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https://www.readbyqxmd.com/read/28813755/genetics-of-alcoholism
#1
Ena C Zhu, Timothy J Soundy, Yueshan Hu
Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk...
May 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28813744/alkaptonuria-a-case-report-with-diagnostic-challenge
#2
Vasantha L Gali, Amy M Kerkvliet, Jacob M Kusmak, Jana K Elwood
Alkaptonuria is a rare autosomal recessive metabolic disorder caused by deficiency of homogentisic acid (HGA) oxidase, the only enzyme capable of catabolizing HGA. Deficiency of this enzyme leads to excess HGA which deposits in the connective tissue. We present a case of a 64-year-old woman who was referred to the dermatology clinic for a full body mole check and skin cancer screening. Clinically she had blue/gray pigmentation of the external ear and sclera. Also she had a domed papule on the left cheek with punctate gray pigmentation which was biopsied...
August 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#3
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#4
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813442/a-parallel-metaheuristic-for-large-mixed-integer-dynamic-optimization-problems-with-applications-in-computational-biology
#5
David R Penas, David Henriques, Patricia González, Ramón Doallo, Julio Saez-Rodriguez, Julio R Banga
BACKGROUND: We consider a general class of global optimization problems dealing with nonlinear dynamic models. Although this class is relevant to many areas of science and engineering, here we are interested in applying this framework to the reverse engineering problem in computational systems biology, which yields very large mixed-integer dynamic optimization (MIDO) problems. In particular, we consider the framework of logic-based ordinary differential equations (ODEs). METHODS: We present saCeSS2, a parallel method for the solution of this class of problems...
2017: PloS One
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#6
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28811829/metabolomics-analysis-for-defining-serum-biochemical-markers-in-colorectal-cancer-patients-with-qi-deficiency-syndrome-or-yin-deficiency-syndrome
#7
Fangfang Tao, Ping Lü, Chunbo Xu, Mengmeng Zheng, Wenhong Liu, Minhe Shen, Shanming Ruan
Colorectal cancer is one of the leading causes of tumor-associated death, and traditional Chinese medicine (TCM) classifies colorectal cancer into various subtypes mainly according to the symptomatic pattern identification (ZHENG). Here, we investigated the difference in metabolic profiles of serum by comparing colorectal cancer subjects with Nondeficiency (ND), Qi deficiency (QD), and Yin deficiency (YD). The ratio of subjects with carcinoembryonic antigen (CEA) was higher in YD pattern, and the ratio of subjects with carbohydrate antigen 19-9 (CA19-9) was higher both in YD and in QD, compared with ND...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28811713/clinical-significance-of-glycemic-parameters-on-venous-thromboembolism-risk-prediction-in-gastrointestinal-cancer
#8
Fiorella Guadagni, Silvia Riondino, Vincenzo Formica, Girolamo Del Monte, Anna Maria Morelli, Jessica Lucchetti, Antonella Spila, Roberta D'Alessandro, David Della-Morte, Patrizia Ferroni, Mario Roselli
AIM: To investigate the possible predictive role of routinely used glycemic parameters for a first venous thromboembolism (VTE) episode in gastrointestinal (GI) cancer ambulatory patients - with or without clinically diagnosed type 2 diabetes (T2D) or obesity - treated with chemotherapy. METHODS: Pre-treatment fasting blood glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model of risk assessment (HOMA) were retrospectively evaluated in a cohort study of 342 GI cancer patients...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811683/methylenetetrahydrofolate-reductase-c677t-polymorphism-and-risk-for-male-infertility-in-asian-population
#9
Vandana Rai, Pradeep Kumar
Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of folate pathway and required for DNA synthesis and methylation. MTHFE C677T polymorphisms is reported as risk factors for various diseases and disorders like birth defects, metabolic, neurological, psychiatric disorders, and cancers. Several studies have investigated association between the MTHFR C677T polymorphism and male infertility. To assess the risk associated with MTHFR C677T polymorphism in Asian population, a meta-analysis was performed...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#10
Georg Emons, Melanie Spitzner, Sebastian Reineke, Janneke Möller, Noam Auslander, Frank Kramer, Yue Hu, Tim Beissbarth, Hendrik A Wolff, Margret Rave-Fränk, Elisabeth Heßmann, Jochen Gaedcke, B Michael Ghadimi, Steven Johnsen, Thomas Ried, Marian Grade
Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#11
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811347/tifa-signaling-in-gastric-epithelial-cells-initiates-the-cag-type-4-secretion-system-dependent-innate-immune-response-to-helicobacter-pylori-infection
#12
Alevtina Gall, Ryan G Gaudet, Scott D Gray-Owen, Nina R Salama
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#13
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28811309/cellular-and-molecular-mechanisms-coordinating-pancreas-development
#14
REVIEW
Aimée Bastidas-Ponce, Katharina Scheibner, Heiko Lickert, Mostafa Bakhti
The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28810235/obesity-as-a-conditioning-factor-for-high-altitude-diseases
#15
Rocío San Martin, Julio Brito, Patricia Siques, Fabiola León-Velarde
Obesity, a worldwide epidemic, has become a major health burden because it is usually accompanied by an increased risk for insulin resistance, diabetes, hypertension, cardiovascular diseases, and even some kinds of cancer. It also results in associated increases in healthcare expenditures and labor and economic consequences. There are also other fields of medicine and biology where obesity or being overweight play a major role, such as high-altitude illnesses (acute mountain sickness, hypoxic pulmonary hypertension, and chronic mountain sickness), where an increasing relationship among these two morbid statuses has been demonstrated...
August 16, 2017: Obesity Facts
https://www.readbyqxmd.com/read/28810149/o2-%C3%A2-and-h2o2-mediated-disruption-of-fe-metabolism-causes-the-differential-susceptibility-of-nsclc-and-gbm-cancer-cells-to-pharmacological-ascorbate
#16
Joshua D Schoenfeld, Zita A Sibenaller, Kranti A Mapuskar, Brett A Wagner, Kimberly L Cramer-Morales, Muhammad Furqan, Sonia Sandhu, Thomas L Carlisle, Mark C Smith, Taher Abu Hejleh, Daniel J Berg, Jun Zhang, John Keech, Kalpaj R Parekh, Sudershan Bhatia, Varun Monga, Kellie L Bodeker, Logan Ahmann, Sandy Vollstedt, Heather Brown, Erin P Shanahan Kauffman, Mary E Schall, Ray J Hohl, Gerald H Clamon, Jeremy D Greenlee, Matthew A Howard, Michael K Schultz, Brian J Smith, Dennis P Riley, Frederick E Domann, Joseph J Cullen, Garry R Buettner, John M Buatti, Douglas R Spitz, Bryan G Allen
No abstract text is available yet for this article.
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#17
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrate that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation accompanied with a relative decrease in the proliferation of MUC1-overexpressing cells compared to steady state conditions...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#18
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#19
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28808224/off-label-use-of-crizotinib-as-a-neoadjuvant-treatment-for-a-young-patient-when-conventional-chemotherapy-gave-no-benefits-in-stage-iiia-non-small-cell-lung-cancer
#20
Delphine Dumont, Pascal Dô, Delphine Lerouge, Gaëtane Planchard, Marc Riffet, Catherine Dubos-Arvis, Serge Danhier, Radj Gervais
BACKGROUND The treatment of locally advanced non-small cell lung cancer involves a combination of chemotherapy, surgery, and radiotherapy. Each case is discussed and the best strategy is chosen individually, following international guidelines. CASE REPORT A 37-year-old man was diagnosed with locally advanced broncho-pulmonary adenocarcinoma (stage IIIA). The disease was stable after 2 cycles of cisplatin plus Navelbine used as neoadjuvant therapy. FISH analysis revealed an ALK rearrangement. The patient then received unlicensed crizotinib as second-line neoadjuvant treatment, which led to an almost complete radiological and metabolic response...
August 15, 2017: American Journal of Case Reports
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