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Cancer Biology Commons

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Articles 1 - 4 of 4

Full-Text Articles in Cancer Biology

Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany Aug 2017

Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany

UMass Metabolic Network Publications

Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of (15)N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of ...


Micrornas Of The Mir-17~92 Cluster Regulate Multiple Aspects Of Pancreatic Tumor Development And Progression, Brian J. Quattrochi, Anushree Gulvady, David R. Driscoll, Makoto Sano, David S. Klimstra, Christopher E. Turner, Brian C. Lewis May 2017

Micrornas Of The Mir-17~92 Cluster Regulate Multiple Aspects Of Pancreatic Tumor Development And Progression, Brian J. Quattrochi, Anushree Gulvady, David R. Driscoll, Makoto Sano, David S. Klimstra, Christopher E. Turner, Brian C. Lewis

Open Access Articles

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that lacked ...


Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai May 2016

Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Pancreatic cancer (PanCa) has a dismal prognosis with five-year survival rates under 5%. PanCa is usally diagnosed at very late stages and even if diagnosed early, surgery is rarely an option. These factors contribute towards the bleak statistics for PanCa Chemo and radiation treatments having deleterious side-effects. There is therefore a clinical, unmet need for novel, targeted treatments with low morbidity in PanCa. Gemzar® (gemcitabine-HCl) is an FDA (Food and Drug Administration) approved chemotherapeutic drug that has been used to treat PanCa. However, intrinsic and acquired chemoresistance to gemcitabine contribute to the poor prognosis of PanCa. A combination of Abraxane ...


Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White May 2013

Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White

UT GSBS Dissertations and Theses (Open Access)

The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce ...