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Quinto di Treviso, Italy

Dei Tos A.P.,Treviso General Hospital
Seminars in Diagnostic Pathology | Year: 2013

Soft tissue sarcomas represent an heterogenous group of malignancies. They represent a diagnostic challenge, and their accurate classification impact over treatment options. Sarcomas, similarly to hematologic neoplasm, often harbor relatively specific genetic aberrations, the recognition of which can be used to improved diagnostic accuracy. This review will focus on the clinical relevance of molecular analysis in soft tissue sarcomas, trying to elucidate its role as a diagnostic tool as well as a potential prognostic/predictive marker. © 2013 Elsevier Inc. Source

Mastrangelo G.,University of Padua | Coindre J.-M.,Bergonie Institute | Ducimetiere F.,University of Lyon | Dei Tos A.P.,Treviso General Hospital | And 11 more authors.
Cancer | Year: 2012

Background: The objectives of this study were to measure the incidence of sarcomas, including viscerally sited tumors that are not reported in cancer statistics, and to draw explanatory clues from a large and reliable sarcoma incidence data set. Methods: Cases of sarcomas regardless of primary site (except bone and joints) were collected during 2 years in 3 European regions totaling approximately 26,000,000 person-years. The sources used were pathology reports and hospital discharges forms. Diagnoses were reviewed by expert sarcoma pathologists and were classified according to 2002 World Health Organization criteria. Soft tissue sarcomas (STS) were considered those located in arms, legs, trunk, head, neck, and retroperitoneum; visceral sarcomas (VS) were considered those that arose in internal organs. Rates were age standardized using the European (ASR-E) and the USA standard population. The rate of coexistence of VS and STS was calculated by dividing the 2 corresponding ASRs. Results: There were 1558 sarcomas, 968 STS, and 590 VS. The ASRs-USA per 100,000 person-years was 5.12 × 105 among males and 4.58 × 105 among females for all sarcomas. For males and females, respectively, the ASR-E per 100,000 person-years was 3.58 × 105 and 2.55 × 105, respectively, for STS; 1.47 × 10 5 and 1.97 × 105, respectively, for VS; and 0.55 × 105 and 0.10 × 105, respectively, for Kaposi sarcoma. The coexistence rate of VS and STS was 0.41 for males and 0.77 for females. For dermatofibrosarcoma (both sexes), uterine sarcoma, liposarcoma (females), and leiomyosarcoma, including or excluding the uterus (females), the age-specific rates depicted a curve with a rapid increasing trend until ages 40 to 50 years and little variation thereafter. Conclusions: Compared with the incidence of STS, VS incidence made up an additional 41% in males and 77% in females. Because the shape of age-specific curves for some histotypes was similar to that of breast cancer, the authors concluded that sex hormones (plus many chemicals that act as endocrine disruptors) may be involved in carcinogenesis. This evidence could pave the way to investigate alternative treatments and to explore etiology. Cancer 2012. © 2012 American Cancer Society. Source

Sanfilippo R.,Adult Mesenchymal Tumor Medical Oncology Unit | Dei Tos A.P.,Treviso General Hospital | Casali P.G.,Adult Mesenchymal Tumor Medical Oncology Unit
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: Myxoid/round cell liposarcoma (MRCL) represents about 10% of all soft-tissue sarcomas. Therapeutic options for this subgroup of tumours are limited, essentially doxorubicin-based regimens and trabectedin. Recently, the mammalian target of rapamycin (mTOR) pathway has been identified as a therapeutic target in several sarcomas. MRCLs should be included among these, as various molecular aberrations of the mTOR pathway have been recently reported. RECENT FINDINGS: PI3KCA mutations were identified in 10-20% of MRCLs. Other molecular aberrations include loss of PTEN, Akt activation and overexpression of IGF1R. Recently, two minor responses to mTOR inhibitors were reported. SUMMARY: The relatively high frequency of mTOR signalling pathway alterations in MRCL provides a preclinical rationale for considering mTOR inhibition as a potential novel therapeutic strategy warranting further investigation. Copyright © Lippincott Williams & Wilkins. Source

Lorenzetto E.,Italian National Cancer Institute | Brenca M.,Italian National Cancer Institute | Boeri M.,Italian National Cancer Institute | Verri C.,Italian National Cancer Institute | And 9 more authors.
Oncotarget | Year: 2014

The transcriptional coactivator YAP1 is a critical effector of the human Salvador-Warts-Hippo pathway. Literature data report apparently discrepant results on the carcinogenic role of YAP1, which acts either as oncogene or as tumor suppressor in different in vitro and in vivo models. Furthermore, genomic amplification events of 11q22 locus encompassing YAP1 gene have been detected in multiple tumor types but there is limited direct evidence about the oncogenic role of endogenous YAP1 within in the amplicon. We screened a panel of human tumor samples and cancer cell lines and identified that the YAP1 amplification event is actually present in up to 23% of the cases. We exploited EKVX (lung cancer), CaSki (cervical cancer) and RO82 (thyroid cancer) cell lines harboring both genomic YAP1 amplification and YAP1 protein overexpression, in order to study the effects of downregulation of endogenous YAP1 by RNA-interference strategies. Class comparison analysis of gene expression profiling data identified 707 statistically significantly modulated genes (multivariable global test p-value = 0.002) that were functionally annotated for cell proliferation and cellular movement ontologies. Mechanistic studies of the identified perturbed pathways revealed that YAP1 silencing significantly decreased cell proliferation and cell cycle perturbation associated with upregulation of p21 and p27 cell-cycle inhibitors, reduced cell migration (p<0.048) and anchorage-independent growth (p<0.02). In CaSki cell line, YAP1 silencing induced significantly increased sensitivity and cell-death response to cisplatin treatment (p=0.011) as well as reduction of in-vivo tumorigenic potential (p=0.027). Overall, these results establish that YAP1 is a direct oncogenic target of the 11q22 amplicon in previously unreported cancer types and support the relevance of such genetic aberration in carcinogenesis in a fraction of multiple tumor types. Source

Vincenzi B.,Biomedical University of Rome | Silletta M.,Biomedical University of Rome | Schiavon G.,Royal Marsden Hospital | Frezza A.M.,Biomedical University of Rome | And 5 more authors.
Expert Opinion on Investigational Drugs | Year: 2013

Background: To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs). Methods: From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m2 for three consecutive days every 21 days until disease progression or intolerable toxicity. Results: Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21%), stable disease (SD) in six patients (43%) and progressive disease (PD) in five patients (36%), with a clinical benefit rate (RECIST PR±SD > 6 months) of 64%. The median time of progression was 20 weeks (range: 9-34 weeks) and the median overall survival was 43 weeks (range: 17-65 weeks). The main toxicities were neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and skin reactions (57%). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity. Conclusions: Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes. © 2012 Informa UK, Ltd. Source

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