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Pancreatic cancer and metabolism

Sumit Sahni, Kyung Chan Park, Zaklina Kovacevic, Des R Richardson
N-myc downstream regulated gene 1 (NDRG1) is an intriguing metastasis suppressor protein, which plays an important role in suppressing multiple oncogenic signaling pathways. Interestingly, multiple isoforms of NDRG1 have been identified, although the molecular mechanisms involved in their generation remains elusive. Herein, we demonstrate the role of two mechanisms involving autophagic and proteasomal machinery as part of an intricate system to generate different NDRG1 isoforms. Examining multiple pancreatic cancer cell-types using immunoblotting demonstrated three major isoforms of NDRG1 at approximately 41-, 46- and 47-kDa...
February 11, 2019: Biochimica et biophysica acta. Molecular basis of disease
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Brittany Durden, Roey Hadad, Santanu Banerjee, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory protein 78 (GRP78), the master regulator of the UPR, plays a role in proliferation, invasion, and metastasis in cancer. Cancer stem cells (CSCs) make up a crucial component of the tumor heterogeneity in pancreatic cancer, as well as other cancers. "Stemness" in pancreatic cancer defines a population of cells within the tumor that have increased therapeutic resistance as well as survival advantage...
February 12, 2019: Cell Death & Disease
Jinghui Jiang, Yingchao Fan, Wei Zhang, Yuling Shen, Tingting Liu, Ming Yao, Jianren Gu, Hong Tu, Yu Gan
Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies. Here, we investigated the direct effect of adiponectin on human pancreatic cancer in vitro and in vivo . Our results showed that adiponectin treatment significantly inhibited the proliferation of human pancreatic cancer cells...
2019: International Journal of Biological Sciences
Xuhui Ma, Boya Li, Jie Liu, Yan Fu, Yongzhang Luo
BACKGROUND: Pancreatic cancer is one of the most malignant cancers. The overall 5-year survival rate of its patients is 8%, the lowest among major cancer types. It is very urgent to study the development mechanisms of this cancer and provide potential targets for therapeutics design. Glucose, one of the most essential nutrients, is highly exploited for aerobic glycolysis in tumor cells to provide building blocks. However, the glucose consumption manner in pancreatic cancer cells is unclear...
February 11, 2019: Journal of Experimental & Clinical Cancer Research: CR
Kilmer S McCully
The objective of the proposed clinical interventional trial is to demonstrate the efficacy of a novel therapeutic strategy in subjects with cancer and hyperhomocysteinemia. Following discovery of abnormal homocysteine thiolactone metabolism in cultured malignant cells, thioretinamide, the amide synthesized from retinoic acid and homocysteine thiolactone, and thioretinaco, the complex formed from cobalamin and thioretinamide, were demonstrated to have antineoplastic, anticarcinogenic, and anti-atherogenic properties in animal models...
2019: Methods in Molecular Biology
Li Jiao, Suman Maity, Cristian Coarfa, Kimal Rajapakshe, Liang Chen, Feng Jin, Vasanta Putluri, Lesley F Tinker, Qianxing Mo, Fengju Chen, Subrata Sen, Haleh Sangi-Haghpeykar, Hashem B El-Serag, Nagireddy Putluri
To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case-control targeted metabolomics study using pre-diagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the liquid chromatography-mass spectrometry to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired t-test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference...
February 5, 2019: Cancer Prevention Research
Ying Li, Xiaojuan Yang, Xiaoning Kang, Shanglong Liu
Long noncoding RNAs (lncRNAs) are a new class of regulators. LncRNAs are defined as endogenous transcribed RNA molecules with transcript length of >200 nt. Accumulating evidence has shown that lncRNAs are involved in many physiological processes such as cell cycle regulation, cell apoptosis and survival, cancer migration and metabolism. However, the biological and molecular mechanisms of lncRNAs in pancreatic cancer are still unclear. Recent studies have reported that many lncRNAs are dysregulated in pancreatic cancer and closely associated with tumorigenesis, diagnosis and prognosis...
February 1, 2019: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Xiaodong Tang, Shuanghai Liu, Dawei Chen, Zhenguo Zhao, Jiahua Zhou
Fat mass and obesity-associated (FTO) protein has been identified as a critical demethylase in regulating cellular mRNA stability by removing N6 -methyladenosine (m6 A) residues in mRNA. Even though the role of FTO in body energy metabolism has been well established, its role in cancer cell homeostasis remains unclear. In the present study, by using RNA interference, it was indicated that FTO is required for pancreatic cancer cell proliferation. Knockdown of FTO resulted in compromised proliferation of pancreatic cancer cells...
February 2019: Oncology Letters
Pyone Myat Thu, Zu-Guo Zheng, Ya-Ping Zhou, Yan-Yan Wang, Xin Zhang, Dan Jing, Hui-Min Cheng, Ji Li, Ping Li, Xiaojun Xu
Despite the massive efforts to develop the treatment of pancreatic cancers, no effective application exhibits satisfactory clinical outcome. Macropinocytosis plays a critical role for continuous proliferation of pancreatic ductal adenocarcinoma (PDAC). In this study, we generated a screening method and identified phellodendrine chloride (PC) as a potential macropinocytosis inhibitor. PC significantly inhibited the viability of KRAS mutant pancreatic cancer cells (PANC-1 and MiaPaCa-2) in a dose-dependent manner; however, it did not affect the wild type KRAS pancreatic cancer cells (BxPC-3)...
February 1, 2019: European Journal of Pharmacology
Melanie S Patzak, Vijayalakshmi Kari, Shilpa Patil, Feda H Hamdan, Robert G Goetze, Marius Brunner, Jochen Gaedcke, Julia Kitz, Duncan I Jodrell, Frances M Richards, Christian Pilarsky, Robert Gruetzmann, Petra Rümmele, Thomas Knösel, Elisabeth Hessmann, Volker Ellenrieder, Steven A Johnsen, Albrecht Neesse
BACKGROUND: Cytosolic 5'-nucleotidase 1A (NT5C1A) dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. Here, we investigate NT5C1A expression in pancreatic ductal adenocarcinoma (PDAC) and its impact on gemcitabine metabolism and therapeutic efficacy. METHODS: NT5C1A expression was determined by semiquantitative immunohistochemistry using tissue microarrays. Gemcitabine metabolites and response were assessed in several human and murine PDAC cell lines using crystal violet assays, Western blot, viability assays, and liquid chromatography tandem mass-spectrometry (LC-MS/MS)...
January 29, 2019: EBioMedicine
Chongbiao Huang, Yang Li, Zengxun Li, Yang Xu, Na Li, Yi Ge, Jie Dong, Antao Chang, Tiansuo Zhao, Xiuchao Wang, Hongwei Wang, Shengyu Yang, Keping Xie, Jihui Hao, He Ren
PURPOSE: Oxygen and glucose deprivation is a common feature of the solid tumor. Regulatory network underlying the adaptation of cancer cells to harsh microenvironment remains unclear. We determined the mechanistic role of LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) in cancer cell survival under oxygen-glucose deprivation conditions. EXPERIMENTAL DESIGN: The expression level of LIMS1 was determined by immunohistochemical staining and analysing the mRNA expression profiles from The Cancer Genome Atlas of three human solid tumors...
January 24, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huiqin Liu, Mengnan Sun, Zhengsheng Liu, Chao Kong, Weijian Kong, Junxiao Ye, Jianan Gong, David C S Huang, Feng Qian
Pancreatic ductal adenocarcinoma (PDAC) is a dominantly (~95%) KRAS-mutant cancer that has extremely poor prognosis, in part this is due to its strong intrinsic resistance towards almost all therapeutic agents. PDAC relies heavily on KRAS-transformed metabolism, including enhanced macropinocytosis and catabolism of extracellular albumin, to maintain its proliferation and progression. However, it has yet to be validated that whether such transformed metabolism could be exploited for the drug delivery to open therapeutic windows of cytotoxic agents in KRAS-mutant PDAC...
January 14, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Gurmehr Brar, Hidekazu Tsukamoto
Alcohol and high-fat diet are two major risk factors responsible for metabolic diseases, which are manifested as steatohepatitis and liver cancer in the liver, and chronic pancreatitis and pancreatic adenocarcinoma (PDAC) in the pancreas. These metabolic diseases are becoming increasingly prevalent around the globe, and more importantly, their two major etiologies commonly coexist to precipitate the disease processes. To highlight the importance of these metabolic diseases, Japanese Society of Gastroenterology (JSGE) and National Institute on Alcoholism and Alcohol Abuse of National Institute of Health cosponsored the JSGE's 7th International Forum jointly held with the 12th International Symposium on ALPD and Cirrhosis...
January 14, 2019: Journal of Gastroenterology
Yang Cheng, Kunyuan Wang, Lanlan Geng, Jingjing Sun, Wanfu Xu, Dingli Liu, Sitang Gong, Yun Zhu
BACKGROUND: Pancreatic carcinoma (PC) is one of the most aggressive cancers affecting human health. It is essential to identify candidate biomarkers for the diagnosis and prognosis of PC. The present study aimed to investigate the diagnosis and prognosis biomarkers of PC. METHODS: Differentially expressed genes (DEGs) were identified from the mRNA expression profiles of GSE62452, GSE28735 and GSE16515. Functional analysis and the protein-protein interaction network analysis was performed to explore the biological function of the identified DEGs...
January 10, 2019: EBioMedicine
Jia-Wei Lv, Zi-Qi Zheng, Zi-Xian Wang, Guan-Qun Zhou, Lei Chen, Yan-Ping Mao, Ai-Hua Lin, Russel J Reiter, Jun Ma, Yu-Pei Chen, Ying Sun
We performed comprehensive genomic analyses of the melatonergic system within the tumor microenvironment and their clinical relevance across a broad spectrum of solid tumors. RNA-seq data from The Cancer Genome Atlas (TCGA) of 14 solid tumors representing 6,658 human samples were analyzed. The tumor melatonergic system was characterised by the rates of melatonin synthesis and metabolism using a two-gene expression model (melatonin synthesis/metabolism index). We calculated three indexes according to different melatonin metabolism isoenzymes (Index-I [ASMT:CYP1A1], Index-II [ASMT:CYP1A2], and Index-III [ASMT:CYP1B1])...
January 14, 2019: Journal of Pineal Research
Altay Myssayev, Ayan Myssayev, Reiko Ideguchi, Susumu Eguchi, Tomohiko Adachi, Yorihisa Sumida, Shuichi Tobinaga, Masataka Uetani, Takashi Kudo
PURPOSE: Pancreatic cancer is the 4th most common cause of cancer death in Japan and exhibits a 5-year overall survival rate of approximately 7%. The accurate diagnosis of pancreatic cancer is important for determining the optimal management strategy. Fludeoxyglucose-positron emission tomography (FDG PET) integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for detecting and evaluating various cancers, and it is used for staging, detecting local recurrence and distant metastasis, measuring therapeutic effects, and predicting prognosis in pancreatic cancer patients...
2019: PloS One
Alessandro Carrer, Sophie Trefely, Steven Zhao, Sydney Campbell, Robert J Norgard, Kollin C Schultz, Simone Sidoli, Joshua L D Parris, Hayley C Affronti, Sharanya Sivanand, Shaun Egolf, Yogev Sela, Marco Trizzino, Alessandro Gardini, Benjamin A Garcia, Nathaniel W Snyder, Ben Z Stanger, Kathryn Wellen
Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Since acetyl-CoA abundance regulates global histone acetylation, we hypothesized that altered acetyl-CoA metabolism might contribute to metabolic or epigenetic alterations that promote tumorigenesis. We found that acetyl-CoA abundance is elevated in KRAS mutant acinar cells and that its use in the mevalonate pathway supports acinar-to-ductal metaplasia (ADM)...
January 9, 2019: Cancer Discovery
Anastasiya Yakovenko, Miles Cameron, Jose Gilberto Trevino
Pancreatic cancer (PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies...
December 27, 2018: World Journal of Gastrointestinal Surgery
An Uche, Ritika Vankina, Jun Gong, May Cho, James J Yeh, Phyllis Kim, Kathy Pan
Capecitabine-induced hypertriglyceridemia (CIHT) represents an increasingly significant treatment-related adverse event from capecitabine given its potential for both acute complications (acute pancreatitis) and chronic metabolic complications (cardiovascular disease). The incidence of CIHT is relatively rare and the majority of cases thus far reported have been managed with lipid-lowering therapy and/or discontinuation of capecitabine followed by resumption of the drug upon normalization of triglyceride levels...
December 2018: Journal of Gastrointestinal Oncology
Sung Hwan Lee, Ho Kyoung Hwang, Woo Jung Lee, Mijin Yun, Chang Moo Kang
Background/Aims: 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancer. Methods: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study...
December 24, 2018: Gut and Liver
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