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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/28822617/microbiota-dysbiosis-in-select-human-cancers-evidence-of-association-and-causality
#1
REVIEW
Jie Chen, Jada C Domingue, Cynthia L Sears
The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host's nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers...
August 16, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28820316/cell-cycle-related-metabolism-and-mitochondrial-dynamics-in-a-replication-competent-pancreatic-beta-cell-line
#2
Chiara Montemurro, Suryakiran Vadrevu, Tatyana Gurlo, Alexandra E Butler, Kenny E Vongbunyong, Anton Petcherski, Orian S Shirihai, Leslie S Satin, Daniel Braas, Peter C Butler, Slavica Tudzarova
Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca(2+) are critical for permitting cells to progress through the cell cycle...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819421/simultaneous-quantification-of-serum-multi-phospholipids-as-potential-biomarkers-for-differentiating-different-pathophysiological-states-of-lung-stomach-intestine-and-pancreas
#3
Yumei Guo, Junling Ren, Xiaoou Li, Xiaofeng Liu, Ning Liu, Yanmin Wang, Zhili Li
Background: Aberrant lipid metabolism is closely associated with cancer. Materials & Methods: Serum levels of sphingomyelins (SM) (34:1), phosphatidylcholine (PC) (34:2), PC(34:1), PC(36:4), PC(36:3), and PC(36:2) in 1449 serum samples (including 599 normal controls, 69 patients with benign lung diseases (BLDs), 61 with benign colorectal diseases, 54 with benign gastric diseases, 67 with benign pancreatic diseases, and 246 with lung cancer (LC), 144 with colorectal cancer, 94 with gastric cancer, 115 with pancreatic cancer) were quantified simultaneously based on their respective calibration equations with correlation coefficient of >0...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819370/metformin-inhibits-gemcitabine-induced-apoptosis-in-pancreatic-cancer-cell-lines
#4
Dietmar Zechner, Ann-Christin Albert, Florian Bürtin, Brigitte Vollmar
Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. In this study we used three distinct pancreatic cancer cell lines and evaluated cell death by trypan blue assay and Western Blots using antibodies directed against cleaved caspase 3 and PARP. Surprisingly, we observed that 20mM metformin did not enhance, but rather inhibited gemcitabine induced cell death in murine 7265PDA, 6606PDA and 6606l cells. Microenvironmental aspects such as oxygen supply or the pH value did not influence the inhibition of cancer cell apoptosis by metformin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28817367/nutrition-implications-for-long-term-survivors-of-pancreatic-cancer-surgery
#5
Maria Q B Petzel, Leah Hoffman
With slowly increasing survival rates in pancreatic cancer and international consensus guidelines recommending surgical resection of premalignant lesions, survival post-pancreatic resection is increasing. With longer survival time, the significant comorbidities of such major surgery have far-reaching effects on the nutrition status of the survivor of pancreatic cancer. This review describes the many nutrition-related side effects of pancreatic surgery, including the development of pancreatic enzyme insufficiency, micronutrient deficiencies, diabetes, fatty liver, and metabolic bone disease...
August 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#6
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28811309/cellular-and-molecular-mechanisms-coordinating-pancreas-development
#7
REVIEW
Aimée Bastidas-Ponce, Katharina Scheibner, Heiko Lickert, Mostafa Bakhti
The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#8
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrate that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation accompanied with a relative decrease in the proliferation of MUC1-overexpressing cells compared to steady state conditions...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#9
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
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...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#10
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28801636/inhibition-of-hypoxic-response-decreases-stemness-and-reduces-tumorigenic-signaling-due-to-impaired-assembly-of-hif1-transcription-complex-in-pancreatic-cancer
#11
Olivia McGinn, Vineet K Gupta, Patricia Dauer, Nivedita Arora, Nikita Sharma, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801576/disrupting-glutamine-metabolic-pathways-to-sensitize-gemcitabine-resistant-pancreatic-cancer
#12
Ru Chen, Lisa A Lai, Yumi Sullivan, Melissa Wong, Lei Wang, Jonah Riddell, Linda Jung, Venu G Pillarisetty, Teresa A Brentnall, Sheng Pan
Pancreatic cancer is a lethal disease with poor prognosis. Gemcitabine has been the first line systemic treatment for pancreatic cancer. However, the rapid development of drug resistance has been a major hurdle in gemcitabine therapy leading to unsatisfactory patient outcomes. With the recent renewed understanding of glutamine metabolism involvement in drug resistance and immuno-response, we investigated the anti-tumor effect of a glutamine analog (6-diazo-5-oxo-L-norleucine) as an adjuvant treatment to sensitize chemoresistant pancreatic cancer cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796151/potential-development-of-tumor-targeted-oral-anti-cancer-prodrugs-amino-acid-and-dipeptide-monoester-prodrugs-of-gemcitabine
#13
Yasuhiro Tsume, Adam J Drelich, David E Smith, Gordon L Amidon
One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine...
August 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28774338/-18-f-fdg-pet-ct-response-in-a-phase-1-2-trial-of-nab-paclitaxel-plus-gemcitabine-for-advanced-pancreatic-cancer
#14
Ronald L Korn, Daniel D Von Hoff, Mitesh J Borad, Markus F Renschler, Desmond McGovern, R Curtis Bay, Ramesh K Ramanathan
BACKGROUND: Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine. METHODS: Tumors were measured by [(18)F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m(2) plus gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle...
August 3, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28771714/multifunctional-curcumin-mediate-multitherapeutic-effects
#15
Adeeb Shehzad, Munibah Qureshi, Muhammad Nabeel Anwar, Young Sup Lee
Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases...
August 3, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28767399/effect-of-p53-on-pancreatic-cancer-glucose-tolerance-abnormalities-by-regulating-transglutaminase-2-in-resistance-to-glucose-metabolic-stress
#16
Xiao Su, Xiangyi He, Qiwen Ben, Weiyi Wang, Huan Song, Qiao Ye, Yi Zang, Weiguang Li, Ping Chen, Weiyan Yao, Yaozong Yuan
Pancreatic ductal adenocarcinoma (PanCa) is an extremely lethal disease characterized by mutations of p53 in up to 70% of cases. Our previous studies have confirmed that hyperglycemia may be the first clinical manifestation for the early diagnosis of PanCa. In this article, we showed that targeted knockdown of TG2 or p53 in tumor cells led to decreased cell survival in response to glucose deprivation, while this phenomenon was abolished by combined inhibition of TG2 and p53. We observed that inhibition of TG2 or p53 sensitized glucose deprivation resistance through an intracellular reactive oxygen species (ROS) pathway and the induction of Bcl-2...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28760782/cdk4-6-inhibition-on-glucose-and-pancreatic-beta-cell-homeostasis-in-young-and-aged-rats
#17
Aida I Sacaan, Stephane Thibault, Miyoun Hong, Nagesha G Kondegowda, Timothy C Nichols, Rosemary Li, Carolina Rosselot, Winston Evering, Rafael Fenutria, Allison Vitsky, Thomas Brown, Martin B Finkelstein, Adolfo Garcia-Ocaña, Nasir K Khan, Andrew F Stewart, Rupangi C Vasavada
Genetic deletion of cyclin-dependent kinase 4 (CDK4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one of the first selective CDK4/6 inhibitors approved for the treatment of advanced breast cancer, is currently being investigated as an adjuvant treatment in patients with early-stage breast cancer and in a variety of cancers covering a wide-range of patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile...
July 31, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28753646/associations-between-self-reported-diabetes-and-78-circulating-markers-of-inflammation-immunity-and-metabolism-among-adults-in-the-united-states
#18
Alison L Van Dyke, Krystle A Lang Kuhs, Meredith S Shiels, Jill Koshiol, Britton Trabert, Erikka Loftfield, Mark P Purdue, Nicolas Wentzensen, Ruth M Pfeiffer, Hormuzd A Katki, Allan Hildesheim, Troy J Kemp, Ligia A Pinto, Anil K Chaturvedi, Mahboobeh Safaeian
Inflammation is increasingly thought to be associated with diabetes; however, only a few inflammation markers have been assessed concurrently in relation to history of diabetes. In the most comprehensive evaluation of inflammation markers and diabetes to date using a Luminex bead-based assay, we measured 78 inflammation-, immune-, and metabolic-related markers detectable in at least 10% of serum samples collected from participants from the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial (n = 1,814)...
2017: PloS One
https://www.readbyqxmd.com/read/28741686/gpr55-receptor-antagonist-decreases-glycolytic-activity-in-panc-1-pancreatic-cancer-cell-line-and-tumor-xenografts
#19
Michel Bernier, Jonathan Catazaro, Nagendra S Singh, Artur Wnorowski, Anna Boguszewska-Czubara, Krzysztof Jozwiak, Robert Powers, Irving W Wainer
The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#20
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
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