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Bravaccini S.,Biosciences Laboratory | Granato A.M.,Immunotherapy and Somatic Cell Therapy Unit | Medri L.,Pathology Unit | Foca F.,Unit of Biostatistics and Clinical Trials | And 10 more authors.
Cellular Oncology | Year: 2013

Purpose: The increasing use of breast-conserving surgery makes it essential to identify biofunctional profiles responsible for the progression of in situ to invasive carcinomas to facilitate the detection of lesions that are most likely to relapse or progress and, thus, to be able to offer patients tailored treatment options. Our objective was to analyse and compare biofunctional profiles in ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC). We also aimed to identify markers in tumor and normal surrounding tissues that may be predictive of locoregional recurrence in patients with DCIS. Methods: Biofunctional parameters including mitotic activity, estrogen receptor, progesterone receptor, microvessel density (MVD), c-kit and p27 expression were evaluated in 829 in situ and invasive carcinomas. The impact of the biomarker profiles of DCIS, IDC and normal surrounding tissues on loco-regional recurrence was analyzed. Results: A progressive increase in cell proliferation and a concomitant decrease in steroid hormone receptor-positive lesions was observed during the transition from in situ to invasive carcinomas, as also within each subgroup as grade increased. Conversely, p27 expression and MVD dramatically decreased during the transition from in situ to invasive carcinomas. Finally, we found that a low c-kit expression was indicative of IDC relapse. Conclusions: Cell proliferation, hormonal and differentiation characteristics differed in DCIS with respect to IDC, and the main variation in the transition between the two histologic lesions was the decrease in p27 expression and MVD. © 2013 International Society for Cellular Oncology. Source

Farolfi A.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Ridolfi L.,Immunotherapy and Somatic Cell Therapy Unit | Guidoboni M.,Immunotherapy and Somatic Cell Therapy Unit | Milandri C.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | And 4 more authors.
Journal of Chemotherapy | Year: 2011

The liver is the primary site of metastases in most uveal melanoma patients. We retrospectively investigated intraarterial chemotherapy (iAC) as treatment for patients with hepatic melanoma metastases. twenty-three patients (18 with uveal melanoma) received fotemustine (14 patients, 61.9%) or carboplatin (9 patients, 31.1%) via hepatic iAC delivery. the catheter was introduced through percutaneous access to the femoral artery with drugs delivered directly to the hepatic artery, and was removed at the end of each treatment cycle. A total of 3 cycles was planned, repeated every 21 days. However, patients with a clinical response could receive more than 3 cycles, provided that the toxic effects were acceptable. iAC was well tolerated and no catheter-related complications or grade 4 toxicities were reported. Considering only uveal melanoma patients, the overall response rate and disease control rate was 16.7% and 38.9%, respectively. median time to progression was 6.2 months (95% Ci 3.7-10.5) and median overall survival was 21 months (95% Ci 8-39). iAC is well tolerated and is a valid choice for patients with a poor prognosis since median survival rates are among the longest reported. © E.S.I.F.T. srl - Firenze. Source

Chiarion-Sileni V.,Melanoma and Skin Cancer Unit | Guida M.,Istituto Oncologico | Ridolfi L.,Immunotherapy and Somatic Cell Therapy Unit | Romanini A.,Medical Oncology Unit | And 6 more authors.
British Journal of Cancer | Year: 2011

Background:This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients.Methods:A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m 2 per day; days 1-5) or intravenous dacarbazine (800 mg m 2; day 1), in combination with intravenous cisplatin (75 mg m 2; day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI).Results:A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n74, CDI: n75). The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P0.22). In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation. Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm. No difference in toxicity was observed between the two arms.Conclusion:The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen. Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies. © 2011 Cancer Research UK All rights reserved. Source

Venanzi F.M.,University of Camerino | Petrini M.,Immunotherapy and Somatic Cell Therapy Unit | Fiammenghi L.,Immunotherapy and Somatic Cell Therapy Unit | Bolli E.,University of Camerino | And 7 more authors.
Cancer Immunology, Immunotherapy | Year: 2010

Previous studies have shown that tumor endothelial markers (TEMs 1-9) are up modulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. We recently reported that monocyte-derived DCs used for vaccination trials may accumulate high levels of TEM8 gene transcripts. Here, we investigate whether TEM8 expression in DC preparations represents a specific tumor-associated change of potential clinical relevance. TEM8 expression at the mRNA and protein level was evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis in human clinical grade DCs utilized for the therapeutic vaccination of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma). The analyses revealed that DCs from patients markedly differ in their ability to up-modulate TEM8. Indeed, mDCs from eight non-progressing patients [median overall survival (OS) = 32 months, all positive to the delayed-type hypersensitivity test (DTH)], had similar TEM8 mRNA expression levels [mDCs vs. immature iDCs; mean fold increase (mfi) = 1.97] to those found in healthy donors (mfi = 2.7). Conversely, mDCs from nine progressing patients (OS < 5 months, all but one with negative DTH) showed an increase in TEM8 mRNA levels (mfi = 12.88, p = 0.0018). The present observations suggest that TEM8 expression levels in DC-based therapeutic vaccines would allow the selection of a subgroup of patients who are most likely to benefit from therapeutic vaccination. © 2009 Springer-Verlag. Source

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