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Pancreatic Neoplasms: HELP
Articles by Niccola Funel
Based on 56 articles published since 2010
(Why 56 articles?)

Between 2010 and 2020, N. Funel wrote the following 56 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
Pages: 1 · 2 · 3
51 Article Mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas. 2010

Corbo, Vincenzo / Ritelli, Rossana / Barbi, Stefano / Funel, Niccola / Campani, Daniela / Bardelli, Alberto / Scarpa, Aldo. ·ARC-NET Research Center, University of Verona, Policlinico GB Rossi, Verona, Italy. ·PLoS One · Pubmed #20838624.

ABSTRACT: BACKGROUND: Protein kinases are key regulators of cellular processes (such as proliferation, apoptosis and invasion) that are often deregulated in human cancers. Accordingly, kinase genes have been the first to be systematically analyzed in human tumors leading to the discovery that many oncogenes correspond to mutated kinases. In most cases the genetic alterations translate in constitutively active kinase proteins, which are amenable of therapeutic targeting. Tumours of the pancreas are aggressive neoplasms for which no effective therapeutic strategy is currently available. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a DNA-sequence analysis of a selected set of 35 kinase genes in a panel of 52 pancreatic exocrine neoplasms, including 36 pancreatic ductal adenocarcinoma, and 16 ampulla of Vater cancer. Among other changes we found somatic mutations in ATM, EGFR, EPHA3, EPHB2, and KIT, none of which was previously described in cancers. CONCLUSIONS/SIGNIFICANCE: Although the alterations identified require further experimental evaluation, the localization within defined protein domains indicates functional relevance for most of them. Some of the mutated genes, including the tyrosine kinases EPHA3 and EPHB2, are clearly amenable to pharmacological intervention and could represent novel therapeutic targets for these incurable cancers.

52 Article Study of apoptosis induction and deoxycytidine kinase/cytidine deaminase modulation in the synergistic interaction of a novel ceramide analog and gemcitabine in pancreatic cancer cells. 2010

Giovannetti, E / Leon, L G / Bertini, S / Macchia, M / Minutolo, F / Funel, N / Alecci, C / Giancola, F / Danesi, R / Peters, G J. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. ·Nucleosides Nucleotides Nucleic Acids · Pubmed #20544530.

ABSTRACT: This study investigated the interaction between the novel ceramide analog AL6 and gemcitabine in MIA PaCa-2 and PANC-1 pancreatic cancer cell lines, harboring different polymorphic variants of the gemcitabine catabolism enzyme cytidine deaminase (CDA). AL6 dose-dependently inhibited cell growth, induced apoptosis and synergistically enhanced the cytotoxic activity of gemcitabine. Moreover, it triggered apoptosis, which was significantly enhanced by the combination, and increased the ratio between gene expression of the activating enzyme deoxycytidine kinase (dCK) and CDA, potentially favoring gemcitabine activity. In conclusion, AL6 displays synergistic cytotoxic activity, enhances apoptosis, and favorably modulates enzymes involved in gemcitabine metabolism, supporting future investigation of this combination in pancreatic cancer.

53 Article Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. 2010

Hwang, Jin-Hyeok / Voortman, Johannes / Giovannetti, Elisa / Steinberg, Seth M / Leon, Leticia G / Kim, Yong-Tae / Funel, Niccola / Park, Joo Kyung / Kim, Min A / Kang, Gyeong Hoon / Kim, Sun-Whe / Del Chiaro, Marco / Peters, Godefridus J / Giaccone, Giuseppe. ·Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. ·PLoS One · Pubmed #20498843.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy. METHODOLOGY/PRINCIPAL FINDINGS: Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166-0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280-0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells. CONCLUSIONS SIGNIFICANCE: Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.

54 Article MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. 2010

Giovannetti, Elisa / Funel, Niccola / Peters, Godefridus J / Del Chiaro, Marco / Erozenci, Leyla A / Vasile, Enrico / Leon, Leticia G / Pollina, Luca E / Groen, Annemieke / Falcone, Alfredo / Danesi, Romano / Campani, Daniela / Verheul, Henk M / Boggi, Ugo. ·VU University Medical Center, Amsterdam, the Netherlands. ·Cancer Res · Pubmed #20460539.

ABSTRACT: MicroRNA-21 (miR-21) was reported to be overexpressed and contributes to invasion and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether miR-21 expression was associated with the overall survival (OS) of PDAC patients treated with gemcitabine and to provide mechanistic insights for new therapeutic targets. miR-21 expression was evaluated in cells (including 7 PDAC cell lines, 7 primary cultures, fibroblasts, and a normal pancreatic ductal cell line) and tissues (neoplastic specimens from 81 PDAC patients and normal ductal samples) isolated by laser microdissection. The role of miR-21 on the pharmacologic effects of gemcitabine was studied with a specific miR-21 precursor (pre-miR-21). Patients with high miR-21 expression had a significantly shorter OS both in the metastatic and in the adjuvant setting. Multivariate analysis confirmed the prognostic significance of miR-21. miR-21 expression in primary cultures correlated with expression in their respective tissues and with gemcitabine resistance. Pre-miR-21 transfection significantly decreased antiproliferative effects and apoptosis induction by gemcitabine, whereas matrix metalloproteinase (MMP)-2/MMP-9 and vascular endothelial growth factor expression were upregulated. Addition of inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin resulted in decrease of phospho-Akt and prevented pre-miR-21-induced resistance to the proapoptotic effects of gemcitabine. miR-21 expression correlated with outcome in PDAC patients treated with gemcitabine. Modulation of apoptosis, Akt phosphorylation, and expression of genes involved in invasive behavior may contribute to the role of miR-21 in gemcitabine chemoresistance and to the rational development of new targeted combinations.

55 Minor The odd case of a small and mucinous-like acinar cell cystoadenocarcinoma of the pancreas. 2012

Perrone, Vittorio G / Mariniello, Donatella M / De Lio, Nelide / Caniglia, Fabio / Cappelli, Carla / Campani, Daniela / Funel, Niccola / Amorese, Gabriella / Boggi, Ugo. · ·Pancreatology · Pubmed #23127530.

ABSTRACT: -- No abstract --

56 Minor Correlation of basal EGFR expression with pancreatic cancer grading but not with clinical outcome after gemcitabine-based treatment. 2011

Funel, N / Vasile, E / Del Chiaro, M / Boggi, U / Falcone, A / Campani, D / Scarpa, A / Giovannetti, E. · ·Ann Oncol · Pubmed #21196439.

ABSTRACT: -- No abstract --