Veneto Institute of Oncology

Padova, Italy

Veneto Institute of Oncology

Padova, Italy
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Grigoletto A.,University of Padua | Maso K.,University of Padua | Mero A.,University of Padua | Rosato A.,University of Padua | And 4 more authors.
Journal of Drug Delivery Science and Technology | Year: 2016

Drug and protein delivery techniques and methods, which, in most cases, are concurrently investigated from the very time a new molecular entity is proposed, have become valuable tools for the development of numerous therapeutic molecules. Attracting the attention of academia and industrial researchers, several polymer conjugation methodologies have been shown to have a wide range of applications and a success rate that have been confirmed by the numerous conjugates already in clinical use or under investigation in on-going clinical trials. Having attained a high level of sophistication, this technology is able to generate homogeneous conjugates by exploiting specifically designed coupling strategies (based, for example, on the use of enzymes), which ensure good product characterization, high activity retention, and batch-to-batch reproducibility. Poly(ethylene glycol) (PEG), which is the current gold standard for stealth polymers in the emerging field of polymer-based drug delivery, is in competition with other polymers that have convenient features such as biodegradability. PEG still holds first place as far as PEGylated derivatives under investigation in clinical trials are concerned, and it will presumably remain the polymer of choice even in the future as further improvements such as the development of new copolymers based on PEG or PEG derivatives will overcome for example the hurdle of biodegradability. © 2015 Elsevier B.V. All rights reserved.

Mingozzi E.,GfK Eurisko S.r.l. | Fregosi S.,GfK Eurisko S.r.l. | Gandini S.,Italian National Cancer Institute | Stanganelli I.,Scientific Institute of Romagna for the Study and Treatment of Tumors | And 2 more authors.
Dermatology | Year: 2013

A nationwide survey of the diagnostic-therapeutic models used in Italian hospitals for the treatment of melanoma was performed. The study was conducted using paper-assisted personal interviews in hospitals throughout the country [De Vaus DA: Surveys in Social Research, ed 4. London, Routledge, 1995]. Face-to-face interviews were conducted by interviewers specialized in medical research. These 45-minute interviews took place in the office/clinic of the interviewee, during which the interviewer compiled and checked questionnaires for completeness and accuracy. In each hospital, clinicians responsible for the diagnosis, therapy or follow-up phases of melanoma care were interviewed according to their area of expertise. When possible, interviewees included a dermatologist, a surgeon and an oncologist from each hospital. Copyright © 2013 S. Karger AG, Basel.

Comino-Mendez I.,Hereditary Endocrine Cancer Group | Comino-Mendez I.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Gracia-Aznarez F.J.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Gracia-Aznarez F.J.,Human Genetics Group | And 33 more authors.
Nature Genetics | Year: 2011

Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. © 2011 Nature America, Inc. All rights reserved.

Pasquali S.,University of Sydney | Pasquali S.,University of Padua | Pasquali S.,Veneto Institute of Oncology | van der Ploeg A.P.T.,University of Sydney | And 6 more authors.
Pigment Cell and Melanoma Research | Year: 2013

Recently developed lymphatic-specific immunohistochemical markers can now be utilized to assess intratumoral and/or peritumoral lymphatic vessel density (LVD), to detect lymphatic vessel invasion (LVI) by melanoma cells and to identify lymphatic marker expression in melanoma cells themselves. We systematically reviewed the available evidence for the expression of lymphatic markers as predictors of regional node metastasis and survival in melanoma patients. The currently available evidence suggests that LVD (particularly in a peritumoral location) and LVI are predictors of sentinel node metastasis and poorer survival. Nevertheless, adherence to international guidelines in the conduct and reporting of the studies was generally poor, with wide methodologic variations and heterogeneous findings. Larger, carefully conducted and well-reported studies that confirm these preliminary findings are required before it would be appropriate to recommend the routine application of costly and time-consuming immunohistochemistry for lymphatic markers in the routine clinical assessment of primary cutaneous melanomas. © 2013 John Wiley & Sons A/S.

Qin Y.,University of Texas Health Science Center at San Antonio | Yao L.,University of Texas Health Science Center at San Antonio | King E.E.,University of Texas Health Science Center at San Antonio | Buddavarapu K.,University of Texas Health Science Center at San Antonio | And 13 more authors.
Nature Genetics | Year: 2010

Pheochromocytomas, which are catecholamine-secreting tumors of neural crest origin, are frequently hereditary. However, the molecular basis of the majority of these tumors is unknown. We identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 103 samples, we detected truncating germline TMEM127 mutations in approximately 30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas without a known genetic cause. The wild-type allele was consistently deleted in tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. Pheochromocytomas with mutations in TMEM127 are transcriptionally related to tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro gain-of-function and loss-of-function analyses indicate that TMEM127 is a negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane system and colocalizes with perinuclear (activated) mTOR, suggesting a subcompartmental-specific effect. Our studies identify TMEM127 as a tumor suppressor gene and validate the power of hereditary tumors to elucidate cancer pathogenesis. © 2010 Nature America, Inc. All rights reserved.

Iacobone M.,Veneto Institute of Oncology | Citton M.,Veneto Institute of Oncology | Scarpa M.,Veneto Institute of Oncology | Viel G.,Veneto Institute of Oncology | And 2 more authors.
British Journal of Surgery | Year: 2015

Background: Subclinical Cushing's syndrome (SCS) is a condition of biochemical cortisol excess without the classical clinical features of overt hypercortisolism; it may be associated with some consequences of metabolic syndrome. The most appropriate treatment remains controversial. This study aimed to assess the outcomes of adrenalectomy for SCS. Methods: A systematic review was performed. MEDLINE, Embase and Cochrane Databases (1980-2013) were searched for studies reporting the outcomes of unilateral adrenalectomy with respect to hypertension, diabetes, dyslipidaemia, obesity and osteoporosis in patients with SCS. Studies with a questionable diagnosis of SCS, bilateral adrenal involvement and insufficient data were excluded. Results: Of the 105 papers screened, seven were selected; there were six retrospective studies and one randomized clinical trial, including 230 patients. Data analysis was limited by heterogeneity in definition of SCS and endpoints. Hypercortisolism was cured in all operated patients. Laparoscopy was the preferred approach, with a morbidity rate of 0.8 per cent. A beneficial effect of surgery on blood pressure, glucometabolic control and obesity was evident in all studies, with cure or improvement in 72, 46 and 39 per cent of patients respectively, compared with conservative management. The results for lipid metabolism were equivocal, because of a decrease in triglyceridaemia but discordant effects on cholesterol metabolism among the different studies. No beneficial effects on osteoporosis were found. Conclusion: Laparoscopic adrenalectomy seems to be beneficial in reversing several metabolic effects of hypercortisolism, with a low morbidity rate. However, the heterogeneity and low quality of the available studies preclude definitive recommendations. © 2015 BJS Society Ltd.

Opocher G.,Veneto Institute of Oncology | Opocher G.,University of Padua | Schiavi F.,Veneto Institute of Oncology
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2010

Pheochromocytoma and paraganglioma are tumors of the sympathetic or parasympathetic paraganglia. Pheochromocytoma is the tumor of the main sympathetic paraganglia, which is the adrenal medulla. The sympathetic paraganglioma secretes catecholamine while the parasympathetic do not. Both of them originate from neural crest cells and share similar mechanisms of tumor development. The same genetic alteration may predispose to the development of sympathetic and parasympathetic paraganglioma. The best known hereditary forms of pheochromocytoma and paraganglioma are the von Hippel-Lindau disease, in which pheochromocytoma may be associated with CNS hemangioblastoma, retinal angioma, pancreatic endocrine tumor/cysts and renal clear cell carcinoma/cysts; the multiple endocrine neoplasia type 2, in which pheochromocytoma is associated with medullary thyroid carcinoma and primary hyperparathyroidism, Type 1 neurofibromatosis, the most frequent hereditary cancer syndrome. Finally, it has been characterized the paraganglioma syndrome in which sympathetic and parasympathetic paraganglioma are variously associated. The list of predisposing gene is quite long and comprises VHL, RET, NF1, SDHB, SDHC, SDHD, SDHAF2. More rarely, two other genes may predispose to pheochromocytoma/paraganglioma development: KIF1Bbeta and PHD2. A mechanism conducing to a defective apoptosis is the common pathways of those genes. Finally, there is also good evidence of the role of other genes, not yet completely identified. © 2010 Elsevier Ltd. All rights reserved.

Rumiato E.,Veneto Institute of Oncology | Boldrin E.,Veneto Institute of Oncology | Amadori A.,Veneto Institute of Oncology | Amadori A.,University of Padua | Saggioro D.,Veneto Institute of Oncology
Cancer Chemotherapy and Pharmacology | Year: 2013

Purpose: 5-fluorouracil (5-FU) has been widely used since the 1980s, and it remains the backbone of many chemotherapeutic combination regimens. However, its use is often limited by the occurrence of severe toxicity. Although several reports have shown the detrimental effect of some dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS) gene polymorphisms in patients undergoing 5-FU-based treatment, they account for only a minority of toxicities. Methods: Looking for new candidate genetic variants associated with 5-FU-induced toxicity, we used the innovative genotyping microarray Affymetrix Drug-Metabolizing Enzymes and Transporters (DMET)™ Plus GeneChip that interrogates 1,936 genetic variants distributed in 231 genes involved in drug metabolism, excretion, and transport. To reduce variability, we analyzed samples from colorectal cancer patients who underwent fairly homogenous treatments (i.e., Machover or Folfox) and experienced G3 or G4 toxicity; control patients were matched for therapy and selected from those who did not disclose toxicity (G0-G1). Results: Pharmacogenetic genotyping showed no significant difference in DPYD and TYMS genetic variants distribution between cases and controls. However, other polymorphisms could account for 5-FU-induced toxicity, with the CHST1 rs9787901 and GSTM3 rs1799735 having the strongest association. Conclusions: Although exploratory, this study suggests that genetic polymorphisms not directly related to 5-FU pharmacokinetics and pharmacodynamics are involved in 5-FU-induced toxicity. Our data also indicates DMET™ microarray as a valid approach to discover new genetic determinants influencing chemotherapy-induced toxicity. © 2013 Springer-Verlag Berlin Heidelberg.

Scarpa M.,Veneto Institute of Oncology | Valente S.,Veneto Institute of Oncology | Alfieri R.,Veneto Institute of Oncology | Cagol M.,Veneto Institute of Oncology | And 3 more authors.
World Journal of Gastroenterology | Year: 2011

This study is aimed to assess the long-term health-related quality of life (HRQL) of patients after esophagectomy for esophageal cancer in comparison with es-tablished norms, and to evaluate changes in HRQL during the different stages of follow-up after esophageal resection. A systematic review was performed by searching medical databases (Medline, Embase and the Cochrane Library) for potentially relevant studies that appeared between January 1975 and March 2011. Studies were included if they addressed the question of HRQL after esophageal resection for esophageal cancer. Two researchers independently performed the study selection, data extraction and analysis processes. Twenty-one observational studies were included with a total of 1282 (12-355) patients. Five studies were performed with short form-36 (SF-36) and 16 with European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 (14 of them also utilized the disease-specific OES18 or its previous version OES24). CastoroThe analysis of long-term generic HRQL with SF-36 showed pooled scores for physical, role and social function after esophagectomy similar to United States norms, but lower pooled scores for physical function, vitality and general health perception. The analysis of HRQL conducted using the Global EORTC C30 global scale during a 6-mo follow-up showed that global scale and physical function were better at the baseline. The symptom scales indicated worsened fatigue, dyspnea and diarrhea 6 mo after esophagectomy. In contrast, however, emotional function had significantly improved after 6 mo. In conclusion, short- and long-term HRQL is deeply affected after esophagectomy for cancer. The impairment of physical function may be a long-term consequence of esophagectomy involving either the respiratory system or the alimentary tract. The short- and long-term improvement in the emotional function of patients who have undergone successful operations may be attributed to the impression that they have survived a near-death experience. © 2011 Baishideng. All rights reserved.

Ulisse S.,University of Rome La Sapienza | Baldini E.,University of Rome La Sapienza | Sorrenti S.,University of Rome La Sapienza | Barollo S.,Veneto Institute of Oncology | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: The urokinase plasminogen activating system is implicated in neoplastic progression, and high tissue levels of urokinase plasminogen activating system components correlate with poor prognosis in various human cancers. Objective: The objective of the study was to investigate the prognostic relevance of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR), and the plasminogen activator inhibitor 1 (PAI-1) in human papillary thyroid cancer (PTC). Design: The expression of uPA, uPAR, and PAI-1 genes was analyzed in PTC and normal matched tissues by quantitative RT-PCR. The case study consisted of 99 patients (21 males and 78 females) affected by PTC including 77 classical, 15 follicular, four tall cell, and three oncocytic variants. Forty-one patients had lymph node metastases at the time of diagnosis. All the patients underwent thyroidectomy and radioiodine therapy followed by thyroid hormone replacement therapy. Follow-up data were available for 76 patients up to 64 months. Results: The uPA, uPAR, and PAI-1 mRNA levels were significantly higher in PTC compared with normal matched tissues by 9.63 ± 1,29-, 4.82 ± 0.45-, and 5.64 ± 0.71-fold, respectively. The increased expression of uPA and uPAR correlated statistically with advanced pT and N status. The uPA was also significantly associated with advanced tumor node metastasis stages. The Kaplan-Meier analysis showed a significant association of uPA and uPAR levels with reduced patient disease-free interval (DFI), and this association was stronger in stage I patients. Conclusion: The study demonstrated that in PTC the increased gene expression of uPA and uPAR is associated with tumor invasiveness, advanced stages, and shorter DFI, suggesting their prognostic relevance. These observations warrant further investigation in larger patient populations with longer follow-up. Copyright © 2011 by The Endocrine Society.

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