the efficacy of sunitinib in patients with liposarcoma, the patient was treated with sunitinib at 37.5 mg daily in 4-week cycles on a compassionate use basis. Until November 2012 he received a total of 23 cycles of sunitinib treatment achieving a stable disease in all sites. Therapy with sunitinib is still ongoing without side effects. CONCLUSION: Our findings confirm that sunitinib may be a useful therapeutic tool in the treatment of some cases of pre-treated liposarcoma.




TÍTULO / TITLE:  - Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal  tumors.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):522. doi: 10.1007/s12032-013-0522-y. Epub 2013 Mar 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0522-y

AUTORES / AUTHORS:  - Gao J; Tian Y; Li J; Sun N; Yuan J; Shen L

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China.

RESUMEN / SUMMARY:  - The aim of this study was to investigate the associations between secondary mutations of c-KIT/PDGFRalpha and acquired imatinib resistance or efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors (GISTs). Mutations of c-KIT (exons 9, 11, 13, 14, 17, and 18) and PDGFRalpha (exons 12 and 18) in tumor samples of 50 patients were analyzed by direct sequencing. A total of 50 samples before imatinib and 52 samples after imatinib were collected. Among 52 samples after imatinib, 38 samples were imatinib resistant and 14 samples were imatinib sensitive. All patients before imatinib treatment had primary mutations  of c-KIT exon 11 (n = 45) or exon 9 (n = 5), and no PDGFRalpha mutations were found in these patients. After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. In our study, 19 patients  received sunitinib treatment after the failure of imatinib, and it seemed that the median progression-free survival (7 vs. 19 months, P = 0.244) in patients with secondary mutations (n = 13) was lower than that in patients without secondary mutations (n = 6). Secondary mutations of c-KIT were significantly associated with acquired resistance to imatinib in Chinese GIST patients, and whether secondary mutations of c-KIT could influence the efficacy of sunitinib needed to be further investigated.




TÍTULO / TITLE:  - Antitumor efficacy of the heparanase inhibitor SST0001 alone and in combination with antiangiogenic agents in the treatment of human pediatric sarcoma models.

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

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Mar 1. pii: S0006-2952(13)00146-9. doi: 10.1016/j.bcp.2013.02.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.02.023

AUTORES / AUTHORS:  - Cassinelli G; Lanzi C; Tortoreto M; Cominetti D; Petrangolini G; Favini E; Zaffaroni N; Pisano C; Penco S; Vlodavsky I; Zunino F

INSTITUCIÓN / INSTITUTION:  - Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

RESUMEN / SUMMARY:  - The activity of heparanase is responsible for heparan sulfate cleavage, thus resulting in the release of heparan sulfate-bound growth factors. Since heparanase activity is upregulated in several tumor types and is implicated in the malignant behavior, the enzyme is regarded as a promising target for antitumor therapy. Based on previous evidence that the heparanase inhibitor SST0001, a non-anticoagulant N-acetylated glycol split heparin, is effective against an Ewing’s sarcoma model, the present study was performed to extend the preclinical evaluation of SST0001 to a panel of pediatric sarcoma models, representative of various tumor histotypes (soft tissue and bone sarcomas) and to further elucidate its mode of action. SST0001 treatment downregulated several angiogenic factors in the conditioned media of sarcoma cells, inhibited the pro-invasive effect of heparin-binding factors (VEGF, bFGF, HGF, PDGF), and abrogated PDGF receptor tyrosine phosphorylation. Subcutaneous administration of  SST0001 was very effective, resulting in a significant growth inhibition (range,  64-95%) of all tested tumor xenografts. The efficacy of SST0001 was enhanced in combination with antiangiogenic agents (bevacizumab, sunitinib) as documented by  the high rate of complete response. The synergistic effect of SST0001 in combination with antiangiogenic agents is consistent with the heparanase mode of  action and with the relevant role of heparin-binding proangiogenic/growth factors in the malignant behavior of sarcoma cells.




TÍTULO / TITLE:  - Retract-ligate-unroof-biopsy: a novel approach to the diagnosis and therapy of large nonpedunculated stromal tumors.

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

REVISTA / JOURNAL:  - Gastrointest Endosc. 2013 Jan 29. pii: S0016-5107(12)02972-0. doi: 10.1016/j.gie.2012.11.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2012.11.024

AUTORES / AUTHORS:  - Binmoeller KF; Shah JN; Bhat YM; Kane SD

INSTITUCIÓN / INSTITUTION:  - Paul May and Frank Stein Interventional Endoscopy Center, California Pacific Medical Center, San Francisco, California, USA.

RESUMEN / SUMMARY:  - BACKGROUND: We report a novel technique of retract-ligate-unroof-biopsy (RLUB) for the diagnosis and treatment of large nonpedunculated upper GI stromal tumors  originating from the muscularis propria. OBJECTIVE: Proof-of-concept evaluation of the RLUB technique. DESIGN: Pilot and feasibility study. SETTING: Tertiary care center. PATIENTS: Sixteen patients (median age 71 years) fulfilling the following inclusion criteria: poor surgical candidates with lesions that are broad based with a benign appearance, originating from the muscularis propria, size 2 cm or larger. INTERVENTIONS: A double-channel endoscope was used to simultaneously retract the stromal tumor while advancing an endoloop beyond the tumor for ligation. The overlying tissue was incised (“unroofed”) to expose and partially enucleate the tumor, and multiple biopsy samples were obtained. After unroofing, an additional endoloop was placed below the previous one by using the  loop-over-loop technique to reinforce enucleation and ischemic ablation. MAIN OUTCOME MEASUREMENTS: Successful ligation, immunohistochemistry and mitotic index yield, therapeutic ablation, adverse events. RESULTS: Technical success was achieved in 13 of 16 patients (81%). Immunohistology of biopsy specimens: GI stromal tumor (n = 10), leiomyoma (n = 3). Twelve of 13 patients (92%) with follow-up (median 22 weeks, range 1-82.5 weeks) had confirmed tumor ablation by endoscopy and EUS. One patient with partial resolution was re-treated, but was subsequently lost to follow-up. Delayed bleeding occurred in 2 patients that required hospitalization and blood transfusions, both successfully controlled with repeat endolooping. One patient reported transient pain. LIMITATIONS: Single center, single operator, small sample size. CONCLUSIONS: The RLUB technique is feasible as a platform for full-thickness treatment of stromal tumors. Limitations encountered included technical challenges and delayed bleeding. Further developmental work is needed.




TÍTULO / TITLE:  - Analysis of orbital plain radiographs for orbital deformities in neurofibromatosis type 1 patients, with special reference to alterations of the orbital rim as indicators of adjacent plexiform neurofibroma.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):1081-90.

AUTORES / AUTHORS:  - Friedrich RE; Rother J; Christ G; Lehmann M; Eulenburg CG; Giese M; Scheuer HA

INSTITUCIÓN / INSTITUTION:  - DMD, NF Laboratory, Lottestr. 55, D-22529 Hamburg, Germany. rfriedrich@uke.de.

RESUMEN / SUMMARY:  - Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease. Some stigmata of NF1 occur in the orbital region. The aim of this study was to reveal  whether alterations of the orbital rim visible on plain radiographs may indicate  the presence of a plexiform neurofibroma (PNF), a tumour almost exclusively diagnosed in NF1. MATERIAL AND METHODS: The plain orbital radiographs of 73 patients with NF1 (female: N=37, male: N=36) were investigated for alterations of the orbit. The group was further distinguished according to the presence of orbital PNF (N=53) and/or sphenoid wing dysplasia (N=30). Radiographs from patients with NF1 and with exclusion of PNF in the orbitofacial region were used  for comparison (N=20). A special cephalometric analysis (Dental Vision) was adapted to the demands of this study. RESULTS: Patients with NF1 not affected by  an orbitofacial PNF exhibited symmetrical orbits. Unilateral increase in orbital  height was associated with ipsilateral PNF. The width of orbits affected by a PNF was often slightly increased compared to the non-affected side. The determination of cephalometrically-defined angles disclosed an erection of the PNF-affected orbit compared to the medio-sagittal plane. CONCLUSION: Plain radiographs are often the first diagnostic measure used to determine skeletal alterations. This study shows that certain parameters of the orbital rim are useful indicators of a PNF in patients who are unilaterally affected by this lesion in the orbital or orbitotemporal region.




TÍTULO / TITLE:  - Osteochondroma of the right coronoid process (Jacob disease): a case report.

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

REVISTA / JOURNAL:  - Cranio. 2013 Jan;31(1):66-9.

AUTORES / AUTHORS:  - Aoki N; Okamura K; Niino D; Iwamoto O; Kusukawa J

INSTITUCIÓN / INSTITUTION:  - Dental and Oral Medical Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. nobuko-aoki@hotmail.co.jp

RESUMEN / SUMMARY:  - Oscar Jacob was the first to describe osteochondroma of the coronoid process, naming it “Jacob disease.” Jacob disease rarely occurs in the oral and maxillofacial regions. The tumor usually grows progressively, leading to a mushroom-shaped enlargement of the process, and a joint-like structure is found between the coronoid process and the inner aspect of the zygomatic arch. Most of  these lesions grow like a mushroom on, and do not destroy, the coronoid process.  The major symptoms include restricted mouth opening and morphological changes to  the zygoma. The authors present a case report on an 18-year-old male patient with pain in the right zygoma. Interincisal maximum mouth opening was 51 mm. An intraoral coronoidectomy was performed.




TÍTULO / TITLE:  - Total artificial heart support with two continuous-flow ventricular assist devices in a patient with an infiltrating cardiac sarcoma.

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

REVISTA / JOURNAL:  - ASAIO J. 2013 Mar-Apr;59(2):178-80. doi: 10.1097/MAT.0b013e3182816cd9.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MAT.0b013e3182816cd9

AUTORES / AUTHORS:  - Pirk J; Maly J; Szarszoi O; Urban M; Kotulak T; Riha H; Neuzil P; Netuka I

INSTITUCIÓN / INSTITUTION:  - Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

RESUMEN / SUMMARY:  - Primary cardiac sarcoma is normally fatal, but cardiac replacement may provide some hope for long-term survival. A 38 year-old man with cardiac sarcoma, involving the interventricular septum and posterior wall with intermittent mitral obstruction, underwent implantation of two HeartMate II ventricular assist devices for total artificial heart support. After cardiectomy, the HeartMate sewing rings were sewn to the right neoatrium and the left atrial remnants. After the outflow grafts were sewn end to end to the pulmonary artery and aorta, the two drivelines were externalized through the abdominal wall, and perfusion started. The postoperative course was complicated by respiratory and renal dysfunction, which resolved. After 6 months of support, the patient has normal organ function and is ambulatory. Follow-up oncologic evaluation of positron emission tomography-computed tomography scan is negative.




TÍTULO / TITLE:  - Phase 2 study of preoperative image-guided intensity-modulated radiation therapy  to reduce wound and combined modality morbidities in lower extremity soft tissue  sarcoma.

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

REVISTA / JOURNAL:  - Cancer. 2013 Feb 19. doi: 10.1002/cncr.27951.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27951

AUTORES / AUTHORS:  - O’Sullivan B; Griffin AM; Dickie CI; Sharpe MB; Chung PW; Catton CN; Ferguson PC; Wunder JS; Deheshi BM; White LM; Kandel RA; Jaffray DA; Bell RS

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound  complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development  of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%),  1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained. 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.




TÍTULO / TITLE:  - Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: Comparison of RECIST, Choi and volumetric criteria.

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

REVISTA / JOURNAL:  - Eur J Radiol. 2013 Mar 18. pii: S0720-048X(13)00122-8. doi: 10.1016/j.ejrad.2013.02.034.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.02.034

AUTORES / AUTHORS:  - Schramm N; Englhart E; Schlemmer M; Hittinger M; Ubleis C; Becker CR; Reiser MF; Berger F

INSTITUCIÓN / INSTITUTION:  - Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich,  Marchioninistrasse 15, 81377 Munich, Germany. Electronic address: Nicolai.schramm@med.uni-muenchen.de.

RESUMEN / SUMMARY:  - PURPOSE: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). PATIENTS AND METHODS: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable  disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan-Meier statistics. RESULTS: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib  showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20)  20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. CONCLUSION: One year after modification of  therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated.




TÍTULO / TITLE:  - Cooperation between osteoblastic cells and endothelial cells enhances their phenotypic responses and improves osteoblast function.

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

REVISTA / JOURNAL:  - Biotechnol Lett. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10529-013-1170-1

AUTORES / AUTHORS:  - Dariima T; Jin GZ; Lee EJ; Wall IB; Kim HW

INSTITUCIÓN / INSTITUTION:  - Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330714, Republic of Korea.

RESUMEN / SUMMARY:  - Osteogenesis requires close co-operation with angiogenesis to create vascularized bone tissue. In this study, an indirect co-culture model using osteoblasts (OBs), primary endothelial cells (ECs) and Matrigel interlayer was established to understand the impact of each cell type on the other. ECs synergistically enhanced osteoblastic gene expression by OBs, while OBs were capable of supporting tubule-like structures formed by ECs on Matrigel, enhancing mean tubule length from 146.5 +/- 23.5 mum in ECs alone to 192 +/- 28.6 mum in co-culture (p < 0.05). Similar improvements were noted in terms of tubule number. An applicability study of the co-culture model to bone tissue engineering, performed on a biopolymer fibrous membrane, showed substantially enhanced deposition of calcified nodules. These results demonstrate the efficacy of co-culture with ECs to improve osteogenesis for bone tissue engineering.




TÍTULO / TITLE:  - Primary Angiosarcoma of Bone: A Retrospective Analysis of 60 Patients From 2 Institutions.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827defa1

AUTORES / AUTHORS:  - Palmerini E; Maki RG; Staals EL; Alberghini M; Antonescu CR; Ferrari C; Ruggieri P; Mavrogenis A; Bertoni F; Cesari M; Paioli A; Marchesi E; Picci P; Ferrari S

INSTITUCIÓN / INSTITUTION:  - Departments of *Chemotherapy double daggerOrthopaedic Surgery section signSurgical Pathology paragraph signResearch Laboratory, Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Bologna, Italy Departments of daggerMedicine parallelPathology, Memorial Sloan-Kettering Cancer Center, New York, NY.

RESUMEN / SUMMARY:  - BACKGROUND:: Angiosarcoma of bone is a rare high-grade malignant vascular tumor.  The literature regarding treatment and outcome of patients with this tumor is limited.We performed a 2 institutional retrospective study to analyze treatment and survival of patients with angiosarcoma of bone. PATIENTS AND METHODS:: We reviewed patients with the histologic diagnosis of primary angiosarcoma of bone treated from 1980 to 2009. Demographic details, histology, treatment, and survival were reviewed. RESULTS:: A total of 38 men and 22 women (median age, 54  y) were recruited. Most lesions occurred in the femur and the pelvis. Metastatic  disease at presentation was diagnosed in 24 patients (40%). Forty-three patients  underwent surgery, with 30 of them achieving surgical complete remission (SCR). Radiotherapy was applied to 17 patients, and chemotherapy to 13/35 and 15/22 patients with localized and metastatic disease, respectively.The 5-year overall survival (OS) was 20%: 33% for patients with localized disease and 0% for metastatic patients. Higher 5-year OS was reported for patients who achieved SCR  (46%) than for those who did not (0%). In nonmetastatic patients, a trend toward  improved survival was observed after SCR and adjuvant chemotherapy based on cisplatin, doxorubicin, and ifosfamide.Fifteen patients received chemotherapy for metastases. Two RECIST partial responses of 13 evaluable patients were documented [paclitaxel (n=1) and doxorubicin (n=1)]. Stable disease was observed in 2 patients. CONCLUSIONS:: Complete surgical resection is essential for outcome. Survival of patients with metastatic or unresectable disease is very poor. Activity of taxanes and anthracycline was observed in the metastatic setting and  merits further evaluation.




TÍTULO / TITLE:  - Sinonasal Disease in Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome.

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

REVISTA / JOURNAL:  - Laryngoscope. 2013 Apr;123(4):823-8. doi: 10.1002/lary.23758. Epub 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23758

AUTORES / AUTHORS:  - Deklotz TR; Kim HJ; Kelly M; Collins MT

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Georgetown University Hospital, Washington, D.C., U.S.A.

RESUMEN / SUMMARY:  - OBJECTIVES/HYPOTHESIS: To characterize the spectrum, symptoms, progression, and effects of endocrine dysfunction on sinonasal disease in polyostotic fibrous dysplasia (PFD) and McCune-Albright Syndrome (MAS). STUDY DESIGN: Retrospective review. METHODS: A prospectively followed cohort of subjects with PFD/MAS underwent a comprehensive evaluation that included otolaryngologic and endocrine  evaluation, and imaging studies. Head and facial computed tomography scans were analyzed, and the degree of fibrous dysplasia (FD) was graded using a modified Lund-MacKay scale. Those followed for >4 years were analyzed for progression. RESULTS: A total of 106 patients meeting inclusion criteria were identified with  craniofacial FD. A majority (92%) demonstrated sinonasal involvement. There were  significant positive correlations between the sinonasal FD scale score and chronic congestion, hyposmia, growth hormone excess, and hyperthyroidism (P < .05 for all). Significant correlations were not found for headache/facial pain or recurrent/chronic sinusitis. Thirty-one subjects met the criteria for longitudinal analysis (follow-up mean, 6.3 years; range, 4.4-9 years). Those who  demonstrated disease progression were significantly younger than those who did not (mean age, 11 vs. 25 years). Progression after age of 13 years was uncommon (n = 3) and minimal. Concomitant endocrinopathy or bisphosphonate use did not have any significant effect on progression of disease. CONCLUSIONS: Sinonasal involvement of fibrous dysplasia in PFD/MAS is common. Symptoms are usually few and mild, and disease progression occurs primarily in young subjects. Concomitant endocrinopathy is associated with disease severity, but not progression.




TÍTULO / TITLE:  - Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations.

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

REVISTA / JOURNAL:  - Exp Cell Res. 2013 Mar 25. pii: S0014-4827(13)00131-6. doi: 10.1016/j.yexcr.2013.03.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexcr.2013.03.023

AUTORES / AUTHORS:  - Becerikli M; Jacobsen F; Rittig A; Kohne W; Nambiar S; Mirmohammadsadegh A; Stricker I; Tannapfel A; Wieczorek S; Epplen JT; Tilkorn D; Steinstraesser L

INSTITUCIÓN / INSTITUTION:  - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.

RESUMEN / SUMMARY:  - Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their  contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and  HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations.




TÍTULO / TITLE:  - External validation of a prognostic nomogram for overall survival in women with uterine leiomyosarcoma.

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

REVISTA / JOURNAL:  - Cancer. 2013 Mar 1. doi: 10.1002/cncr.27971.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27971

AUTORES / AUTHORS:  - Iasonos A; Keung EZ; Zivanovic O; Mancari R; Peiretti M; Nucci M; George S; Colombo N; Carinelli S; Hensley ML; Raut CP

INSTITUCIÓN / INSTITUTION:  - Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York. iasonosa@mskcc.org.

RESUMEN / SUMMARY:  - BACKGROUND: There is no validated system to identify prognostically distinct cohorts of women with uterine leiomyosarcoma (ULMS). By using an independent, pooled, multi-institutional, international patient cohort, the authors validated  a recently proposed ULMS nomogram. METHODS: The ULMS nomogram incorporated 7 clinical characteristics (age, tumor size, tumor grade, cervical involvement, locoregional metastases, distant metastases, and mitotic index (per 10 high-power fields) to predict overall survival (OS) after primary surgery. Independent cohorts from 2 sarcoma centers were included. Eligible women, at minimum, underwent a hysterectomy for primary, locally advanced, or metastatic ULMS and received part of their care at 1 of the centers between 1994 and 2010. RESULTS: In total, 187 women with ULMS were identified who met the above criteria described above (median age, 51 years; median tumor size, 9 cm; median mitotic index, 20 per 10 high-power fields). Tumors generally were high grade (88%), FIGO stage I or II (61%) without cervical involvement (93%) and without locoregional metastases (77%) or distant metastases (83%). The median OS and the 5-year OS rate were 4.5 years (95% confidence interval, 3.2-5.3 years) and 46%, respectively; and 65 women (35%) remained alive at last follow-up. The nomogram concordance index was 0.67(standard error, 0.02), which was as high as the concordance index from the initial cohort used for nomogram development. The concordance between actual OS and nomogram predictions suggests excellent calibration because predictions were within 1% of actual 5-year OS rates for patients with a predicted 5-year OS of less than 0.68. CONCLUSIONS: The ULMS nomogram was externally validated using independent cohorts. These findings support the international use of the ULMS nomogram prognostic of OS in ULMS. Cancer 2012. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2012 American Cancer Society.




TÍTULO / TITLE:  - Congenital Kaposiform Hemangioendothelioma with Kasabach-Merritt Phenomenon Successfully Treated with Low-Dose Radiation Therapy.

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

REVISTA / JOURNAL:  - Pediatr Dermatol. 2013 Mar 5. doi: 10.1111/pde.12090.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pde.12090

AUTORES / AUTHORS:  - Malhotra Y; Yang CS; McNamara J; Antaya RJ

INSTITUCIÓN / INSTITUTION:  - Division of Neonatology, Yale University, New Haven, Connecticut; Division of Neonatology, Maria Fareri Children’s Hospital, New York Medical College, Westchester, New York.

RESUMEN / SUMMARY:  - Kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon is a life-threatening vasculopathy. The current mainstay treatment for KHEs is corticosteroids and chemotherapy, but these medications do not work for all patients and carry significant side effects. We report a neonate with a large congenital KHE who responded extremely well to low-dose radiation therapy.




TÍTULO / TITLE:  - Atrial myxoma mimicking a clot in transit.

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

REVISTA / JOURNAL:  - J Am Coll Cardiol. 2013 Apr 9;61(14):e159. doi: 10.1016/j.jacc.2012.07.081.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jacc.2012.07.081

AUTORES / AUTHORS:  - McCulloch MD; Smedira NG; Hawwa AG; Tan CD; Rodriguez LL

INSTITUCIÓN / INSTITUTION:  - Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.




TÍTULO / TITLE:  - Novel Dedifferentiated Liposarcoma Xenograft Models Reveal PTEN Down-Regulation as a Malignant Signature and Response to PI3K Pathway Inhibition.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Apr;182(4):1400-11. doi: 10.1016/j.ajpath.2013.01.002. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2013.01.002

AUTORES / AUTHORS:  - Smith KB; Tran LM; Tam BM; Shurell EM; Li Y; Braas D; Tap WD; Christofk HR; Dry SM; Eilber FC; Wu H

INSTITUCIÓN / INSTITUTION:  - Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Institute for Molecular Medicine, David Geffen School of Medicine, University of  California, Los Angeles, Los Angeles, California.

RESUMEN / SUMMARY:  - Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate. Treatment is generally limited to surgery and radiation, which emphasizes the need for better understanding of this disease. Because very  few in vivo and in vitro models can reproducibly recapitulate the human disease,  we generated several xenograft models from surgically resected human dedifferentiated liposarcoma. All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages. Importantly, xenograftability was directly correlated with disease-specific survival of liposarcoma patients. Thus, the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens. Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature, including down-regulated PTEN tumor-suppressor gene expression and a progenitor-like phenotype. When treated with the PI3K/AKT/mTOR pathway inhibitor  rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene  expression profile. These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care.




TÍTULO / TITLE:  - Elevated TNFR1 and Serotonin in bone metastasis are correlated with poor survival following bone metastasis diagnosis for both carcinoma and sarcoma primary tumors.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3416

AUTORES / AUTHORS:  - Chiechi A; Novello C; Magagnoli G; Petricoin EF 3rd; Deng J; Benassi MS; Picci P; Vaisman II; Espina V; Liotta LA

INSTITUCIÓN / INSTITUTION:  - Center for Applied Proteomics and Molecular Medicine, George Mason University.

RESUMEN / SUMMARY:  - PURPOSE: There is an urgent need for therapies that will reduce the mortality of  patients with bone metastasis. In this study we profiled the protein signal pathway networks of the human bone metastasis microenvironment. The goal was to identify sets of interacting proteins that correlate with survival time following the first diagnosis of bone metastasis. EXPERIMENTAL DESIGN: Using Reverse Phase  Protein Microarray technology we measured the expression of 88 end-points in the  bone microenvironment of 159 bone metastasis tissue samples derived from patients with primary carcinomas and sarcomas. RESULTS: Metastases originating from different primary tumors showed similar levels of cell signaling across tissue types for the majority of proteins analyzed, suggesting that the bone microenvironment strongly influences the metastatic tumor signaling profiles. In  a training set (72 samples), TNFR1, alone (p=0.0013) or combined with Serotonin (p=0.0004), TNFalpha (p=0.0214) and RANK (p=0.0226), was associated with poor survival, regardless of the primary tumor of origin. Results were confirmed by: a) analysis of an independent validation set (71 samples) and b) independent bioinformatic analysis using a support vector machine learning model. Spearman’s  rho analysis revealed a highly significant number of interactions intersecting with ERalpha S118, Serotonin, TNFalpha, RANKL and MMPs in the bone metastasis signaling network, regardless of the primary tumor. The interaction network pattern was significantly different in the short versus long survivors. CONCLUSIONS: TNFR1 and neuroendocrine-regulated protein signal pathways appear to play an important role in bone metastasis and may constitute a novel drug-targetable mechanism of seed-soil cross-talk in bone metastasis.




TÍTULO / TITLE:  - Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Feb 1. doi: 10.1038/modpathol.2012.242.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.242

AUTORES / AUTHORS:  - Stricker TP; Henriksen KJ; Tonsgard JH; Montag AG; Krausz TN; Pytel P

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA.

RESUMEN / SUMMARY:  - About 50% of all malignant peripheral nerve sheath tumors (MPNSTs) arise as neurofibromatosis type 1 associated lesions. In those patients malignant peripheral nerve sheath tumors are thought to arise through malignant transformation of a preexisting plexiform neurofibroma. The molecular changes associated with this transformation are still poorly understood. We sought to test the hypothesis that dysregulation of expression of kinases contributes to this malignant transformation. We analyzed expression of all 519 kinase genes in  the human genome using the nanostring nCounter system. Twelve cases of malignant  peripheral nerve sheath tumor arising in a background of preexisting plexiform neurofibroma were included. Both components were separately sampled. Statistical  analysis compared global changes in expression levels as well as changes observed in the pairwise comparison of samples taken from the same surgical specimen. Immunohistochemical studies were performed on tissue array slides to confirm expression of selected proteins. The expression pattern of kinase genes can separate malignant peripheral nerve sheath tumors and preexisting plexiform neurofibromas. The majority of kinase genes is downregulated rather than overexpressed with malignant transformation. The patterns of expression changes are complex without simple recurring alteration. Pathway analysis demonstrates that differentially expressed kinases are enriched for kinases involved in the direct regulation of mitosis, and several of these show increased expression in malignant peripheral nerve sheath tumors. Immunohistochemical studies for the mitotic regulators BUB1B, PBK and NEK2 confirm higher expression levels at the protein level. These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of kinase genes. The patterns of these changes are complex and heterogeneous. There  is no single unifying alteration. Kinases involved in mitotic regulation are particularly enriched in the pool of differentially expressed kinases. Some of these are overexpressed and are therefore possible targets for kinase inhibitors.Modern Pathology advance online publication, 1 February 2013; doi:10.1038/modpathol.2012.242.




TÍTULO / TITLE:  - Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA.

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

REVISTA / JOURNAL:  - Bone. 2013 Feb 26. pii: S8756-3282(13)00087-2. doi: 10.1016/j.bone.2013.02.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bone.2013.02.016

AUTORES / AUTHORS:  - Mutsaers AJ; Ng AJ; Baker EK; Russell MR; Chalk AM; Wall M; Liddicoat BJ; Ho PW; Slavin JL; Goradia A; Martin TJ; Purton LE; Dickins RA; Walkley CR

INSTITUCIÓN / INSTITUTION:  - St. Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia.

RESUMEN / SUMMARY:  - Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents. Osteoblastic osteosarcoma represents the major  subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes. We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre:lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans. We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype. In contrast to other osteosarcoma models  that have used Cre:lox mediated gene deletion, this model was generated through shRNA-based knockdown of p53. As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre:lox and shRNA. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer.




TÍTULO / TITLE:  - Secondary syphilis mimicking Kaposi sarcoma in an HIV patient.

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

REVISTA / JOURNAL:  - Eur J Dermatol. 2013 Feb 1;23(1):120-1. doi: 10.1684/ejd.2012.1905.

            ●● Enlace al texto completo (gratuito o de pago) 1684/ejd.2012.1905

AUTORES / AUTHORS:  - Gori A; Maio V; Grazzini M; Rossari S; Papi F; Massi D; Giorgi L; Zuccati G; de Giorgi V

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology.




TÍTULO / TITLE:  - Bone scintigraphy may help differentiate bone sclerotic lesions from osteoblastic metastases in tuberous sclerosis patients with concomitant pulmonary adenocarcinoma.

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

REVISTA / JOURNAL:  - Clin Imaging. 2013 Mar;37(2):382-5. doi: 10.1016/j.clinimag.2012.06.004. Epub 2012 Jul 15.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.06.004

AUTORES / AUTHORS:  - Song L; Zhang Y; Zhang W

INSTITUCIÓN / INSTITUTION:  - The Department of Nuclear Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China.

RESUMEN / SUMMARY:  - Tuberous sclerosis (TS) is a multisystem disorder characterized by widespread hamartomas in multiple organs, including the skeleton. We present a case of bone  involvement in a patient with TS and concomitant pulmonary adenocarcinoma. Bone scintigraphy is useful in distinguishing the TS bone lesions from osteoblastic metastases.




TÍTULO / TITLE:  - Inflammatory fibroid polyps of the gastrointestinal tract: spectrum of clinical,  morphologic, and immunohistochemistry features.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Apr;37(4):586-92. doi: 10.1097/PAS.0b013e31827ae11e.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e31827ae11e

AUTORES / AUTHORS:  - Liu TC; Lin MT; Montgomery EA; Singhi AD

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.

RESUMEN / SUMMARY:  - Inflammatory fibroid polyps (IFPs) are rare, benign tumors that can arise throughout the gastrointestinal tract. Although the molecular pathogenesis of these lesions has been well characterized, their morphologic features often vary. We report the clinicopathologic findings of the largest series of IFPs to date. A total of 83 IFPs seen at our institution were collected between 1999 and 2012. The specimens included 64 biopsies and 19 resections. A review of the clinical features identified a modest female predominance (47 women and 36 men) with patients ranging in age from 26 to 87 years (mean, 60 y). Involved sites included the esophagus (n=2), stomach (n=31; mainly antrum), small intestines (n=17), appendix (n=1), large intestines (n=31; majority within the rectosigmoid), and anal canal (n=1). Although most patients had a nonspecific presentation, those with small intestinal lesions frequently presented with intussusception. Grossly, the tumors ranged in size from 0.2 to 4.2 cm (mean, 1.7 cm). Histologically, IFPs were centered within the submucosa in all resection specimens, but mucosal extension was found in 74 of 83 (89%) cases. The tumors varied in both cellularity and degree of vascularity. However, the characteristic feature of perivascular onion skinning was present in only 54% (45/83) of the cases. In addition, a short fascicular growth pattern was also noted in 36% (30 of 83) of cases, whereas both features were present in 14 cases (17%). Eosinophils were present in 94% (78 of 83) of cases but varied widely in number from abundant (20/hpf) to sparse (1/hpf). Interestingly, in those cases with sparse eosinophils, prominent hyalinization was also present (11 of 78, 13%). In addition, although the majority of IFPs expressed CD34, 6 of 44 (14%) were negative. No associated dysplasia or malignancy was seen. IFPs represent a diverse set of submucosal-based lesions that commonly extend into the mucosa, making them amenable to endoscopic biopsy. Although their classic histologic features of perivascular onion skinning and predominance of eosinophils are well  described, they may alternatively present with a short fascicular growth pattern, a sparse number of eosinophils, and prominent hyalinization.




TÍTULO / TITLE:  - Custom-made wrist prosthesis in a patient with giant cell tumor of the distal radius.

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

REVISTA / JOURNAL:  - Arch Orthop Trauma Surg. 2013 Mar 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00402-013-1692-y

AUTORES / AUTHORS:  - Damert HG; Altmann S; Kraus A

INSTITUCIÓN / INSTITUTION:  - Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke University,  Leipziger Strasse 44, 39120, Magdeburg, Germany.

RESUMEN / SUMMARY:  - INTRODUCTION: Treatment for giant cell tumors of the distal radius is challenging when motion is to be preserved. As standard wrist prostheses typically do not achieve favorable results, we treated a 36-year-old man with giant cell tumor of  the distal radius with a new, custom-made implant. METHODS: A custom-made wrist prosthesis with a long shaft was designed according to the patient’s X-ray findings. After complete tumor resection, the prosthesis was subsequently implanted into the distal radius without complications. RESULTS: Two months after surgery, range of motion was 30 degrees -0-25 degrees for extension/flexion, 10 degrees -0-5 degrees for ulnar/radial abduction, 80 degrees -0-0 for pronation/supination, complete range of motion for the fingers, and a grip strength of 6 kg. Two years after surgery, implant position was still correct and range of motion was 45 degrees -0-10 degrees for extension/flexion, 10 degrees -0-20 degrees for ulnar/radial abduction, and 80 degrees -0-10 degrees for pronation/supination. Grip strength was 16 kg, and DASH score was 25 compared to  39 before surgery. The patient returned to work as a craftsman. CONCLUSION: Custom-made wrist prostheses could become a practical option in patients with large defects of the distal radius who desire to preserve wrist motion.




TÍTULO / TITLE:  - Localized and metastatic myxoid/round cell liposarcoma: Clinical and molecular observations.

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

REVISTA / JOURNAL:  - Cancer. 2013 Feb 7. doi: 10.1002/cncr.27847.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27847

AUTORES / AUTHORS:  - Hoffman A; Ghadimi MP; Demicco EG; Creighton CJ; Torres K; Colombo C; Peng T; Lusby K; Ingram D; Hornick JL; Wang WL; Ravi V; Lazar AJ; Lev D; Pollock RE

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; The Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - BACKGROUND.: Myxoid liposarcoma (MLPS), a disease especially of young adults with potential for local recurrence and metastasis, currently lacks solid prognostic factors and therapeutic targets. The authors of this report evaluated the natural history and outcome of patients with MLPS and commonly deregulated protein biomarkers. METHODS.: Medical records were retrospectively reviewed for patients  who presented to the authors’ institution with localized (n = 207) or metastatic  (n = 61) MLPS (1990 to 2010). A tissue microarray of MLPS patient specimens (n =  169) was constructed for immunohistochemical analysis of molecular markers. RESULTS.: The 5-year and 10-year disease-specific survival rates among patients with localized disease were 93% and 87%, respectively; male gender, age >45 years, and recurrent tumor predicted poor outcome. The local recurrence rate was  7.4%, and the risk of local recurrence was associated with recurrent tumors and nonextremity disease location. Male gender was the main risk factor for metastatic disease, which occurred in 13% of patients. Forty percent of patients  who had localized disease received chemotherapy, mostly in the neoadjuvant setting. Immunohistochemical analysis revealed significantly higher expression of C-X-C chemokine receptor type 4 (CXCR4) and platelet-derived growth factor beta (PDGFR-beta) in metastatic lesions versus localized lesions. Tumors with a round  cell phenotype expressed increased levels of CXCR4, p53, adipophilin, PDGFR-alpha, PDGFR-beta, and vascular endothelial growth factor relative to myxoid phenotype. Only the receptor tyrosine kinase encoded by the AXL gene (AXL) was identified as a prognosticator of disease-specific survival in univariate analysis. CONCLUSIONS.: In this study, the authors identified clinical and molecular outcome prognosticators for patients with MLPS as well as several potential therapeutic targets. 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.




TÍTULO / TITLE:  - Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas.

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

REVISTA / JOURNAL:  - Genes Chromosomes Cancer. 2013 Mar 18. doi: 10.1002/gcc.22055.

            ●● Enlace al texto completo (gratuito o de pago) 1002/gcc.22055

AUTORES / AUTHORS:  - Bianchini L; Birtwisle L; Saada E; Bazin A; Long E; Roussel JF; Michiels JF; Forest F; Dani C; Myklebost O; Birtwisle-Peyrottes I; Pedeutour F

INSTITUCIÓN / INSTITUTION:  - Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France; Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR 7284/INSERM  U1081, University of Nice-Sophia Antipolis, Nice, France. laurence.bianchini@unice.fr.

RESUMEN / SUMMARY:  - Most lipomas are characterized by translocations involving the HMGA2 gene in 12q14.3. These rearrangements lead to the fusion of HMGA2 with an ectopic sequence from the translocation chromosome partner. Only five fusion partners of  HMGA2 have been identified in lipomas so far. The identification of novel fusion  partners of HMGA2 is important not only for diagnosis in soft tissue tumors but also because these genes might have an oncogenic role in other tumors. We observed that t(1;12)(p32;q14) was the second most frequent translocation in our  series of lipomas after t(3;12)(q28;q14.3). We detected overexpression of HMGA2 mRNA and protein in all t(1;12)(p32;q14) lipomas. We used a fluorescence in situ  hybridization-based positional cloning strategy to characterize the 1p32 breakpoint. In 11 cases, we identified PPAP2B, a member of the lipid phosphate phosphatases family as the 1p32 target gene. Reverse transcription-polymerase chain reaction analysis followed by nucleotide sequencing of the fusion transcript indicated that HMGA2 3’ untranslated region (3’UTR) fused with exon 6  of PPAP2B in one case. In other t(1;12) cases, the breakpoint was extragenic, located in the 3’region flanking PPAP2B 3’UTR. Moreover, in one case showing a t(1;6)(p32;p21) we observed a rearrangement of PPAP2B and HMGA1, which suggests that HMGA1 might also be a fusion partner for PPAP2B. Our results also revealed that adipocytic differentiation of human mesenchymal stem cells derived from adipose tissue was associated with a significant decrease in PPAP2B mRNA expression suggesting that PPAP2B might play a role in adipogenesis. © 2013 Wiley Periodicals, Inc.




TÍTULO / TITLE:  - Risk factors for seropositivity to Kaposi’s sarcoma associated herpesvirus (KSHV) among children in Uganda.

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

REVISTA / JOURNAL:  - J Acquir Immune Defic Syndr. 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/QAI.0b013e31828a7056

AUTORES / AUTHORS:  - Wakeham K; Webb EL; Sebina I; Nalwoga A; Muhangi L; Miley W; Johnston WT; Ndibazza J; Whitby D; Newton R; Elliott AM

INSTITUCIÓN / INSTITUTION:  - 1Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda 2Department of Health Sciences, University of York, UK 3London School of Hygiene and Tropical Medicine, UK 4Viral Oncology Section, AIDS and Cancer Virus Program, SAIC-Frederick, Frederick National Laboratory for Cancer Research, USA 5International Agency for Research on Cancer, Lyon, France.

RESUMEN / SUMMARY:  - BACKGROUND:: Determinants of Kaposi’s sarcoma associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic, are not well understood. Local environmental factors, including other infectious agents, may be key. METHODS:: Within the context of a  well-characterised birth cohort we examined associations between various factors  and antibodies against KSHV, measured in stored plasma samples from 1823 mother-child pairs in Entebbe, Uganda. RESULTS:: Seroprevalence increased with increasing age of the child (p=0.0003) and was higher among those with KSHV seropositive mothers than in those without (12% vs. 9%; odds ratio (OR) 1.4, 95%  confidence interval (CI) 1.1-2.0). It was also higher among children with HIV infection (29% vs. 10%; OR 3.1, 95% CI 1.2-8.3) or malaria parasitaemia (30% vs 10%; OR 4.1, 95% CI 2.4-7.0), than in children without. These associations were not explained by socioeconomic status. CONCLUSION:: The finding that KSHV serostatus is associated with malaria parasitaemia in children is novel. In a country endemic for KSHV, malaria may be a co-factor for KSHV infection or reactivation among children.




TÍTULO / TITLE:  - Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for palliative treatment of malignant ascites from gastrointestinal stromal tumours.

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

REVISTA / JOURNAL:  - J Palliat Care. 2012 Winter;28(4):293-6.

AUTORES / AUTHORS:  - Ong E; Diven C; Abrams A; Lee E; Mahadevan D

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Arizona College of Medicine, 1501 N. Campbell Avenue, P.O. Box 245131, Tucson, Arizona 85724-5058, USA. eong@surgery.arizona.edu




TÍTULO / TITLE:  - Endoglin (CD105) expression on microvessel endothelial cells in juvenile nasopharyngeal angiofibroma: Tissue microarray analysis and association with prognostic significance.

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

REVISTA / JOURNAL:  - Head Neck. 2013 Mar 8. doi: 10.1002/hed.23210.

            ●● Enlace al texto completo (gratuito o de pago) 1002/hed.23210

AUTORES / AUTHORS:  - Wang JJ; Sun XC; Hu L; Liu ZF; Yu HP; Li H; Wang SY; Wang DH

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - BACKGROUND: The purpose of this study was to examine endoglin (CD105) expression  on microvessel endothelial cells (ECs) in juvenile nasopharyngeal angiofibroma (JNA) and its relationship with recurrence. METHODS: Immunohistochemistry was performed to detect CD105 expression in a tissue microarray from 70 patients with JNA. Correlation between CD105 expression on microvessel ECs and clinicopathological features, as well as tumor recurrence, were analyzed. RESULTS: Immunohistochemistry revealed CD105 expression on ECs but not in stroma  of patients with JNA. Chi-square analysis indicated CD105-based microvessel density (MVD) was correlated with JNA recurrence (p = .013). Univariate and multivariate analyses determined that MVD was a significant predictor of time to  recurrence (p = .009). The CD105-based MVD was better for predicting disease recurrence (AUROC: 0.673; p = .036) than other clinicopathological features. CONCLUSIONS: MVD is a useful predictor for poor prognosis of patients with JNA after curative resection. Angiogenesis, which may play an important role in the occurrence and development of JNA, is therefore a potential therapeutic target for JNA. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.




TÍTULO / TITLE:  - Changes in Health Status Among Aging Survivors of Pediatric Upper and Lower Extremity Sarcoma: A Report From the Childhood Cancer Survivor Study.

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

REVISTA / JOURNAL:  - Arch Phys Med Rehabil. 2013 Feb 1. pii: S0003-9993(13)00097-X. doi: 10.1016/j.apmr.2013.01.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.apmr.2013.01.013

AUTORES / AUTHORS:  - Marina N; Hudson MM; Jones KE; Mulrooney DA; Avedian R; Donaldson SS; Popat R; West DW; Fisher P; Leisenring W; Stovall M; Robison LL; Ness KK

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Stanford University & Lucile Packard Children’s Hospital, Palo Alto, CA. Electronic address: nmarina@stanford.edu.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate health status and participation restrictions in survivors  of childhood extremity sarcomas. DESIGN: Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003,  or 2007 were included. SETTING: Cohort study of survivors of extremity sarcomas.  PARTICIPANTS: Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5%  white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age. RESULTS: In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation. CONCLUSIONS: Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.




TÍTULO / TITLE:  - Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma.

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

REVISTA / JOURNAL:  - Genes Chromosomes Cancer. 2013 Mar 5. doi: 10.1002/gcc.22050.

            ●● Enlace al texto completo (gratuito o de pago) 1002/gcc.22050

AUTORES / AUTHORS:  - Mosquera JM; Sboner A; Zhang L; Kitabayashi N; Chen CL; Sung YS; Wexler LH; Laquaglia MP; Edelman M; Sreekantaiah C; Rubin MA; Antonescu CR

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, NY. jmm9018@med.cornell.edu.

RESUMEN / SUMMARY:  - Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so-called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF-NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7-month-old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT-PCR, which showed fusion of SRF  exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3-month-old and a 4-week-old child. In the latter tumor, TEAD1 was identified by  rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. Despite similar histomorphology in adults and young children, these results suggest that spindle  cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2-rearranged spindle cell RMS occurring in young childhood and the so-called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2). © 2013 Wiley-Liss,Inc.




TÍTULO / TITLE:  - A Prognostic Nomogram for Prediction of Recurrence in Desmoid Fibromatosis.

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

REVISTA / JOURNAL:  - Ann Surg. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31828c8a30

AUTORES / AUTHORS:  - Crago AM; Denton B; Salas S; Dufresne A; Mezhir JJ; Hameed M; Gonen M; Singer S; Brennan MF

INSTITUCIÓN / INSTITUTION:  - Departments of *Surgery daggerBiostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY double daggerAix-Marseille Universite, INSERM U911 and Timone Hospital, Department of Medicine, Division of  Adult Oncology, Marseille, France section signLeon Berard Center, INSERM U590, 69373, Lyon, France paragraph signDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.

RESUMEN / SUMMARY:  - OBJECTIVE:: To construct a postoperative nomogram to estimate the risk of local recurrence for patients with desmoid tumors. BACKGROUND:: The standard management of desmoid tumors is resection, but many recur locally. Other options include observation or novel chemotherapeutics, but little guidance exists on selecting treatment. METHODS:: Patients undergoing resection during 1982-2011 for primary or locally recurrent desmoids were identified from a single-institution prospective database. Cox regression analysis was used to assess risk factors and to create a recurrence nomogram, which was validated using an international, multi-institutional data set. RESULTS:: Desmoids were treated surgically in 495 patients (median follow-up of 60 months). Of 439 patients undergoing complete gross resection, 100 (23%) had recurrence. Five-year local recurrence-free survival was 69%. Eight patients died of disease, all after R2 resection. Adjuvant radiation was not associated with improved local recurrence-free survival. In multivariate analysis, factors associated with recurrence were extremity location, young age, and large tumor size, but not margin. Abdominal wall tumors had the best outcome (5-year local recurrence-free survival rate of 91%). Age, site, and size were used to construct a nomogram with concordance index of 0.703 in internal validation and 0.659 in external validation. Integration of additional variables (R1 margin, sex, depth, and primary vs recurrent presentation) did not importantly improve concordance (internal concordance index of 0.707). CONCLUSIONS:: A postoperative nomogram including only size, site, and age predicts local recurrence and can aid in counseling patients. Systemic therapies may be appropriate for young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions.




TÍTULO / TITLE:  - Osteoblastoma of the ilium mimicking sacroiliitis.

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

REVISTA / JOURNAL:  - Arthritis Rheum. 2013 Mar 4. doi: 10.1002/art.37915.

            ●● Enlace al texto completo (gratuito o de pago) 1002/art.37915

AUTORES / AUTHORS:  - Modaressi K; Phd BF; Bode P; Sutter R; Meili S; Weber U

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedics, University of Zurich, Orthopedic University Hospital  Balgrist, Zurich, Switzerland. kourosh.modaressi@balgrist.ch.




TÍTULO / TITLE:  - Osteosarcoma of the mastoid process following radiation therapy of mucoepidermoid carcinoma of the parotid gland—a case report.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:223-5.

AUTORES / AUTHORS:  - Brusic SK; Pusic M; Cvjetkovic N; Karnjus R; Candrlic B; Kukuljan M; Kastelan ZM; Miletic D

INSTITUCIÓN / INSTITUTION:  - University of Rijeka, Rijeka University Hospital Center, Department of Radiology, Rijeka, Croatia. skukicbr@hotmail.com

RESUMEN / SUMMARY:  - Radiation therapy is frequently used method in treatment of the head and neck malignancies. Osteosarcoma is a rare complication of radiation therapy and usually occurs after a long latent period. We report the case of 75-year-old female with osteosarcoma of the mastoid process. Twelve years before presentation she received radiation therapy after total parotidectomy and radical neck dissection in treatment of mucoepidermoid carcinoma of the parotid gland. Diagnostic procedures included contrast-enhanced CT and MRI of the head and neck  and HRCT of the temporal bone. The final diagnosis of the low grade osteosarcoma  was confirmed by biopsy. Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma.




TÍTULO / TITLE:  - Magnetic resonance imaging-guided focused ultrasound surgery for symptomatic uterine fibroids: estimation of treatment efficacy using thermal dose calculations.

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

REVISTA / JOURNAL:  - Eur J Obstet Gynecol Reprod Biol. 2013 Mar 21. pii: S0301-2115(13)00112-7. doi: 10.1016/j.ejogrb.2013.02.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejogrb.2013.02.023

AUTORES / AUTHORS:  - Yoon SW; Cha SH; Ji YG; Kim HC; Lee MH; Cho JH

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, CHA Bundang Medical Center, CHA University, Republic of Korea. Electronic address: jansons@cha.ac.kr.

RESUMEN / SUMMARY:  - OBJECTIVE: To study the correlation between the predicted thermal dose volume (TDV) and the actual ablation volumes in MR-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine fibroids, and to follow up the outcome for 12 months post-treatment. STUDY DESIGN: Phase-difference fast spoiled gradient-echo  MR images were used to analyze thermal change during the energy deliveries of MRgFUS in 60 consecutive patients treated for symptomatic uterine fibroids. The TDV obtained through analysis of these MR images was compared with the non-perfused volume (NPV) measured on post-treatment contrast enhanced T1-weighted images. Final values of TDV ratio and NPV ratio were obtained by dividing these values by original fibroid volume. Patients were followed for 12 months post-treatment to assess symptomatic relief using the symptom severity score (SSS). RESULTS: Treatments in which we managed to reach a TDV ratio larger  than 27% of the treated fibroid yielded a ratio of NPV to TDV of 1.1+/-0.5, indicating accurate control of the non-invasive procedure. Patient symptoms, as measured by the SSS, continuously decreased from a mean baseline score of 50+/-22 to 19+/-12 (P<0.0001) 12 months post-treatment. CONCLUSIONS: At large treatment volumes (exceeding 27% TDV ratio), thermal dose estimates correspond very closely to non-perfused volumes measured immediately post treatment. These large treatment volumes result in continuous clinical improvement throughout the first  12 months after MRgFUS.




TÍTULO / TITLE:  - A whole-genome RNA interference screen for human cell factors affecting myxoma virus replication.

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

REVISTA / JOURNAL:  - J Virol. 2013 Apr;87(8):4623-41. doi: 10.1128/JVI.02617-12. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.02617-12

AUTORES / AUTHORS:  - Teferi WM; Dodd K; Maranchuk R; Favis N; Evans DH

INSTITUCIÓN / INSTITUTION:  - Department of Medical Microbiology & Immunology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.

RESUMEN / SUMMARY:  - Myxoma virus (MYXV) provides an important model for investigating host-pathogen interactions. Recent studies have also highlighted how mutations in transformed human cells can expand the host range of this rabbit virus. Although virus growth depends upon interactions between virus and host proteins, the nature of these interactions is poorly understood. To address this matter, we performed small interfering RNA (siRNA) screens for genes affecting MYXV growth in human MDA-MB-231 cells. By using siRNAs targeting the whole human genome (21,585 genes), a subset of human phosphatases and kinases (986 genes), and also a custom siRNA library targeting selected statistically significant genes (“hits”) and nonsignificant genes (“nonhits”) of the whole human genome screens (88 genes), we identified 711 siRNA pools that promoted MYXV growth and 333 that were inhibitory. Another 32 siRNA pools (mostly targeting the proteasome) were toxic.  The overall overlap in the results was about 25% for the hits and 75% for the nonhits. These pro- and antiviral genes can be clustered into pathways and related groups, including well-established inflammatory and mitogen-activated protein kinase pathways, as well as clusters relating to beta-catenin and the Wnt signaling cascade, the cell cycle, and cellular metabolism. The validity of a subset of these hits was independently confirmed. For example, treating cells with siRNAs that might stabilize cells in G1, or inhibit passage into S phase, stimulated MYXV growth, and these effects were reproduced by trapping cells at the G1/S boundary with an inhibitor of cyclin-dependent kinases 4/6. By using 2-deoxy-d-glucose and plasmids carrying the gene for phosphofructokinase, we also confirmed that infection is favored by aerobic glycolytic metabolism. These studies provide insights into how the growth state and structure of cells affect  MYXV growth and how these factors might be manipulated to advantage in oncolytic  virus therapy.




TÍTULO / TITLE:  - Long-term efficacy of imatinib for treatment of metastatic GIST.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2135-8


INSTITUCIÓN / INSTITUTION:  - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA, spatel@mdanderson.org.

RESUMEN / SUMMARY:  - PURPOSE: Imatinib is an effective and approved treatment for advanced gastrointestinal stromal tumor (GIST). Continuous imatinib treatment is recommended by current guidelines. This review summarizes the long-term efficacy  and safety of imatinib for patients with metastatic GIST. METHODS: Key clinical studies were reviewed-including B2222, S0033, and BFR14-with particular emphasis  on recently reported results of the long-term clinical outcome of imatinib for metastatic GIST. RESULTS: The B2222 and S0033 studies recently reported 10-year follow-up results that demonstrate the long-term efficacy of imatinib. Furthermore, results from the BFR14 study demonstrate that imatinib treatment should not be interrupted and that the efficacy of imatinib following reintroduction is inferior compared with the continuous administration group. The S0033 study also supports the importance of dose optimization and dose escalation of imatinib in patients with KIT exon 9 mutations or progressive disease. These studies demonstrate that individual patient characteristics should be evaluated for optimal patient management. Managing adverse events proactively is very important to maintain compliance. CONCLUSIONS: The results from these studies demonstrate that long-term imatinib extends survival in patients with advanced GIST. Furthermore, these studies support the safety of long-term imatinib therapy in this patient population.




TÍTULO / TITLE:  - Modulation of stretch-induced myocyte remodelling and gene expression by nitric oxide: A novel role for lipoma preferred partner in myofibrillogenesis.

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

REVISTA / JOURNAL:  - Am J Physiol Heart Circ Physiol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1152/ajpheart.00004.2013

AUTORES / AUTHORS:  - Hooper CL; Paudyal A; Dash PR; Boateng SY

INSTITUCIÓN / INSTITUTION:  - 1University of Reading.

RESUMEN / SUMMARY:  - Prolonged hemodynamic load eventually leads to maladaptive cardiac adaptation and heart failure. Signalling pathways that underlie these changes are still poorly understood. The adaptive response to mechanical load is mediated by mechanosensors which convert the mechanical stimuli into a biological response. We examined the effect of cyclic mechanical stretch on myocyte adaptation using neonatal rat ventricular myocytes with 10% (adaptive) or 20% (maladaptive) maximum strain, 1Hz for 48hours to mimic in vivo mechanical stress. Cells were also treated with and without L-NAME, a general nitric oxide synthase (NOS) inhibitor to suppress NO production. Maladaptive 20% mechanical stretch led to a  significant loss of intact sarcomeres which was rescued by L-NAME (P<0.05, n>/=5  cultures). We hypothesized that the mechanism was through NO-induced alteration of myocyte gene expression. L-NAME up-regulated the mechanosensing proteins Muscle LIM protein (MLP (by 100%, p<0.05, n=3 cultures)) and lipoma preferred partner, a novel cardiac protein (LPP (by 80%, p<0.05, n=3 cultures)). L-NAME also significantly altered the subcellular localisation of LPP and MLP in a manner that favoured growth and adaptation. These findings suggest that NO participates in stretch-mediated adaptation. The use of isoform selective NOS inhibitors indicated a complex interaction between iNOS and nNOS isoforms regulate gene expression. LPP knockdown by siRNA led to formation of alpha-actinin aggregates and z-bodies showing that myofibrillogenesis was impaired. There was an up-regulation of MUL1 ubiquitin ligase by 75% (P<0.05, n=5 cultures). These data indicate that NO contributes to stretch-mediated adaptation via the up-regulation of proteins associated mechansensing and myofibrillogenesis.




TÍTULO / TITLE:  - Kaposi’s-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4 T cell proliferation.

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

REVISTA / JOURNAL:  - Virology. 2013 Mar 16. pii: S0042-6822(13)00123-2. doi: 10.1016/j.virol.2013.02.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.virol.2013.02.018

AUTORES / AUTHORS:  - Liu W; Qin Y; Bai L; Lan K; Wang JH

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai, China; Graduate School of the Chinese  Academy of Sciences, Beijing, China.

RESUMEN / SUMMARY:  - Infection of Kaposi’s sarcoma-associated herpesvirus (KSHV) is commonly occurred  in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect  of KSHV on DC-HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4+ T cells, demonstrating the immunosuppression  induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC-HIV-1 interaction to elucidate HIV/AIDS pathogenesis.




TÍTULO / TITLE:  - Vitamin d and the risk of uterine fibroids.

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

REVISTA / JOURNAL:  - Epidemiology. 2013 May;24(3):447-53. doi: 10.1097/EDE.0b013e31828acca0.

            ●● Enlace al texto completo (gratuito o de pago) 1097/EDE.0b013e31828acca0

AUTORES / AUTHORS:  - Baird DD; Hill MC; Schectman JM; Hollis BW

INSTITUCIÓN / INSTITUTION:  - From the aEpidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC; bDepartment of Radiology, George Washington University Medical Center, George Washington University, Washington, DC; cDepartment of Health Care Sciences, George Washington University Medical Center, George Washington University, Washington, DC; and dDepartment of Pediatrics, The  Medical University of South Carolina, Charleston, SC.

RESUMEN / SUMMARY:  - BACKGROUND: : Uterine leiomyomata (also known as fibroids) are benign tumors of uterine smooth muscle that are characterized by overproduction of extracellular matrix. Fibroids are the leading indication for hysterectomy in the United States. The active metabolite of vitamin D has been shown to inhibit cell proliferation and extracellular matrix production in fibroid tissue culture and to reduce fibroid volume in the Eker rat. No previous study has examined whether  vitamin D is related to fibroid status in women. METHODS: : The National Institute of Environmental Health Sciences Uterine Fibroid Study enrolled randomly selected 35- to 49-year-old women who were members of an urban health plan during 1996-1999. Fibroid status was determined by ultrasound screening of premenopausal women (620 blacks, 416 whites). Vitamin D status was assessed in stored plasma by radioimmunoassay of 25-hydroxyvitamin D (25(OH)D) and questionnaire data on sun exposure. Associations were evaluated with logistic regression, controlling for potential confounders. RESULTS: : Only 10% of blacks  and 50% of whites had levels of 25(OH)D regarded as sufficient (>20 ng/ml). Women with sufficient vitamin D had an estimated 32% lower odds of fibroids compared with those with vitamin D insufficiency (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] = 0.48-0.96). The association was similar for blacks and whites. Self-reported sun exposure >/=1 hour per day (weather permitting) was also associated with reduced odds of fibroids (aOR = 06. [0.4-0.9]), with no evidence of heterogeneity by ethnicity. CONCLUSIONS: : The consistency of findings for questionnaire and biomarker data, the similar patterns seen in blacks and whites, and the biological plausibility provide evidence that sufficient vitamin D is associated with a reduced risk of uterine fibroids.




TÍTULO / TITLE:  - Interactions of the Kaposi’s Sarcoma-Associated Herpesvirus Nuclear Egress Complex: ORF69 Is a Potent Factor for Remodeling Cellular Membranes.

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

REVISTA / JOURNAL:  - J Virol. 2013 Apr;87(7):3915-29. doi: 10.1128/JVI.03418-12. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03418-12

AUTORES / AUTHORS:  - Luitweiler EM; Henson BW; Pryce EN; Patel V; Coombs G; McCaffery JM; Desai PJ

INSTITUCIÓN / INSTITUTION:  - Viral Oncology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

RESUMEN / SUMMARY:  - All herpesviruses encode a complex of two proteins, referred to as the nuclear egress complex (NEC), which together facilitate the exit of assembled capsids from the nucleus. Previously, we showed that the Kaposi’s sarcoma-associated herpesvirus (KSHV) NEC specified by the ORF67 and ORF69 genes when expressed in insect cells using baculoviruses for protein expression forms a complex at the nuclear membrane and remodels these membranes to generate nuclear membrane-derived vesicles. In this study, we have analyzed the functional domains of the KSHV NEC proteins and their interactions. Site-directed mutagenesis of gammaherpesvirus conserved residues revealed functional domains of these two proteins, which in many cases abolish the formation of the NEC and remodeling of  nuclear membranes. Small in-frame deletions within ORF67 in all cases result in loss of the ability of the mutant protein to induce cellular membrane proliferation as well as to interact with ORF69. Truncation of the C terminus of  ORF67 that resides in the perinuclear space does not impair the functions of ORF67; however, deletion of the transmembrane domain of ORF67 produces a protein  that cannot induce membrane proliferation but can still interact with ORF69 in the nucleus and can be tethered to the nuclear membrane by virtue of its interaction with the wild-type-membrane-anchored ORF67. In-frame deletions in ORF69 have varied effects on NEC formation, but all abolish remodeling of nuclear membranes into circular structures. One mutant interacts with ORF67 as well as the wild-type protein but cannot function in membrane curvature and fission events that generate circular vesicles. These studies genetically confirm that ORF67 is required for cellular membrane proliferation and that ORF69 is the factor required to remodel these duplicated membranes into circular-virion-size vesicles. Furthermore, we also investigated the NEC encoded by Epstein-Barr virus (EBV). The EBV complex comprised of BFRF1 and BFLF2 was visualized at the nuclear membrane using autofluorescent protein fusions. BFRF1 is a potent inducer of membrane proliferation; however, BFLF2 cannot remodel these membranes into circular structures. What was evident is the superior remodeling activity of ORF69, which could convert the host membrane proliferations induced by BFRF1 into circular structures.




TÍTULO / TITLE:  - Rapidly Growing Cardiac Papillary Fibroelastoma in a Teenager with Sickle Cell Disease.

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

REVISTA / JOURNAL:  - Echocardiography. 2013 Mar 12. doi: 10.1111/echo.12158.

            ●● Enlace al texto completo (gratuito o de pago) 1111/echo.12158

AUTORES / AUTHORS:  - Sernich S; Craver R; Pettitt TW; Caspi J; Ascuitto R

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, LSU School of Medicine, New Orleans, Louisiana; Children’s Hospital of New Orleans, New Orleans, Louisiana.




TÍTULO / TITLE:  - Exonic Mutations of TSC2/TSC1 Are Common but Not Seen in All Sporadic Pulmonary Lymphangioleiomyomatosis.

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

REVISTA / JOURNAL:  - Am J Respir Crit Care Med. 2013 Mar 15;187(6):663-5.

            ●● Enlace al texto completo (gratuito o de pago) 1164/ajrccm.187.6.663

AUTORES / AUTHORS:  - Badri KR; Gao L; Hyjek E; Schuger N; Schuger L; Qin W; Chekaluk Y; Kwiatkowski DJ; Zhe X




TÍTULO / TITLE:  - Chromatin Immunoprecipitation and Microarray Analysis Suggest Functional Cooperation between Kaposi’s Sarcoma-Associated Herpesvirus ORF57 and K-bZIP.

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

REVISTA / JOURNAL:  - J Virol. 2013 Apr;87(7):4005-16. doi: 10.1128/JVI.03459-12. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03459-12

AUTORES / AUTHORS:  - Hunter OV; Sei E; Richardson RB; Conrad NK

INSTITUCIÓN / INSTITUTION:  - UT Southwestern Medical Center, Department of Microbiology, Dallas, Texas, USA.

RESUMEN / SUMMARY:  - The Kaposi’s sarcoma-associated herpesvirus (KSHV) open reading frame 57 (ORF57)-encoded protein (Mta) is a multifunctional regulator of viral gene expression. ORF57 is essential for viral replication, so elucidation of its molecular mechanisms is important for understanding KSHV infection. ORF57 has been implicated in nearly every aspect of viral gene expression, including transcription, RNA stability, splicing, export, and translation. Here we demonstrate that ORF57 interacts with the KSHV K-bZIP protein in vitro and in cell extracts from lytically reactivated infected cells. To further test the biological relevance of the interaction, we performed a chromatin immunoprecipitation and microarray (ChIP-chip) analysis using anti-ORF57 antibodies and a KSHV tiling array. The results revealed four specific areas of enrichment, including the ORF4 and K8 (K-bZIP) promoters, as well as oriLyt, all  of which interact with K-bZIP. In addition, ORF57 associated with DNA corresponding to the PAN RNA transcribed region, a known posttranscriptional target of ORF57. All of the peaks were RNase insensitive, demonstrating that ORF57 association with the viral genome is unlikely to be mediated exclusively by an RNA tether. Our data demonstrate that ORF57 associates with the viral genome by using at least two modes of recruitment, and they suggest that ORF57 and K-bZIP coregulate viral gene expression during lytic infection.




TÍTULO / TITLE:  - Myxoma and vaccinia viruses bind differentially to human leukocytes.

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

REVISTA / JOURNAL:  - J Virol. 2013 Apr;87(8):4445-60. doi: 10.1128/JVI.03488-12. Epub 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.03488-12

AUTORES / AUTHORS:  - Chan WM; Bartee EC; Moreb JS; Dower K; Connor JH; McFadden G

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Genetics and Microbiology.

RESUMEN / SUMMARY:  - Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family Poxviridae, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that ex vivo treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34(+) hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV  specifically recognizes and eliminates the cancer cells in the autografts is not  understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin beta1. We have constructed MYXV and VACV  virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked  only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that  the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.




TÍTULO / TITLE:  - Long telomeres in peripheral blood leukocytes are associated with an increased risk of soft tissue sarcoma.

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

REVISTA / JOURNAL:  - Cancer. 2013 Feb 13. doi: 10.1002/cncr.27984.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27984

AUTORES / AUTHORS:  - Xie H; Wu X; Wang S; Chang D; Pollock RE; Lev D; Gu J

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; State Key Laboratory of Reproductive Medicine, Department of Breast Surgery, Nanjing Maternity and Child Health Care Hospital Affiliated With  Nanjing Medical University, Nanjing, China.

RESUMEN / SUMMARY:  - BACKGROUND: Human telomeres consisting of long, tandem repeats of the nucleotide  sequence TTAGGG at the chromosome ends are essential for maintaining chromosomal  stability. Previous epidemiologic studies have indicated that shorter telomere length in peripheral blood leukocytes (PBLs) is associated with the development of many cancers. However, the relation between PBL telomere length and the risk of soft tissue sarcoma (STS) has not been investigated. METHODS: The relative telomere length (RTL) was determined in PBLs using real-time polymerase chain reaction in this case-control study. The study participants included 137 patients with histologically confirmed STS (cases) who had received no prior chemotherapy  or radiotherapy and 137 healthy controls who were frequency-matched to cases on age, sex, and ethnicity. RESULTS: Patients in the case group had significantly longer RTL than controls (1.46 +/- 0.42 for cases vs 1.15 +/- 0.39 for controls;  P < .001). By using median RTL in the controls as a cutoff level, individuals who had long telomere length were associated with a significantly increased risk of STS compared with those who had short telomere length (adjusted odds ratio, 4.71; 95% confidence interval, 2.63-8.44). When participants were categorized further into 3 or 4 groups according to the tertile or quartile RTL values of healthy controls, a significant dose-response relation was observed between longer RTL and increased risks of STS. CONCLUSIONS: The current results provided the first epidemiologic evidence that longer telomere length in PBLs is associated significantly with an increased risk of STS, potentially suggesting an important  role for telomere maintenance in STS development. 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.




TÍTULO / TITLE:  - Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: Effective photoinduced in vitro killing of osteosarcoma.

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

REVISTA / JOURNAL:  - J Control Release. 2013 Mar 21. pii: S0168-3659(13)00155-7. doi: 10.1016/j.jconrel.2013.03.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jconrel.2013.03.012

AUTORES / AUTHORS:  - Duchi S; Sotgiu G; Lucarelli E; Ballestri M; Dozza B; Santi S; Guerrini A; Dambruoso P; Giannini S; Donati D; Varchi G

INSTITUCIÓN / INSTITUTION:  - Osteoarticolar Regeneration Laboratory, Rizzoli Orthopaedic Institute (IOR), Via  di Barbiano 1/10, 40136, Bologna, Italy.

RESUMEN / SUMMARY:  - Mesenchymal stem cells (MSC) have the unique ability to home and engraft in tumor stroma. These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma. In the present study, we investigate whether fluorescent core-shell PMMA nanoparticles (FNPs) post-loaded with a photosensitizer, namely meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) and uploaded by MSC could trigger osteosarcoma (OS) cell death in vitro upon specific photoactivation. In co-culture studies we demonstrate using laser confocal microscopy and time lapse  imaging, that only after laser irradiation MSC loaded with photosensitizer-coated fluorescent NPs (TPPS@FNPs) undergo cell death and release reactive oxygen species (ROS) which are sufficient to trigger cell death of all OS cells in the culture. These results encourage further studies aimed at proving the efficacy of this novel tri-component system for PDT applications.




TÍTULO / TITLE:  - Letter to the Editor: Chordoma stem cells.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):913-4. doi: 10.3171/2012.3.JNS12478. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.3.JNS12478

AUTORES / AUTHORS:  - Lee CH; Chang WC; Yeh CC; Jiang PJ; Sytwu HK; Hueng DY

INSTITUCIÓN / INSTITUTION:  - Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.




TÍTULO / TITLE:  - Role of Dynamic MRI and Clinical Assessment in Predicting Histologic Response to  Neoadjuvant Chemotherapy in Bone Sarcomas.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827b4f6f

AUTORES / AUTHORS:  - Amit P; Patro DK; Basu D; Elangovan S; Parathasarathy V

INSTITUCIÓN / INSTITUTION:  - *Department of Orthopaedics, Acharyashree Bhikshu Government Hospital, New Delhi  Departments of daggerOrthopaedics double daggerPathology section signRadiodiagnosis parallelRadiotherapy, JIPMER, Pondicherry, India.

RESUMEN / SUMMARY:  - BACKGROUND:: Neoadjuvant chemotherapy has become the first-line therapy in management of malignant bone tumors. Response to it is best assessed with evaluation of tumor necrosis postoperatively. This study was carried out to evaluate the role of clinical parameters and dynamic magnetic resonance imaging (MRI) to predict the histologic response before surgery. MATERIALS AND METHODS::  Our study included 14 patients (12 osteosarcoma and 2 malignant fibrous histiocytoma) with mean age of 21.8 years, treated with neoadjuvant chemotherapy  followed by surgery, who were evaluated clinically and with dynamic MRI twice, before starting chemotherapy and before surgery. Clinical parameters (pain, tumor girth, maximum tumor diameter, surface temperature, and consistency) and dynamic  MRI parameter (slope of signal intensity-time curve) were correlated with histologic response (percentage of necrosis) using Pearson and Spearman correlation test. RESULTS:: Significant correlation with histologic necrosis was  seen in change in pain, tumor girth, maximum tumor diameter, surface temperature, and dynamic MRI slope (P<0.01). Change in consistency did not show significant correlation (P>0.05). Complete relieve of pain with reduction of >4 grades, >/=5% reduction in tumor girth, >/=8% reduction in tumor diameter, attainment of normal body temperature or decrease of >/=2 degrees F temperature, and >/=60% reduction  in slope proved to be an indicator of good histologic response. CONCLUSIONS:: Both dynamic MRI and clinical evaluation are reliable methods of assessment of response of the bone tumors to neoadjuvant chemotherapy.




TÍTULO / TITLE:  - Degraded iota-carrageenan can induce apoptosis in human osteosarcoma cells via the Wnt/beta-catenin signaling pathway.

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

REVISTA / JOURNAL:  - Nutr Cancer. 2013;65(1):126-31. doi: 10.1080/01635581.2013.741753.

            ●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.741753


INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedics, First Affiliated Hospital of China Medical University, Shenyang, China. jinzheFH@163.com

RESUMEN / SUMMARY:  - Osteosarcoma (OS) is a high-grade malignant bone tumor. Therefore, using both in  vitro and in vivo assays, the effects of degraded iota-Carrageenan (iota-CGN) on  a human osteosarcoma cell line, HOS, were examined. Degraded iota-CGN was observed to induce apoptosis and G(1) phase arrest in HOS cells. Moreover, degraded iota-CGN suppressed tumor growth in established xenograft tumor models.  Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors treated with native iota-CGN or PBS. In addition, the formation of intratumoral microvessels was inhibited following treatment with degraded iota-CGN. In Western blot assays, degraded iota-CGN was found to inhibit the Wnt/beta-catenin signaling pathway. Overall, these studies demonstrate the antitumor activity of degraded iota-CGN toward the OS cell line, HOS. Moreover, valuable insight into the mechanisms mediated by degraded iota-CGN was obtained,  potentially leading to the identification of novel treatments for OS. However, additional studies are needed to confirm these results in other cell types, particularly in human umbilical vein endothelial cells.




TÍTULO / TITLE:  - Midterm Results after Uterine Artery Embolization Versus MR-Guided High-Intensity Focused Ultrasound Treatment for Symptomatic Uterine Fibroids.

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

REVISTA / JOURNAL:  - Cardiovasc Intervent Radiol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00270-013-0582-6

AUTORES / AUTHORS:  - Froeling V; Meckelburg K; Scheurig-Muenkler C; Schreiter NF; Kamp J; Maurer MH; Beck A; Hamm B; Kroencke TJ

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Charite-Universitatsmedizin Berlin, Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany, vera.froeling@charite.de.

RESUMEN / SUMMARY:  - PURPOSE: To compare the rate of reintervention and midterm changes in symptom severity (SS) and Total health-related quality of life (HRQoL) scores after uterine artery embolization (UAE) and magnetic resonance-guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. METHODS: Eighty  women (median age 38.3 years), equally eligible for MR-g HIFU and UAE who underwent one of both treatments between 2002 and 2009 at our institution, were included. The primary end point of the study was defined as the rate of reintervention after both therapies. The secondary outcome was defined as changes in SS and Total HRQoL scores after treatment. SS and Total HRQoL scores before treatment and at midterm follow-up (median 13.3 months) were assessed by the uterine fibroid symptom and quality-of-life questionnaire (UFS-QoL) and compared. RESULTS: The rate of reintervention was significantly lower after UAE than after  MR-g HIFU (p = 0.002). After both treatments, SS and Total HRQoL scores improved  significantly from baseline to follow-up (UAE: p < 0.001, p < 0.001; MR-g HIFU: p = 0.002, p < 0.001). Total HRQoL scores were significantly higher after UAE than  after MR-g HIFU (p = 0.032). Changes in the SS scores did not differ significantly for both treatments (p = 0.061). CONCLUSION: UAE and MR-g HIFU significantly improved the health-related quality of life of women with symptomatic uterine fibroids. After UAE, the change in Total HRQoL score improvement was significantly better, and a significantly lower rate of reintervention was observed.




TÍTULO / TITLE:  - A Disintegrin And Metalloproteinase 12 produced by tumour cells accelerates osteosarcoma tumour progression and associated osteolysis.

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

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Mar 11. pii: S0959-8049(13)00150-0. doi: 10.1016/j.ejca.2013.02.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.020

AUTORES / AUTHORS:  - Georges S; Chesneau J; Hervouet S; Taurelle J; Gouin F; Redini F; Padrines M; Heymann D; Fortun Y; Verrecchia F

INSTITUCIÓN / INSTITUTION:  - LUNAM Universite, France; INSERM, UMR-S 957, Nantes, France; Universite de Nantes, Laboratoire de Physiopathologie de la Resorption Osseuse et Therapie des  Tumeurs Osseuses Primitives, Nantes, France; CHU de Nantes, Nantes, France; Equipe labellisee Ligue contre le Cancer 2012, Nantes, France.

RESUMEN / SUMMARY:  - BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents for whom the prognosis remains unfavourable despite treatment protocols that combine chemotherapy and surgery. Metalloproteinases decisively contribute to cancer development and promotion by regulating cell growth, angiogenesis or inflammation. However, their role in osteosarcoma remains still unknown. METHODS: A screening of a large panel of metalloproteinases and their inhibitors, carried out in osteolytic (K7M2 and POS-1) or osteoblastic (MOS-J) mouse osteosarcoma models, shows that a member of a family of cell surface metallopeptidases, A Disintegrin And Metalloproteinase 12 (ADAM12), is highly expressed in the K7M2 and POS-1 cell lines and weakly expressed in the MOS-J cell line. To investigate whether ADAM12, involved in several pathologic conditions characterised by abnormal cell growth, plays a role in osteosarcoma tumour growth, ADAM12 was overexpressed in MOS-J and downregulated in K7M2 cells. RESULTS: In vivo experiments demonstrated that ADAM12 favours tumour growth, leading to a significant modification in animal survival. In vitro assays showed  that ADAM12 knockdown in K7M2 cells slows cell proliferation. In addition, the study of microarchitectural parameters, assessed by micro-computed tomography (CT) analysis, showed that ADAM12 favours bone osteolysis, as demonstrated both in an ADAM12 overexpressing (MOS-J) and a knockdown (K7M2) model. Histological analysis showed that ADAM12 inhibited osteoblast activity and therefore enhanced  bone resorption. CONCLUSIONS: Our study demonstrates that ADAM12 expression not only favours tumour growth but also associates enhanced osteolysis with a significant reduction in animal survival, suggesting that ADAM12 could be a new therapeutic target in osteosarcoma.




TÍTULO / TITLE:  - Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb 26. doi: 10.3892/or.2013.2306.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2306

AUTORES / AUTHORS:  - Spina A; Sorvillo L; Chiosi E; Esposito A; Di Maiolo F; Sapio L; Caraglia M; Naviglio S

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Medical School, I80138 Naples, Italy.

RESUMEN / SUMMARY:  - Novel therapeutic approaches are required for the treatment of osteosarcoma. Combination chemotherapy is receiving increased attention in order to identify compounds that may increase the therapeutic index of clinical anticancer drugs. In this regard, naturally occurring molecules with antitumor activity and with limited toxicity to normal tissues have been suggested as possible candidates for investigation of their synergistic efficacy in combination with antineoplastic drugs. Inorganic phosphate (Pi) is an essential nutrient for living organisms. Relevantly, Pi has emerged as an important signaling molecule capable of modulating multiple cellular functions by altering signal transduction pathways,  gene expression and protein abundance in many cell types. Previously, we showed that Pi inhibits proliferation and aggressiveness of U2OS human osteosarcoma cells and that Pi is capable of inducing sensitization of osteosarcoma cells to doxorubicin in a p53-dependent manner. In this study, we extended the role of Pi  in the chemosensitivity of osteosarcoma cells to other anticancer drugs. Specifically, we report and compare the antiproliferative effects of a combination between Pi and doxorubicin, Taxol® and 5-fluorouracil (5-FU) treatments. We found that Pi increases the antiproliferative response to both Taxol and doxorubicin to a similar extent. On the other hand, Pi did not potentiate the anticancer effects induced by 5-FU. These effects were paralleled  by apoptosis induction and were cell cycle-dependent. The clinical significance of our data and their potential therapeutic applications for improving osteosarcoma treatment are discussed.




TÍTULO / TITLE:  - Opposite cytokine synthesis by fibroblasts in contact co-culture with osteosarcoma cells compared with transwell co-cultures.

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

REVISTA / JOURNAL:  - Cytokine. 2013 Apr;62(1):48-51. doi: 10.1016/j.cyto.2013.02.028. Epub 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2013.02.028

AUTORES / AUTHORS:  - David MS; Kelly E; Zoellner H

INSTITUCIÓN / INSTITUTION:  - Cellular and Molecular Pathology Research Unit, Dept. Oral Pathology, Westmead Centre for Oral Health, Westmead Hospital, The University of Sydney, Westmead, NSW 2145, Australia.

RESUMEN / SUMMARY:  - We recently reported exchange of membrane and cytoplasm during contact co-culture between human Gingival Fibroblasts (h-GF) and SAOS-2 osteosarcoma cells, a process we termed ‘cellular sipping’ to reflect the manner in which cells become  morphologically diverse through uptake of material from the opposing cell type, independent of genetic change. Cellular sipping is increased by Tumor Necrosis Factor-alpha (TNF-alpha), and we here show for the first time altered cytokine synthesis in contact co-culture supporting cellular sipping compared with co-culture where h-GF and SAOS-2 were separated in transwells. SAOS-2 had often undetectably low cytokine levels, while Interleukin-6 (IL-6), Granulocyte Colony  Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) were secreted primarily by TNF-alpha stimulated h-GF and basic Fibroblast Growth Factor (FGF) was prominent in h-GF lysates (p<0.001). Contact co-cultures permitting cellular sipping had lower IL-6, G-CSF and GM-CSF levels,  as well as higher lysate FGF levels compared with TNF-alpha treated h-GF alone (p<0.05). The opposite was the case for co-cultures in transwells, with increased IL-6, G-CSF and GM-CSF levels (p<0.03) and no clear difference in FGF. We thus demonstrate significant phenotypic change in cultures where cellular sipping occurs, potentially contributing to tumor inflammatory responses.




TÍTULO / TITLE:  - Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Mar 18. pii: S0046-8177(13)00026-9. doi: 10.1016/j.humpath.2013.01.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2013.01.006

AUTORES / AUTHORS:  - de Graaff MA; Cleton-Jansen AM; Szuhai K; Bovee JV

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.

RESUMEN / SUMMARY:  - Recently, heterozygous mutations in exon 2 of the mediator complex subunit 12 gene have been described in 50% to 70% of uterine leiomyomas; the recurrent nature of these mutations suggests an important role in their pathogenesis. Mediator complex subunit 12 is involved in regulation of transcription and Wnt signaling. So far, little is known about the pathogenesis of the different subtypes of extrauterine leiomyomas and leiomyosarcomas. We performed mutation analysis of mediator complex subunit 12 and immunohistochemistry for beta-catenin, using 69 tumors of 64 patients including 19 uterine leiomyomas, 6 abdominal leiomyomas, 9 angioleiomyomas, 5 piloleiomyomas, and 7 uterine and 23 soft tissue leiomyosarcomas. In line with previous observations, 58% of uterine leiomyomas carried a mediator complex subunit 12 mutation. However, all other extrauterine leiomyomas were negative with the exception of 1 abdominal leiomyoma with a likely primary uterine origin. Of the 30 leiomyosarcomas, only 1 uterine tumor harbored a mutation. A new observation is the identification of 3 tumors with a homozygous mutation; a monosomy X or interstitial deletion was excluded. beta-Catenin immunohistochemistry showed nuclear positivity in only 55% of the mediator complex subunit 12-mutated uterine leiomyomas, suggesting the involvement of pathways other than canonical Wnt signaling in tumorigenesis. Interestingly, 80% of mediator complex subunit 12 wild-type sporadic piloleiomyomas displayed nuclear beta-catenin positivity, indicating its involvement in this leiomyoma subtype. The lack of mediator complex subunit 12 mutations in extrauterine leiomyomas and leiomyosarcomas indicates that these tumors arise through a different pathway, emphasizing the genetic heterogeneity of smooth muscle tumors.




TÍTULO / TITLE:  - Ionizing radiation exposure and the development of soft-tissue sarcomas in atomic-bomb survivors.

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

REVISTA / JOURNAL:  - J Bone Joint Surg Am. 2013 Feb 6;95(3):222-9. doi: 10.2106/JBJS.L.00546.

            ●● Enlace al texto completo (gratuito o de pago) 2106/JBJS.L.00546

AUTORES / AUTHORS:  - Samartzis D; Nishi N; Cologne J; Funamoto S; Hayashi M; Kodama K; Miles EF; Suyama A; Soda M; Kasagi F

INSTITUCIÓN / INSTITUTION:  - Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan. dsamartzis@msn.com

RESUMEN / SUMMARY:  - BACKGROUND: Very high levels of ionizing radiation exposure have been associated  with the development of soft-tissue sarcoma. The effects of lower levels of ionizing radiation on sarcoma development are unknown. This study addressed the role of low to moderately high levels of ionizing radiation exposure in the development of soft-tissue sarcoma. METHODS: Based on the Life Span Study cohort  of Japanese atomic-bomb survivors, 80,180 individuals were prospectively assessed for the development of primary soft-tissue sarcoma. Colon dose in gray (Gy), the  excess relative risk, and the excess absolute rate per Gy absorbed ionizing radiation dose were assessed. Subject demographic, age-specific, and survival parameters were evaluated. RESULTS: One hundred and four soft-tissue sarcomas were identified (mean colon dose = 0.18 Gy), associated with a 39% five-year survival rate. Mean ages at the time of the bombings and sarcoma diagnosis were 26.8 and 63.6 years, respectively. A linear dose-response model with an excess relative risk of 1.01 per Gy (95% confidence interval [CI]: 0.13 to 2.46; p = 0.019) and an excess absolute risk per Gy of 4.3 per 100,000 persons per year (95% CI: 1.1 to 8.9; p = 0.001) were noted in the development of soft-tissue sarcoma. CONCLUSIONS: This is one of the largest and longest studies (fifty-six years from the time of exposure to the time of follow-up) to assess ionizing radiation effects on the development of soft-tissue sarcoma. This is the first study to suggest that lower levels of ionizing radiation may be associated with the development of soft-tissue sarcoma, with exposure of 1 Gy doubling the risk of soft-tissue sarcoma development (linear dose-response). The five-year survival rate of patients with soft-tissue sarcoma in this population was much lower than  that reported elsewhere.




TÍTULO / TITLE:  - Dermatofibrosarcoma Protuberans in Childhood Treated with Slow Mohs Micrographic  Surgery.

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

REVISTA / JOURNAL:  - Pediatr Dermatol. 2013 Feb 22. doi: 10.1111/pde.12039.

            ●● Enlace al texto completo (gratuito o de pago) 1111/pde.12039

AUTORES / AUTHORS:  - Barysch MJ; Weibel L; Neuhaus K; Subotic U; Scharer L; Donghi D; Hafner J; Braun R; Lauchli S; Dummer R; Schiestl C

INSTITUCIÓN / INSTITUTION:  - Department of Plastic and Reconstructive Surgery, University Children’s Hospital  Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Children’s Research Center, Zurich, Switzerland.

RESUMEN / SUMMARY:  - Dermatofibrosarcoma protuberans (DFSP) in childhood is a rare tumor with high recurrence rates. Wide local excision can result in disfiguring mutilation, whereas Mohs micrographic surgery (MMS) reduces surgical margins. MMS in children is not performed routinely, as the required infrastructures such as a histopathology lab in close proximity to the operating room is often lacking. We  retrospectively reviewed children diagnosed with DFSP treated at our hospital over 2 years. We recorded surgical treatment details, including margins, duration of inpatient stay, outcome, follow-up, and molecular genetic tumor tissue analysis. Four children with a median age of 6.8 years (range 6.0-8.8 years) were identified who had a diagnostic delay of a median of 2.5 years (range 0.5-4.0 years); all underwent complete tumor excision using the slow MMS technique using  vacuum-assisted closure systems between repeated excisions and before wound closure. The median maximal safety margins were 1.5 cm (range 1.0-3.0 cm). By using vacuum-assisted closure systems, no dressing changes were needed, pain was  limited, and full mobility was maintained in all children. The median total time  in the hospital was 11 days (range 10-14 days). No relapses occurred during a median follow-up of 25.8 months (range 11.3-32.6 months). Collagen 1A1/platelet-derived growth factor B (COL1A1/PDGFB) translocation on chromosomes  17 and 22 was detected in all three analyzable specimens. Lesions suspected of being DFSP warrant prompt histologic evaluation; interdisciplinary management is  mandatory in particular for children. Micrographic surgery allows smaller surgical margins than wide excision and should be considered as the treatment of  choice in children with DFSP. The interim usage of vacuum-assisted closure systems increases patient comfort. Translocations in the COL1A1/PDGFB gene imply  susceptibility to targeted treatment modalities for therapy-resistant cases.




TÍTULO / TITLE:  - An unusual case of severe aortic valve stenosis in an adult caused by aortic valve inflammatory myofibroblastic tumor.

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

REVISTA / JOURNAL:  - J Thorac Cardiovasc Surg. 2013 Feb 9. pii: S0022-5223(13)00056-1. doi: 10.1016/j.jtcvs.2013.01.028.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.01.028

AUTORES / AUTHORS:  - Zhao D; Wang C; Guo C

INSTITUCIÓN / INSTITUTION:  - Department of Cardiac Surgery, Zhongshan Hospital Fudan University and Shanghai Institute of Cardiovascular Diseases, Shanghai, People’s Republic of China.




TÍTULO / TITLE:  - Induction of Cell Cycle Arrest and Apoptosis in Human Osteosarcoma U-2 OS Cells by Solanum lyratum Extracts.

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

REVISTA / JOURNAL:  - Nutr Cancer. 2013 Apr;65(3):469-79. doi: 10.1080/01635581.2013.757627.

            ●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.757627

AUTORES / AUTHORS:  - Lin YT; Huang AC; Kuo CL; Yang JS; Lan YH; Yu CC; Huang WW; Chung JG

INSTITUCIÓN / INSTITUTION:  - a Department of Biological Science and Technology , China Medical University , Taichung , Taiwan.

RESUMEN / SUMMARY:  - This research focused on a Chinese herb medicine, Solanum lyratum Thunb (Solanaceae) by ethanol extracts (SLE) for investigating the molecular anticancer mechanism in vitro for exploring the means of cell death through the effects on mitochondrial function. We found that SLE induced cytotoxic effects in human osteosacroma U-2 OS cells, and these effects include cell morphological changes,  a decrease of the percentage of viable cells and induction of apoptosis. The results suggest that cell death induced by SLE is closely related to apoptosis based on the observations of DAPI staining and sub-G1 phase in U-2 OS cells. Flow cytometric assays also showed that SLE promoted the production of reactive oxygen species and nitric oxide but decreased the levels of mitochondrial membrane potential and promoted the activations of caspase-8 and -9 in U-2 OS cells. SLE inhibited the level of Bcl-2 but promoted the Bax level, and both proteins led to the release of cytochrome c from mitochondria to cytosol and activation of caspase-9 and -3, resulting in the apoptotic death which is mediated through the  mitochondrial pathway. Taken together, SLE was demonstrated to be effective in killing U-2 OS osteosacroma cells via the ROS-promoted and mitochondria- and caspase-dependent apoptotic pathways.




TÍTULO / TITLE:  - Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Feb 1. doi: 10.1038/modpathol.2012.223.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.223

AUTORES / AUTHORS:  - Tabareau-Delalande F; Collin C; Gomez-Brouchet A; Decouvelaere AV; Bouvier C; Larousserie F; Marie B; Delfour C; Aubert S; Rosset P; de Muret A; Pages JC; de Pinieux G

INSTITUCIÓN / INSTITUTION:  - 1] Department of Pathology, Tours University Hospital and University Francois Rabelais, Tours, France [2] Laboratory of Biochemistry and Molecular Biology, Trousseau University Hospital and University Francois Rabelais, Tours, France.

RESUMEN / SUMMARY:  - GNAS (guanine nucleotide-binding protein/alpha-subunit) mutations that induce the activation of G-protein alpha-subunit participate in the pathogenesis of fibrous  dysplasia. The aim of this study was to evaluate the sensitivity and specificity  of GNAS mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia. GNAS mutations were investigated by three techniques: high-resolution  melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the GNAS mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9). GNAS mutations in conventional fibrous dysplasia were detected in the same proportion  (47%) as in the other histological subtypes (47%, P=0.96), regardless of sex (P=0.44), age (P=0.90) and location (P=1). GNAS mutations were not detected in any other fibro-osseous lesions. The GNAS mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of GNAS mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.Modern Pathology advance  online publication, 1 February 2013; doi:10.1038/modpathol.2012.223.




TÍTULO / TITLE:  - Critical appraisal of volumetric-modulated arc therapy compared with electrons for the radiotherapy of cutaneous Kaposi’s sarcoma of lower extremities with bone sparing.

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

REVISTA / JOURNAL:  - Br J Radiol. 2013 Mar;86(1023):20120543. doi: 10.1259/bjr.20120543. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1259/bjr.20120543

AUTORES / AUTHORS:  - Nicolini G; Abraham S; Fogliata A; Jordaan A; Clivio A; Vanetti E; Cozzi L

INSTITUCIÓN / INSTITUTION:  - Medical Physics Unit, Radiotherapy Department, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. giorgia.nicolini@eoc.ch

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate the use of volumetric-modulated arc therapy [VMAT, RapidArc® (RA); Varian Medical Systems, Palo Alto, CA] for the treatment of cutaneous Kaposi’s sarcoma (KS) of lower extremities with adequate target coverage and high bone sparing, and to compare VMAT with electron beam therapy. METHODS: 10 patients were planned with either RA or electron beams. The dose was  prescribed to 30 Gy, 10 fractions, to mean the planning target volume (PTV), and  significant maximum dose to bone was limited to 30 Gy. Plans were designed for 6-MV photon beams for RA and 6 MeV for electrons. Dose distributions were computed with AcurosXB® (Varian Medical Systems) for photons and with a Monte Carlo algorithm for electrons. RESULTS: V(90%) was 97.3+/-1.2 for RA plans and 78.2+/-2.6 for electrons; similarly, V(107%) was 2.5+/-2.2 and 37.7+/-3.4, respectively. RA met coverage criteria. Concerning bone sparing, D(2%) was 29.6+/-1.1 for RA and 31.0+/-2.4 for electrons. Although acceptable for bone involvement, pronounced target coverage violations were obtained for electron plans. Monitor units were similar for electrons and RA, although for the latter they increased when superior bone sparing was imposed. Delivery times were 12.1+/-4.0 min for electrons and 4.8+/-1.3 min for the most modulated RA plans. CONCLUSION: High plan quality was shown for KS in the lower extremities using VMAT, and this might simplify their management in comparison with the more conventional usage of electrons, particularly in institutes with limited staff resources and heavy workloads. ADVANCES IN KNOWLEDGE: VMAT is also dosimetrically extremely advantageous in a typology of treatments where electron beam therapy is mainly considered to be effective owing to the limited penetration of the beams.




TÍTULO / TITLE:  - Overexpression of Integrin-beta1 in Leiomyoma Promotes Cell Spreading and Proliferation.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3647

AUTORES / AUTHORS:  - Chen HM; Lin YH; Cheng YM; Wing LY; Tsai SJ

INSTITUCIÓN / INSTITUTION:  - Institute of Basic Medical Sciences (H.-M.C., L.-Y.C.W., S.-J.T.) and Departments of Physiology (Y.-H.L., L.-Y.C.W., S.-J.T.) and Obstetrics and Gynecology (Y.-M.C.), College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.

RESUMEN / SUMMARY:  - Context:Uterine leiomyoma, the most common tumors found in the women of the reproductive age, may cause abnormal uterine bleeding and be life threatening. Compared with myometrium, leiomyoma contains excessive extracellular matrix (ECM). However, the pathological roles of ECM in the development of leiomyoma remain largely unknown. Integrins are the major adhesion molecules on cell surface to interact with ECM. The interactions of ECM with integrins regulate cell adhesion and initiate signals for cell growth, differentiation, and migration.Objective:The aim of this study was to investigate the expression and functional role of integrin-beta1 in leiomyoma pathogenesis.Design:Levels of integrin-beta1 protein were determined by Western blotting in paired normal and leiomyomal tissues (n = 15). Knockdown of integrin-beta1 and inhibition of ECM-integrin interaction by disintegrin were used to evaluate the impact of integrin-beta1 in cell adhesion, spreading, and proliferation.Results:Levels of integrin-beta1 were significantly up-regulated in leiomyomal cells compared with  their normal counterparts. Knockdown of integrin-beta1 did not affect cell adhesion on fibronectin or laminin matrix but significantly inhibits cell spreading ability. Consistent with this notion, the phosphorylation of focal adhesion kinase and the recruitment of paxillin to the focal contact were decreased in integrin-beta1 knockdown cells, which attenuates contraction force.  The inability of cell spreading leads to inhibition of cyclin D1 expression and impedes cell cycle progression. More importantly, disruption of ECM-integrin interaction by the small protein, disintegrin inhibited cyclin D1 expression and  cell proliferation.Conclusion:These data demonstrate that integrin-beta1 is a critical ligand to enhance cell-ECM contact force and thus promotes cell proliferation. Disruption of ECM-integrin-beta1 signaling may serve as an option  to inhibit the progression of leiomyoma.




TÍTULO / TITLE:  - Chemical constituents of volatile oil from Pyrolae herba and antiproliferative activity against SW1353 human chondrosarcoma cells.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Apr;42(4):1452-8. doi: 10.3892/ijo.2013.1816. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1816

AUTORES / AUTHORS:  - Cai L; Ye H; Li X; Lin Y; Yu F; Chen J; Li H; Liu X

INSTITUCIÓN / INSTITUTION:  - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China.

RESUMEN / SUMMARY:  - The objective of the present study was to identify chemical constituents of volatile oil from Pyrolae herba (PHVO) and evaluate the antiproliferative activity of PHVO against SW1353 human chondrosarcoma cells. The volatile oil from Pyrolae herba was prepared by hydrodistillation and characterized by gas chromatography-mass spectroscopy (GC-MS). A total of 12 components in PHVO were identified representing 81.62% of the total integrated chromatographic peaks. The major compounds were found to be n-hexadecanoic acid (29.29%), cedrol (17.08%), 6,10,14-trimethyl-2-pentadecanone (9.59%) and cis-9-octadecadienoic acid (8.23%). The antiproliferative activity of PHVO against SW1353 cells was investigated using MTT assay, flow cytometry and western blot analysis. Our results demonstrated that PHVO inhibited SW1353 cell viability in a dose- and time-dependent manner. Furthermore, PHVO treatment decreased the number of cells  entering the S phase and caused a reduction in the expression of cyclin D1, cyclin-dependent kinase (CDK)4 and CDK6, whereas it caused an increase in the expression of p21. PHVO demonstrated potent antitumor activity against SW1353 cells, suggesting its potential use as a therapeutic agent in the treatment of chondrosarcoma.




TÍTULO / TITLE:  - Silencing SATB1 inhibits proliferation of human osteosarcoma U2OS cells.

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

REVISTA / JOURNAL:  - Mol Cell Biochem. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1591-0

AUTORES / AUTHORS:  - Zhang H; Qu S; Li S; Wang Y; Li Y; Wang Y; Wang Z; Li R

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of  Medicine, Jilin University, Changchun, 130021, People’s Republic of China.

RESUMEN / SUMMARY:  - It has been shown that over-expression of Special AT-rich binding protein 1 (SATB1) in breast cancer predicts a poor prognosis. This study was aimed at investigating the effects of silencing SATB1 on mesenchymal derived human osteosarcoma U2OS cells and the underlying mechanisms. The expressions of SATB1 and the related genes in the cells were detected by qRT-PCR and/or Western Blotting. SATB1 silencing was achieved by stable transfection with the vectors expressing small hairpin RNA versus SATB1. Cell proliferation was detected in a microplate reader with Cell Counting Kit-8 and the cell cycle was analyzed by flow cytometry using a cell cycle detection kit. The study found that SATB1 was particularly over-expressed in human osteosarcoma U2OS. Silencing SATB1 inhibited the proliferation of U2OS. It was found that inhibition of cell proliferation resulted from cell cycle arrest due to down-regulated expression of CFGF and JunB. The over-expression of SATB1 is responsible for abnormal proliferation of mesenchymal derived human Osteosatcoma U2OS cells, indicating that silencing SATB1 expression in the cells might be developed as an efficient osteosarcoma therapy. CTGF and JunB were involved in SATB1-mediated proliferation of U2OS cells.




TÍTULO / TITLE:  - Pediatric mast cell sarcoma of temporal bone with novel L799F (2395 C>T) KIT mutation, mimicking histiocytic neoplasm.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Mar;37(3):453-8. doi: 10.1097/PAS.0b013e31828446d6.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e31828446d6

AUTORES / AUTHORS:  - Kim YS; Wu H; Pawlowska AB; Bautista-Quach MA; Huang Q; Gaal K; Chang KL

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010,  USA. ykim@coh.org

RESUMEN / SUMMARY:  - Mast cell sarcoma (MCS) is an extremely rare neoplasm with a clinically aggressive course. Because of its rarity, its morphologic and molecular characteristics are still not well defined. We report a case of a 15-year-old girl with MCS of the temporal bone extending into the posterior fossa creating a  mass effect. The lesion mimicked a histiocytic neoplasm morphologically, but showed a novel KIT missense mutation, L799F (2395 C>T). The KIT D816V mutation is frequently found in systemic mastocytosis, but it has not been documented in the  few reported human MCS cases. However, 1 reported case of MCS has shown a different alteration in the KIT gene. Our case is the first MCS case with L799F mutation, located between the catalytic loop (790 to 797) and the activation loop (810 to 837) of the KIT gene, and only the second case of MCS with KIT mutation documented in the literature. Proximity of the L799F mutation to the enzymatic region of the KIT tyrosine kinase domain may induce resistance to tyrosine kinase inhibitors.




TÍTULO / TITLE:  - Epigenetically induced changes in nuclear textural patterns and gelatinase expression in human fibrosarcoma cells.

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

REVISTA / JOURNAL:  - Cell Prolif. 2013 Apr;46(2):127-36. doi: 10.1111/cpr.12021.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cpr.12021

AUTORES / AUTHORS:  - Poplineau M; Doliwa C; Schnekenburger M; Antonicelli F; Diederich M; Trussardi-Regnier A; Dufer J

INSTITUCIÓN / INSTITUTION:  - Unite MEDyC, URCA-CNRS FRE 3481, SFR Cap-Sante, Faculte de Pharmacie, Universite  de Reims, Reims, France.

RESUMEN / SUMMARY:  - OBJECTIVE: Chromatin texture patterns of tumour cell nuclei can serve as cancer biomarkers, either to define diagnostic classifications or to obtain relevant prognostic information, in a large number of human tumours. Epigenetic mechanisms, mainly DNA methylation and histone post-translational modification, have been shown to influence chromatin packing states, and therefore nuclear texture. The aim of this study was to analyse effects of these two mechanisms on  chromatin texture, and also on correlation with gelatinase expression, in human fibrosarcoma tumour cells. MATERIALS AND METHODS: We investigated effects of DNA  hypomethylating agent 5-aza-2’-deoxycytidine (5-azadC) and histone deacetylase inhibitor trichostatin A (TSA) on nuclear textural characteristics of human HT1080 fibrosarcoma cells, evaluated by image cytometry, and expression of gelatinases MMP-2 and MMP-9, two metalloproteinases implicated in cancer progression and metastasis. RESULTS: 5-azadC induced significant variation in chromatin higher order organization, particularly chromatin decondensation, associated with reduction in global DNA methylation, concomitantly with increase  in MMP-9, and to a lesser extent, MMP-2 expression. TSA alone did not have any effect on HT1080 cells, but exhibited differential activity when added to cells treated with 5-azadC. When treated with both drugs, nuclei had higher texture abnormalities. In this setting, reduction in MMP-9 expression was observed, whereas MMP-2 expression remained unaffected. CONCLUSIONS: These data show that hypomethylating drug 5-azadC and histone deacetylase inhibitor TSA were able to induce modulation of higher order chromatin organization and gelatinase expression in human HT1080 fibrosarcoma cells.




TÍTULO / TITLE:  - The Combination of Sorafenib and Everolimus abrogates mTORC-1 and mTORC2 up-regulation in preclinical models of Osteosarcoma.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2293

AUTORES / AUTHORS:  - Pignochino Y; Dell’aglio C; Basirico M; Capozzi F; Soster M; Marchio S; Bruno S; Gammaitoni L; Sangiolo D; Torchiaro E; D’Ambrosio L; Fagioli F; Ferrari S; Alberghini M; Picci P; Aglietta M; Grignani G

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment.

RESUMEN / SUMMARY:  - PURPOSE: The multikinase inhibitor sorafenib displays antitumor activity in preclinical models of osteosarcoma. However, in sorafenib-treated metastatic-relapsed osteosarcoma patients, disease stabilization and tumor shrinkage were short-lived and drug resistance occurred. We explored the sorafenib treatment escape mechanisms to overcome their drawbacks. Experimental design: Immunoprecipitation, Western blotting, and immunohistochemistry were employed to analyze the mammalian target of rapamycin (mTOR) pathway (mTORC1 and  mTORC2). Cell viability, colony growth, and cell migration were evaluated in different osteosarcoma cell lines (MNNG-HOS, HOS, KHOS/NP, MG63, U-2OS, SJSA-1, SAOS-2) after scalar dose treatment with sorafenib (10-0.625 muM), rapamycin-analog everolimus (100-6.25 nM), and combinations of the two. Cell cycle, reactive oxygen species (ROS) production, and apoptosis were assessed by flow cytometry. NOD/SCID mice injected with MNNG-HOS cells were utilized to determine anti-tumor and anti-metastatic effects. Angiogenesis and vascularization were evaluated in vitro by exploiting endothelial branching morphogenesis assays and in vivo in xenografted mice and chorioallantoic membranes. RESULTS: After sorafenib treatment, mTORC1 signaling was reduced (downstream target P-S6) while mTORC2 was increased (phospho-mTOR Ser2481) in MNNG-HOS xenografts compared to vehicle-treated mice. Combining sorafenib with everolimus resulted in complete abrogation of both mTORC1 (through ROS-mediated AMPK activation) and mTORC2 (through complex disassembly). The sorafenib/everolimus combination yielded: 1) enhanced anti-proliferative and pro-apoptotic effects, 2) impaired tumor growth, 3) potentiated anti-angiogenesis, and 4) reduced migratory and metastatic potential. CONCLUSION: mTORC2 activation is an escape mechanism from sorafenib treatment. When sorafenib is combined with everolimus, its anti-tumor activity is increased by complete inhibition of the mTOR pathway in the preclinical setting.




TÍTULO / TITLE:  - Osteoblastic potency of bone marrow cells cultivated on functionalized biometals  with cyclic RGD-peptide.

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

REVISTA / JOURNAL:  - J Biomed Mater Res A. 2013 Mar 25. doi: 10.1002/jbm.a.34590.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jbm.a.34590

AUTORES / AUTHORS:  - Jager M; Boge C; Janissen R; Rohrbeck D; Hulsen T; Lensing-Hohn S; Krauspe R; Herten M

INSTITUCIÓN / INSTITUTION:  - Orthopaedic Department, University of Duisburg-Essen, Germany; Orthopaedic Department, Heinrich-Heine-University Medical School, Dusseldorf, Germany.

RESUMEN / SUMMARY:  - The fixation of cementless endoprostheses requires excellent fixation at the bone implant interface. Although the surface structures of these implants are designed to promote osteoblastic differentiation, poor bone quality may prevent or delay osseointegration. There is evidence that RGD peptides known as recognition motifs for various integrins, promote cellular adhesion, influence cellular proliferation, and differentiation of local cells. In this study, five different  metal surfaces were analyzed: Sandblasted (TiSa) and polished (TiPol) Ti6Al4V, porocoated (CCPor) and polished (CCPol) cobalt chrome and polished stainless steel (SS) were coated by ethanol amine and poly(ethylene glycol) to attach covalently RGD peptides. Human mesenchymal stromal cells of healthy donors were cultivated onto prior functionalized metal surfaces for 14 days without osteogenic stimulation. Cell proliferation and differentiation were quantitatively evaluated for native (I), NaOH pre-activated (II), NaOH pre-activated, and PEG-coated (III) as well as for RGD (IV) coated surfaces. The  RGD immobilization efficiency was analyzed by epi-fluorescence spectroscopy, cell morphology was documented by light and scanning electron microscopy. The RGD-binding efficiency was TiSa > TiPol > SS > CCPor > CCPol. RGD coated surfaces showed the highest average cell proliferation on CCPol > SS > CCPor > TiSa >/= TiPol, whereas cellular differentiation mostly correlated with the observed proliferation results, such as CCPol > TiSa > SS > CCPor > TiPol. Considering statistical analyses (significance level of alpha = 0.05), the RGD-coating of all biometals in comparison and in respect of their particular controls showed no significant improvement in cellular proliferation and osteoblastic differentiation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.




TÍTULO / TITLE:  - NAD(P)H Quinone Oxidoreductase 1 (NQO1)-Bioactivated Pronqodine A Regulates Prostaglandin Release from Human Synovial Sarcoma Cells.

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

REVISTA / JOURNAL:  - J Nat Prod. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1021/np300643f

AUTORES / AUTHORS:  - Nakae K; Adachi H; Sawa R; Hosokawa N; Hatano M; Igarashi M; Nishimura Y; Akamatsu Y; Nomoto A

INSTITUCIÓN / INSTITUTION:  - Institute of Microbial Chemistry (BIKAKEN) , 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

RESUMEN / SUMMARY:  - Natural products have contributed to the elucidation of biological mechanisms as  well as drug discovery research. Even now, the expectation for natural products is undiminished. We screened prostaglandin release inhibitors that had no effect  on in vitro cyclooxygenase activity derived from natural product sources and discovered pronqodine A. Using spectral analysis and total synthesis, the structure of pronqodine A was shown to be a benzo[d]isothiazole-4,7-dione analogue. Evaluation of the biological activity of pronqodine A revealed that the NAD(P)H dehydrogenase quinone 1 (NQO1) converted pronqodine A into a two-electron reductive form. The reductive form underwent autoxidation and reversed to its native form immediately with the generation of reactive oxygen species. Further investigations proved that pronqodine A inhibited cyclooxygenase enzyme activity  only in the presence of NQO1. Pronqodine A acts as a potential bioreductive compound, inhibiting prostaglandin release in selectively activated NQO1-expressing cells.




TÍTULO / TITLE:  - Extracellular domain c-kit mutation with duplication of Ser501Ala502 found in gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than that with duplication of Ala502Tyr503.

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

REVISTA / JOURNAL:  - Lab Invest. 2013 Mar 4. doi: 10.1038/labinvest.2013.43.

            ●● Enlace al texto completo (gratuito o de pago) 1038/labinvest.2013.43

AUTORES / AUTHORS:  - Liu NN; Ohkouchi M; Hashikura Y; Kajimoto N; Matsuda I; Isozaki K; Toh Y; Takahashi T; Nishida T; Hirota S

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.

RESUMEN / SUMMARY:  - The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene, which encodes KIT receptor tyrosine kinase. Most of the mutations are located at exon 11, but some are at exon 9 or at other exons. Mutation types at exon 11 vary, while most mutations at exon 9 are a particular duplication of Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently a duplication of Ser501Ala502 (KIT-Dup-Ser501Ala502) at exon 9 has been reported in two cases of pediatric mastocytosis and one case of adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not been reported in GISTs, we found two GIST cases possessing the mutation in 45 GIST cases with exon 9 c-kit gene mutations,  among a total of approximately 500 GIST cases examined. In this report, we briefly summarize clinicopathological findings of the two cases, and characterize the biology of the mutation. When autophosphorylation of KIT-Dup-Ser501Ala502 was examined by transient transfection of c-kit cDNA with Dup-Ser501Ala502 into CHO-K1 cells, KIT-Dup-Ser501Ala502 was ligand-independently activating. The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation of KIT-Dup-Ser501Ala502 at a concentration of 0.1 muM, whereas it inhibited that of  KIT-Dup-Ala502Tyr503 at a concentration of 10 muM. Constitutive activation of KIT-Dup-Ser502Ala503 was not inhibited by nilotinib even at a concentration of 10 muM but that of KIT-Dup-Ala501Tyr502 was almost completely inhibited at a concentration of 1 muM. The results suggest that imatinib and nilotinib could be  more effective on GISTs with KIT-Dup-Ser501Ala502 than those with KIT-Dup-Ala502Tyr503. In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503.Laboratory Investigation advance online publication, 4 March 2013; doi:10.1038/labinvest.2013.43.




TÍTULO / TITLE:  - Similarities in the Endocrine-Disrupting Potencies of Indoor Dust and Flame Retardants by Using Human Osteosarcoma (U2OS) Cell-Based Reporter Gene Assays.

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

REVISTA / JOURNAL:  - Environ Sci Technol. 2013 Mar 19;47(6):2898-908. doi: 10.1021/es304691a. Epub 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1021/es304691a

AUTORES / AUTHORS:  - Suzuki G; Tue NM; Malarvannan G; Sudaryanto A; Takahashi S; Tanabe S; Sakai S; Brouwer A; Uramaru N; Kitamura S; Takigami H

INSTITUCIÓN / INSTITUTION:  - Center for Material Cycles and Waste Management Research, National Institute for  Environmental Studies , Tsukuba, Japan, Tsukuba 305-8506, Japan.

RESUMEN / SUMMARY:  - Indoor dust is a sink for many kinds of pollutants, including flame retardants (FRs), plasticizers, and their contaminants and degradation products. These pollutants can be migrated to indoor dust from household items such as televisions and computers. To reveal high-priority end points of and contaminant  candidates in indoor dust, using CALUX reporter gene assays based on human osteosarcoma (U2OS) cell lines, we evaluated and characterized the endocrine-disrupting potencies of crude extracts of indoor dust collected from Japan (n = 8), the United States (n = 21), Vietnam (n = 10), the Philippines (n = 17), and Indonesia (n = 10) and for 23 selected FRs. The CALUX reporter gene assays used were specific for compounds interacting with the human androgen receptor (AR), estrogen receptor alpha (ERalpha), progesterone receptor (PR), glucocorticoid receptor (GR), and peroxisome proliferator-activated receptor gamma2 (PPARgamma2). Indoor dust extracts were agonistic to ERalpha, GR, and PPARgamma2 and antagonistic against AR, PR, GR, and PPARgamma2. In comparison, a  majority of FRs was agonistic to ERalpha and PPARgamma2 only, and some FRs demonstrated receptor-specific antagonism against all tested nuclear receptors. Hierarchical clustering clearly indicated that agonism of ERalpha and antagonism  of AR and PR were common, frequently detected end points for indoor dust and tested FRs. Given our previous results regarding the concentrations of FRs in indoor dust and in light of our current results, candidate contributors to these  effects include not only internationally controlled brominated FRs but also alternatives such as some phosphorus-containing FRs. In the context of indoor pollution, high-frequency effects of FRs such as agonism of ERalpha and antagonism of AR and PR are candidate high-priority end points for further investigation.




TÍTULO / TITLE:  - Familial multiple discoid fibromas: unique histological features and therapeutic  response to topical rapamycin.

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

REVISTA / JOURNAL:  - Br J Dermatol. 2013 Mar 18. doi: 10.1111/bjd.12315.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bjd.12315

AUTORES / AUTHORS:  - Wee JS; Chong H; Natkunarajah J; Mortimer PS; Moosa Y

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, St George’s Hospital, London, U.K.

RESUMEN / SUMMARY:  - Familial multiple discoid fibromas (FMDF) is a rare genodermatosis that bears some resemblance to Birt-Hogg-Dube syndrome (BHD) but is not associated with FLCN (folliculin) mutations or systemic manifestations. It is characterised by the development of papules over the face and pinnae early in life. Histological findings are fibrovascular tumours adjacent to hair follicles without the features of fibrofolliculomas, which have been termed discoid fibromas. We present siblings with multiple papules over the face and pinnae that developed in childhood. Histological specimens from both siblings demonstrated discoid fibromas, but with some lesions exhibiting an unusual keloidal-like pattern with  thick hyalinised collagen fibres surrounded by plump spindle and histiocyte-like  cells. FLCN gene mutations were not found. We report on clinical improvement with topical rapamycin solution (1mg/1ml) applied daily to the face for 4 months. Therapeutic response to topical rapamycin may provide a clue to the underlying genetic basis of this condition.




TÍTULO / TITLE:  - Efficacy and safety of daily repeated sonographically guided high-intensity focused ultrasound treatment of uterine fibroids: preliminary study.

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

REVISTA / JOURNAL:  - J Ultrasound Med. 2013 Mar;32(3):397-406.

AUTORES / AUTHORS:  - Cho JY; Kim SH; Kim SY; Moon SK; Li J

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Seoul National University College of Medicine, Seoul 110-744, Korea. radjycho@snu.ac.kr

RESUMEN / SUMMARY:  - OBJECTIVES: To evaluate the efficacy and safety of repeated low-dose sonographically guided high-intensity focused ultrasound (HIFU) treatment of uterine fibroids. METHODS: Between April and December 2010, 24 consecutive premenopausal women with symptomatic uterine fibroids were enrolled in this study. The treatment was performed with an HIFU unit without anesthesia or sedative administration and Foley catheter insertion. The treatment was performed 40 to 70 min/d according to the tumor volume. The entire treatment was finished after 4 to 6 days of treatment. We assessed the differences in the symptom severity score, tumor volume, and contrast-enhanced volume at baseline and 1 and  3 months after treatment. The clinical success rates according to tumor volume and contrast-enhanced volume reductions and echogenicity and vascular flow changes were analyzed. The clinical success rates according to the baseline characteristics of fibroids were analyzed. We assessed adverse events during and  after treatment. RESULTS: The symptom severity score, tumor volume, and contrast-enhanced volume decreased significantly after repeated low-dose HIFU treatment (P < .05). There were significant correlations between tumor volume and contrast-enhanced volume reduction and the decrease in the symptom severity score. The clinical success rates were significantly different according to the tumor vascularity on color Doppler sonography and the degree of enhancement on magnetic resonance imaging. Skin burns and other serious adverse events did not develop. CONCLUSIONS: Although this preliminary report had several limitations, daily repeated HIFU treatment of uterine fibroids may be a useful and safe method and can be used as a different option for HIFU treatment in patients who prefer treatment without anesthesia or sedation.




TÍTULO / TITLE:  - CT-based response assessment of advanced gastrointestinal stromal tumor: Dual energy CT provides a more predictive imaging biomarker of clinical benefit than RECIST or Choi criteria.

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

REVISTA / JOURNAL:  - Eur J Radiol. 2013 Feb 11. pii: S0720-048X(13)00016-8. doi: 10.1016/j.ejrad.2013.01.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.01.006

AUTORES / AUTHORS:  - Meyer M; Hohenberger P; Apfaltrer P; Henzler T; Dinter DJ; Schoenberg SO; Fink C

INSTITUCIÓN / INSTITUTION:  - Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Electronic address: mr.meyer.mathias@gmail.com.

RESUMEN / SUMMARY:  - OBJECTIVES: Dual-energy CT (DECT) allows quantification of intravenously injected iodinated contrast media in tumors, and therefore may be considered as a surrogate marker for perfusion and tumor vascularity. This study evaluated whether newly developed DECT response criteria allow better correlation with survival than established response criteria. METHODS: Seventeen patients with advanced GIST treated with tyrosine-kinase-inhibitors were assessed by contrast-enhanced DECT 2 and 6 months after beginning of treatment. Response to treatment of 165 tumor lesions was evaluated according to RECIST, Choi criteria and newly developed DECT criteria, defining non-responders as an increase of both tumor size >20% and iodine related attenuation or either a >50% increase of tumor size or iodine related attenuation. All other patients were classified as responders. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier analysis. RESULTS: Choi criteria and DECT showed a significantly longer median PFS of patients rated as responders than patients rated as non-responders (9-29 months vs. 2-6 months; p<0.02) at follow-up. Only DECT analysis at 6 months follow-up allowed a valid prediction of OS. CONCLUSION: This study indicates that DECT allows a better prediction of therapeutic benefit  in advanced GIST patients treated with tyrosine-kinase-inhibitors than established response criteria. However, the most important predictive biomarker of therapeutic benefit was absence of progression, no matter which response evaluation criteria were applied.




TÍTULO / TITLE:  - Solitary Fibrous Tumor of the Sinonasal Cavity: CT and MR Imaging Findings.

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

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3485

AUTORES / AUTHORS:  - Yang BT; Song ZL; Wang YZ; Dong JY; Wang ZC

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China; and Department of Radiology, Zaozhuang Municipal Hospital, Shandong Province, China.

RESUMEN / SUMMARY:  - SUMMARY:SFT is a rare lesion of the sinonasal cavity. We retrospectively reviewed 5 patients with histopathologically proved sinonasal SFTs to determine their CT and MR imaging features. All patients underwent paranasal sinus CT and MR imaging. Four SFTs occurred in the nasal cavity, and 1, in the maxillary sinus. All SFTs had well-defined margins, and the mean maximum diameter was 55 mm. On nonenhanced CT, 5 SFTs appeared homogeneously isoattenuating to gray matter. The  most common manifestations of bony involvement were bony remodeling and thinning. On MR imaging, 5 SFTs were isointense to gray matter on T1-weighted images, and the lesions were isointense in 3 and hypointense in 2 patients on T2-weighted images. The lesions showed heterogeneously marked enhancement on postenhanced MR  images. Four patients underwent dynamic contrast-enhanced MR imaging, and the TICs showed a washout pattern. A familiarity with the imaging findings of sinonasal SFT may help to diagnose this entity.




TÍTULO / TITLE:  - Effect of long term imatinib on bone in adults with chronic myelogenous leukemia  and gastrointestinal stromal tumors.

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

REVISTA / JOURNAL:  - Leuk Res. 2013 Mar 5. pii: S0145-2126(13)00043-X. doi: 10.1016/j.leukres.2013.02.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.02.005

AUTORES / AUTHORS:  - Berman E; Girotra M; Cheng C; Chanel S; Maki R; Shelat M; Strauss HW; Fleisher M; Heller G; Farooki A

INSTITUCIÓN / INSTITUTION:  - Leukemia Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, USA. Electronic address: bermane@mskcc.org.

RESUMEN / SUMMARY:  - Patients with chronic myelogenous leukemia (CML) or gastrointestinal stromal tumors (GIST) who take imatinib have abnormalities of bone metabolism. However, it is unclear what impact these changes have on bone mineral density (BMD). We prospectively analayzed levels of osteocalcin, a marker of bone formation secreted by osteoblasts, and serum N-telopeptide of type I collagen (NTX), a marker of bone resorption, as well as other minerals involved in bone metabolism  in 19 patients with either CML or GIST We correlated these results with changes in bone mineral density as measured by serial dual energy X-ray absorptiometry (DEXA) scans over a two year period. Osteocalcin levels were low in 95% of patients and 37% had no measurable amount. Levels of NTX were less consistent. Nine patients (47%) had a decrease in BMD, four patients (2%) had an increase in  BMD, and six patients (32%) had no change. There was no correlation between metabolic markers and change in BMD. We suggest that ongoing management of patients who take imatinib should include monitoring of bone health on a long term basis.




TÍTULO / TITLE:  - Designing novel therapies against sarcomas in the era of personalized medicine and economic crisis.

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

REVISTA / JOURNAL:  - Curr Pharm Des. 2013 Feb 4.

AUTORES / AUTHORS:  - Manara MC; Garofalo C; Ferrari S; Belfiore A; Scotlandi K

INSTITUCIÓN / INSTITUTION:  - Development of Biomolecular therapies, Experimental Oncology Lab and 2Clinical Oncology, Via Di Barbiano 1/10, 40136 Rizzoli Institute, Bologna, Italy. katia.scotlandi@ior.it.

RESUMEN / SUMMARY:  - Drug “repurposing” is the process of finding new therapeutic indications for existing drugs, and can be considered as a more efficient and realistic strategy  for the design of therapies against rare diseases than the current efforts to develop targeted-drugs. In this review, we explore the difficulties related to the identification and development of tailored therapies for individual patients  with sarcomas, which are relatively rare diseases characterized by an extreme genetic and histologic variability. Overall, sarcomas comprise about 1% of all adult tumors and 10% of pediatric cancers. They are conventionally divided in bone and soft-tissue sarcomas, considering their site of origin. However, each group is highly heterogeneous and recent global characterization of their genetic alterations has clearly identified the existence of peculiarities that render these group of tumors even more “orphan” for pharmaceutical companies to develop  and market specific- targeted drugs. The present review highlights key examples of molecular targets identification in bone sarcomas, reexamining the history of  insulin-like growth factor receptor (IGF-IR) and its role in physiology and in cancer as well as developments regarding phase I to II clinical trials of agents  directed against this receptor. The IGF system is quite complex, with many players in the field. Insulin receptor function in cancer cells has certainly been underestimated, but also little attention was paid to the type of ligands that are mainly involved in each tumor type. Strategies considering the system in its complex are encouraged and, in this context, drugs aimed at reducing circulating insulin levels, such as metformin, should receive attention as potential anti-cancer agents.




TÍTULO / TITLE:  - Variable ALK protein and ALK gene staining in inflammatory myofibroblastic tumors.

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

REVISTA / JOURNAL:  - Pediatr Dev Pathol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 2350/13-03-1311-LET.1


INSTITUCIÓN / INSTITUTION:  - University of Rochester Medical Center, Department of Pathology and Laboratory Medicine.

RESUMEN / SUMMARY:  - Abstract Not applicable.




TÍTULO / TITLE:  - Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing’s sarcoma.

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

REVISTA / JOURNAL:  - Electrophoresis. 2013 Mar 11. doi: 10.1002/elps.201200661.

            ●● Enlace al texto completo (gratuito o de pago) 1002/elps.201200661

AUTORES / AUTHORS:  - Haga A; Ogawara Y; Kubota D; Kitabayashi I; Murakami Y; Kondo T

INSTITUCIÓN / INSTITUTION:  - Division of Pharmacoproteomics, National Cancer Center Research Institute, 5-1-1  Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Faculty of Industrial Science and Technology, Department of Biological Science and Technology, Tokyo University of  Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan.

RESUMEN / SUMMARY:  - Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing’s sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to  characterize the NPM protein complex in Ewing’s sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing’s sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing’s sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing’s sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing’s sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery.




TÍTULO / TITLE:  - RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects.

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

REVISTA / JOURNAL:  - J Rheumatol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 3899/jrheum.120845

AUTORES / AUTHORS:  - Corrado A; Neve A; Macchiarola A; Gaudio A; Marucci A; Cantatore FP

INSTITUCIÓN / INSTITUTION:  - From the Rheumatology Clinic, Department of Medical and Occupational Sciences, University of Foggia; Orthopedic Surgery Unit, Ospedali Riuniti di Foggia, Foggia, Italy.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate the expression of Dickkopf-1 protein factor (DKK-1), DKK-2, and beta-catenin, components of the Wnt pathway, in human osteoarthritic (OA) and osteoporotic (OP) osteoblasts and to correlate it to cell metabolic activity, proliferation, and receptor activator of nuclear factor-kappaB ligand/osteoprotegerin (RANKL/OPG) expression. METHODS: Primary human osteoblast  cultures were obtained from healthy, OA, and OP donors. In each cell population we evaluated DKK-1, DKK-2, nonphosphorylated beta-catenin and RANKL/OPG expression, osteocalcin and alkaline phosphatase (ALP) synthesis, and cell proliferation, both in basal condition and after vitamin D3 stimulation. RESULTS: DKK-1 and DKK-2 showed opposite patterns of expression in OA and OP osteoblasts.  The RANKL/OPG ratio was significantly higher in the OP group because of a greater expression of RANKL, whereas it was significantly lower in the OA group because of a higher expression of OPG. Treatment with vitamin D3 increased the RANKL/OPG  ratio and DKK-2 expression and reduced DKK-1 expression in each cell population,  but did not affect beta-catenin levels. Both osteocalcin and ALP production and cell proliferation were enhanced in OA cells and reduced in the OP ones. CONCLUSION: These data confirm that OA and OP are characterized by opposite bone  changes, consisting of reduced bone remodeling processes with increased osteoblast activity in OA, and enhanced bone resorptive activity with reduction of osteoblast metabolism in OP, and suggest that the Wnt pathway is involved in the pathogenesis of both diseases.




TÍTULO / TITLE:  - Induction of apoptosis in osteosarcoma s180 cells by polysaccharide from dictyophora indusiata.

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

REVISTA / JOURNAL:  - Cell Biochem Funct. 2013 Feb 10. doi: 10.1002/cbf.2961.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cbf.2961

AUTORES / AUTHORS:  - Zhong B; Ma Y; Fu D; Zhang C

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedic Surgery, Shanghai 6th People’s Hospital, Shanghai Jiao  Tong University, Shanghai, China.

RESUMEN / SUMMARY:  - Polysaccharides have shown great importance in cancer therapy. The current study  showed that a polysaccharide from Dictyophora indusiata (PDI) also possessed anti-cancer properties. Methyl thiazolyl tetrazolium assay revealed a dose-dependent reduction of osteosarcoma S180 growth in response to PDI treatment. Apoptosis was observed following treatments with PDI, as reflected by  the appearance of the subdiploid fraction and DNA fragmentations. We then investigated effects of PDI on expression of apoptosis-associated genes and the results revealed an increase of expression of bcl-2 and decreases of cdk4 and p53 protein levels. Finally, PDI treatment significantly increased the activation of  caspase-3, a key executioner of apoptosis. These findings indicate that PDI may act as a chemopreventive and/or chemotherapeutic agent in osteosarcoma cells by reducing cell viability and inducing apoptosis. Copyright © 2013 John Wiley & Sons, Ltd.




TÍTULO / TITLE:  - Racial differences in fibroid prevalence and ultrasound findings in asymptomatic  young women (18-30 years old): a pilot study.

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

REVISTA / JOURNAL:  - Fertil Steril. 2013 Mar 15. pii: S0015-0282(13)00274-4. doi: 10.1016/j.fertnstert.2013.02.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.fertnstert.2013.02.017

AUTORES / AUTHORS:  - Marsh EE; Ekpo GE; Cardozo ER; Brocks M; Dune T; Cohen LS

INSTITUCIÓN / INSTITUTION:  - Division of Reproductive Endocrinology and Infertility, Department of Obstetrics  and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: erica-marsh@northwestern.edu.

RESUMEN / SUMMARY:  - OBJECTIVE: 1) To determine the prevalence of fibroids in asymptomatic young black and white women (ages 18-30 y); 2) to determine other differences in uterine and  adnexal anatomy; and 3) to obtain preliminary data for sample size calculations.  DESIGN: Pilot cross-sectional study. SETTING: Academic medical center. PATIENT(S): One hundred one nonparous black and white women, ages 18-30 years, with no known diagnosis of fibroids or clinically suggestive symptoms. INTERVENTION(S): A transvaginal ultrasound was performed in the follicular phase  in all subjects. MAIN OUTCOME MEASURE(S): 1) Presence of fibroids; 2) endometrial thickness; 3) ovarian findings. RESULT(S): Of the 101 participants (mean age 24.5 +/- 3.5 y), 43% self-identified as black and 57% as white. The prevalence of ultrasound-diagnosed fibroids was 15% overall (26% in black women and 7% in white women). The mean fibroid size was 2.3 +/- 2.1 cm. There was a significant difference in endometrial thickness between races, even after adjusting for contraception use and fibroid presence. CONCLUSION(S): Racial differences in fibroid prevalence exist even before women become symptomatic. Findings of thicker endometrium in black women could have clinical implications and warrants  further investigation.




TÍTULO / TITLE:  - Accuracy of segmental multi-frequency bioelectrical impedance analysis for assessing whole-body and appendicular fat mass and lean soft tissue mass in frail women aged 75 years and older.

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

REVISTA / JOURNAL:  - Eur J Clin Nutr. 2013 Apr;67(4):395-400. doi: 10.1038/ejcn.2013.9. Epub 2013 Feb  6.

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


INSTITUCIÓN / INSTITUTION:  - Research Team for Promoting Independence of the Elderly, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

RESUMEN / SUMMARY:  - BACKGROUND/OBJECTIVE: We aimed to examine the accuracy of segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) for the assessment of  whole-body and appendicular fat mass (FM) and lean soft tissue mass (LM) in frail older women, using dual-energy X-ray absorptiometry (DXA) as a reference method.  SUBJECTS/METHODS: All 129 community-dwelling Japanese frail older women with a mean age of 80.9 years (range, 75-89 years) from the Frailty Intervention Trial were recruited. The agreements between SMF-BIA and DXA for whole-body and appendicular body composition were assessed using simple linear regression and Bland-Altman analysis. RESULTS: High coefficients of determination (R(2)) for whole-body FM (R(2)=0.94, s.e. of estimate (SEE)=1.2 kg), whole-body LM (R(2)=0.85, SEE=1.4 kg), and appendicular FM (R(2)=0.82, SEE=1.1 kg) were observed between SMF-BIA and DXA. The R(2) coefficient for appendicular LM was moderate (R(2)=0.76, SEE=0.8 kg). Bland-Altman plots demonstrated that there was  systematic (constant) bias (that is, DXA minus SMF-BIA) with overestimation of whole-body FM (bias=-1.2 kg, 95% confidence interval (CI)=-1.5 to -0.1) and underestimation of whole-body LM (bias=2.1 kg, 95% CI=1.8-2.3) by SMF-BIA. Similar, the appendicular measurements also demonstrated systematic bias with overestimation of appendicular FM (bias=-0.3 kg, 95% CI=-0.5 to -0.1) and underestimation of whole-body LM (bias=1.5 kg, 95% CI=1.4-1.7) by SMF-BIA. In addition, the individual level accuracy demonstrated a non-proportional bias for  whole-body LM (r=0.08, P=0.338) and appendicular FM (r=0.07, P=0.413). CONCLUSIONS: SMF-BIA had acceptable accuracy for the estimation of whole-body and appendicular FM and LM in frail older women, although SMF-BIA underestimated LM and overestimated FM relative to DXA.




TÍTULO / TITLE:  - Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases.

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

REVISTA / JOURNAL:  - Arch Gynecol Obstet. 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00404-013-2766-3

AUTORES / AUTHORS:  - Iwasaki SI; Sudo T; Miwa M; Ukita M; Morimoto A; Tamada M; Ueno S; Wakahashi S; Yamaguchi S; Fujiwara K; Sakuma Y; Mikami Y; Nishimura R

INSTITUCIÓN / INSTITUTION:  - Department of Gynecologic Oncology, Hyogo Cancer Center, 13-70 Kita-Oji, Akashi,  6738558, Japan.

RESUMEN / SUMMARY:  - PURPOSE: Endometrial stromal sarcomas (ESSs) are rare tumors and are divided into two groups: low-grade endometrial stromal sarcoma (ESS-LG) and undifferentiated endometrial sarcoma (UES). The purpose of this study was to compare the clinicopathological features and immunophenotypes of ESS-LG and UES. METHODS: The authors evaluated 16 patients diagnosed with ESS at the Hyogo Cancer Center, reviewed their files and data, and performed an immunohistochemical study for oncogenic proteins (EGFR, PDGFR-alpha, and PDGFR-beta) and cell cycle regulators  (cyclin D1, cyclin E, p16(INK4a), p21(cip1), p27(kip1), and p53) to compare ESS-LG and UES using the World Health Organization (WHO) classification. RESULTS: Four cases (25 %) were classified as ESS-LGs and 12 (75 %) as UES. Patients with  UES had a significantly worse overall survival than did those with ESS-LG (p = 0.0445). Although no ESS-LGs showed expression of p16(INK4a), 10 of 12 (83 %) UESs showed expression of p16(INK4a). UESs showed a trend toward higher expression of cyclin D1, p21(cip1), and p53 compared with ESS-LGs. CONCLUSIONS: Our data emphasize the clinical importance of the WHO classification of ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.




TÍTULO / TITLE:  - Microarray expression profile of long noncoding RNAs in human osteosarcoma.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Apr 5;433(2):200-6. doi: 10.1016/j.bbrc.2013.02.083. Epub 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.083

AUTORES / AUTHORS:  - Li JP; Liu LH; Li J; Chen Y; Jiang XW; Ouyang YR; Liu YQ; Zhong H; Li H; Xiao T

INSTITUCIÓN / INSTITUTION:  - Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha 410010, PR China.

RESUMEN / SUMMARY:  - Long noncoding RNAs (lncRNAs) are pervasively transcribed and have a critical role in genome regulation. Alterations in the expression of several lncRNAs have  been observed in some types of cancers; however, the contributions of lncRNAs to  osteosarcoma remain unknown. Here, we describe the expression profile of lncRNAs  in osteosarcomas compared with paired adjacent noncancerous tissue using microarray analysis. In our study, 25,733 lncRNAs were expressed in osteosarcoma; 403 lncRNAs were consistently over-regulated and 798 lncRNAs were consistently under-regulated in all samples analyzed (2.0-fold, p<0.05). Quantitative real-time polymerase chain reaction (PCR) was used to validate six over-regulated and four under-regulated lncRNAs. Bioinformatic analysis (gene ontology analysis, pathway analysis and network analysis) was used for further research. Pathway analysis indicated that 32 pathways corresponded to under-regulated transcripts and that 34 pathways corresponded to over-regulated transcripts (p-value cut-off  is 0.05). Our results are the first to reveal differentially expressed lncRNAs in osteosarcoma and suggest that lncRNAs may be novel candidate biomarkers for the diagnosis of osteosarcoma and potential targets for therapy.




TÍTULO / TITLE:  - Ectopic production of human chorionic gonadotropin by synovial sarcoma of the hip.

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

REVISTA / JOURNAL:  - Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):468-71. doi: 10.1097/AOG.0b013e31826d3121.

AUTORES / AUTHORS:  - Stevens EE; Aquino J; Barrow N; Lee YC

INSTITUCIÓN / INSTITUTION:  - SUNY Downstate Medical Center, Department of Obstetrics & Gynecology-Division of  Gynecologic Oncology, Brooklyn, New York 11203, USA. erin.stevens@downstate.edu

RESUMEN / SUMMARY:  - BACKGROUND: Human chorionic gonadotropin (hCG) is a marker of pregnancy and a tumor marker for some gynecologic malignancies, including germ cell tumors and gestational trophoblastic neoplasia. Rarely, hCG is secreted by nongynecologic tumors, confounding the diagnosis. CASE: A 45-year-old woman was evaluated for a  persistently elevated beta-hCG. Diagnosis of her primary malignancy, synovial sarcoma of the hip, was delayed as more common etiologies were considered, including ectopic pregnancy and gestational trophoblastic neoplasm. The workup eventually led to the diagnosis using imaging studies but ultimately resulted in  a 3-month delay and unnecessary medical and surgical treatments. CONCLUSION: This case highlights the importance of nongynecologic malignancies when evaluating patients with a persistent beta-hCG.




TÍTULO / TITLE:  - The expression and functionality of stromal caveolin 1 in human adenomyosis.

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

REVISTA / JOURNAL:  - Hum Reprod. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/humrep/det042

AUTORES / AUTHORS:  - Zhao L; Zhou S; Zou L; Zhao X

INSTITUCIÓN / INSTITUTION:  - Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, 610041 Chengdu, P. R. China.

RESUMEN / SUMMARY:  - STUDY QUESTION: What is the expression pattern and functionality of caveolin 1 (CAV1) in the endometrium of patients with adenomyosis? SUMMARY ANSWER: The stromal CAV1 expression is down-regulated that leads to the release of a variety  of molecules that either enhance the metastatic capacity of endometrial cells or  contribute to adenomyosis-associated dysmenorrhea. WHAT IS KNOWN ALREADY: Adenomyosis is characterized by invasion of endometrium into the uterine myometrium. CAV1 has been linked to tumor progression and clinical outcome in a variety of human malignancies; however, its role in adenomyosis development and adenomyosis-associated dysmenorrhea is still poorly recognized. STUDY DESIGN, SIZE, DURATION: We retrospectively analyzed the expression levels of CAV1 and RANTES protein using immunohistochemistry in 65 patients who were pathologically  diagnosed with adenomyosis and 12 control women without related pathology, who were subjected to surgery between 2009 and 2010. Endometrial tissues from six additional normal females without related pathology were collected from 2011 to 2012; these tissues were subjected to subsequent primary cell culture experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression of CAV1 and RANTES was examined by immunohistochemistry in ectopic endometrium and paired eutopic endometrium of 65 adenomyosis patients and 12 control patients. Primary endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs) were isolated from 6 additional control females without related pathology. The expression of CAV1 in ESCs was either (i) inhibited by siRNA transfection and methyl-beta-cyclodextrin (MbetaCD) treatment or (ii) increased by pcDNA3.1/CAV1 transfection. The impact of each treatment on the proliferation, migration and invasion of both ESCs and EECs was evaluated by methylthiazolydiphenyl-tetrazolium assay, colony formation assay, Transwell migration and invasion assay. Furthermore, ESC treatment with MbetaCD and siCAV1  was assessed for the effect on the expression of a panel of inflammatory cytokines. The levels of two pain mediators, nitric oxide (NO) and prostaglandin  E2 (PGE2), were assessed in CAV-1-depleted and control ESCs, whereas immunoblotting was performed to characterize signaling pathways downstream to loss of stromal CAV1 in endometrium. The correlation between dysmenorrhea severity and stromal CAV1 and RANTES expression was further examined using ‘Pearson’s’ correlation analysis. MAIN RESULTS: Stromal CAV1 expression in ectopic endometrium of adenomyosis patients was significantly lower than that of  paired eutopic endometrium or normal controls as analyzed by immunohistochemistry (P < 0.001). Although no significant difference was observed in the proliferation of CAV1-depleted ESCs when compared with control group, EECs cultured with conditioned media from CAV1-depleted ESCs demonstrated a significantly elevated proliferation rate when compared with those treated with control ESC-conditioned  media. Moreover, both CAV1-depleted ESCs and EECs cultured with conditioned media from CAV1-depleted ESCs showed enhanced migration and invasion capacity when compared with control group (P < 0.05). In contrast, incubation with conditioned  media of ESCs with enforced CAV1 expression led to decreased proliferation capacity of EECs. Furthermore, the expression of RANTES in ESCs treated with MbetaCD and siCAV1 was significantly increased. Stromal RANTES expression in the  ectopic endometrium of adenomyosis patients was significantly higher than that of paired eutopic endometrium or normal controls as analyzed by immunohistochemistry (P = 0.0026). Stromal CAV1 expression in eutopic endometrium was significantly lower in women with more severe dysmenorrhea (P < 0.05) and was negatively correlated with dysmenorrhea severity in adenomyosis patients (r(2) = 0.1549; P = 0.012, ‘Pearson’s’ chi(2) test), whereas stromal RANTES expression in eutopic endometrium was significantly higher in women with more severe dysmenorrhea (P <  0.05) and was positively correlated with dysmenorrhea severity in adenomyosis patients (r(2) = 0.1646; P = 0.0094, ‘Pearson’s’ chi(2) test). Silencing of CAV1  in ESCs led to increased release of NO and PGE2 when compared with control and was associated with enhanced activity of ERK-FAK signaling pathway. LIMITATIONS,  REASONS FOR CAUTION: This study assessed the functional role of stromal CAV1 and  RANTES in a small number of human adenomyosis samples by immunohistochemistry and in primary human ESCs by functional studies. In future investigations, a larger sample size should be adopted and the functional role of stromal CAV1 should be further characterized in animal models. WIDER IMPLICATIONS OF THE FINDINGS: Loss  of stromal CAV1 expression may play a critical role in the pathogenesis of adenomyosis and is correlated with adenomyosis-related dysmenorrhea. STUDY FUNDING: National Basic Research Program of China and Ph.D. Programs Foundation of Ministry of Education of China. COMPETING INTEREST: None.




TÍTULO / TITLE:  - Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells.

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

REVISTA / JOURNAL:  - Int J Gynecol Cancer. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1097/IGC.0b013e31828c9581

AUTORES / AUTHORS:  - Li B; Takeda T; Tsuiji K; Wong TF; Tadakawa M; Kondo A; Nagase S; Yaegashi N

INSTITUCIÓN / INSTITUTION:  - *Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine, Osaka; and daggerDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.

RESUMEN / SUMMARY:  - OBJECTIVE: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated  the efficacy of curcumin on autophagy in LMS cells. METHODS: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to  rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western  blotting for cleaved poly (ADP-ribose) polymerase (PARP). RESULTS: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase ½ activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase ½ pathway and curcumin-induced autophagy. CONCLUSIONS: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.




TÍTULO / TITLE:  - A Composite Neoplastic Lesion of the Vulva With Mixed Features of Fibroadenoma and Hidradenoma Papilliferum Combined With Pseudoangiomatous Stromal Hyperplasia  Containing Multinucleated Giant Cells.

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

REVISTA / JOURNAL:  - Am J Dermatopathol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1097/DAD.0b013e31828742e4

AUTORES / AUTHORS:  - Konstantinova AM; Kacerovska D; Michal M; Kazakov DV

INSTITUCIÓN / INSTITUTION:  - *Department of Pathology, Clinical Oncological Scientific and Practical Centre for Specialized Medical Care, Saint Petersburg, Russia; daggerDepartment of Pathology Medical Faculty, Saint Petersburg State University, Russia; double daggerSikl’s Department of Pathology, Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic; and section signDepartment of Pathology, Medical Faculty, Bioptical Laboratory, Pilsen, Czech Republic.

RESUMEN / SUMMARY:  - : Anogenital mammary-like glands (AGMLG) are nowadays considered a normal component of the anogenital area. Lesions affecting AGMLG are similar to those seen in breast. We present a case of a complex neoplastic lesion of the AGMLG with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia. Multinucleated cells were detected in the  pseudoangiomatous stromal hyperplasia areas as seen in some patients with neurofibromatosis type 1. The neoplasm is similar to rare mammary composite neoplasms that feature simultaneously patterns of a fibroepithelial neoplasms and intraductal papilloma.




TÍTULO / TITLE:  - Kaposi sarcoma trends in Uganda and Zimbabwe: A sustained decline in incidence?

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 22. doi: 10.1002/ijc.28125.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28125

AUTORES / AUTHORS:  - Chaabna K; Bray F; Wabinga HR; Chokunonga E; Borok M; Vanhems P; Forman D; Soerjomataram I

INSTITUCIÓN / INSTITUTION:  - Section of Cancer Information, International Agency for Research on Cancer, Lyon, France.

RESUMEN / SUMMARY:  - Trends in Kaposi sarcoma (KS) incidence over four decades were described for Zimbabwe and Uganda. KS data were retrieved from the population-based cancer registries of Bulawayo (1963-1971) and Harare (1990-2005), Zimbabwe and Kyadondo, Uganda (1960-1971 and 1991-2007). Joinpoint regression models were used to analyze time trends of KS incidence. Trends were compared to HIV/AIDS trends and  were also described as rates versus birth cohort by age. In both countries, an increased incidence of KS accompanied the emergence of the HIV/AIDS epidemic (p-value < 0.0001). In Zimbabwe, KS incidence (both sexes, all ages) changed in parallel to that of HIV/AIDS prevalence, whereas in Uganda, despite an observed decrease in HIV/AIDS prevalence since 1992, we observed a decrease in KS incidence in men younger than 50 years (Annual Percent Change, APC after 1991 = -4.5 [-5.6; -3.4], p-value < 0.05) but not in men aged >50 years (APC after 1991  = 1.0 [-2.8; 5.0]) nor in women (APC = 1.0 [-0.6; 2.6]). In both populations, a period effect at older ages was observed, with initial increases in incidence in  men followed subsequently by a downturn in rates of the same magnitude. The uniformly declining rates in younger men (aged less than 30 years) suggested that a recent cohort effect was also in operation with a reduced risk in generations born after the mid-1950s in Uganda and in the mid-1960s in Zimbabwe. The combined introduction of antiretroviral therapy and effective prevention programmes against HIV/AIDS appeared to be the key contributors to the KS decline observed in both Uganda and Zimbabwe.




TÍTULO / TITLE:  - Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63.

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

REVISTA / JOURNAL:  - Bone. 2013 Mar 5. pii: S8756-3282(13)00093-8. doi: 10.1016/j.bone.2013.02.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bone.2013.02.021

AUTORES / AUTHORS:  - Liu L; Xu Y; Reiter RJ

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedics, East Hospital, Tongji University School of Medicine,  Shanghai, China; Trauma Center, East Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Trauma, East Hospital, Tongji University  School of Medicine, Shanghai, China. Electronic address: li_feng_liu@hotmail.com.

RESUMEN / SUMMARY:  - It seems established that the onset of osteosarcoma and the reduction in melatonin production run in parallel; this suggests that the decline in the cancer-inhibiting agent, melatonin, may contribute to the occurrence of osteosarcoma and that melatonin supplementation may have promise for preventing the development and progression of this condition. There is, however, no direct evidence regarding an antiproliferative effect of melatonin in osteosarcoma cells. In the current study, we examined whether melatonin inhibits the proliferation of human osteosarcoma cell line MG-63. MTT staining showed that at  4mM-10mM concentrations, melatonin significantly reduced the MG-63 cell proliferation in a dose-dependent and time-dependent manner. Flow cytometry documented that 4mM melatonin significantly increased the fraction of cells in the G0/G1 phase of the cell cycle, while simultaneously reducing the proportion in the S and G2/M phases. Western blot and real-time PCR analyses further confirmed that melatonin’s inhibitory effect was possibly because of downregulation of cyclin D1 and CDK4, related to the G1 phase, and of cyclin B1 and CDK1, related to the G2/M phase. There was no downregulation of cyclin E, CDK2, and cyclin A, which are related to G1/S transition and S phase. These findings provide evidence that melatonin may significantly inhibit human osteosarcoma cell proliferation in a dose-dependent and time-dependent manner and this inhibition involves the downregulation of cyclin D1, CDK4, cyclin B1 and CDK1.




TÍTULO / TITLE:  - Radiofrequency ablation in the treatment of osteoid osteoma: results and complications.

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

REVISTA / JOURNAL:  - Pediatr Radiol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00247-013-2636-y

AUTORES / AUTHORS:  - Earhart J; Wellman D; Donaldson J; Chesterton J; King E; Janicki JA

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedic Surgery, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Percutaneous radiofrequency ablation (RFA) for treatment of osteoid osteoma is effective and avoids the potential complications of open surgical resection. This study evaluates the efficacy of RFA at a single tertiary-care pediatric hospital and highlights an important complication. MATERIALS AND METHODS: The medical records of 21 cases of RFA in 21 children between 2004 and 2010 were reviewed retrospectively for demographic data, lesion site, access point and technique for ablation, clinical outcome and complications. RESULTS: Clinical follow-up was available for 17/21 children (81%) at an average of 17.0 months (range 0.5-86.1 months). No persistence or recurrence of pre-procedural pain was noted. Two children (9.5%) had a complication, including a burn to the local skin and muscle requiring local wound care, and a late subtrochanteric femur fracture treated successfully with open reduction internal fixation. CONCLUSION: RFA is a safe and effective alternative to surgical resection of the  osteoid osteoma nidus. When accessing the proximal femur, the risk of late post-procedural fracture must be considered and discussed with the family. An understanding of biomechanical principles in the proximal femur might provide an  effective strategy for limiting this risk.




TÍTULO / TITLE:  - Stages I to II WHO 2003-defined low-grade endometrial stromal sarcoma: how much primary therapy is needed and how little is enough?

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

REVISTA / JOURNAL:  - Int J Gynecol Cancer. 2013 Mar;23(3):488-93. doi: 10.1097/IGC.0b013e318247aa14.

            ●● Enlace al texto completo (gratuito o de pago) 1097/IGC.0b013e318247aa14

AUTORES / AUTHORS:  - Feng W; Hua K; Malpica A; Zhou X; Baak JP

INSTITUCIÓN / INSTITUTION:  - Department of Gynaecology, Hospital of Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Before 2003, invasive endometrial stromal sarcomas (ESS) were classified into 2 categories, low-grade and high-grade ESS, according to the mitotic index. In 2003, the World Health Organization changed the definition and  the diagnostic criteria. Before 2003, 20% to 35% low-grade ESS recurred, but WHO  2003-defined low-grade ESS has 10 years’ recurrence rates of less than 10%. With  so few recurrences, the balance between treatment guaranteeing cure and overtreatment (“not too little” or “too much”) becomes increasingly important. However, primary treatment practices range from limited surgery only to extensive surgery combined with adjuvant chemotherapy and radiotherapy. We focused on the primary treatment of early-stage WHO 2003-defined low-grade ESS. METHODS: We evaluated the effect of different therapeutic strategies in 57 patients with International Federation of Gynecology and Obstetrics 2009 stages I to II expert-reviewed WHO 2003-defined low-grade ESS treated at a single institution between 1992 and 2007. RESULTS: The patients’ median age was 43 years (range, 19-63 years). After 68 months’ median follow-up (range, 17-140 months), recurrence and mortality rates were 9% and 2%, respectively. The patients with WHO 2003-defined low-grade ESS with ovary-preserving primary surgery had a much higher recurrence rate (75%) than those without (2%; P < 0.0001). Lymphadenectomy, radical abdominal hysterectomy, and omentectomy did not influence survival. Ten patients refused chemotherapy. With univariate analysis,  multiple-agent chemotherapy improved the prognosis (P = 0.02) With multivariate analysis, only ovary preservation-or-not surgery had independent prognostic value. CONCLUSIONS: In International Federation of Gynecology and Obstetrics 2009 stage I to stage II WHO 2003-defined low-grade ESS, total abdominal hysterectomy  with bilateral salpingo-oophorectomy is sufficient surgery, but ovary-preserving  primary surgery increases the risk of recurrence. More extensive surgical procedures than total abdominal hysterectomy with bilateral salpingo-oophorectomy do not improve prognosis in early-stage WHO 2003-defined low-grade ESS. Chemotherapy may improve progression-free survival in early-stage low-grade ESS,  but a large sample size is needed to confirm this.




TÍTULO / TITLE:  - Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate.

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

REVISTA / JOURNAL:  - Acta Histochem. 2013 Mar 1. pii: S0065-1281(13)00018-4. doi: 10.1016/j.acthis.2013.01.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.acthis.2013.01.004

AUTORES / AUTHORS:  - Gangoiti MV; Anbinder PS; Cortizo AM; McCarthy AD

INSTITUCIÓN / INSTITUTION:  - LIOMM, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calle 47 y 115, CP (1900) La Plata, Argentina. Electronic address: mvgangoiti@biol.unlp.edu.ar.

RESUMEN / SUMMARY:  - Advanced glycation endproducts (AGEs) accumulate with age in various tissues, and are further increased in patients with Diabetes mellitus, in which they are believed to contribute to the development and progression of chronic complications that include a decrease in bone quality. Bisphosphonates are anti-osteoporotic drugs that have been used for the treatment of patients with diabetic bone alterations, although with contradictory results. In the present study, we have evaluated the in vitro alterations on osteoblastic morphology by environmental scanning electron microscopy, in actin cytoskeleton and apoptosis induced by AGEs, as well as the modulation of these effects by alendronate (an N-containing bisphosphonate). Our present results provide evidence for disruption induced by AGEs of the osteoblastic actin cytoskeleton (geodesic domes) and significant alterations in cell morphology with a decrease in cell-substratum interactions leading to an increase in apoptosis of osteoblasts and a decrease in osteoblastic proliferation. High concentrations of alendronate (10-5M, such as could be expected in an osteoclastic lacuna) further increase osteoblastic morphological and cytoskeletal alterations. However, low doses of alendronate (10-8M, compatible with extracellular fluid levels to which an osteoblast could be exposed for most of its life cycle) do not affect cell morphology, and in addition are able to prevent AGEs-induced alterations and consequently apoptosis  of osteoblasts.




TÍTULO / TITLE:  - GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 31. pii: S0046-8177(12)00425-X. doi: 10.1016/j.humpath.2012.11.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.11.003

AUTORES / AUTHORS:  - Cimino-Mathews A; Subhawong AP; Illei PB; Sharma R; Halushka MK; Vang R; Fetting JH; Park BH; Argani P

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231. Electronic address: acimino@jhmi.edu.

RESUMEN / SUMMARY:  - GATA3 plays an integral role in breast luminal cell differentiation and is implicated in breast cancer progression. GATA3 immunohistochemistry is a useful marker of breast cancer; however, its use in specific subtypes is unclear. Here,  we evaluate GATA3 expression in 86 invasive ductal carcinomas including triple-negative, Her-2, and luminal subtypes, in addition to 13 metaplastic carcinomas and in 34 fibroepithelial neoplasms. In addition, we report GATA3 expression in matched primary and metastatic breast carcinomas in 30 patients with known estrogen receptor (ER), progesterone receptor (PR), and Her-2 status,  including 5 with ER and/or PR loss from primary to metastasis. Tissue microarrays containing 5 to 10 cores per tumor were stained for GATA3, scored as follows: 0 (0-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). GATA3 labeling was seen in 67% (66/99) of primary ductal carcinomas including 43% of triple-negative and 54% of metaplastic carcinomas. In contrast, stromal GATA3 labeling was seen in only 1 fibroepithelial neoplasm. GATA3 labeling was seen in  90% (27/30) of primary breast carcinomas in the paired cohort, including 67% of triple-negative carcinomas. GATA3 labeling was overwhelmingly maintained in paired metastases. Notably, GATA3 was maintained in all “luminal loss” metastases, which showed ER and/or PR loss. In conclusion, GATA3 expression is maintained between matched primary and metastatic carcinomas including ER-negative cases. GATA3 can be particularly useful as a marker for metastatic breast carcinoma, especially triple-negative and metaplastic carcinomas, which lack specific markers of mammary origin. Finally, GATA3 labeling may help distinguish metaplastic carcinoma from malignant phyllodes tumors.




TÍTULO / TITLE:  - GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Mar 15. doi: 10.1038/modpathol.2013.31.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2013.31

AUTORES / AUTHORS:  - Shi RR; Li XF; Zhang R; Chen Y; Li TJ

INSTITUCIÓN / INSTITUTION:  - Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.

RESUMEN / SUMMARY:  - Differential diagnosis of fibrous dysplasia and ossifying fibroma may often pose  problems for pathologists. The purpose of this study was to evaluate the value of mutational analysis of the GNAS gene in differentiating these two conditions. DNA samples from patients with fibrous dysplasia (n=30) and ossifying fibroma (n=21)  were collected to analyze the presence of GNAS mutations at exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. In all, 90% (27/30) of cases with fibrous dysplasia showed missense mutations of codon 201 at exon 8, with a predilection of arginine-to-histidine substitution (p.R201H, 70%) as opposed to arginine-to-cysteine substitution (p.R201C, 30%), whereas no mutation was detected at exon 9. No mutation was found in all 21 cases with ossifying fibroma. In addition, a meta-analysis of previously published reports on GNAS mutations in fibrous dysplasia and ossifying fibroma was performed to substantiate our findings. A total of 24 reports including 307 cases of fibrous dysplasia and 23 cases of ossifying fibroma were reviewed. The overall incidence of GNAS mutations in fibrous dysplasia was 86% (264/307), and the major types of mutations were also R201H (53%) and R201C (45%). No GNAS mutation was detected in all patients with ossifying fibroma. We also reported one case with uncertain diagnosis due to overlapping clinicopathological features of fibrous dysplasia and ossifying fibroma. An R201H mutation was detected in this case, thus confirming a diagnosis of fibrous dysplasia. Taken together, our findings indicate that mutational analysis of GNAS gene is a reliable adjunct to differentiate ossifying fibroma and fibrous dysplasia of the jaws.Modern Pathology advance online publication, 15 March 2013; doi:10.1038/modpathol.2013.31.




TÍTULO / TITLE:  - Impact of 18F-FDG PET/CT Imaging in Therapeutic Decisions for Malignant Solitary  Fibrous Tumor of the Pelvis.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31828165c1

AUTORES / AUTHORS:  - Yan J; Jones RL; Lewis DH; Eary JF

INSTITUCIÓN / INSTITUTION:  - From the * Department of Radiology, University of Washington Medical Center, and  daggerDivision of Medical Oncology, University of Washington Medical Center, Seattle, WA.

RESUMEN / SUMMARY:  - The decision to give neoadjuvant chemotherapy in patients with localized high-risk soft tissue sarcoma is often based on tumor grade evaluated from biopsies, but biopsies can have the inherent issue of sampling bias. Incorporation of SUVmax and heterogeneity assessed by F-FDG PET/CT could be other crucial components in the effort to tailor treatment to an individual patient, providing valuable parameters to guide the selection of the most appropriate management schedule for an individual. We present 1 representative case describing how FDG PET/CT can assist in clinical management decisions for treatment of malignant solitary fibrous tumor of the pelvis.




TÍTULO / TITLE:  - Intratesticular kaposiform haemangioendothelioma in adults: a report of two cases.

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

REVISTA / JOURNAL:  - J Clin Pathol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2013-201478

AUTORES / AUTHORS:  - Costa FD; Folpe AL

INSTITUCIÓN / INSTITUTION:  - Department of Anatomic Pathology, Hospital AC Camargo, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - Kaposiform haemangioendothelioma is a very rare vascular tumour of intermediate (borderline) malignancy, typically occurring in the skin and soft tissues of the  extremities in infants and children. We report two morphologically and immunophenotypically classical cases occurring in the testicular parenchyma of old adults, review the literature on vascular tumours of the testis and discuss the differential diagnosis of these unusual cases.




TÍTULO / TITLE:  - Lipoma of the Colon: Should Asymptomatic Tumors be Treated?

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

REVISTA / JOURNAL:  - Am Surg. 2013 Mar;79(3):335.

AUTORES / AUTHORS:  - Goyal V; Ungsanan P




TÍTULO / TITLE:  - Implantation of a stent graft in the right pulmonary artery enables radical resection of a central endothelial sarcoma of the left pulmonary artery.

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

REVISTA / JOURNAL:  - J Vasc Surg. 2013 Mar 1. pii: S0741-5214(13)00009-8. doi: 10.1016/j.jvs.2012.11.131.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jvs.2012.11.131

AUTORES / AUTHORS:  - Kissling P; Brosi P; Kull C; Toia D; Maurer CA

INSTITUCIÓN / INSTITUTION:  - Department of General, Visceral, Vascular and Thoracic Surgery, Hospital of Liestal, University of Basel, Liestal, Switzerland.

RESUMEN / SUMMARY:  - In a patient with a huge endothelial sarcoma of the left pulmonary artery, we report successful implantation of a stent graft in the right pulmonary artery, including the pulmonary arterial trunk. This preoperative measure enabled a safe  and radical left-sided pneumonectomy, including the tumor and the central parts of the left pulmonary artery. No major blood loss occurred, and neither use of a  heart-lung machine nor cardiopulmonary bypass was necessary.




TÍTULO / TITLE:  - Diffusion-weighted imaging for evaluation of uterine arterial embolization of fibroids.

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

REVISTA / JOURNAL:  - Magn Reson Med. 2013 Feb 25. doi: 10.1002/mrm.24624.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mrm.24624

AUTORES / AUTHORS:  - Faye N; Pellerin O; Thiam R; Chammings F; Brisa M; Marques E; Cuenod CA; Sapoval M; Fournier LS

INSTITUCIÓN / INSTITUTION:  - Universite Paris Descartes Sorbonne Paris Cite, INSERM UMR-S970, Cardiovascular Research Center-PARCC, Paris, France.

RESUMEN / SUMMARY:  - PURPOSE: To determine whether diffusion-weighted imaging (DWI) characteristics could predict the effectiveness of uterine arterial embolization in treatment of  fibroids. METHODS: This retrospective study included 17 women (27 fibroids) who underwent uterine arterial embolization for fibroids. MR imaging (1.5 T) was performed before, 1 week and 6 months after uterine arterial embolization. The volume, T2 signal, T1 signal, enhancement after contrast media injection, DWI signal (b = 500 s/mm(2) ) and apparent diffusion coefficient (ADC) were assessed  for fibroids. RESULTS: DWI signal or ADC, whether before or 1 week after the procedure, did not show a statistical relationship to success of uterine arterial embolization. On the 1-week follow-up, 22% of fibroids enhanced vs. 85% on baseline, P < 0.0001 and DW signal intensity increased. ADC values in fibroids decreased between baseline and 1-week (1.61 vs. 1.53 x 10(-3) mm(2) /s, P = 0.13). On 6-months, ADC continued to decrease compared with baseline (1.27 x 10(-3) mm(2) /s, P = 0.002), but with a lower signal on DWI. No changes were observed in myometrium ADC at any time point. CONCLUSION: Our study demonstrated  that DWI and ADC reflected early and delayed changes in fibroids after embolization; however, we were not able to demonstrate a statistically significant relationship with outcome. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.




TÍTULO / TITLE:  - Src kinases mediate VEGFR2 transactivation by the osteostatin domain of PTHrP to  modulate osteoblastic function.

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

REVISTA / JOURNAL:  - J Cell Biochem. 2013 Feb 26. doi: 10.1002/jcb.24482.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24482

AUTORES / AUTHORS:  - Garcia-Martin A; Acitores A; Maycas M; Villanueva-Penacarrillo ML; Esbrit P

INSTITUCIÓN / INSTITUTION:  - Laboratorio de Metabolismo Mineral y Oseo, Instituto de Investigacion Sanitaria (IIS)-Fundacion Jimenez Diaz and Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RETICEF)-Instituto de Salud Carlos III, Madrid, España.

RESUMEN / SUMMARY:  - Parathyroid hormone-related protein (PTHrP) stimulates osteoblastic function through its N- and C-terminal domains. Since the osteogenic action of the latter  domain appears to depend at least in part on its interaction with the vascular endothelial growth factor (VEGF) system, we aimed to explore the putative mechanism underlying this interaction in osteoblasts. Using native conditions for protein extraction and immunoblotting, we found that both PTHrP (107-139) and the shorter PTHrP (107-111) peptide (known as osteostatin), at 100 nM, promoted the appearance of a VEGF receptor (VEGFR) 2 protein band of apparent Mr. wt. 230 kDa, which likely represents its activation by dimer formation, in mouse osteoblastic  MC3T3-E1 cells. Moreover, osteostatin (100 nM) maximally increased VEGFR2 phosphorylation at Tyr-1059 within 5-10 min in both MC3T3-E1 and rat osteoblastic osteosarcoma UMR-106 cells. This phosphorylation elicited by osteostatin appears  to be VEGF-independent, but prevented by the VEGFR2 activation inhibitor SU1498 and also by the Src kinase inhibitors SU6656 and PP1. Furthermore, osteostatin induced phosphorylation of Src, extracellular signal-regulated kinase (ERK) and Akt with a similar time course to that observed for VEGFR2 activation in these osteoblastic cells. This osteostatin-dependent induction of ERK and Akt activation was abrogated by SU6656. Up-regulation of VEGF and osteoprotegerin gene expression as well as the pro-survival effect after osteostatin treatment were all prevented by both SU1498 and SU6656 in these osteoblastic cells. Collectively, these findings demonstrate that the osteostatin domain of C-terminal PTHrP phosphorylates VEGFR2 through src activation, which represents a mechanism for modulating osteoblastic function. J. Cell. Biochem. © 2013 Wiley  Periodicals, Inc.




TÍTULO / TITLE:  - Decidualized adenomyosis during pregnancy and post delivery: three cases of magnetic resonance imaging findings.

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

REVISTA / JOURNAL:  - Abdom Imaging. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00261-013-9988-5

AUTORES / AUTHORS:  - Shitano F; Kido A; Fujimoto K; Umeoka S; Himoto Y; Kiguchi K; Kondoh E; Mikami Y; Konishi I; Togashi K

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

RESUMEN / SUMMARY:  - Adenomyosis is a common gynecologic disease. Pregnancy with adenomyosis is on the increase due to a tendency of delay with first pregnancies and various infertility treatments involved in the process. We encountered decidualized adenomyosis in three patients during pregnancy, who were suspected by magnetic resonance (MR) imaging and were followed monitored post delivery. The MR imaging  findings of adenomyosis during pregnancy showed low signal intensity areas with embedded bright foci that expanded to a few mm in diameter on half Fourier single-shot turbo spin-echo images. This finding may reflect decidual change of the stroma within the ectopic endometrium caused during pregnancy. The MR imaging findings of adenomyosis after childbirth showed hemorrhage inside the lesion, which were assumed to be led by rapid decrease in a blood flow to adenomyosis post childbirth.




TÍTULO / TITLE:  - Inorganic Phosphate as A Signaling Molecule: A Potential Strategy in Osteosarcoma Treatment.

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

REVISTA / JOURNAL:  - Curr Pharm Des. 2013 Feb 4.

AUTORES / AUTHORS:  - Spina A; Sorvillo L; Esposito A; Borgia A; Sapio L; Naviglio S

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Medical School, Via L. De Crecchio 7, 80138 Naples, Italy. silvio.naviglio@unina2.it.

RESUMEN / SUMMARY:  - Inorganic phosphate (Pi) is an essential nutrient to living organisms. It plays a key role in diverse biological processes, including osteoblast differentiation and skeletal mineralization. Maintenance of proper Pi homeostasis is a critical event, as any deviation from that state can lead to several acute and chronic disease states and influence the ageing process and lifespan. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, renal tubular reabsorption and depends mainly on the activity of Na/Pi cotransporters. Pi is abundant in the diet and intestinal absorption of Pi is efficient and minimally regulated. The kidney is a major regulator of Pi homeostasis and can increase or  decrease its Pi reabsorptive capacity to accommodate Pi need. Relevantly, Pi is emerging as an important signalling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression and  protein abundance in many cell types. However, little is known about the initial  events involving the detection of changes in serum or local Pi concentrations and the subsequent downstream regulation cascade. Previously, we provided evidence that Pi inhibits proliferation and aggressiveness of human osteosarcoma U2OS cells identifying adenylate cyclase, beta3 integrin, Rap1, ERK1/2 as proteins whose expression and function are relevantly affected in response to Pi. More recently, we demonstrated that Pi is capable also of inducing sensitization of osteosarcoma cells to doxorubicin in a p53-dependent manner and through a mechanism involving ERK1/2 down-regulation. This review summarizes the current knowledge regarding inorganic phosphate as a novel specific signaling molecule in bone and other cell types in mammals and discuss how targeting Pi levels at local sites might represent a potential strategy for improving osteosarcoma therapy.




TÍTULO / TITLE:  - Genome-wide analyses on high-grade osteosarcoma: Making sense of a genomically most unstable tumor.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 22. doi: 10.1002/ijc.28124.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28124

AUTORES / AUTHORS:  - Kuijjer ML; Hogendoorn PC; Cleton-Jansen AM

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

RESUMEN / SUMMARY:  - High-grade osteosarcoma is an extremely genomically unstable tumor. This, together with other challenges, such as the heterogeneity within and between tumor samples, and the rarity of the disease, renders it difficult to study this  tumor on a genome-wide level. Now that most laboratories change from genome-wide  microarray experiments to Next-Generation Sequencing it is important to discuss the lessons we have learned from microarray studies. In this review, we discuss the challenges of high-grade osteosarcoma data analysis. We give an overview of microarray studies that have been conducted so far on both osteosarcoma tissue samples and cell lines. We discuss recent findings from integration of different  data types, which is particularly relevant in a tumor with such a complex genomic profile. Finally, we elaborate on the translation of results obtained with bioinformatics into functional studies, which has lead to valuable findings, especially when keeping in mind that no new therapies with a significant impact on survival have been developed in the past decades.




TÍTULO / TITLE:  - Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment.

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

REVISTA / JOURNAL:  - J Dermatol Sci. 2013 Mar 6. pii: S0923-1811(13)00064-9. doi: 10.1016/j.jdermsci.2013.02.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jdermsci.2013.02.008

AUTORES / AUTHORS:  - Hoshina D; Abe R; Yoshioka N; Saito N; Hata H; Fujita Y; Aoyagi S; Shimizu H

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the  therapy development is the limitation of experimental models. OBJECTIVE: We established a novel experimental angiosarcoma model. METHODS: From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor. RESULTS: First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2  phosphorylation all were unaffected in HAMON after sunitinib treatment. CONCLUSION: A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.




TÍTULO / TITLE:  - Pinacidil stimulates osteoblast function in osteoblastic MC3T3-E1 cells.

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

REVISTA / JOURNAL:  - Immunopharmacol Immunotoxicol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 3109/08923973.2013.773447


INSTITUCIÓN / INSTITUTION:  - Research Institute of Endocrinology, Kyung Hee University Hospital , Seoul , Republic of Korea and.

RESUMEN / SUMMARY:  - Abstract This study examined the effect of pinacidil, a nonselective adenosine triphosphate-sensitive potassium channel opener, on the function of osteoblastic  MC3T3-E1 cells. Pinacidil caused a significant elevation of collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis and mineralization in the cells (p < 0.05). Pinacidil significantly decreased the production of osteoclast  differentiation inducing factors such as TNF-alpha, IL-6 and receptor activator of nuclear factor-kappaB ligand in the presence of antimycin A, which inhibits mitochondrial electron transport. Moreover, pinacidil prevented antimycin A-induced reactive oxygen species and nitrotyrosine production. These results demonstrate that pinacidil may have positive effects on skeletal structure.




TÍTULO / TITLE:  - MED12 exon 2 mutations in histopathological uterine leiomyoma variants.

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

REVISTA / JOURNAL:  - Eur J Hum Genet. 2013 Feb 27. doi: 10.1038/ejhg.2013.33.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ejhg.2013.33

AUTORES / AUTHORS:  - Makinen N; Vahteristo P; Kampjarvi K; Arola J; Butzow R; Aaltonen LA

INSTITUCIÓN / INSTITUTION:  - Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.

RESUMEN / SUMMARY:  - Uterine leiomyomas, or fibroids, are the most common human tumors. Based on histopathology, they can be divided into common leiomyomas and various relatively rare subtypes that mimic malignancy in one or more aspects. Recently, we showed that exon 2 of mediator complex subunit 12 (MED12) is mutated in up to 70% of common fibroids. To investigate the frequency of MED12 exon 2 mutations in histopathological uterine leiomyoma variants, we screened altogether 206 lesions, including 69 histopathologically common leiomyomas, 59 cellular (23 cellular and  36 highly cellular), 18 atypical and 26 mitotically active leiomyomas, as well as 34 uterine fibroid samples from 14 hereditary leiomyomatosis and renal cell cancer patients with a heterozygous germ line mutation in fumarate hydratase (FH). The uterine leiomyoma variants harbored MED12 exon 2 mutations significantly less frequently than common leiomyomas (P=2.93 x 10(-8)). In all, 6 mutations were detected among cellular fibroids (6/67; 8.96%), 3 among atypical fibroids (3/18; 16.67%) and 10 among mitotically active fibroids (10/26; 38.46%). Only mitotically active fibroids displayed a mutation frequency that was not statistically different from common leiomyomas (P=0.11). Three MED12 exon 2 mutations were detected among 34 tumors with a heterozygous germ line FH mutation (P=5.28 x 10(-7)). None of these tumors displayed biallelic inactivation of FH. Our results suggest that MED12 mutation positivity is a key characteristic of common leiomyomas. Cellular and atypical fibroids, in particular, may arise through different molecular mechanisms. The results also propose that MED12 and biallelic FH mutations may be mutually exclusive.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.33.




TÍTULO / TITLE:  - Fuyuan Decoction inhibits nitric oxide production via inactivation of nuclear factor-kappaB in SW1353 chondrosarcoma cells.

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

REVISTA / JOURNAL:  - J Ethnopharmacol. 2013 Apr 19;146(3):853-8. doi: 10.1016/j.jep.2013.02.014. Epub  2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jep.2013.02.014

AUTORES / AUTHORS:  - Jia P; Chen G; Zhou G; Zhong Y; Li R

INSTITUCIÓN / INSTITUTION:  - Department of Combination of Chinese and Western Medicine, the First Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400016, PR China. Electronic address: jiap008@yahoo.com.cn.

RESUMEN / SUMMARY:  - ETHNOPHARMACOLOGICAL RELEVANCE: Fuyuan Decoction (FYD) is an empirical formula of treating Bi Zheng in traditional Chinese medicine (TCM). Despite the fact that the efficiency of FYD on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. This study was to investigate the effects and mechanisms of FYD on nitric oxide (NO) production and nuclear factor (NF)-kappaB activation in interleukin (IL)-1beta-stimulated chondrocytes.  MATERIALS AND METHODS: SW1353 human chondrosarcoma cells were pretreated with various concentrations of FYD-containing serum (FYD-CS), and then were stimulated by IL-1beta. Amounts of NO were determined by Griess reaction assay. Inducible NO synthase (iNOS) expression, inhibitor-kappaBalpha (IkappaBalpha) degradation and  nuclear translocation of p65 protein were determined by Western blot assay. DNA binding activity of NF-kappaB was determined by ELISA assay using Trans AM() kit  for p65. RESULTS: 10% and 20% (v/v) FYD-CS significantly decreased NO production  in a concentration-dependent manner (p<0.05 or p<0.01) as compared to control in  IL-1beta-induced SW1353 cells. Besides, 10% and 20% FYD-CS also significantly reduced iNOS protein expression by about 60% and 70% (both p<0.01), respectively. Furthermore, 10% and 20% FYD-CS markedly decreased IkappaBalpha degradation by about 45% and 26% (p<0.01 or p<0.05), lessened P65 content in the nucleus by about 28% and 60% (both p<0.01), and repressed DNA binding activity of P65 by about 30% and 45% (both p<0.01) in IL-1beta-induced SW1353 cells. CONCLUSIONS: These findings suggested that FYD could inhibit NO production and iNOS expression in IL-1beta-induced chondrocytes through suppressing NF-kappaB activation.




TÍTULO / TITLE:  - Successful treatment of an unresectable inflammatory myofibroblastic tumor of the frontal bone using a cyclooxygenase-2 inhibitor and methotrexate.

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

REVISTA / JOURNAL:  - Intern Med. 2013;52(5):623-8. Epub 2013 Mar 1.

AUTORES / AUTHORS:  - Kusunoki-Nakamoto F; Matsukawa T; Tanaka M; Miyagawa T; Yamamoto T; Shimizu J; Ikemura M; Shibahara J; Tsuji S

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.

RESUMEN / SUMMARY:  - Inflammatory myofibroblastic tumor (IMT) is a disease characterized by tumorous lesions consisting of myofibroblastic spindle cells and inflammatory cells that occur primarily in the soft tissues and viscera of children and young adults. Total excision is the most effective therapy. Steroids have been used to treat unresectable lesions with some success. We herein report a case of IMT involving  the frontal bone accompanied by pachymeningitis. The tumor was characterized by an aggressive clinical course that was refractory to prednisolone. Performing total excision seemed difficult. Celecoxib and methotrexate were effective treatments. Our experience suggests the efficacy of celecoxib and methotrexate as alternatives for treating unresectable IMT.




TÍTULO / TITLE:  - High expression of survivin in sacral chordoma.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):529. doi: 10.1007/s12032-013-0529-4. Epub 2013 Mar 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0529-4

AUTORES / AUTHORS:  - Chen C; Yang HL; Chen KW; Wang GL; Lu J; Yuan Q; Gu YP; Luo ZP

INSTITUCIÓN / INSTITUTION:  - Department of Orthopedics, 1st Affiliated Hospital and Orthopedic Institute, Soochow University, Suzhou 215007, Jiangsu, China.

RESUMEN / SUMMARY:  - Chordoma is a rare and invasive malignant tumor which primarily relies on surgical treatments. Anticipation of its recurrence and patient survival longevity has been a critical issue of the treatments. This retrospective study examined the survivin expression of sacral chordoma in 30 patients undergoing surgery in our hospital from January 2000 to July 2010, and compared it with chordoma recurrence. Survivin expression was 70 % positive in 30 patients. The positive expression of survivin with recurrence was significantly higher than that without recurrence (p = 0.017) and was inversely related to the continuous disease-free survival time (p < 0.001). Survivin expression was associated with recurrence. The correlation suggested that the survivin expression could be used  as an independent predictor of recurrence and could be a potential bio-target gene of angiogenesis in sacral chordoma.




TÍTULO / TITLE:  - The AIDS epidemic, then and now.

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

REVISTA / JOURNAL:  - J Am Acad Dermatol. 2013 Mar;68(3):507-8. doi: 10.1016/j.jaad.2012.10.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jaad.2012.10.020


INSTITUCIÓN / INSTITUTION:  - University of California Medical Center, San Francisco, California 94114-2512, USA. marcconant@hotmail.com




TÍTULO / TITLE:  - CT and MRI of radiation-induced sarcomas of the head and neck following radiotherapy for nasopharyngeal carcinoma.

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

REVISTA / JOURNAL:  - Clin Radiol. 2013 Mar 8. pii: S0009-9260(13)00033-0. doi: 10.1016/j.crad.2013.01.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.crad.2013.01.004

AUTORES / AUTHORS:  - Cai PQ; Wu YP; Li L; Zhang R; Xie CM; Wu PH; Xu JH

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Oncology in South China, 651 Dongfengdong Road, Guangzhou, Guangdong 510060, PR China; Department of Radiology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, PR China.

RESUMEN / SUMMARY:  - AIM: To investigate the radiological findings of head and neck radiation-induced  sarcomas (RISs) following radiotherapy for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-nine patients with RISs were identified. Imaging characteristics on computed tomography (CT) and magnetic resonance imaging (MRI), including lesion location, extent, size, margin, internal architecture, pattern,  and degree of enhancement, together with patient characteristics at NPC diagnosis and latency periods, were reviewed. RESULTS: The study included 20 women and 39 men, with a median age of 49 years (range 30-71 years). The median latency was 9  years (range 3-37 years). The median radiation dose at the site of RIS was 66 Gy  (range 44-78 Gy). The most common histological RIS types were fibrosarcoma (44.1%) and osteosarcoma (30.5%). The most common RIS sites were the paranasal sinuses and the nasal cavity (39%), the neck (16.9%), and the mandible (15.3%). The mean size was 5.1 cm (range 1.2-8.6 cm). Overall, 78% of lesions extended to  adjacent spaces and 66.1% were accompanied by bone destruction. Heterogeneous density/signal intensity before and after enhancement was seen in all lesions on  imaging. Marked lesion enhancement was noted in 49 cases (76.3%). CONCLUSIONS: The radiologist should be aware of the different sites at which RISs occur and the radiological appearance of the wide variety of RIS subtypes. Careful imaging  follow-up is necessary for early detection of RISs in patients with NPC after radiotherapy.




TÍTULO / TITLE:  - A Population-based Series of Ovarian Carcinosarcomas with Long-term Follow-up.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):1003-8.

AUTORES / AUTHORS:  - Paulsson G; Andersson S; Sorbe B

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University Hospital, SE-701 85 Orebro, Sweden. bengt.sorbe@orebroll.se.

RESUMEN / SUMMARY:  - Aim: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors. PATIENTS AND METHODS: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test. RESULTS: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor.  FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were non-significant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy. CONCLUSION: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.




TÍTULO / TITLE:  - Use of PAX8 and GATA3 in diagnosing sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Feb 28. pii: S0046-8177(13)00011-7. doi: 10.1016/j.humpath.2012.12.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.012

AUTORES / AUTHORS:  - Chang A; Brimo F; Montgomery EA; Epstein JI

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.

RESUMEN / SUMMARY:  - Immunohistochemistry for PAX8 and GATA3 are sensitive markers for renal cell carcinoma and urothelial carcinoma, respectively. However, there are limited data on these markers in sarcomatoid renal cell carcinoma (SARCRCC) and sarcomatoid urothelial carcinoma (SARCUC). Tissue microarrays (TMAs) were constructed from 45 cases of SARCRCC and 45 cases of SARCUC of the lower urinary tract, with an additional 11 SARCUCs of the upper tract. PAX8 and GATA3 were also evaluated in TMAs from 161 sarcomas from other sites, 14 atypical epithelioid angiomyolipomas  (AMLs) of the kidney, 23 bladder inflammatory myofibroblastic tumors (IMTs), and  2 bladder and 4 renal leiomyosarcomas. In the SARCRCC, PAX8 and GATA3 were positive in the sarcomatoid areas in 31 (69%) and 0 (0%) of cases, respectively.  In the bladder SARCUC, GATA3 and PAX8 were positive in 14 (31%) and 2 (4%) of cases, respectively. Of the 11 SARCUCs of the upper urinary tract, 2 (18%) cases  were PAX8 positive and 2 (18%) separate cases were GATA3 positive. Only 1 tumor present on the sarcoma TMAs, a Ewing sarcoma/primitive neuroectodermal tumor, was PAX8 positive, and all sarcomas were GATA3 negative. Of the AMLs, IMTs, and leiomyosarcoma, only 1 case of IMT showed moderate GATA3 positivity, and all were negative for PAX8. PAX8 can be used to distinguish SARCCRCC from atypical epithelioid AMLs and primary renal or retroperitoneal sarcomas. However, in a kidney/renal pelvic tumor, PAX8 shows overlap in staining between SARCUC and SARCRCC. GATA3 lacks sensitivity but is more specific for SARCUC.




TÍTULO / TITLE:  - Monitoring the Adequacy of Surgical Margins After Resection of Bone and Soft-Tissue Sarcoma.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2863-8

AUTORES / AUTHORS:  - Biau DJ; Weiss KR; Bhumbra RS; Davidson D; Brown C; Griffin A; Wunder JS; Ferguson PC

INSTITUCIÓN / INSTITUTION:  - Departement de chirurgie orthopedique, Hopital Cochin, Paris, France, david.biau@cch.aphp.fr.

RESUMEN / SUMMARY:  - PURPOSE: Local recurrence of a bone or soft-tissue sarcoma is a devastating complication. Minimizing the proportion of positive surgical margins, or tumor contamination, during resection is of paramount importance. METHODS: Resections of sarcomas were prospectively evaluated and considered inadequate if unplanned microscopic or macroscopic positive surgical margins were identified or if inadvertent tumor contamination of the wound occurred. Monitoring of performance  was continuously performed with a statistical process control method, the cumulative sum test, and regular meetings were held to discuss the reasons for failures. A target performance of 5 % inadequate procedures was chosen. RESULTS:  A total of 146 sarcomas-106 soft tissue and 40 bone-were resected during the monitoring period. Six (4 %) procedures were considered inadequate: three patients had inadvertent tumor contamination of the wound, two patients had unplanned microscopic positive margins, and one patient had both. Performance was considered to be adequate during the whole monitoring period. CONCLUSIONS: With adequate preoperative planning and surgical technique, the risk of an inadequate  resection can be limited. Implementation of a statistical process control method  allows for ongoing performance monitoring and ensures that quality remains adequate over time.




TÍTULO / TITLE:  - Diagnostic and prognostic morphometric features in WHO2003 invasive endometrial stromal tumours.

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

REVISTA / JOURNAL:  - Histopathology. 2013 Apr;62(5):688-694. doi: 10.1111/j.1365-2559.2011.04120.x.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1365-2559.2011.04120.x

AUTORES / AUTHORS:  - Feng W; Malpica A; Yinhua Y; Janssen E; Gudlaugsson E; Zhou X; Baak JP

INSTITUCIÓN / INSTITUTION:  - Department of Gynaecology and Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China Departments of Pathology and Gynecologic Oncology Department of Experimental Therapeutics, the University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Pathology, Stavanger University Hospital, Stavanger The Gade Institute, University of Bergen, Bergen, Norway Department of Pathology, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - Aims: The aim of this study was to determine the value of morphometric features in distinguishing mild and moderate atypia and predicting the recurrence of World Health Organization 2003-defined endometrial stromal sarcoma and highly malignant undifferentiated endometrial sarcoma. Methods and results: Nuclear and cytological size, shape and arrangement were morphometrically evaluated in 41 cases with consensus no/mild (n = 38) or moderate (n = 3) atypia. None of the cases showed necrosis. The prognostic value of these features in predicting recurrence was also assessed. Seven features differed. The mean and standard deviation of the nuclear volume and the distance between the nuclei were the best discriminators between the no/mild and moderate atypia, with the maximum of the nuclear volume being a practically and rapidly evaluable alternative. With the use of these features, all mild and moderate atypias were correctly classified. Seven cases recurred. The distance between the nuclei and the percentage of nuclei with one neighbour (assessed with morphometric minimum spanning tree analysis) predicted recurrence. Conclusions: In invasive endometrial stromal tumours, morphometric features are useful diagnostic support tools for distinguishing mild from moderate atypia and predicting recurrence.




TÍTULO / TITLE:  - Radiographic Superimposition and Mandibular Peripheral Osteoma: The Importance of Clinical and CT Findings.

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

REVISTA / JOURNAL:  - J Craniofac Surg. 2013 Mar;24(2):e141-2. doi: 10.1097/SCS.0b013e31827c7e87.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SCS.0b013e31827c7e87

AUTORES / AUTHORS:  - Boffano P; Gallesio C; Roccia F; Berrone S

INSTITUCIÓN / INSTITUTION:  - From the Division of Maxillofacial Surgery, Head and Neck Department, San Giovanni Battista Hospital, University of Turin, Turin, Italy.

RESUMEN / SUMMARY:  - Peripheral osteomas are benign, slow-growing osteogenic tumors that are caused by centrifugal growth of the periosteum and develop as masses attached to the cortical plates.The pathogenesis of osteomas is unclear, and embryologic, traumatic, inflammatory, metaplastic, and genetic causes have been proposed. A solitary peripheral osteoma of the jaws is uncommon.The purpose of this paper is  to present a peculiar case of mandibular peripheral osteoma with a particular radiographic superimposition that stress the importance of clinical and CT findings.




TÍTULO / TITLE:  - Clinical benefit of trabectedin in uterine adenosarcoma.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):501. doi: 10.1007/s12032-013-0501-3. Epub 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0501-3

AUTORES / AUTHORS:  - Schroeder BA; Rodler ET; Loggers ET; Pollack SM; Jones RL

INSTITUCIÓN / INSTITUTION:  - Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, Seattle, WA, USA.

RESUMEN / SUMMARY:  - Uterine adenosarcoma is an extremely rare uterine malignancy, and the utility of  chemotherapy in this disease is not well defined. This study assessed the safety  and efficacy of trabectedin in patients with recurrent/metastatic uterine adenosarcoma with sarcomatous overgrowth. A retrospective search of a prospectively maintained database was performed to identify patients with adenosarcoma treated with trabectedin between 2010 and 2012, within a compassionate use trial. Three patients with recurrent/metastatic uterine adenosarcoma treated with trabectedin were identified. All three patients tolerated the drug well. Two patients obtained prolonged clinical benefit from treatment, one having received 17 cycles and another 11 cycles of therapy. Trabectedin is well tolerated and has clinical activity in recurrent/metastatic uterine adenosarcoma.




TÍTULO / TITLE:  - An unusual mole: an adult case of Dabska tumour.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Nov;36 Suppl 2:171-2.

AUTORES / AUTHORS:  - Bernic A; Novosel I; Krizanac S

INSTITUCIÓN / INSTITUTION:  - Dr. Ivo Pedisic, General Hospital, Department of ENT Surgery, Sisak, Croatia. abernic@gmail.com

RESUMEN / SUMMARY:  - In 1969 Dabska and her colleagues described for the first time this rare malignant tumour, also later known as a malignant endovascular papillary angioendothelioma of childhood. Overall, depending amongst other factors on its location, it is thought to have a generally favourable prognosis and a wide local excision seems to be the treatment of choice. We here present a very rare and unusual case of a 63 year old woman with a 20 year history of slow-growing right  buccal dermatological lesion which resembled a common mole. The histopathological diagnosis of Dabska Tumour was made following the hematoxylin and eosin (H&E) biopsy. The analysis revealed multiple delicate interconnecting vascular channels with papillary plugs, some of which containing hyalinized core, projecting into the lumen lined by atypical plumped endothelial cells.




TÍTULO / TITLE:  - Evidence for Ca-regulated ATP release in gastrointestinal stromal tumors.

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

REVISTA / JOURNAL:  - Exp Cell Res. 2013 Mar 13. pii: S0014-4827(13)00109-2. doi: 10.1016/j.yexcr.2013.03.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexcr.2013.03.001

AUTORES / AUTHORS:  - Berglund E; Berglund D; Akcakaya P; Ghaderi M; Dare E; Berggren PO; Kohler M; Aspinwall CA; Lui WO; Zedenius J; Larsson C; Branstrom R

INSTITUCIÓN / INSTITUTION:  - Section for Endocrine and Sarcoma Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, L1:03, Stockholm, Sweden.  Electronic address: erik.berglund@ki.se.

RESUMEN / SUMMARY:  - Gastrointestinal stromal tumors (GISTs) are thought to originate from the electrically active pacemaker cells of the gastrointestinal tract. Despite the presence of synaptic-like vesicles and proteins involved in cell secretion it remains unclear whether GIST cells possess regulated release mechanisms. The GIST tumor cell line GIST882 was used as a model cell system, and stimulus-release coupling was investigated by confocal microscopy of cytoplasmic free Ca2+ concentration ([Ca2+]i), flow cytometry, and luminometric measurements of extracellular ATP. We demonstrate that GIST cells have an intact intracellular Ca2+-signaling pathway that regulates ATP release. Cell viability and cell membrane integrity was preserved, excluding ATP leakage due to cell death and suggesting active ATP release. The stimulus-secretion signal transduction is at least partly dependent on Ca2+ influx since exclusion of extracellular Ca2+ diminishes the ATP release. We conclude that measurements of ATP release in GISTs may be a useful tool for dissecting the signal transduction pathway, mapping exocytotic components, and possibly for the development and evaluation of drugs.  Additionally, release of ATP from GISTs may have importance for tumor tissue homeostasis and immune surveillance escape.




TÍTULO / TITLE:  - Multiple papillary fibroelastomas as a cause of recurrent syncope.

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

REVISTA / JOURNAL:  - J Thorac Cardiovasc Surg. 2013 Feb 8. pii: S0022-5223(13)00033-0. doi: 10.1016/j.jtcvs.2013.01.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.01.008

AUTORES / AUTHORS:  - Jonjev ZS; Torbica V; Mojasevic R

INSTITUCIÓN / INSTITUTION:  - Clinic of Cardiovascular Surgery, Institute for Cardiovascular Diseases of Vojvodina, University in Novi Sad, Sremska Kamenica, Serbia. Electronic address:  jonjevz@lycos.com.




TÍTULO / TITLE:  - Diagnostic utility of aP2/FABP4 expression in soft tissue tumours.

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

REVISTA / JOURNAL:  - Virchows Arch. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00428-013-1392-6

AUTORES / AUTHORS:  - Kashima TG; Turley H; Dongre A; Pezzella F; Athanasou NA

INSTITUCIÓN / INSTITUTION:  - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX7, HE, UK.

RESUMEN / SUMMARY:  - Adipocyte P2 (aP2), also known as fatty acid-binding protein 4 (FABP4), is a fatty acid-binding protein found in the cytoplasm of cells of adipocyte differentiation. In this study, we examined a large number of soft tissue tumours with a commercial polyclonal anti-aP2/FABP4 antibody and a newly developed mouse  monoclonal antibody raised against this protein to determine the diagnostic utility of aP2/FABP4 as a marker of tumours of adipose differentiation. A mouse monoclonal antibody, clone 175d, was raised against a mixture of synthetic peptides corresponding to the amino acid sequence of residues 10-28 and 121-132 of the human aP2/FABP4 protein. Antigen expression with polyclonal and monoclonal antibodies was immunohistochemically determined in paraffin sections of normal adipose tissue and a wide range of benign and malignant primary soft tissue tumours (n = 200). aP2/FABP4 was expressed around the cytoplasmic lipid vacuole in white and brown fat cells in benign lipomas and hibernomas. Immature fat cells and lipoblasts in spindle cell/pleomorphic lipoma, atypical lipomatous tumour/well-differentiated liposarcoma, myxoid/round cell liposarcoma and pleomorphic liposarcoma also reacted strongly for aP2/FABP4. No specific staining was seen in non-adipose benign and malignant mesenchymal and non-mesenchymal tumours. aP2/FABP4 is expressed by mature and immature fat cells and is a marker  of tumours of adipose differentiation. Immunophenotypic aP2/FABP4 expression is useful in identifying lipoblasts, and immunohistochemistry with polyclonal/monoclonal anti-aP2/FABP4 antibodies should be useful in distinguishing liposarcoma from other malignancies, particularly round cell, myxoid and pleomorphic soft tissue sarcomas.




TÍTULO / TITLE:  - Risedronate increases osteoblastic differentiation and function through connexin43.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Mar 1;432(1):152-6. doi: 10.1016/j.bbrc.2013.01.068. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.068

AUTORES / AUTHORS:  - Jeong HM; Jin YH; Choi YH; Chung JO; Cho DH; Chung MY; Civitelli R; Chung DJ; Lee KY

INSTITUCIÓN / INSTITUTION:  - College of Pharmacy and Research Institute of Drug Development, Chonnam National  University, Gwangju 500-757, Republic of Korea.

RESUMEN / SUMMARY:  - Bisphosphonates are potent antiresorptive drugs which have antifracture efficacy  by reducing bone turnover rate and increasing bone mineral density. In addition to inhibiting osteoclast function, bisphosphonates have been reported to also promote survival of osteocyte and osteoblast via an anti-apoptotic effect, mediated by opening of hemi-gap junction channels formed by connexin43 (Cx43). In this study, we investigated the effect of risedronate, one amino-bisphosphonate,  on osteoblast differentiation and Cx43 expression using the mesenchymal cell line C2C12. Risedronate dose-dependently increased the activity of osterix (OSE)-luciferase containing Runx2 response element with highest activity at 50muM. The activity of osteocalcin (OC)- and bone sialoprotein (BSP)-luciferase reporters, markers of osteoblast differentiation, were also increased by risedronate. When risedronate and BMP2 were used in combination, alkaline phosphatase (ALP) activity increased to a larger extent than when BMP2 was used alone. Risedronate as well as the pro-osteogenic transcription factors, Runx2, Osterix or Dlx5, increased transcriptional activity of the Cx43 promoter in a dose-dependent manner. In the presence of Runx2 or Dlx5, risedronate had an additive effect on Cx43 promoter activity. Accordingly, risedronate increased protein expression of Cx43, Runx2, Osterix, and Dlx5. These results suggest that  risedronate promotes osteoblastic differentiation and positively regulates Cx43 gene transcription.




TÍTULO / TITLE:  - miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2  pathway in osteosarcoma.

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

REVISTA / JOURNAL:  - FEBS Lett. 2013 Mar 15. pii: S0014-5793(13)00205-6. doi: 10.1016/j.febslet.2013.03.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.febslet.2013.03.007

AUTORES / AUTHORS:  - Chen L; Wang Q; Wang GD; Wang HS; Huang Y; Liu XM; Cai XH

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command,  Wuhan, China.

RESUMEN / SUMMARY:  - Several miRNAs have been implicated in the development and progression of osteosarcoma (OS). In this study, we found that miR-16 is downregulated in OS cell lines and tissues. Overexpression of miR-16 suppresses OS cell proliferation and tumor growth in nude mice. Furthermore, we confirmed that IGF1R is a direct target of miR-16. Mechanistic investigation revealed that miR-16 overexpression inhibits the Raf1-MEK1/2-ERK1/2 pathway. In clinical specimens, IGF1R levels inversely correlate with miR-16 expression. Our results provide significant clues regarding the role of miR-16 as a tumor suppressor by targeting IGF1R in OS.




TÍTULO / TITLE:  - Pyomyoma after uterine artery embolization.

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

REVISTA / JOURNAL:  - Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):431-3. doi: 10.1097/AOG.0b013e31827e8e8f.

AUTORES / AUTHORS:  - Rosen ML; Anderson ML; Hawkins SM

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics & Gynecology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Pyomyoma (suppurative leiomyoma of the uterus) is a rare condition resulting from infarction and infection of a leiomyoma. It can lead to sepsis and death unless treated with antibiotics and aggressive surgical intervention. CASE: A 47-year-old multigravid woman with symptomatic uterine leiomyomas presented with fever, pelvic pain, and leukocytosis after uncomplicated uterine artery embolization. Pyomyoma was suspected after computed tomography scan demonstrated  an enlarged, heterogeneous uterus containing copious myometrial air. She underwent supracervical hysterectomy, lysis of adhesions, and right salpingo-oophorectomy. CONCLUSION: Surgical management of pyomyoma may be necessary early in the management of pyomyoma after uterine artery embolization.




TÍTULO / TITLE:  - Iliocaval and aortoiliac reconstruction following en bloc retroperitoneal leiomyosarcoma resection.

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

REVISTA / JOURNAL:  - J Vasc Surg. 2013 Mar;57(3):850. doi: 10.1016/j.jvs.2012.01.048.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jvs.2012.01.048

AUTORES / AUTHORS:  - Ohman JW; Chandra V; Poultsides G; Harris EJ

INSTITUCIÓN / INSTITUTION:  - Department of Cardiothoracic and Vascular Surgery, The University of Texas Health Science Center at Houston, Houston, Tex.




TÍTULO / TITLE:  - Dermoscopy of dermatofibrosarcoma protuberans: a study of 15 cases.

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

REVISTA / JOURNAL:  - Br J Dermatol. 2013 Mar 18. doi: 10.1111/bjd.12318.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bjd.12318

AUTORES / AUTHORS:  - Bernard J; Poulalhon N; Argenziano G; Debarbieux S; Dalle S; Thomas L

INSTITUCIÓN / INSTITUTION:  - Department of dermatology, Lyon 1 university, Centre Hospitalier Lyon Sud, 69495, Pierre Benite Cedex, France.

RESUMEN / SUMMARY:  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant cutaneous  tumour of which diagnosis is often delayed because of the lack of early clinical  clues. OBJECTIVES: To describe the main dermoscopic features of DFSP. METHODS: We performed dermoscopic examination in 15 unselected, consecutive cases of biopsy-proven DFSP. First, six dermoscopic features were identified collegially;  then all cases were reviewed separately by 6 experimented dermoscopists. In a given lesion, only features recognised by all dermoscopists were taken into account. RESULTS: The median number of dermoscopic features was 4 per lesion. The following dermoscopic features were found: delicate pigmented network (87%); vessels (80%); structureless light brown areas (73%); shiny white streaks (67%);  pink background coloration (67%) and structureless hypo- or depigmented areas (60%). When detected, vessels were of arborizing type in 11 of 12 cases, and presented as either unfocused only, or both unfocused and focused. CONCLUSIONS: this first approach to the dermoscopic spectrum of DFSP identifies 6 dermoscopic  features (often associated in a multicomponent pattern) and a peculiar vascular pattern. Whether dermoscopy can help suspect DFSP remains to be established by further studies.




TÍTULO / TITLE:  - Severe rhizomelic chondrodysplasia punctata in a fetus due to maternal mixed connective tissue disorder.

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

REVISTA / JOURNAL:  - Genet Couns. 2012;23(4):487-91.

AUTORES / AUTHORS:  - Nayak SS; Adiga PK; Rai L; Girisha KM

INSTITUCIÓN / INSTITUTION:  - Division of Medical Genetics, Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, India.

RESUMEN / SUMMARY:  - Maternal systemic lupus erythematosus and autoimmune diseases have been extremely rarely reported to cause rhizomelic chondrodysplasia punctata. We report on a fetus aborted spontaneously at 21 weeks of gestation due to complications of maternal mixed connective tissue disorder. The fetus had micrognathia, a depressed nasal bridge, flat nose, long philtrum, short columella and rhizomelia. Radiographic study showed stippling of carpal and tarsal bones, short humeri and  coronal clefts in the vertebrae. Ossification centers were present at the lower end of the femora and upper end of the tibiae.




TÍTULO / TITLE:  - Kaposis sarcoma-associated herpesvirus ORF36 protein induces chromosome condensation and phosphorylation of histone H3.

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

REVISTA / JOURNAL:  - Acta Virol. 2013;57(1):75-9.

AUTORES / AUTHORS:  - Kim S; Cha S; Jang JH; Kim Y; Seo T

RESUMEN / SUMMARY:  - Kaposis sarcoma-associated herpesvirus (KSHV) has been known as an agent causing  Kaposis sarcoma, primary effusion lymphoma, and multicentric Castlemans disease.  In the lytic phase of the virus cycle, various viral genes are expressed, which causes host cell dysregulation. Among the lytic genes, viral protein kinase (vPK) encoded by ORF36 is a member of serine/threonine protein kinase (CHPK) family, which is involved in viral gene expression, viral DNA replication and encapsidation, and nuclear egress of virions. Recent studies have shown that the  BGLF4 protein of Epstein-Barr virus (EBV), a member of the CHPK family, alters the host cell chromatin structure through phosphorylation of its key regulators.  The role of KSHV ORF36 in cellular mitotic events, however, is not yet understood. In the current study, we showed that KSHV ORF36 induced chromosome condensation and phosphorylation of histone H3 on Ser 10, which are known as cellular mitosis markers. These processes have occurred in a kinase activity-dependent manner. Keywords: Kaposis sarcoma-associated herpesvirus; viral protein kinase; ORF36; chromosome condensation; histone H3; phosphorylation.




TÍTULO / TITLE:  - Expression of receptor for hyaluronan-mediated motility (RHAMM) in ossifying fibromas.

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

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Apr;28(4):473-80. Epub 2013 Feb 5.

AUTORES / AUTHORS:  - Hatano H; Ogawa I; Shigeishi H; Kudo Y; Ohta K; Higashikawa K; Takechi M; Takata T; Kamata N

INSTITUCIÓN / INSTITUTION:  - Department of Oral and Maxillofacial Surgery, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

RESUMEN / SUMMARY:  - Fibro-osseous lesions of the jaw are poorly understood because of a significant overlap of clinical, radiological and histological features among the various types, though they present distinct patterns of disease progression. An ossifying fibroma is associated with significant cosmetic and functional disturbances, as it shows expansive proliferation. Thus, it is important to establish a specific marker, as well as clearly elucidate its etiology for diagnosis and proper treatment. We previously established immortalized cell lines from human ossifying fibromas of the jaw and found that they highly expressed the receptor for hyaluronan (HA)-mediated motility (RHAMM). In this study, we examined the expression of RHAMM mRNA in 65 fibro-osseous lesions, including ossifying fibroma, fibrous dysplasia and osseous dysplasia, as well as 5 normal jaws, using real-time RT-PCR and immunohistochemistry assays. RHAMM mRNA and protein expression were significantly elevated in the ossifying fibroma specimens. These  results suggest that detection of upregulated RHAMM expression in an ossifying fibroma assists with differential diagnosis and has a key role in elucidation of  its pathophysiology.




TÍTULO / TITLE:  - MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months after Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol.

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

REVISTA / JOURNAL:  - Cardiovasc Intervent Radiol. 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00270-013-0561-y

AUTORES / AUTHORS:  - Das R; Gonsalves M; Vlahos I; Manyonda I; Belli AM

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, St George’s Healthcare NHS Trust, Blackshaw, London, SW17 0QT, UK, rajdas@nhs.net.

RESUMEN / SUMMARY:  - PURPOSE: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on  6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. METHODS: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic  MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction, presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid  Symptom and Quality of Life questionnaire (UFS-QOL). RESULTS: Magnetic resonance  angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of  all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. CONCLUSION: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL  scores were achieved.




TÍTULO / TITLE:  - Management of intravascular leiomyomatosis: Laparoscopic surgery for ordinary uterine fibroids led to an extraordinary finding.

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

REVISTA / JOURNAL:  - Am J Obstet Gynecol. 2013 Apr;208(4):333.e1-2. doi: 10.1016/j.ajog.2013.02.044. Epub 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajog.2013.02.044

AUTORES / AUTHORS:  - Lakhi N; Serur E; Chi DS

INSTITUCIÓN / INSTITUTION:  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York. Electronic address: nlakhi@yahoo.com.

RESUMEN / SUMMARY:  - An unexpected diagnosis of intravascular leiomyomatosis was made during a laparoscopic procedure. As the extent of the disease was unknown, the initial procedure was limited to laparoscopic hysterectomy and salpingo-oophorectomy. Postoperative computed tomography imaging demonstrated intravascular leiomyomatosis extending into the suprarenal inferior vena cava. The patient underwent exploratory laparotomy to excise residual tumor.




TÍTULO / TITLE:  - Lymphangioleiomyomatosis Screening in Women with Tuberous Sclerosis.

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

REVISTA / JOURNAL:  - Chest. 2013 Mar 28. doi: 10.1378/chest.12-2813.

            ●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-2813

AUTORES / AUTHORS:  - Cudzilo CJ; Szczesniak RD; Brody AS; Rattan M; Krueger DA; Bissler JJ; Franz DN; McCormack FX; Young LR

RESUMEN / SUMMARY:  - ABSTRACT BACKGROUND: Lymphangioleiomyomatosis (LAM) occurs in at least 40% of women with Tuberous Sclerosis Complex (TSC), as diagnosed based on chest CT scan  findings. Early identification may inform life style choices and treatment decisions. Here we report LAM prevalence in a large TSC Clinic and propose an approach to CT screening for LAM in women with TSC. METHODS: We retrospectively reviewed initial chest CT scans of all female TSC patients age >/=15 years seen at our center over a 12-year period. Each CT image slice was manually scored for  the presence or absence of cysts, and the diagnosis of LAM was made if at least four characteristic thin-walled cysts were present. RESULTS: Of 133 female TSC patients, 101 had chest CT scans available for review. 48 (47.5%) met criteria for TSC-LAM on the initial CT scan. The risk of LAM was age-dependent, rising by  about 8% per year. The prevalence of LAM was 27% in subjects &lt;21 years and 81% in subjects &gt;40 years. Among asymptomatic subjects with LAM, 84% had cysts present in the single image at level of the carina. Most subjects with LAM eventually developed pulmonary symptoms (63%), and 12.5% died due to LAM. CONCLUSIONS: These results suggest that most women with TSC ultimately develop cystic changes consistent with LAM, and that most cases can be identified from a  single CT slice at the level of the carina. TSC-LAM was associated with appreciable morbidity and mortality in our referral population. An age-based approach using limited CT scanning methods may facilitate screening and subsequent treatment decisions with decreased radiation exposure in this at-risk  population.




TÍTULO / TITLE:  - Solitary fibrous tumors of the thorax: nomenclature, epidemiology, radiologic and pathologic findings, differential diagnoses, and management.

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

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Mar;200(3):W238-48. doi: 10.2214/AJR.11.8430.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.11.8430

AUTORES / AUTHORS:  - Chick JF; Chauhan NR; Madan R

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.




TÍTULO / TITLE:  - Inflammatory Myofibroblastic Tumor of the Kidney.

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

REVISTA / JOURNAL:  - J Urol. 2013 Mar 15. pii: S0022-5347(13)03682-3. doi: 10.1016/j.juro.2013.03.036.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2013.03.036

AUTORES / AUTHORS:  - Jenkins LC; Whittington E; Ciancio G; Jorda M

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Transplant Institute, Jackson Memorial Hospital, Miami, Florida.




TÍTULO / TITLE:  - Leiomyosarcoma of the Epididymis.

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

REVISTA / JOURNAL:  - J Urol. 2013 Feb 26. pii: S0022-5347(13)00358-3. doi: 10.1016/j.juro.2013.02.082.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2013.02.082


INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.




TÍTULO / TITLE:  - Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):499. doi: 10.1007/s12032-013-0499-6. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0499-6

AUTORES / AUTHORS:  - Cai H; Lin L; Cai H; Tang M; Wang Z

INSTITUCIÓN / INSTITUTION:  - Pediatric Orthopedic Department, Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200031, China.

RESUMEN / SUMMARY:  - MicroRNA-210 (miR-210) plays important roles in the regulation of cell growth, angiogenesis, and apoptosis in different cancer type. Previous study of miRNA expression profiling found that miR-210 was significantly elevated in osteosarcoma samples. However, its roles in this disease have not been fully elucidated. Thus, the aim of this study was to investigate the association of miR-210 expression with clinicopathologic features and prognosis in patients with osteosarcomas. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression level of miR-210 in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. MiR-210 expression was significantly increased in osteosarcoma tissues compared with that in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-210 upregulation more frequently occurred in osteosarcoma tissues with large tumor size (P = 0.02), poor response to preoperative chemotherapy (P = 0.008), and positive metastasis (P = 0.01). Moreover, miR-210 upregulation was associated with significantly decreased overall survival (P = 0.007) and progression-free survival (P = 0.01). In the Cox proportional hazard model, it was confirmed that its expression in the biopsy samples was an independent prognostic factor of unfavorable survival in osteosarcoma (for overall survival: P = 0.01; for progression-free survival: P =  0.02). These findings suggested that miR-210 upregulation showed a strong correlation with tumor aggressive progression of pediatric osteosarcoma and could help prognostic screening of patients with this malignancy.




TÍTULO / TITLE:  - Low-grade central osteosarcoma arising from bone infarct.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 31. pii: S0046-8177(12)00439-X. doi: 10.1016/j.humpath.2012.11.011.

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

AUTORES / AUTHORS:  - Endo M; Yoshida T; Yamamoto H; Ishii T; Setsu N; Kohashi K; Matsunobu T; Iwamoto Y; Oda Y

INSTITUCIÓN / INSTITUTION:  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 812-8582.

RESUMEN / SUMMARY:  - Bone infarct-associated sarcoma is a rare sarcoma, accounting for less than 1% of all bone sarcomas. Its histology usually reflects a high-grade sarcoma, such as malignant fibrous histiocytoma of bone or conventional osteosarcoma. Low-grade sarcoma arising from bone infarct has not been described well in the literature.  Here, we present a 17-year follow-up of a female patient with bone infarct in her right humerus, from which a low-grade central osteosarcoma developed during follow-up. A histologic diagnosis of low-grade central osteosarcoma was confirmed by immunohistochemical expression of MDM2 and CDK4. She underwent a wide resection surgery. As of 4 years after surgery, she has remained free of any evidence of recurrence or metastasis. Here, we present clinical and pathologic findings of our case in detail and discuss the differential diagnoses of this extremely rare condition.




TÍTULO / TITLE:  - Prognostic indicators in WHO 2003 low-grade endometrial stromal sarcoma.

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

REVISTA / JOURNAL:  - Histopathology. 2013 Apr;62(5):675-87. doi: 10.1111/j.1365-2559.2011.04115.x. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1365-2559.2011.04115.x

AUTORES / AUTHORS:  - Feng W; Hua K; Gudlaugsson E; Yu Y; Zhou X; Baak JP

INSTITUCIÓN / INSTITUTION:  - Department of Gynaecology, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China Department of Pathology, Stavanger University Hospital, Stavanger Clinicla Institute-1, University in Bergen, Bergen, Norway Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX,  USA Department of Pathology, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - Aims: Endometrial stromal sarcoma (ESS) has traditionally been divided into low and high grade, but the World Health Organization (WHO, 2003) has changed the definition. Since 2003, many studies have used the old criteria, and few have focused on WHO 2003-defined ESS low grade (ESS-LG). The aim of this study was to  investigate prognosticators in ESS-LG. Methods and results: We reviewed the WHO 2003 diagnostic criteria in 91 tumours (previously classified as ESS low and high grade). There were 68 cases of ESS-LG and 23 of undifferentiated endometrial sarcoma (UES). In the ESS-LG cases, the prognostic value of clinicopathological variables was studied. With a median follow-up of 79 months (range: 20-474 months), the recurrence and death rates were 5/68 (7%) and 1/68 (1.5%) in the ESS-LG cases. Ovarian preservation or no ovarian preservation (P < 0.0001, hazard ratio (HR) 10.4) and mitotic activity index (MAI) (0-3 versus >3, P = 0.005, HR 8.6) had independent prognostic value. Other frequently used MAI thresholds - age, tumour diameter, and vessel invasion - were not prognostic. Among patients without ovarian preservation (n = 61), none of 53 with MAI 0-3 suffered recurrence, contrasting with two of eight (25%) of those with MAI >3 (P = 0.003); one of these two recurrence patients died (P = 0.02). Among patients with ovarian preservation (n = 7), three (43%) suffered recurrence but none died, and MAI had  no additional prognostic value. Conclusions: In ESS-LG, ovarian preservation and  MAI >3 are associated with increased risk of recurrence.




TÍTULO / TITLE:  - AIRP Best Cases in Radiologic-Pathologic Correlation: Alveolar Soft-Part Sarcoma.

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

REVISTA / JOURNAL:  - Radiographics. 2013 Mar;33(2):585-93. doi: 10.1148/rg.332115173.

            ●● Enlace al texto completo (gratuito o de pago) 1148/rg.332115173

AUTORES / AUTHORS:  - Itani M; Shabb NS; Haidar R; Khoury NJ

INSTITUCIÓN / INSTITUTION:  - Departments of Diagnostic Radiology, Pathology and Laboratory Medicine, and Surgery, American University of Beirut Medical Center, Riad El-Solh, Beirut, Lebanon 1107-2020.




TÍTULO / TITLE:  - Response to commentary on ‘Angiosarcoma as a Potential Consequence of Autologous  Lymph Node Transplantation for Lymphoedema’

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

REVISTA / JOURNAL:  - Eur J Vasc Endovasc Surg. 2013 Mar 2. pii: S1078-5884(13)00084-1. doi: 10.1016/j.ejvs.2013.01.035.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejvs.2013.01.035


INSTITUCIÓN / INSTITUTION:  - Unite de Lymphologie, Hopital Cognacq-Jay, 15 rue Eugene Millon, 75015 Paris, France. Electronic address: stephane.vignes@cognacq-jay.fr.




TÍTULO / TITLE:  - Angiosarcoma as a Potential Consequence of Autologous Lymph Node Transplantation  for Lymphoedema.

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

REVISTA / JOURNAL:  - Eur J Vasc Endovasc Surg. 2013 Mar 1. pii: S1078-5884(13)00085-3. doi: 10.1016/j.ejvs.2013.01.036.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejvs.2013.01.036

AUTORES / AUTHORS:  - Samimi M; Maruani A; Vaillant L; Lorette G

INSTITUCIÓN / INSTITUTION:  - Dermatology Department, Universite Francois Rabelais, University Hospital of Tours, France; INRA ISP, UMR 1282, Tours, Universite Francois Rabelais, Tours, France. Electronic address: samimi.mahtab@yahoo.fr.




TÍTULO / TITLE:  - The expression and characterization of endoglin in uterine leiomyosarcoma.

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

REVISTA / JOURNAL:  - Clin Exp Metastasis. 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10585-013-9574-9

AUTORES / AUTHORS:  - Mitsui H; Shibata K; Mano Y; Suzuki S; Umezu T; Mizuno M; Yamamoto E; Kajiyama H; Kotani T; Senga T; Kikkawa F

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, 466-8550, Japan.

RESUMEN / SUMMARY:  - Endoglin (CD105), an accessory receptor of transforming growth factor-beta, is expressed in vascular endothelial cells. Recently, it was reported that endoglin  expression was significantly associated with poorer survival in several cancers.  In this study, we evaluated the role of endoglin in uterine leiomyosarcoma. We examined the expression of endoglin in 22 uterine leiomyosarcomas and the association between their expression and the outcome. Additionally, to evaluate the function of endoglin, we used SKN cells, a human uterine leiomyosarcoma cell  line. We generated SKN cells stably transfected with plasmids encompassing shRNA  targeting endoglin (shEng cells), and compared the ability of proliferation, migration, and invasion to control shRNA-transfected cells (shCon cells). We compared the level of VEGF and matrix metalloproteinases (MMP) in culture supernatants of shEndoglin and shControl cells. Nine patients were endoglin-positive and 13 patients were -negative. The endoglin-positive group had a significantly poorer overall survival and progression-free survival than the endoglin-negative group. In an in vitro study, there was no difference in cell proliferation between shEng and shCon cells. On the other hand, shEng cells showed a lower ability for migration and invasion than shControl cells. The activity of MMP-9 and VEGF level in the supernatant from shEng cells were lower than in shCon cells. In uterine leiomyosarcoma, endoglin expression was associated with a poor prognosis. It was suggested that endoglin up-regulated invasion and VEGF secretion. The investigation of endoglin may lead to a new strategy in uterine leiomyosarcoma therapy.




TÍTULO / TITLE:  - ERCP with intracholedocal biopsy for the diagnosis of biliary tract rhabdomyosarcoma in children.

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

REVISTA / JOURNAL:  - Pediatr Surg Int. 2013 Feb 17.

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AUTORES / AUTHORS:  - Scottoni F; De Angelis P; Dall’oglio L; Francalanci P; Monti L; de Ville de Goyet J

INSTITUCIÓN / INSTITUTION:  - Hepatobiliopancreatic Surgery Unit, Department of Pediatric Surgery and Transplantation, Bambino Gesu Children’s Hospital, IRCCS, Piazza San Onofrio 4, 00165, Rome, Italy, fscottoni@msn.com.

RESUMEN / SUMMARY:  - Rhabdomyosarcoma is the most common tumor of the biliary tract in children. Although some features at preoperative radiographic studies (ultrasound, CT, MRI) may be suggestive of BT-RMS, until few years ago the final diagnosis was obtained by either operative or transcutaneous biopsy, thus exposing to a risk of regional dissemination. More recent and still anecdotal, is the histological diagnosis on  tissue obtained by transluminal biopsy either during transhepatic cholangiography or endoscopic retrograde cholangio-pancreatography (ERCP), the latter having the  major advantage of a much lower risk of loco-regional dissemination. We present two cases of BT-RMS that were histologically diagnosed by intracholedocal biopsy  performed during ERCP, after being suspected at conventional imaging.




TÍTULO / TITLE:  - Aggressive locoregional management of recurrent peritoneal sarcomatosis.

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

REVISTA / JOURNAL:  - J Surg Oncol. 2013 Mar;107(4):329-34. doi: 10.1002/jso.23232. Epub 2013 Feb 5.