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Cancer metabolism

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https://www.readbyqxmd.com/read/29454261/frequency-of-somatic-tp53-mutations-in-combination-with-known-pathogenic-mutations-in-colon-adenocarcinoma-non-small-cell-lung-carcinoma-and-gliomas-as-identified-by-next-generation-sequencing
#1
Zahra Shajani-Yi, Francine B de Abreu, Jason D Peterson, Gregory J Tsongalis
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective...
February 13, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29453983/aldolase-a-overexpression-is-associated-with-poor-prognosis-and-promotes-tumor-progression-by-the-epithelial-mesenchymal-transition-in-colon-cancer
#2
Feng Ye, Yixing Chen, Lu Xia, Jiabian Lian, Shuyu Yang
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453779/mitochondrial-cytochrome-p450-cyp-1b1-is-responsible-for-melatonin-induced-apoptosis-in-neural-cancer-cells
#3
Zhenlong Yu, Xiangge Tian, Yuling Peng, Zheng Sun, Chao Wang, Ning Tang, Bin Li, Yuqing Jian, Wei Wang, Xiaokui Huo, Xiaochi Ma
Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the anti-tumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453600/argininosuccinate-synthetase-1-ass1-loss-in-high-grade-neuroendocrine-carcinomas-of-the-urinary-bladder-implications-for-targeted-therapy-with-adi-peg-20
#4
Sounak Gupta, Divya Sahu, John S Bomalaski, Igor Frank, Stephen A Boorjian, Prabin Thapa, John C Cheville, Donna E Hansel
High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas...
February 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29453534/nanoparticles-caused-oxidative-imbalance
#5
Mariusz Zuberek, Agnieszka Grzelak
Application of nanomaterials in nearly every single branch of industry results in their accumulation in both abiotic environment and tissues of living organisms. Despite the common use of nanomaterials, we are not able to precisely define their toxicity towards humans and surrounding biota. Although we were able to determine final effects of chronic exposure to nanoparticles which consist of many pathologies such as respiratory diseases, allergies, diseases of cardiovascular system, disorders in embryonic life differentiation and growth disorders, toxic effects on the immune system and cancers...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#6
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453319/leptin-signaling-mediates-obesity-associated-csc-enrichment-and-emt-in-preclinical-tnbc-models
#7
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453315/autophagic-flux-is-regulated-by-interaction-between-the-c-terminal-domain-of-patched1-and-atg101
#8
Lucy X Chen, Cintli C Morales-Alcala, Natalia A Riobo-Del Galdo
The Hedgehog (Hh) receptor Patched1 (PTCH1) is a well-known tumor suppressor that in its active form represses Smoothened (SMO) activity, inhibits proliferation, and induces apoptosis. The cytoplasmic C-terminal domain (CTD) regulates PTCH1 turnover and nucleates a pro-apoptotic complex. In this study, it was mechanistically determined that Autophagy Related 10 (ATG101), essential for mammalian autophagy, physically interacts with the CTD of PTCH1 and connects it to the ULK complex, which stimulates the autophagy machinery in response to changes in nutrient availability...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452772/metabolic-and-lipidomic-reprogramming-in-renal-cell-carcinoma-subtypes-reflects-regions-of-tumor-origin
#9
Elke Schaeffeler, Florian Büttner, Anna Reustle, Verena Klumpp, Stefan Winter, Steffen Rausch, Pascale Fisel, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Judith Wahrheit, Denise Sonntag, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab
BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets...
February 13, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29452095/the-role-of-free-fatty-acid-receptor-4-ffa4-in-human-cancers-and-cancer-cell-lines
#10
REVIEW
Ilya S Senatorov, Nader H Moniri
A dietary influence on cancer progression has been evident for many decades, and dietary fatty acids, particularly long chain mono- and polyunsaturated fatty acids, have been shown to play significant roles in influencing growth of a variety of human cancers. The discovery of the family of cell-surface free-fatty acid receptors, which include the long-chain fatty acid receptors FFA1 and FFA4, suggest that many of the effects of dietary fats could be receptor-mediated. FFA4 is ubiquitously expressed and has recently been shown to modulate a variety of important anti-inflammatory and metabolic processes...
February 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29451603/from-medicinal-chemistry-to-human-health-current-approaches-to-drug-discovery-for-cancer-and-neglected-tropical-diseases
#11
Leonardo G Ferreira, Glaucius Oliva, Adriano D Andricopulo
Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline...
February 15, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29451296/investigation-of-the-urinary-metabolic-variations-and-the-application-in-bladder-cancer-biomarker-discovery
#12
Xiaoyan Liu, Xiangming Cheng, Xiang Liu, Lu He, Wenli Zhang, Yajie Wang, Wei Sun, Zhigang Ji
Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In the present study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and bladder cancer patients showed that the urine metabolome was relatively stable...
February 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29451272/the-ndpk-nme-superfamily-state-of-the-art
#13
EDITORIAL
Mathieu Boissan, Uwe Schlattner, Marie-Lise Lacombe
Nucleoside diphosphate kinases (NDPK) are nucleotide metabolism enzymes encoded by NME genes (also called NM23). Given the fact that not all NME-encoded proteins are catalytically active NDPKs and that NM23 generally refers to clinical studies on metastasis, we use here NME/NDPK to denote the proteins. Since their discovery in the 1950's, NMEs/NDPKs have been shown to be involved in multiple physiological and pathological cellular processes, but the molecular mechanisms have not been fully determined. Recent progress in elucidating these underlying mechanisms has been presented by experts in the field at the 10th International Congress on the NDPK/NME/AWD protein family in October 2016 in Dubrovnik, Croatia, and is summarized in review articles or original research in this and an upcoming issue of Laboratory Investigation...
February 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29450944/nrf2-addiction-in-cancer-cells
#14
REVIEW
Hiroshi Kitamura, Hozumi Motohashi
The KEAP1-NRF2 system is a pivotal defense mechanism against oxidative and electrophilic stress. While transient NRF2 activation in response to stress is beneficial for health, persistent NRF2 activation in cancer cells has deleterious effects on cancer-bearing hosts by conferring therapeutic resistance and aggressive tumorigenic activity on cancer cells. Because NRF2 increases the anti-oxidant and detoxification capability of cancer cells, persistently high levels of NRF2 activity enhance therapeutic resistance of the cancer cells...
February 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#15
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29450776/modulatory-role-of-gstt1-and-gstm1-in-punjabi-agricultural-workers-exposed-to-pesticides
#16
Meenakshi Ahluwalia, Anupam Kaur
Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk...
February 15, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29450727/metabolic-implications-of-hypoxia-and-pseudohypoxia-in-pheochromocytoma-and-paraganglioma
#17
REVIEW
Katarina Kluckova, Daniel A Tennant
Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant phenotypes such as epithelial-mesenchymal transition, stem cell-like characteristics and metabolic transformation. However, hypoxia-associated phenotypes are often observed in cancer in the absence of hypoxia, a phenotype known as pseudohypoxia, which is very well documented in specific tumour types, including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL tumours carry a germ line mutation in one of a number of susceptibility genes of which those that are found in succinate dehydrogenase (SDH) or in von Hippel-Lindau (VHL) genes manifest a strong pseudohypoxic phenotype...
February 15, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29450724/chromaffin-cell-biology-inferences-from-the-cancer-genome-atlas
#18
REVIEW
Lauren Fishbein, Matthew D Wilkerson
Pheochromocytomas and paragangliomas (PCC/PGLs) are rare neuroendocrine tumors that are unusually diverse in metabolic profiles, in classes of molecular alterations and across a large number of altered genes. The Cancer Genome Atlas (TCGA) comprehensively profiled the molecular landscape of PCC/PGLs and identified novel genomic alterations and a new molecular classification of PCC/PGLs. In this review, we discuss the significant clinico-molecular findings of this integrated profiling study. We then review the molecular data of the TCGA cohort centering around known markers of sympathoadrenal cell lineage to better understand chromaffin cell biology...
February 15, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29450657/in-silico-identification-of-small-molecules-as-novel-lxr-agonists-for-the-treatment-of-cardiovascular-disease-and-cancer
#19
Xin Wang, Kaimin Lu, Hao Luo, Danfeng Liang, Xin Long, Yuan Yuan, Chuanfang Wu, Jinku Bao
Liver X receptor (LXR), a member of the nuclear receptor superfamily, mainly serves as a reverse cholesterol transporter in lipid metabolism. It has been demonstrated that LXR is a promising target for the treatment of cardiovascular diseases. LXR is also involved in cancer metabolism, glucose homeostasis, immunity, and various physiological processes. The antitumor function of LXR has become of great interest to researchers in recent years. However, while it is believed that activating LXR with small molecules could be a promising approach to cancer treatment, effective drugs that target LXR are yet to be reported...
February 15, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29449867/current-therapies-in-alleviating-liver-disorders-and-cancers-with-a-special-focus-on-the-potential-of-vitamin-d
#20
REVIEW
Shahida Khan, Ashraf Ali, Sarah Khan, Ahmed Bakillah, Ghazi Damanhouri, Aziz Khan, Ahmed Makki, Ibtehal AlAnsari, Naheed Banu
Background: Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too. Result: Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders...
2018: Nutrition & Metabolism
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