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Pancreatic Neoplasms: HELP
Articles by Dafydd G. Thomas
Based on 2 articles published since 2010
(Why 2 articles?)

Between 2010 and 2020, Dafydd G. Thomas wrote the following 2 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article Caveolin-1 is Associated with Tumor Progression and Confers a Multi-Modality Resistance Phenotype in Pancreatic Cancer. 2015

Chatterjee, Moumita / Ben-Josef, Edgar / Thomas, Dafydd G / Morgan, Meredith A / Zalupski, Mark M / Khan, Gazala / Andrew Robinson, Charles / Griffith, Kent A / Chen, Ching-Shih / Ludwig, Thomas / Bekaii-Saab, Tanios / Chakravarti, Arnab / Williams, Terence M. ·The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210. · Hospital of the University of Pennsylvania, Philadelphia, PA, 19104. · University of Michigan Medical Center, Ann Arbor, MI, 48109. · Henry Ford Hospital System, West Bloomfield, MI, 48322. ·Sci Rep · Pubmed #26065715.

ABSTRACT: Caveolin-1 (Cav-1) is a 21‚ÄČkDa protein enriched in caveolae, and has been implicated in oncogenic cell transformation, tumorigenesis, and metastasis. We explored roles for Cav-1 in pancreatic cancer (PC) prognostication, tumor progression, resistance to therapy, and whether targeted downregulation could lead to therapeutic sensitization. Cav-1 expression was assessed in cell lines, mouse models, and patient samples, and knocked down in order to compare changes in proliferation, invasion, migration, response to chemotherapy and radiation, and tumor growth. We found Cav-1 is overexpressed in human PC cell lines, mouse models, and human pancreatic tumors, and is associated with worse tumor grade and clinical outcomes. In PC cell lines, disruption/depletion of caveolae/Cav-1 reduces proliferation, colony formation, and invasion. Radiation and chemotherapy up-regulate Cav-1 expression, while Cav-1 depletion induces both chemosensitization and radiosensitization through altered apoptotic and DNA repair signaling. In vivo, Cav-1 depletion significantly attenuates tumor initiation and growth. Finally, Cav-1 depletion leads to altered JAK/STAT, JNK, and Src signaling in PC cells. Together, higher Cav-1 expression is correlated with worse outcomes, is essential for tumor growth and invasion (both in vitro and in vivo), is responsible for promoting resistance to therapies, and may serve as a prognostic/predictive biomarker and target in PC.

2 Article Ribonucleotide reductase M2 does not predict survival in patients with resectable pancreatic adenocarcinoma. 2012

Xie, Hao / Lin, Jingmei / Thomas, Dafydd G / Jiang, Wei / Liu, Xiuli. ·Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195, USA. ·Int J Clin Exp Pathol · Pubmed #22670179.

ABSTRACT: BACKGROUND: Ribonucleotide reductase M2 (RRM2) was associated with pancreatic tumor progression and resistance to gemcitabine. This study aimed to determine if RRM2 protein expression was prognostic in patients with resectable pancreatic adenocarcinoma and predictive of adjuvant gemcitabine benefit. METHODS: 117 patients underwent tumor resection for pancreatic adenocarcinoma from 10/1999 to 12/2007. We constructed tissue microarrays from paraffin-embedded tumors and determined RRM2 protein expression using immunohistochemistry and grouped as negative or positive. We estimated overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and examined the prognostic and predictive value of RRM2 expression using Cox proportional hazards model. RESULTS: RRM2 expression showed no prognostic value in the entire group regarding OS (median OS 30.9 months in RRM2-positive versus 13.7 months in RRM2-negative, P = 0.26) and PFS (median OS 20.6 months in RRM2-positive versus 11.8 months in RRM2-negative, P = 0.46). RRM2 expression did not predict adjuvant gemcitabine benefit in the subgroup of 44 patients who received gemcitabine therapy (median OS 31.2 versus 15.2 months, P = 0.62; median PFS 11.3 versus 14.0 months, P = 0.35). Cox proportional hazards regression showed no prognostic effect of RRM2 expression on OS and PFS in the subgroup of 44 patients. However, the number of positive lymph nodes and perineural invasion were prognostic factors for OS (HR 1.2, P = 0.005) and for PFS (HR 5.5, P = 0.007), respectively. CONCLUSION: RRM2 protein expression in pancreatic adenocarcinoma is neither prognostic nor predictive of adjuvant gemcitabine benefit in patients with resectable pancreatic adenocarcinoma.