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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/28647837/targeting-metabolic-reprogramming-in-kras-driven-cancers
#1
REVIEW
Kenji Kawada, Kosuke Toda, Yoshiharu Sakai
Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect...
June 24, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28645477/the-overexpression-of-cpr-and-p450-3a4-in-pancreatic-cancer-cells-changes-the-metabolic-profile-and-increases-the-cytotoxicity-and-pro-apoptotic-activity-of-acridine-antitumor-agent-c-1748
#2
Barbara Borowa-Mazgaj, Anna Mróz, Ewa Augustin, Ewa Paluszkiewicz, Zofia Mazerska
Drug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and AsPC-1, differing in expression levels of commonly mutated genes for this cancer type, to C-1748 treatment and (ii) the role of P450 3A4 isoenzyme and cytochrome P450 reductase (CPR) in the modulation of this response...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641522/advances-on-ppar%C3%AE-research-in-the-emerging-era-of-precision-medicine
#3
Pinyi Lu, Zhongming Zhao
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily that functions as a ligand-inducible transcription factor. It regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are potent insulin sensitizers that function by activating PPARs, with a high specificity for PPARγ. Due to their ability to preserve pancreatic beta cell function and reduce insulin resistance, TZDs have become one of the most prescribed classes of medications for type 2 diabetes (T2D) since their approval by the US Food and Drug Administration (FDA) and initial use in 1997...
June 21, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#4
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634684/heterogeneity-index-evaluated-by-slope-of-linear-regression-on-18-f-fdg-pet-ct-as-a-prognostic-marker-for-predicting-tumor-recurrence-in-pancreatic-ductal-adenocarcinoma
#5
Yong-Il Kim, Yong Joong Kim, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, Keon Wook Kang
PURPOSE: (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of (18)F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and (18)F-FDG PET/CT parameters. METHODS: A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64...
June 20, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#6
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28627455/gemcitabine-vitamin-e-conjugates-synthesis-characterization-entrapment-into-nanoemulsions-and-in-vitro-deamination-and-antitumor-activity
#7
Ahmed Abu-Fayyad, Sami Nazzal
Gemcitabine is the first line therapy for pancreatic cancer. It is, however, extensively metabolized to the inactive form by deamination enzymatic reaction. Conjugation of gemcitabine with fatty acids on its 4-amino group was found to protect it from deamination deactivation reaction. The objective of the present study was to test the in-vitro anticancer activity of gemcitabine conjugated to the γ-tocotrienol isomer of vitamin E against pancreatic tumor cells. This objective was based on reported studies in which it was demonstrated that free tocotrienol isomers of vitamin E can potentiate the anticancer activity of gemcitabine...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28619945/transcriptional-activation-of-ragd-gtpase-controls-mtorc1-and-promotes-cancer-growth
#8
Chiara Di Malta, Diletta Siciliano, Alessia Calcagni, Jlenia Monfregola, Simona Punzi, Nunzia Pastore, Andrea N Eastes, Oliver Davis, Rossella De Cegli, Angela Zampelli, Luca G Di Giovannantonio, Edoardo Nusco, Nick Platt, Alessandro Guida, Margret Helga Ogmundsdottir, Luisa Lanfrancone, Rushika M Perera, Roberto Zoncu, Pier Giuseppe Pelicci, Carmine Settembre, Andrea Ballabio
The mechanistic target of rapamycin complex 1 (mTORC1) is recruited to the lysosome by Rag guanosine triphosphatases (GTPases) and regulates anabolic pathways in response to nutrients. We found that MiT/TFE transcription factors-master regulators of lysosomal and melanosomal biogenesis and autophagy-control mTORC1 lysosomal recruitment and activity by directly regulating the expression of RagD. In mice, this mechanism mediated adaptation to food availability after starvation and physical exercise and played an important role in cancer growth...
June 16, 2017: Science
https://www.readbyqxmd.com/read/28618995/the-complexity-of-omega-3-fatty-acids-modulation-of-signaling-pathways-related-to-pancreatic-cancer
#9
Carolina Torres, Andrew M Diaz, Daniel R Principe, Paul J Grippo
Cancer is a major public health problem worldwide and is the second leading cause of death in the United States. Although cancer death rate has dropped by 23% since 1991, there are certain types of cancer for which death rates are still increasing such as, pancreatic cancer. There is an urgent need to find new therapies that could help improve this dreadful outcome. In this regard, the role of nutrition in health and disease has attracted much attention. Several dietary ingredients are involved in metabolic, physiological, and cellular signaling affecting tumor growth and progression...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28612706/autophagy-and-its-link-to-type-ii-diabetes-mellitus
#10
Jai-Sing Yang, Chi-Cheng Lu, Sheng-Chu Kuo, Yuan-Man Hsu, Shih-Chang Tsai, Shih-Yin Chen, Yng-Tay Chen, Ying-Ju Lin, Yu-Chuen Huang, Chao-Jung Chen, Wei-De Lin, Wen-Lin Liao, Wei-Yong Lin, Yu-Huei Liu, Jinn-Chyuan Sheu, Fuu-Jen Tsai
Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#11
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28608366/complement-component-1-q-subcomponent-binding-protein-c1qbp-in-lipid-rafts-mediates-hepatic-metastasis-of-pancreatic-cancer-by-regulating-igf-1-igf-1r-signaling
#12
Haojun Shi, Winston Fang, Minda Liu, Deliang Fu
Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown...
June 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28591747/identification-and-causes-of-metabonomic-difference-between-orthotopic-and-subcutaneous-xenograft-of-pancreatic-cancer
#13
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 for1H NMR spectroscopy followed by univariate and multivariate statistical analyses...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590306/pancreatic-stellate-cells-what-s-new
#14
Tony C Y Pang, Jeremy S Wilson, Minoti V Apte
PURPOSE OF REVIEW: Pancreatic stellate cells (PSCs) play an integral role in the pathogenesis of pancreatitis and pancreatic cancer. With the developing knowledge of this important cell type, we are at the cusp of developing effective therapies for the above diseases based upon targeting the PSC and modulating its function. RECENT FINDINGS: The major themes of the recent PSC literature include: PSC interactions with the extracellular matrix and other stromal components; intracellular calcium physiology as drivers of mechanical interactions and necrosis; the relationship between proinflammatory, protumoural, angiogenic, and metabolic pathways in pancreatic necrosis, fibrosis, and carcinogenesis; and targeting of the stroma for antitumoural and antifibrotic effects...
June 5, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28584617/tumor-cells-growth-and-survival-time-with-the-ketogenic-diet-in-animal-models-a-systematic-review
#15
REVIEW
Soheila Khodadadi, Nafiseh Sobhani, Somaye Mirshekar, Reza Ghiasvand, Makan Pourmasoumi, Maryam Miraghajani, Somayeh Shahraki Dehsoukhteh
Recently, interest in targeted cancer therapies via metabolic pathways has been renewed with the discovery that many tumors become dependent on glucose uptake during anaerobic glycolysis. Also the inability of ketone bodies metabolization due to various deficiencies in mitochondrial enzymes is the major metabolic changes discovered in malignant cells. Therefore, administration of a ketogenic diet (KD) which is based on high in fat and low in carbohydrates might inhibit tumor growth and provide a rationale for therapeutic strategies...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28584183/nature-and-nurture-what-determines-tumor-metabolic-phenotypes
#16
REVIEW
Jared R Mayers, Matthew G Vander Heiden
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein...
June 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28573168/analysis-of-in-vivo-interaction-between-rna-binding-proteins-and-their-rna-targets-by-uv-cross-linking-and-immunoprecipitation-clip-method
#17
Pamela Bielli, Claudio Sette
RNA metabolism is tightly controlled across different tissues and developmental stages, and its dysregulation is one of the molecular hallmarks of cancer. Through direct binding to specific sequence element(s), RNA binding proteins (RBPs) play a pivotal role in co- and post-transcriptional RNA regulatory events. We have recently demonstrated that, in pancreatic cancer cells, acquisition of a drug resistant (DR)-phenotype relied on upregulation of the polypyrimidine tract binding protein (PTBP1), which in turn is recruited to the pyruvate kinase pre-mRNA and favors splicing of the oncogenic PKM2 variant...
May 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28569774/rgd-modified-oncolytic-adenovirus-harboring-shpkm2-exhibits-a-potent-cytotoxic-effect-in-pancreatic-cancer-via-autophagy-inhibition-and-apoptosis-promotion
#18
Yanni Xu, Liang Chu, Sujing Yuan, Yuanqin Yang, Yu Yang, Bin Xu, Kangjian Zhang, Xin-Yuan Liu, Ruwei Wang, Ling Fang, Zhinan Chen, Zongsuo Liang
The M2 isoform of pyruvate kinase (PKM2) is a key driver of glycolysis in cancer cells and has critical 'non-metabolic' functions in some cancers; however, the role of PKM2 in pancreatic cancer remains unclear. The aim of the current study was to elucidate the role of PKM2 in pancreatic cancer progression and the potential of PKM2 as a therapeutic target. In this study, we observed that PKM2 is highly expressed in patients with pancreatic cancer and is correlated to survival. Elevated PKM2 expression promoted cell proliferation, migration and tumor formation...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28544376/hif-2%C3%AE-regulates-non-canonical-glutamine-metabolism-via-activation-of-pi3k-mtorc2-pathway-in-human-pancreatic-ductal-adenocarcinoma
#19
Wenzhu Li, Changhao Chen, Xiaohui Zhao, Huilin Ye, Yue Zhao, Zhiqiang Fu, Wenwei Pan, Shangyou Zheng, Lusheng Wei, Tianwen Nong, Zhihua Li, Rufu Chen
Hypoxia-inducible factor-2α (HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28536008/chemosensitization-and-inhibition-of-pancreatic-cancer-stem-cell%C3%A2-proliferation-by-overexpression-of-microrna-205
#20
Amit Kumar Chaudhary, Goutam Mondal, Virender Kumar, Krishna Kattel, Ram I Mahato
Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R cells. Lentivirus-mediated overexpression of miR-205 inhibits MIA PaCa-2R cell proliferation after GEM-treatment...
May 20, 2017: Cancer Letters
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