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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/29215586/investigation-of-polyamine-metabolism-and-homeostasis-in-pancreatic-cancers
#1
Chelsea Massaro, Jenna Thomas, Otto Phanstiel Iv
Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine growth factors. Of all human tissues, the pancreas has the highest level of the native polyamine spermidine. To sustain their high growth rates, PDACs have altered polyamine metabolism, which is reflected in their high intracellular polyamine levels and their upregulated import of exogenous polyamines...
December 7, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29190951/multi-omics-analysis-reveals-that-ornithine-decarboxylase-contributes-to-erlotinib-resistance-in-pancreatic-cancer-cells
#2
Won-Jun Jang, Boyeon Choi, Sang-Hoon Song, Naeun Lee, Dong-Joon Kim, Sooyeun Lee, Chul-Ho Jeong
Molecular and metabolic alterations in cancer cells are one of the leading causes of acquired resistance to chemotherapeutics. In this study, we explored an experimental strategy to identify which of these alterations can induce erlotinib resistance in human pancreatic cancer. Using genetically matched erlotinib-sensitive (BxPC-3) and erlotinib-resistant (BxPC-3ER) pancreatic cancer cells, we conducted a multi-omics analysis of metabolomes and transcriptomes in these cells. Untargeted and targeted metabolomic analyses revealed significant changes in metabolic pathways involved in the regulation of polyamines, amino acids, and fatty acids...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29181837/expression-of-liver-x-receptors-in-normal-and-refractory-carcinoma-tissues-of-the-human-lung-and-pancreas
#3
Korehito Kashiwagi, Mai Yanagida, Daiki Matsui, Mizuko Tanaka, Kotaro Sugimoto, Honglei Chen, Naoki Ichikawa-Tomikawa, Shigeru Marubashi, Hiroyuki Suzuki, Hideki Chiba
Liver X receptors (LXRs) participate not only in maintaining cholesterol homeostasis but also in controlling cellular growth in many types of normal and tumor cells. We previously reported that LXRα was aberrantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines, and that LXR stimulation led to significant reduction of proliferation of HOSCC cells via accelerating cholesterol efflux. Since LXRs and downstream proteins involved in cholesterol metabolism could be also applied as therapeutic targets in small cell lung carcinoma (SCLC) and pancreatic ductal adenocarcinoma (PDAC), we herein analyzed the distribution of LXR proteins in these refractory cancers as well as in normal human lung and pancreatic tissues...
November 28, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/29177584/sirtuin-6-a-possible-therapeutic-target-for-type-2-diabetes
#4
REVIEW
Eun Ju Bae
Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family, localizes in the nucleus and primarily regulates chromatin signaling and genomic integrity. Recent studies established the critical role of SIRT6 in the pathophysiology of metabolic disease, as well as its roles in longevity and cancer. These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes...
November 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29163679/identification-of-molecular-mechanisms-of-glutamine-in-pancreatic-cancer
#5
Zhen-Yi Jia, Tong-Yi Shen, Wei Jiang, Huan-Long Qin
The aim of the present study was to explore the critical genes and molecular mechanisms in pancreatic cancer (PC) cells with glutamine. By analyzing microarray data GSE17632 from the Gene Expression Omnibus database, the DEGs between PC cells treated with glutamine and without glutamine were evaluated. Additionally, function enrichment analyses and protein-protein interaction (PPI) network construction of DEGs were performed. Network module and literature mining analyses were performed to analyze the critical DEGs in PC cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29158292/sphingomyelin-metabolism-is-a-regulator-of-kras-function
#6
Dharini van der Hoeven, Kwang-Jin Cho, Yong Zhou, Xiaoping Ma, Wei Chen, Ali Naji, Dina Montufar-Solis, Yan Zuo, Sarah E Kovar, Kandice R Levental, Jeffrey A Frost, Ransome van der Hoeven, John F Hancock
KRAS must localize to the plasma membrane (PM) for biological activity. We show here that multiple acid sphingomyelinase (ASM) inhibitors, including tricyclic antidepressants, mislocalized phosphatidylserine (PtdSer) and KRASG12V from the PM; resulting in abrogation of KRASG12V signaling and potent, selective growth inhibition of mutant KRAS transformed cancer cells. Concordantly, in nude mice, the ASM inhibitor fendiline decreased the rate of growth of oncogenic KRAS-expressing MiaPaCa-2 tumors, but had no effect on the growth of the wild-type KRAS-expressing BxPC-3 tumors...
November 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29156703/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#7
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...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152137/emodin-and-rhein-decrease-levels-of-hypoxia-inducible-factor-1%C3%AE-in-human-pancreatic-cancer-cells-and-attenuate-cancer-cachexia-in-athymic-mice-carrying-these-cells
#8
Lijuan Hu, Rui Cui, Hongyi Liu, Feng Wang
The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of oxygen-sensitive HIF-1α and constitutive HIF-1β. HIF-1α is undetectable in normal cells, but cancer cells frequently express HIF-1α to support their growth, angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg effect in cancer cells increases energy expenditure and thus participates in cancer-induced metabolic disorder, cancer cachexia. In the present study, we investigated whether two components of Rheum palmatum, emodin and rhein, inhibited HIF-1α expression in human pancreatic cancer cells and whether the inhibiting effect, if any, attenuated cancer cachexia...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151366/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-76-85-edited-by-chinese-journal-of-cancer
#9
EDITORIAL
(no author information available yet)
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77. How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79...
November 20, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#10
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29144412/pancreatic-cancer-chemoresistance-to-gemcitabine
#11
REVIEW
Manoj Amrutkar, Ivar P Gladhaug
Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation...
November 16, 2017: Cancers
https://www.readbyqxmd.com/read/29134652/an-overview-of-polyamine-metabolism-in-pancreatic-ductal-adenocarcinoma
#12
REVIEW
Otto Phanstiel
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest major cancers, with a five year survival rate of less than 8%. With current therapies only giving rise to modest life extension, new approaches are desperately needed. Even though targeting polyamine metabolism is a proven anticancer strategy, there are no reports which thoroughly survey the literature describing the role of polyamine biosynthesis and transport in PDAC. This review seeks to fill this void by describing what is currently known about polyamine metabolism in PDAC and identifies new targets and opportunities to treat this disease...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29123391/surface-enhanced-raman-scattering-investigation-of-targeted-delivery-and-controlled-release-of-gemcitabine
#13
Ty Santiago, Rebecca Sinnott DeVaux, Katarzyna Kurzatkowska, Ricardo Espinal, Jason I Herschkowitz, Maria Hepel
Advanced and metastatic cancer forms are extremely difficult to treat and require high doses of chemotherapeutics, inadvertently affecting also healthy cells. As a result, the observed survival rates are very low. For instance, gemcitabine (GEM), one of the most effective chemotherapeutic drugs used for the treatment of breast and pancreatic cancers, sees only a 20% efficacy in penetrating cancer tissue, resulting in <5% survival rate in pancreatic cancer. Here, we present a method for delivering the drug that offers mitigation of side effects, as well as a targeted delivery and controlled release of the drug, improving its overall efficacy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29120638/discovery-and-optimization-of-potent-cell-active-pyrazole-based-inhibitors-of-lactate-dehydrogenase-ldh
#14
Ganesha Rai, Kyle R Brimacombe, Bryan T Mott, Daniel J Urban, Xin Hu, Shyh-Ming Yang, Tobie D Lee, Dorian M Cheff, Jennifer Kouznetsova, Gloria A Benavides, Katie Pohida, Eric J Kuenstner, Diane K Luci, Christine M Lukacs, Douglas R Davies, David M Dranow, Hu Zhu, Gary Sulikowski, William J Moore, Gordon M Stott, Andrew J Flint, Matthew D Hall, Victor M Darley-Usmar, Leonard M Neckers, Chi V Dang, Alex G Waterson, Anton Simeonov, Ajit Jadhav, David J Maloney
We report the discovery and medicinal chemistry optimization of a novel series of pyrazole-based inhibitors of human lactate dehydrogenase (LDH). Utilization of a quantitative high-throughput screening paradigm facilitated hit identification, while structure-based design and multiparameter optimization enabled the development of compounds with potent enzymatic and cell-based inhibition of LDH enzymatic activity. Lead compounds such as 63 exhibit low nM inhibition of both LDHA and LDHB, submicromolar inhibition of lactate production, and inhibition of glycolysis in MiaPaCa2 pancreatic cancer and A673 sarcoma cells...
November 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#15
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29108266/the-systemic-tumor-response-to-rnase-a-treatment-affects-the-expression-of-genes-involved-in-maintaining-cell-malignancy
#16
Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov, Marina Zenkova
Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#17
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29106450/a-novel-experimental-model-for-human-mixed-acinar-ductal-pancreatic-cancer
#18
Bruno Doiron, Ralph A DeFronzo
Pancreatic cancer has remained refractory to treatment. In large part, this results from the lack of an animal model that mimics pancreatic cancer in man. We describe a novel experimental model of pancreatic cancer that shares the genetic background, histologic features, and natural history of human mixed acinar-ductal carcinoma. Adult wild-type mice received an injection into the pancreatic duct of lentivirus coding two molecules, KrasG12D mutation and shRNA p53, which recapitulate the mechanisms of pancreatic cancer in humans...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29099030/repurposing-established-compounds-to-target-pancreatic-cancer-stem-cells-cscs
#19
REVIEW
Bernhard W Renz, Jan G D'Haese, Jens Werner, C Benedikt Westphalen, Matthias Ilmer
The diagnosis of pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis, in particular, when patients present with unresectable disease. While significant progress has been made in understanding the biology of PDAC, this knowledge has not translated into a clear clinical benefit and current chemotherapeutic strategies only offer a modest improvement in overall survival. Accordingly, novel approaches are desperately needed. One hypothesis that could-at least in part-explain the desolate response of PDAC to chemotherapy is the so-called cancer stem cell (CSC) concept, which attributes specific traits, such as chemoresistance, metastatic potential and a distinct metabolism to a small cellular subpopulation of the whole tumor...
June 19, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29096620/non-invasively-predicting-differentiation-of-pancreatic-cancer-through-comparative-serum-metabonomic-profiling
#20
Shi Wen, Bohan Zhan, Jianghua Feng, Weize Hu, Xianchao Lin, Jianxi Bai, Heguang Huang
BACKGROUND: The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy...
November 2, 2017: BMC Cancer
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