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Cancer metabolism

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https://www.readbyqxmd.com/read/28434145/mtorc1-signaling-in-hepatic-lipid-metabolism
#1
REVIEW
Jinbo Han, Yiguo Wang
The mechanistic target of rapamycin (mTOR) signaling pathway regulates many metabolic and physiological processes in different organs or tissues. Dysregulation of mTOR signaling has been implicated in many human diseases including obesity, diabetes, cancer, fatty liver diseases, and neuronal disorders. Here we review recent progress in understanding how mTORC1 (mTOR complex 1) signaling regulates lipid metabolism in the liver.
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434047/late-renal-toxicity-of-treatment-for-childhood-malignancy-risk-factors-long-term-outcomes-and-surveillance
#2
Roderick Skinner
Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors...
April 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28433864/arsenic-metabolism-and-cancer-risk-a-meta-analysis
#3
REVIEW
Brenda Gamboa-Loira, Mariano E Cebrián, Francisco Franco-Marina, Lizbeth López-Carrillo
OBJECTIVE: To describe the studies that have reported association measures between risk of cancer and the percentage distribution of urinary inorganic arsenic (iAs) metabolites by anatomical site, in non-ecological epidemiological studies. METHODS: Studies were identified in the PubMed database in the period from 1990 to 2015. Inclusion criteria were: non-ecological epidemiological study, with histologically confirmed cancer cases, reporting the percentage distribution of inorganic arsenic (iAs), monomethylated (MMA) and dimethylated (DMA) metabolites, as well as association measures with confidence intervals (CI) between cancer and %iAs and/or %MMA and/or %DMA...
April 20, 2017: Environmental Research
https://www.readbyqxmd.com/read/28433859/photoelectrochemical-immunosensor-for-methylated-rna-detection-based-on-g-c3n4-cds-quantum-dots-heterojunction-and-phos-tag-biotin
#4
Haiyan Wang, Qihai Zhang, Huanshun Yin, Minghui Wang, Wenjing Jiang, Shiyun Ai
N(6)-methyladenosine (m(6)A) is an enigmatic and abundant internal modification in eukaryotic messenger RNA (mRNA), which could affect various aspects of RNA metabolism and mRNA translation. Herein, a novel photoelectrochemical (PEC) immunosensor was constructed for m(6)A detection based on the inhibition of Cu(2+) to the photoactivity of g-C3N4/CdS quantum dots (g-C3N4/CdS) heterojunction, where g-C3N4/CdS heterojunction was used as photoactive material, anti-m(6)A antibody as recognition unit for m(6)A-containing RNA, Phos-tag-biotin as link unit and avidin functionalized CuO as PEC signal indicator...
April 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28433806/polymorphism-of-cyp1a1-gene-variants-rs4646903-and-rs1048943-relation-to-the-incidence-of-cervical-cancer-in-chhattisgarh
#5
Vijaylakshmi Jain, Yashwant K Ratre, Dnyanesh Amle, Pankaj K Mishra, Pradeep K Patra
Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls)...
April 13, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28433698/adipose-crosstalk-with-other-cell-types-in-health-and-disease
#6
REVIEW
Chan Hee J Choi, Paul Cohen
In addition to storing and mobilizing energy, adipocytes secrete circulating factors to signal to other tissues and coordinate energy metabolism. These functions can become disrupted in the setting of obesity, contributing to the development of diabetes, cardiovascular disease, and cancer. Since the discovery of leptin and adiponectin, an increasing number of adipokines have been identified and their functions elucidated. More recent studies have highlighted other modes by which adipose tissue can participate in crosstalk with other cell types and tissues...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#7
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28432871/mir-24-3p-is-overexpressed-in-hodgkin-lymphoma-and-protects-hodgkin-and-reed-sternberg-cells-from-apoptosis
#8
Ye Yuan, Joost Kluiver, Jasper Koerts, Debora de Jong, Bea Rutgers, Fazlyn Reeny Abdul Razak, Martijn Terpstra, Boudewijn Plaat, Ilja M Nolte, Arjan Diepstra, Lydia Visser, Klaas Kok, Anke van den Berg
miRNAs play important roles in biological processes, such as proliferation, metabolism, differentiation, and apoptosis, whereas altered expression levels contribute to diseases, such as cancers. We identified miRNAs with aberrant expression in Hodgkin lymphoma (HL) and investigated their role in pathogenesis. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to germinal center B cells. Three up-regulated miRNAs-miR-23a-3p, miR-24-3p, and miR-27a-3p-were derived from one primary miRNA transcript...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#9
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431259/allosteric-regulation-of-metabolism-in-cancer-endogenous-mechanisms-and-considerations-for-drug-design
#10
REVIEW
Jamie A Macpherson, Dimitrios Anastasiou
Alterations in metabolic processes have been linked to various diseases, including cancer. Although gene expression can dictate long-term metabolic adaptation, many metabolic changes found in cancer are associated with altered allosteric properties of the underlying enzymes. Small molecule-protein interactions and intracellular signalling converge to orchestrate these allosteric mechanisms, which, emerging evidence suggests, constitute a promising therapeutic avenue. In this review we focus on glucose and energy metabolism to illustrate the role of allostery in cancer physiology and we discuss approaches to streamline the process of targeting aberrant allosteric pathways with small molecules...
April 18, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28431245/host-microbe-co-metabolism-dictates-cancer-drug-efficacy-in-c-%C3%A2-elegans
#11
Timothy A Scott, Leonor M Quintaneiro, Povilas Norvaisas, Prudence P Lui, Matthew P Wilson, Kit-Yi Leung, Lucia Herrera-Dominguez, Sonia Sudiwala, Alberto Pessia, Peter T Clayton, Kevin Bryson, Vidya Velagapudi, Philippa B Mills, Athanasios Typas, Nicholas D E Greene, Filipe Cabreiro
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B6, B9, and ribonucleotide metabolism...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431244/bacterial-metabolism-affects-the-c-%C3%A2-elegans-response-to-cancer-chemotherapeutics
#12
Aurian P García-González, Ashlyn D Ritter, Shaleen Shrestha, Erik C Andersen, L Safak Yilmaz, Albertha J M Walhout
The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430653/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#13
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated. Mice were administered diethylnitrosamine-containing water for 2 weeks and were treated with tofogliflozin throughout the experiment...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429737/the-glutamate-cystine-xct-antiporter-antagonizes-glutamine-metabolism-and-reduces-nutrient-flexibility
#14
Chun-Shik Shin, Prashant Mishra, Jeramie D Watrous, Valerio Carelli, Marilena D'Aurelio, Mohit Jain, David C Chan
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc(-)), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429674/targeting-the-role-of-lipoprotein-a-in-stroke
#15
Mahdi Garelnabi, Zahra Mazhar, Andrew Hughes
Stroke is the third leading cause of death in the United States, behind only heart disease and cancer, with over 140,000 associated deaths per year. Considerable research is ongoing to examine the role of modifiable risk factors which may cause or contribute to a stroke occurring. Although age and family history are generally considered to be major risk factors, there are several modifiable and non-modifiable risk factors that are linked to the pathogenesis of a stroke. Lipoprotein (a), or Lp(a), is a type of low-density lipoprotein containing an integral apoB100 component with an attached ApoA1 isoform via a disulfide linkage...
April 21, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#16
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28428965/natural-killer-cells-in-the-orchestration-of-chronic-inflammatory-diseases
#17
REVIEW
Luca Parisi, Barbara Bassani, Marco Tremolati, Elisabetta Gini, Giampietro Farronato, Antonino Bruno
Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28428633/inhibition-of-glutathione-metabolism-attenuates-esophageal-cancer-progression
#18
Liang Peng, Ruixia Linghu, Demeng Chen, Jing Yang, Xiaoxue Kou, Xiang-Zhen Wang, Yi Hu, Yi-Zhou Jiang, Junlan Yang
Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428273/assessing-prostate-cancer-aggressiveness-with-hyperpolarized-dual-agent-3d-dynamic-imaging-of-metabolism-and-perfusion
#19
Hsin-Yu Chen, Peder E Z Larson, Robert A Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B Vigneron
New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) approach with (13)C-pyruvate and (13)C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427834/doped-silica-fibre-thermoluminescence-measurements-of-radiation-dose-in-the-use-of-223-ra
#20
Bradley, S F Abdul Sani, A S Siti Shafiqah, S M Collins, R P Hugtenburg, H A Abdul Rashid, Nurul Najua Zulkepely, M J Maah
Using tailor-made sub-mm dimension doped-silica fibres, thermoluminescent dosimetric studies have been performed for α-emitting sources of (223)RaCl2 (the basis of the Bayer Healthcare product Xofigo®). The use of (223)RaCl2 in the palliative treatment of bone metastases resulting from late-stage castration-resistant prostate cancer focuses on its favourable uptake in metabolically active bone metastases. Such treatment benefits from the high linear energy transfer (LET) and associated short path length (<100µm) of the α-particles emitted by (223)Ra and its decay progeny...
April 14, 2017: Applied Radiation and Isotopes
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