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Pancreatic Neoplasms: HELP
Articles by Viola Caretti
Based on 2 articles published since 2010
(Why 2 articles?)

Between 2010 and 2020, Viola Caretti wrote the following 2 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article Role of CYB5A in pancreatic cancer prognosis and autophagy modulation. 2014

Giovannetti, Elisa / Wang, Qiuyan / Avan, Amir / Funel, Niccola / Lagerweij, Tonny / Lee, Jih-Hsiang / Caretti, Viola / van der Velde, Arjan / Boggi, Ugo / Wang, Yisong / Vasile, Enrico / Peters, Godefridus J / Wurdinger, Thomas / Giaccone, Giuseppe. ·Affiliations of authors: Department of Medical Oncology (EG, AA, GJP) and Department of Neurosurgery (TL, VC, TW), VU University Medical Center, and Centre for Integrative Bioinformatics (AvdV), VU University, Amsterdam, the Netherlands · Department of Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy (NF, UB, EV) · Department of Neurology, Stanford University, Stanford, CA (VC) · Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA (TW) · Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (QW, J-HL, YW, GG). ·J Natl Cancer Inst · Pubmed #24301457.

ABSTRACT: BACKGROUND: Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma (PDAC). This study investigated genes encoded by this cytoband. METHODS: We studied mRNA/protein expression in radically resected (n = 130) and metastatic patients (n = 50). The role of CYB5A was tested in 11 PDAC cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. CYB5A+ orthotopic models (n = 6 mice/group) were monitored by Firefly and Gaussia-luciferase bioluminescence, magnetic resonance imaging, and high-frequency ultrasound. Data were analyzed by t test, Fisher exact-test, log-rank test and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Both resected and metastatic patients with low mRNA or protein expression of CYB5A had statistically significantly shorter survival (eg, median = 16.7 months, 95% confidence interval [CI] = 13.5 to 19.9; vs median = 24.8 months, 95% CI = 12.8 to 36.9; P = .02, two-sided log-rank test; n = 82 radically resected PDACs), and multivariable analyses confirmed prognostic relevance. Moreover, we characterized a novel function to CYB5A, autophagy induction, concomitant with reduced proliferation and migration/invasion of PDAC cells. Network analysis of proautophagic pathways suggested CYB5A interaction with TRAF6, which was confirmed by TRAF6 downregulation after CYB5A reconstitution (-69% in SU.86.86-CYB5A+; P = .005, two-sided t test). CYB5A silencing had opposite effects, restoring TRAF6 expression and wound healing. In vivo studies showed that CYB5A induced autophagy while inhibiting tumor growth/metastasis and increasing survival (median = 57 days, 95% CI = 52 to 61; vs median = 44 days, 95% CI = 21 to 57; P = .03, two-sided log-rank test). CONCLUSIONS: These results define CYB5A as a novel prognostic factor for PDAC that exerts its tumor-suppressor function through autophagy induction and TRAF6 modulation.

2 Article Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma. 2013

Avan, Amir / Caretti, Viola / Funel, Niccola / Galvani, Elena / Maftouh, Mina / Honeywell, Richard J / Lagerweij, Tonny / Van Tellingen, Olaf / Campani, Daniela / Fuchs, Dieter / Verheul, Henk M / Schuurhuis, Gerrit-Jan / Boggi, Ugo / Peters, Godefridus J / W├╝rdinger, Thomas / Giovannetti, Elisa. ·Authors' Affiliations: Departments of Medical Oncology, Hematology, Neurosurgery and Pediatric Oncology/Hematology, Neuro-oncology Research Group, VU University Medical Center; Diagnostic Oncology Division, Netherlands Cancer Institute; VisualSonics, Amsterdam, the Netherlands; Departments of Neurology and Pediatrics, Stanford University School of Medicine, Stanford, California; Division of Surgical Pathology, Division of General and Transplant Surgery, University of Pisa, Pisa, Italy; and Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, Massachusetts. ·Cancer Res · Pubmed #24085787.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here, we developed four orthotopic mouse models using primary human PDAC cells genetically engineered to express firefly- and Gaussia luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and high-frequency ultrasound. In these models, we conducted detailed histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic characteristics were compared with the originator tumor and primary tumor cells using array-based comparative genomic hybridization, using frozen specimens obtained by laser microdissection. Notably, the orthotopic human xenografts in these models recapitulated the phenotype of human PDACs, including hypovascular and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an increased copy number and overexpression of c-Met in one of the models; we examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In particular, we found that crizotinib decreased tumor dimension, prolonged survival, and increased blood and tissue concentrations of gemcitabine, synergizing with a cytidine deaminase-mediated mechanism of action. Together, these more readily imaged orthotopic PDAC models displayed genetic, histopathologic, and metastatic features similar to their human tumors of origin. Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination of drugs warranting clinical evaluation for PDAC treatment.