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Milano, Italy

Gomez-Lira M.,University of Verona | Ferronato S.,University of Verona | Malerba G.,University of Verona | Santinami M.,Unit of Melanoma and Sarcoma | And 5 more authors.
Experimental Dermatology | Year: 2014

Prostaglandins, especially prostaglandin E synthetase (PGE2), influence carcinogenesis by promoting cell proliferation, inhibiting apoptosis, stimulating angiogenesis and mediating immune suppression. Cyclooxygenase-2, coded by the PTGS2 gene, is the key enzyme in the production of prostaglandins. In melanoma, Cox-2 is over expressed in primary malignant melanoma (MM) and in their corresponding metastases. Polymorphisms in the promoter region of PTGS2 gene can modulate gene expression and could modify individual susceptibility to MM. Two hundred and forty melanoma patients and 342 controls were genotyped for polymorphisms -765G>C (rs20417) and -1195A>G (rs689466). Allele -765C frequency was significantly higher in melanoma patients. No allele frequency differences for -1195A>G polymorphism were observed. Haplotype analysis revealed that the haplotypes carrying the minor alleles were associated to a higher risk of melanoma (P = 0.02). Expression analysis showed that allele -765C is associated to a higher gene expression and could represent a risk allele by affecting the functionality of the promoter. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Donini M.,Azienda Istituti Ospitalieri di Cremona | Buti S.,Azienda Istituti Ospitalieri di Cremona | Buti S.,Oncology Unit | Lazzarelli S.,Azienda Istituti Ospitalieri di Cremona | And 11 more authors.
Targeted Oncology | Year: 2015

The aim of this study was to explore the efficacy and toxicities of a combined regimen of bevacizumab plus immunotherapy and chemotherapy (BIC) and the circulating T regulatory cells (Treg) in metastatic renal cell cancer (mRCC). Nephrectomized mRCC patients were enrolled into a multicenter single-arm dose-finding study with five escalated dose levels of chemotherapy with intravenous gemcitabine and 5-fluorouracil associated with fixed intravenous doses of bevacizumab, subcutaneous low doses of interleukin-2, and interferon-α-2a. An expanded cohort (phase II study) was treated at the recommended dose for additional safety and efficacy information according to minimax Simon two-stage design. Blood samples for Treg were collected and evaluated by fluorescence-activated cell sorting (FACS) analysis on cycle 1. Fifty-one patients were entered to receive one of five dose levels. Median age was 58 years (male 67 %, pretreated 49 %): 15 patients were low risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, while 27 and nine were respectively intermediate- and high-risk patients. More frequent grade 3 and 4 toxicities included nonfebrile neutropenia, thrombocytopenia, and fever. Among patients evaluable for response (49), 29.5 % had partial response and 37 % stable disease. Overall median time to progression and median overall survival were 8.8 and 22.67 months, respectively. We observed a rapid increase in the percentage of Treg after immunotherapy and a reduction after bevacizumab only in patient who obtained a partial response or stable disease. The BIC was feasible, well tolerated, and shown interesting activity. Further studies are needed to explore if Treg could have a role in clinical response in mRCC treated with bevacizumab. © 2014, Springer International Publishing Switzerland.

Camisaschi C.,Unit of Immunotherapy | Vallacchi V.,Unit of Immunotherapy | Castelli C.,Unit of Immunotherapy | Rivoltini L.,Unit of Immunotherapy | Rodolfo M.,Unit of Immunotherapy
Expert Review of Molecular Diagnostics | Year: 2014

Melanoma is an immunogenic tumor and immunotherapy treatment has established an increase in disease-free and overall survival in melanoma patients. However, a complex network of immunosuppressive mechanisms has been demonstrated to occur at the tumor site and in locoregional immune districts, such as sentinel lymph nodes (SLNs). The interplay between tumor cells and the local microenvironment leads to a tumor-driven shaping of the immune response that results in a heterogeneous cellular and molecular composition of tumor infiltrating lymphocytes (TILs). Several studies have reported the potential prognostic value of TILs infiltrating primary tumors and the association of 'immune signature' in SLNs and in melanoma metastases with prognosis and responsiveness to immunotherapeutic approaches. However, a systematic and deeper characterization of the local immunological status of TILs and SLNs is still required to refine melanoma stage classification. © 2014 Informa UK, Ltd.

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