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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/29052509/a-yin-yang-1-mir-30a-regulatory-circuit-modulates-autophagy-in-pancreatic-cancer-cells
#1
Chuang Yang, Jing-Jing Zhang, Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Wen-Tao Gao, Kui-Rong Jiang, Yi Miao
BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting...
October 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29049217/identification-of-novel-therapeutic-target-genes-and-pathway-in-pancreatic-cancer-by-integrative-analysis
#2
Bangli Hu, Cheng Shi, Hai-Xing Jiang, Shan-Yu Qin
BACKGROUND: Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis. METHODS: Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and gene coexpression analysis were performed...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#3
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29045397/glucose-feeds-the-tca-cycle-via-circulating-lactate
#4
Sheng Hui, Jonathan M Ghergurovich, Raphael J Morscher, Cholsoon Jang, Xin Teng, Wenyun Lu, Lourdes A Esparza, Tannishtha Reya, Le Zhan, Jessie Yanxiang Guo, Eileen White, Joshua D Rabinowitz
Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29042120/pilot-study-on-the-impact-of-f18-labeled-thymidine-pet-ct-on-gross-tumor-volume-identification-and-definition-for-pancreatic-cancer
#5
Jennifer L Pretz, Michael A Blake, Joseph H Killoran, Harvey J Mamon, Jennifer Y Wo, Andrew X Zhu, Theodore S Hong
PURPOSE: Accurate target definition for radiation therapy planning in localized pancreatic cancer is critical, particularly when using strategies that omit elective coverage. Standard imaging modalities such as computed tomography (CT), magnetic resonance imaging, and endoscopic ultrasound have limited concordance with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can also be difficult to interpret because increased activity is indicative of increased glucose metabolism, rather than cellular proliferation...
September 18, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/29040194/fatty-pancreas-should-we-be-concerned
#6
Shounak Majumder, Nissy A Philip, Naoki Takahashi, Michael J Levy, Vijay P Singh, Suresh T Chari
The metabolic consequences of visceral fat deposition are well known, and the presence of intrapancreatic fat (IPF) has been recognized for decades. However, our knowledge about the distribution of fat in the pancreas and its clinical implications is in a nascent stage. Various terms have been proposed to describe IPF; for the purpose of this narrative review, we chose the general term fatty pancreas. Herein, we describe the radiologic, endoscopic, and histopathologic aspects of diagnosing fatty pancreas and provide an overview of the diseases associated with this condition...
November 2017: Pancreas
https://www.readbyqxmd.com/read/28988620/collapsing-the-metabolic-pon2zi-scheme-in-pancreatic-ductal-adenocarcinoma
#7
Matyas Abel Tsegaye, Zachary T Schafer
A hallmark of pancreatic ductal adenocarcinoma cancer (PDAC) cells is metabolic reprogramming that facilitates tumor progression. In a recent paper published in Molecular Cell, Nagarajan et al. discover that paraoxonase (PON)2 stimulates glucose transporter (GLUT)1-mediated glucose uptake, prevents AMP-activated protein kinase (AMPK)-mediated anoikis, and consequently promotes PDAC development and metastasis.
October 4, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28978166/metabolomic-biomarkers-of-pancreatic-cancer-a-meta-analysis-study
#8
Khyati Y Mehta, Hung-Jen Wu, Smrithi S Menon, Yassi Fallah, Xiaogang Zhong, Nasser Rizk, Keith Unger, Mark Mapstone, Massimo S Fiandaca, Howard J Federoff, Amrita K Cheema
Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977862/identification-and-causes-of-metabonomic-difference-between-orthotopic-and-subcutaneous-xenograft-of-pancreatic-cancer
#9
Bohan Zhan, Shi Wen, Jie Lu, Guiping Shen, Xianchao Lin, Jianghua Feng, Heguang Huang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for(1)H NMR spectroscopy followed by univariate and multivariate statistical analyses...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974775/biochemical-and-cellular-properties-of-insulin-receptor-signalling
#10
REVIEW
Rebecca A Haeusler, Timothy E McGraw, Domenico Accili
The mechanism of insulin action is a central theme in biology and medicine. In addition to the rather rare condition of insulin deficiency caused by autoimmune destruction of pancreatic β-cells, genetic and acquired abnormalities of insulin action underlie the far more common conditions of type 2 diabetes, obesity and insulin resistance. The latter predisposes to diseases ranging from hypertension to Alzheimer disease and cancer. Hence, understanding the biochemical and cellular properties of insulin receptor signalling is arguably a priority in biomedical research...
October 4, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28974531/soils-and-seeds-that-initiate-pancreatic-cancer-metastasis
#11
Christopher R Vakoc, David A Tuveson
Pathways that stimulate metastasis of pancreatic cancer cells are critical for understanding tumor evolution and can serve as potential therapeutic targets. The microenvironment produces a host of metabolic perturbations and tropic factors that may play a formative role in this process. Cancer Discov; 7(10); 1067-8. ©2017 AACR.See related article by Chiou et al., p. 1184.
October 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28969260/tamoxifen-induced-pancreatitis-an-unusual-complication-of-commonly-used-drug
#12
Pritam Suresh Chandra Kataria, Pradip Piraji Kendre, Apurva Ashok Patel, Murtaza Zoher Bohra, Nahush Tahiliani
Tamoxifen is a selective oestrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It possess antagonistic or agonistic activity depending on the tissue location i.e., antagonistic action on breast but agonist action on endometrium and bones. The side effects of tamoxifen include hot flushes, gynaecologic symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep alterations, weight gain, alteration of lipoprotein metabolism, thromboembolic disorder...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28969005/pancreatic-cancer-derived-exosomes-promote-tumor-metastasis-and-liver-pre-metastatic-niche-formation
#13
Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M Hoffman, Jiahua Zhou
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28962872/ucp2-inhibition-induces-ros-akt-mtor-axis-role-of-gapdh-nuclear-translocation-in-genipin-everolimus-anticancer-synergism
#14
Ilaria Dando, Raffaella Pacchiana, Elisa Dalla Pozza, Ivana Cataldo, Stefano Bruno, Paola Conti, Marco Cordani, Anna Grimaldi, Giovanna Butera, Michele Caraglia, Aldo Scarpa, Marta Palmieri, Massimo Donadelli
Several studies indicate that mitochondrial uncoupling protein 2 (UCP2) plays a pivotal role in cancer development by decreasing reactive oxygen species (ROS) produced by mitochondrial metabolism and by sustaining chemoresistance to a plethora of anticancer drugs. Here, we demonstrate that inhibition of UCP2 triggers Akt/mTOR pathway in a ROS-dependent mechanism in pancreatic adenocarcinoma cells. This event reduces the antiproliferative outcome of UCP2 inhibition by genipin, creating the conditions for the synergistic counteraction of cancer cell growth with the mTOR inhibitor everolimus...
September 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28954733/genome-wide-crispr-screen-for-essential-cell-growth-mediators-in-mutant-kras-colorectal-cancers
#15
Tariq M Rana, Edwin H Yau, Indrasena Reddy Kummetha, Gianluigi Lichinchi, Rachel Tang, Yunlin Zhang
Targeting mutant KRAS signaling pathways continues to attract attention as a therapeutic strategy for KRAS-driven tumors. In this study, we exploited the power of the CRISPR-Cas9 system to identify genes affecting the tumor xenograft growth of human mutant KRAS colorectal cancers (KRASMUT CRC). Using pooled lentiviral single guide RNA libraries, we conducted a genome-wide loss-of-function genetic screen in an isogenic pair of human CRC cell lines harboring mutant or wild-type KRAS. The screen identified novel and established synthetic enhancers or synthetic lethals for KRASMUT CRC, including targetable metabolic genes...
September 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28954281/the-role-of-obesity-type-2-diabetes-and-metabolic-factors-in-pancreatic-cancer-a-mendelian-randomization-study
#16
Robert Carreras-Torres, Mattias Johansson, Valerie Gaborieau, Philip C Haycock, Kaitlin H Wade, Caroline L Relton, Richard M Martin, George Davey Smith, Paul Brennan
Background: Risk factors for pancreatic cancer include a cluster of metabolic conditions such as obesity, hypertension, dyslipidemia, insulin resistance, and type 2 diabetes. Given that these risk factors are correlated, separating out causal from confounded effects is challenging. Mendelian randomization (MR), or the use of genetic instrumental variables, may facilitate the identification of the metabolic drivers of pancreatic cancer. Methods: We identified genetic instruments for obesity, body shape, dyslipidemia, insulin resistance, and type 2 diabetes in order to evaluate their causal role in pancreatic cancer etiology...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28934848/profiling-of-serum-metabolites-using-maldi-tof-and-triple-tof-mass-spectrometry-to-develop-a-screen-for-ovarian-cancer
#17
Jun Hwa Lee, Yun Hwan Kim, Kyung-Hee Kim, Jae Youl Cho, Sang Myung Woo, Byong Chul Yoo, Seung Cheol Kim
Purpose: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. Materials and Methods: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis...
September 18, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28928899/hyperpolarized-13-c-diffusion-mrs-of-co-polarized-pyruvate-and-fumarate-to-measure-lactate-export-and-necrosis
#18
Benedikt Feuerecker, Markus Durst, Michael Michalik, Günter Schneider, Dieter Saur, Marion Menzel, Markus Schwaiger, Franz Schilling
Background: Non-invasive tumor characterization and monitoring are among the key goals of medical imaging. Using hyperpolarized (13)C-labelled metabolic probes fast metabolic pathways can be probed in real-time, providing new opportunities for tumor characterization. In this in vitro study, we investigated whether measurement of apparent diffusion coefficient (ADC) measurements and magnetic resonance spectroscopy (MRS) of co-polarized (13)C-labeled pyruvic acid and fumaric acid can non-invasively detect both necrosis and changes in lactate export, which are parameters indicative of tumor aggressiveness...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#19
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#20
Marybeth Anderson, Raoud Marayati, Richard Moffitt, Jen Jen Yeh
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary PDAC patient tumors, supporting a role for glycolysis in promoting human disease. HK2 was most highly expressed in PDAC metastases, suggesting a link between HK2 and aggressive tumor biology...
August 22, 2017: Oncotarget
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