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Esposito F.,The Second University of Naples | Esposito F.,University of Naples Federico II | Boscia F.,University of Naples Federico II | Franco R.,Istituto Nazionale dei Tumori Fondazione G. Pascale | And 5 more authors.
Journal of Pathology

Oestrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of oestrogen are now known to be mediated by oestrogen receptor-α (ERα) and ERβ subtypes, but only ERβ has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas and mixed germ cell tumours, but remains high in teratomas. PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. We have previously described that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mislocalization could be associated with the development of testicular germ cell tumours. Here we show that ERβ interacts with PATZ1 in normal germ cells, while down-regulation of ERβ associates with transcriptional co-regulator PATZ1 delocalization in human testicular seminomas. In addition, we show that the translocation of PATZ1 from the cytoplasm into the nucleus is regulated by cAMP, which also induces increased expression and nuclear localization of ERβ, while this effect is counteracted by using the anti-oestrogen ICI 182-780. © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source

Hoshimoto S.,John Wayne Cancer Institute | Faries M.B.,The Surgical Center | Morton D.L.,The Surgical Center | Shingai T.,John Wayne Cancer Institute | And 8 more authors.
Annals of Surgery

Objective: To verify circulating tumor cell (CTC) prognostic utility in stage IV resected melanoma patients in a prospective international phase III clinical trial. Background: Our studies of melanoma patients in phase II clinical trials demonstrated prognostic significance for CTCs in patients with AJCC stage IV melanoma. CTCs were assessed to determine prognostic utility in follow-up of disease-free stage IV patients pre-and during treatment. Methods: After complete metastasectomy, patients were prospectively enrolled in a randomized trial of adjuvant therapy with a whole-cell melanoma vaccine, Canvaxin, plus Bacille Calmette-Guerin (BCG) versus placebo plus BCG. Blood specimens obtained pretreatment (n = 244) and during treatment (n = 214) were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction (qPCR) for expression of MART-1, MAGE-A3, and PAX3 mRNA biomarkers. Univariate and multivariate Cox analyses examined CTC biomarker expression with respect to clinicopathological variables. Results: CTC biomarker(s) (1) was detected in 54% of patients pretreatment and in 86% of patients over the first 3 months. With a median follow-up of 21.9 months, 71% of patients recurred and 48% expired. CTC levels were not associated with known prognostic factors or treatment arm. In multivariate analysis, pretreatment CTC (> 0 vs. 0 biomarker) status was significantly associated with disease-free survival (DFS; HR 1.64, P = 0.002) and overall survival (OS; HR 1.53, P = 0.028). Serial CTC (>0 vs. 0 biomarker) status was also significantly associated with DFS (HR 1.91, P = 0.02) and OS (HR 2.57, P = 0.012). Conclusion: CTC assessment can provide prognostic discrimination before and during adjuvant treatment for resected stage IV melanoma patients. Study registration ID# NCT00052156. © 2012 by Lippincott Williams & Wilkins. Source

Galatola M.,University of Naples Federico II | Paparo L.,University of Naples Federico II | Duraturo F.,University of Naples Federico II | Turano M.,University of Naples Federico II | And 3 more authors.
BMC Medical Genetics

Background: The "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues.The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration.Methods: We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques.Results: Our data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed.Conclusion: In light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers. © 2012 Galatola et al; licensee BioMed Central Ltd. Source

Capasso M.,CEINGE Biotecnologie Avanzate | Ayala F.,Istituto Nazionale dei Tumori Fondazione G. Pascale | Avvisati R.A.,CEINGE Biotecnologie Avanzate | Russo R.,CEINGE Biotecnologie Avanzate | And 5 more authors.
Journal of Human Genetics

A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)1.21-8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness. © 2010 The Japan Society of Human Genetics. All rights reserved. Source

Boccardi L.,Azienda Ospedaliera San Camillo Forlanini | Cardinale D.,Istituto Europeo di Oncologia | Civelli M.,Istituto Europeo di Oncologia | Lestuzzi C.,Centro Of Riferimento Oncologico Irccs | And 8 more authors.
Journal of Cardiovascular Echography

In the last twenty years, with the improved survival of cancer patients, has significantly increased the detection of cardiovascular complications related to cancer treatment, even very late. To answer this need for cardiovascular protection of cancer patients, the Italian Society of CardiovascularEchography (SIEC), has recently established a Study Group on Echocardio-Oncology. Among the objectives that the Group considered it necessary to identify, there are the promotion of conferences and courses on this subject, and the scientific objectives. In fact, have been defined seven areas of interest to support and promote scientific research in the field of prevention, early diagnosis and effective treatment of myocardial dysfunction from antineoplastic therapy. This first document is the programmatic document of the Study Group. © 2011 Società Italiana di Ecografia Cardiovascolare. Published by Elsevier Srl. All rights reserved. Source

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