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Pancreatic Neoplasms: HELP
Articles by E. Calvo
Based on 3 articles published since 2010
(Why 3 articles?)

Between 2010 and 2020, E. Calvo wrote the following 3 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma. 2016

Thakur, A K / Nigri, J / Lac, S / Leca, J / Bressy, C / Berthezene, P / Bartholin, L / Chan, P / Calvo, E / Iovanna, J L / Vasseur, S / Guillaumond, F / Tomasini, R. ·CRCM, INSERM, U1068, Paoli-Calmettes Institute, Aix-Marseille University, UM 105; CNRS, UMR7258, Marseille, France. · CRCL, INSERM, U1052; CNRS 5286, Centre Léon Bérard, Lyon, France. · PISSARO Proteomic facility, (IRIB), U-Rouen, Mont Saint- Aignan, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, Canada. ·Cell Death Differ · Pubmed #26943320.

ABSTRACT: Advances made in pancreatic cancer therapy have been far from sufficient and have allowed only a slight improvement in global survival of patients with pancreatic ductal adenocarcinoma (PDA). Recent progresses in chemotherapy have offered some hope for an otherwise gloomy outlook, however, only a limited number of patients are eligible because of important cytotoxicity. In this context, enhancing our knowledge on PDA initiation and evolution is crucial to highlight certain weaknesses on which to specifically target therapy. We found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted PDA development. In two relevant and specific engineered pancreatic cancer mouse models, we observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). Through proteomic analysis of conditioned media from TAp73 wild-type (WT) and deficient pancreatic tumor cells, we identified a secreted protein, biglycan (BGN), which is necessary and sufficient to mediate this pro-EMT effect. Interestingly, BGN is modulated by and modulates the transforming growth factor-β (TGF-β) pathway, a key regulator of the EMT process. We further examined this link and revealed that TAp73 impacts the TGF-β pathway by direct regulation of BGN expression and Sma and Mad-related proteins (SMADs) expression/activity. Absence of TAp73 leads to activation of TGF-β signaling through a SMAD-independent pathway, favoring oncogenic TGF-β effects and EMT. Altogether, our data highlight the implication of TAp73 in the aggressiveness of pancreatic carcinogenesis through modulation of the TGF-β signaling. By suggesting TAp73 as a predictive marker for response to TGF-β inhibitors, our study could improve the classification of PDA patients with a view to offering combined therapy involving TGF-β inhibitors.

2 Article Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling. 2015

Secq, V / Leca, J / Bressy, C / Guillaumond, F / Skrobuk, P / Nigri, J / Lac, S / Lavaut, M-N / Bui, T-T / Thakur, A K / Callizot, N / Steinschneider, R / Berthezene, P / Dusetti, N / Ouaissi, M / Moutardier, V / Calvo, E / Bousquet, C / Garcia, S / Bidaut, G / Vasseur, S / Iovanna, J L / Tomasini, R. ·1] CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France [2] Department of Pathology, Hospital North/Mediterranean University, Marseille, France. · CRCM, Cellular Stress, INSERM, U1068, Parc scientifique de Luminy, Paoli-Calmettes Institute, Aix-Marseille University, UM 105, CNRS, UMR7258, Marseille 13009, France. · Neuronexperts, Medical North Faculty, Marseille, France. · Aix-Marseille University, INSERM, CRO2, UMR 911, Marseille 13385, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec City, QCue, Canada. · INSERM UMR 1037, CRCT, University Toulouse III, Toulouse, France. ·Cell Death Dis · Pubmed #25590802.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/β-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.

3 Article Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence. 2014

Grasso, D / Garcia, M N / Hamidi, T / Cano, C / Calvo, E / Lomberk, G / Urrutia, R / Iovanna, J L. ·Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France. · Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec City, QC, Canada. · Laboratory of Epigenetics and Chromatin Dynamics, Gastroenterology Research Unit, Departments of Biochemistry and Molecular Biology, Biophysics, and Medicine, Mayo Clinic, Rochester, MN, USA. ·Cell Death Differ · Pubmed #24902898.

ABSTRACT: Nuclear protein 1 (Nupr1), a small chromatin protein, has a critical role in cancer development, progression and resistance to therapy. Previously, we had demonstrated that Nupr1 cooperates with Kras(G12D) to induce pancreas intraepithelial neoplasias (PanIN) formation and pancreatic ductal adenocarcinoma development in mice. However, the molecular mechanisms by which Nupr1 influences Kras-mediated preneoplastic growth remain to be fully characterized. In the current study, we report evidence supporting a role for Nupr1 as a gene modifier of Kras(G12D)-induced senescence, which must be overcome to promote PanIN formation. We found that genetic inactivation of Nupr1 in mice impairs Kras-induced PanIN, leading to an increase in β-galactosidase-positive cells and an upregulation of surrogate marker genes for senescence. More importantly, both of these cellular and molecular changes are recapitulated by the results of mechanistic experiments using RNAi-based inactivation of Nupr1 in human pancreatic cancer cell models. In addition, the senescent phenotype, which results from Nupr1 inactivation, is accompanied by activation of the FoxO3a-Skp2-p27(Kip1)-pRb-E2F pathway in vivo and in vitro. Thus, combined, these results show, for the first time, that Nupr1 aids oncogenic Kras to bypass senescence in a manner that cooperatively promotes PanIN formation. Besides its mechanistic importance, this new knowledge bears medical relevance as it delineates early pathobiological events that may be targeted in the future as a means to interfere with the formation of preneoplastic lesions early during pancreatic carcinogenesis.