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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/28108468/metabolic-biomarker-signature-to-differentiate-pancreatic-ductal-adenocarcinoma-from-chronic-pancreatitis
#1
Julia Mayerle, Holger Kalthoff, Regina Reszka, Beate Kamlage, Erik Peter, Bodo Schniewind, Sandra González Maldonado, Christian Pilarsky, Claus-Dieter Heidecke, Philipp Schatz, Marius Distler, Jonas A Scheiber, Ujjwal M Mahajan, F Ulrich Weiss, Robert Grützmann, Markus M Lerch
OBJECTIVE: Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose. DESIGN: For a case-control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies...
January 20, 2017: Gut
https://www.readbyqxmd.com/read/28099419/genomic-deletion-of-malic-enzyme-2-confers-collateral-lethality-in-pancreatic-cancer
#2
Prasenjit Dey, Joelle Baddour, Florian Muller, Chia Chin Wu, Huamin Wang, Wen-Ting Liao, Zangdao Lan, Alina Chen, Tony Gutschner, Yaan Kang, Jason Fleming, Nikunj Satani, Di Zhao, Abhinav Achreja, Lifeng Yang, Jiyoon Lee, Edward Chang, Giannicola Genovese, Andrea Viale, Haoqiang Ying, Giulio Draetta, Anirban Maitra, Y Alan Wang, Deepak Nagrath, Ronald A DePinho
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#3
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28086938/alpha-enolase-eno1-controls-alpha-v-beta-3-integrin-expression-and-regulates-pancreatic-cancer-adhesion-invasion-and-metastasis
#4
Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, Francesco Novelli
BACKGROUND: We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#5
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28075451/the-role-of-sphingolipid-signalling-in-diabetes%C3%A2-associated-pathologies-review
#6
Mei Li Ng, Carol Wadham, Olga A Sukocheva
Sphingosine kinase (SphK) is an important signalling enzyme that catalyses the phosphorylation of sphingosine (Sph) to form sphingosine‑1‑phosphate (S1P). The multifunctional lipid, S1P binds to a family of five G protein-coupled receptors (GPCRs). As an intracellular second messenger, S1P activates key signalling cascades responsible for the maintenance of sphingolipid metabolism, and has been implicated in the progression of cancer, and the development of other inflammatory and metabolic diseases...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28073003/employing-metabolism-to-improve-the-diagnosis-and-treatment-of-pancreatic-cancer
#7
REVIEW
Christopher J Halbrook, Costas A Lyssiotis
Pancreatic ductal adenocarcinoma is on pace to become the second leading cause of cancer-related death. The high mortality rate results from a lack of methods for early detection and the inability to successfully treat patients once diagnosed. Pancreatic cancer cells have extensively reprogrammed metabolism, which is driven by oncogene-mediated cell-autonomous pathways, the unique physiology of the tumor microenvironment, and interactions with non-cancer cells. In this review, we discuss how recent efforts delineating rewired metabolic networks in pancreatic cancer have revealed new in-roads to develop detection and treatment strategies for this dreadful disease...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28058076/non-alcoholic-fatty-pancreatic-disease-a-review-of-literature
#8
REVIEW
Hassan Tariq, Suresh Nayudu, Sai Akella, Mariela Glandt, Sridhar Chilimuri
There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome...
December 2016: Gastroenterology Research
https://www.readbyqxmd.com/read/28049396/oxidative-stress-and-antioxidant-potential-of-one-hundred-medicinal-plants
#9
Waseem Hassan, Hamsa Noreen, Shakila Rehman, Shehnaz Gul, Mohammad Amjad Kamal, Jean Paul Kamdem, Bakht Zaman, Joao B T da Rocha
Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc...
January 2, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28046730/su-f-j-07-evaluating-the-adequacy-of-biopsy-specimens-for-genetic-signature-assessment-by-measuring-the-metabolic-activity-in-specimens-obtained-under-18f-fdg-pet-ct-guidance
#10
L Fanchon, J Russell, S Dogan, S Carlin, K Pinker-Domenig, E Yorke, C Ross Schmidtlein, S Fujisawa, K Manova-Todorova, P Zanzonico, J O Deasy, J L Humm, S Solomon, A S Kirov
PURPOSE: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. METHODS: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-((18) F)fluoro-D-glucose ((18) F-FDG) PET/CT guidance...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28042238/drug-metabolism-and-pancreatic-cancer
#11
REVIEW
John Paul E Flores, Robert B Diasio, Muhammad Wasif Saif
Pancreatic cancer remains a fatal disease in the majority of patients. The era of personalized medicine is upon us: customizing therapy according to each patient's individual cancer. Potentially, therapy can be targeted at individuals who would most likely have a favorable response, making it more efficacious and cost effective. This is particularly relevant for pancreatic cancer, which currently portends a very poor prognosis. However, there is much to be done in this field, and more studies are needed to bring this concept to reality...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/28039486/cd147-a-small-molecule-transporter-ancillary-protein-at-the-crossroad-of-multiple-hallmarks-of-cancer-and-metabolic-reprogramming
#12
Agnieszka A Kendrick, Johnathon Schafer, Monika Dzieciatkowska, Travis Nemkov, Angelo D Alessandro, Deepika Neelakantan, Heide L Ford, Chad G Pearson, Colin D Weekes, Kirk C Hansen, Elan Z Eisenmesser
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and correct plasma membrane localization through CD147 transmembrane (TM) region...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28024083/direct-evidence-for-cancer-cell-autonomous-extracellular-protein-catabolism-in-pancreatic-tumors
#13
Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo, Jared R Mayers, Jeffrey Wyckoff, Amanda M Del Rosario, Matthew Whitman, Christopher R Chin, Kendall J Condon, Alex Lammers, Katherine A Kellersberger, Brian K Stall, Gregory Stephanopoulos, Dafna Bar-Sagi, Jongyoon Han, Joshua D Rabinowitz, Michael J Cima, Robert Langer, Matthew G Vander Heiden
Mammalian tissues rely on a variety of nutrients to support their physiological functions. It is known that altered metabolism is involved in the pathogenesis of cancer, but which nutrients support the inappropriate growth of intact malignant tumors is incompletely understood. Amino acids are essential nutrients for many cancer cells that can be obtained through the scavenging and catabolism of extracellular protein via macropinocytosis. In particular, macropinocytosis can be a nutrient source for pancreatic cancer cells, but it is not fully understood how the tumor environment influences metabolic phenotypes and whether macropinocytosis supports the maintenance of amino acid levels within pancreatic tumors...
December 26, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27996048/high-expression-of-gfat1-predicts-poor-prognosis-in-patients-with-pancreatic-cancer
#14
Caiting Yang, Peike Peng, Lili Li, Miaomiao Shao, Junjie Zhao, Lan Wang, Fangfang Duan, Shushu Song, Hao Wu, Jie Zhang, Ran Zhao, Dongwei Jia, Mingming Zhang, Weicheng Wu, Can Li, Yefei Rong, Lei Zhang, Yuanyuan Ruan, Jianxin Gu
Pancreatic cancer is one of the most lethal of all types of cancer, with the 5-year survival rate ranging only at 6-7%. The aberrant glucose metabolism is one of the hallmarks of cancer cells, and as a branch of glucose metabolism, hexosamine biosynthesis pathway (HBP) has been reported to play a critical role in the insulin resistance and progression of cancer. Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme of the HBP; nevertheless, the prognostic value of GFAT1 in pancreatic cancer remains elusive...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27989750/the-antioxidant-uncoupling-protein-2-stimulates-hnrnpa2-b1-glut1-and-pkm2-expression-and-sensitizes-pancreas-cancer-cells-to-glycolysis-inhibition
#15
Jessica Brandi, Daniela Cecconi, Marco Cordani, Margalida Torrens-Mas, Raffaella Pacchiana, Elisa Dalla Pozza, Giovanna Butera, Marcello Manfredi, Emilio Marengo, Jordi Oliver, Pilar Roca, Ilaria Dando, Massimo Donadelli
Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes...
October 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27931833/hyperglycemia-tumorigenesis-and-chronic-inflammation
#16
REVIEW
Shu-Chun Chang, Wei-Chung Vivian Yang
Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27923829/glucose-metabolism-reprogrammed-by-overexpression-of-ikk%C3%AE%C2%B5-promotes-pancreatic-tumor-growth
#17
Haseeb Zubair, Shafquat Azim, Sanjeev Kumar Srivastava, Aamir Ahmad, Arun Bhardwaj, Mohammad Aslam Khan, Girijesh Kumar Patel, Sumit Arora, James Elliot Carter, Seema Singh, Ajay Pratap Singh
Aberrant expression of the kinase IKKε in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKε in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKε in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27921375/visceral-adiposity-and-cancer-survival-a-review-of-imaging-studies
#18
REVIEW
J Xiao, V C Mazurak, T A Olobatuyi, B J Caan, C M Prado
Although obesity is a well-known risk factor for cancer, the association between obesity and cancer survival remains controversial. This is partially due to the inability of conventional obesity measures to directly assess adiposity or adipose tissue distribution. As a metabolic organ, visceral adipose tissue (VAT) secrets a variety of cytokines and cytokine-like factors, potentially affecting cancer survival. The objective of this review was to investigate the influence of imaging-assessed VAT on cancer survival...
December 6, 2016: European Journal of Cancer Care
https://www.readbyqxmd.com/read/27911861/pyruvate-kinase-m2-pkm2-expression-correlates-with-prognosis-in-solid-cancers-a-meta-analysis
#19
Haiyan Zhu, Hui Luo, Xuejie Zhu, Xiaoli Hu, Lihong Zheng, Xueqiong Zhu
Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909909/obesity-biomarkers-metabolism-and-risk-of-cancer-an-epidemiological-perspective
#20
Katharina Nimptsch, Tobias Pischon
Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation...
2016: Recent Results in Cancer Research
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