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Cancer, metabolism

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https://www.readbyqxmd.com/read/28551354/targeting-free-radicals-in-oxidative-stress-related-human-diseases
#1
REVIEW
Patrik Poprac, Klaudia Jomova, Miriama Simunkova, Vojtech Kollar, Christopher J Rhodes, Marian Valko
Cancer and Alzheimer's disease (AD) are characterized by (i) opposing biological mechanisms, (ii) an inverse correlation between their incidences, and (iii) oxidative stress being a common denominator of both diseases. Increased formation of reactive oxygen species (ROS) in cancer cells from oncogenic signaling and/or metabolic disturbances leads to upregulation of cellular antioxidant capacity to maintain ROS levels below a toxic threshold. Combining drugs that induce high levels of ROS with compounds that suppress cellular antioxidant capacity by depleting antioxidant systems [glutathione (GSH), superoxide dismutase (SOD), and thioredoxin (TRX)] and/or targeting glucose metabolism represents a potential anticancer strategy...
May 24, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28551103/inhibition-of-phosphatidylinositol-3-kinase-by-the-furanosesquiterpenoid-hibiscone-c
#2
Caroline Besley, Dena P Rhinehart, Taylor Ammons, Brian C Goess, Jason S Rawlings
The phosphatidylinositol-3-kinase (PI3K) pathway regulates cellular metabolism and is upregulated in many cancers, making it an attractive chemotherapeutic target. Wortmannin is a potent inhibitor of PI3K; however, its potential as a chemotherapeutic is limited due to its instability, lack of selectivity, and lengthy chemical synthesis. In contrast, hibiscone C, a structurally simpler and less studied member of the furanosteroid family, has been expediently prepared by total synthesis. We demonstrate that hibiscone C competitively inhibits PI3K activity in intact cells, slows proliferation, and induces cell death...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28550668/-the-relationship-between-18-f-fdg-pet-ct-metabolic-parameters-and-clinicopathological-features-of-breast-cancer
#3
B Tang, Y Zhang, J Zhou, Y Xu, T R Li, C Y Ding
Objective: To investigate the relationship between metabolic parameters of primary lesion and clinicopathological features of patients with breast cancer. Methods: Clinical data of 78 patients with breast cancer undergone (18)F-FDG PET/CT before surgery was retrospectively analyzed. SUVmax, SUVmean and metabolic tumor volume (MTV) of primary lesions were measured by horizontal, sagittal and coronal position volume section with a threshold of 40% SUVmax. TLG was calculated and the highest SUVmax among metastatic lymph nodes was measured...
April 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#4
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28549934/in-vitro-metabolomic-approaches-to-investigating-the-potential-biological-effects-of-phenolic-compounds-an-update
#5
REVIEW
Úrsula Catalán, Laura Barrubés, Rosa Maria Valls, Rosa Solà, Laura Rubió
Dietary phenolic compounds (PCs) have been receiving interest for their presumed roles in disease prevention. However, there is a lack of studies on the underlying molecular mechanisms. In this regard, in vitro metabolomic approaches are suitable for the investigation of the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been examined for PCs from rosemary (Rosmarinus officinalis), olive oil, and resveratrol using cell-based metabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vitro cell experiment in some cases...
May 23, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28549851/identification-of-pathway-based-prognostic-gene-signatures-in-patients-with-multiple-myeloma
#6
Mohamad Zamani-Ahmadmahmudi, Shahreyar Dabiri, Nadia Nadimi
Molecular profiling is used to extract prognostic gene signatures in different cancers such as multiple myeloma (MM), which is the second most common hematological malignancy. In this study, we utilized gene expression profiles to find biological pathways that could efficiently predict survival time in patients with MM. Four data sets-namely GSE2658 (559 samples), GSE9782 (264 samples), GSE6477 (147 samples), and GSE57317 (55 samples)-were employed. GSE2658 was used as a training data set and the others as validation data sets...
May 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28549626/cell-biology-metabolic-crosstalk-in-glioma
#7
REVIEW
Alison Colquhoun
The renewed interest in cancer metabolism in recent years has been fuelled by the identification of the involvement of key oncogenes and tumour suppressor genes in the control of metabolic pathways. Many of these alterations lead to dramatic changes in bioenergetics, biosynthesis and redox balance within tumour cells. The complex relationship between tumour cell metabolism and the tumour microenvironment has turned this field of biochemistry and cell biology into a challenging and exciting area for study. In the case of gliomas the involvement of altered metabolic pathways including glycolysis, oxidative phosphorylation and glutaminolysis are pointing the way to new possibilities for treatment...
May 23, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28549213/binding-of-copper-and-cisplatin-to-atox1-is-mediated-by-glutathione-through-the-formation-of-metal-sulfur-clusters
#8
Nataliya V Dolgova, Corey Yu, John P Cvitkovic, Miroslav Hodak, Kurt Nienaber, Kelly Lynn Summers, Julien Cotelesage, Jerzy Bernholc, George A Kaminski, Ingrid J Pickering, Graham N George, Oleg Y Dmitriev
Copper is an essential nutrient required for many biological processes involved in primary metabolism, but free cop-per is toxic due to its ability to catalyze formation of free radicals. To prevent toxic effects, in the cell copper is bound to proteins and low molecular weight compounds, such as glutathione, at all times. The widely used chemotherapy agent cisplatin is known to bind to copper-transporting proteins, including copper chaperone Atox1. Cisplatin interac-tions with Atox1 and other copper transporters are linked to cancer resistance to platinum-based chemotherapy...
May 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28549188/eif5a-facilitates-translation-termination-globally-and-promotes-the-elongation-of-many-non-polyproline-specific-tripeptide-sequences
#9
Vicent Pelechano, Paula Alepuz
eIF5A is an essential protein involved in protein synthesis, cell proliferation and animal development. High eIF5A expression is observed in many tumor types and has been linked to cancer metastasis. Recent studies have shown that eIF5A facilitates the translation elongation of stretches of consecutive prolines. Activated eIF5A binds to the empty E-site of stalled ribosomes, where it is thought to interact with the peptidyl-tRNA situated at the P-site. Here, we report a genome-wide analysis of ribosome stalling in Saccharomyces cerevisiae eIF5A depleted cells using 5Pseq...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549153/chippi-a-novel-method-for-mapping-chimeric-protein-protein-interactions-uncovers-selection-principles-of-protein-fusion-events-in-cancer
#10
Milana Frenkel-Morgenstern, Alessandro Gorohovski, Somnath Tagore, Vaishnovi Sekar, Miguel Vazquez, Alfonso Valencia
Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28548968/aldose-reductase-interacts-with-akt1-to-augment-hepatic-akt-mtor-signaling-and-promote-hepatocarcinogenesis
#11
Jia-Xing Zhao, Ya-Wei Yuan, Cheng-Fu Cai, Dong-Yan Shen, Mao-Li Chen, Feng Ye, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Wei Zhang, Ying Long, Yong Zeng, Guo-Dong Ye, Shu-Yu Yang
Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548953/from-rapalogs-to-anti-aging-formula
#12
Mikhail V Blagosklonny
Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548950/enolase-1-stimulates-glycolysis-to-promote-chemoresistance-in-gastric-cancer
#13
Xiaoling Qian, Wenxia Xu, Jinye Xu, Qiqi Shi, Jiaqiu Li, Yu Weng, Zhinong Jiang, Lifeng Feng, Xian Wang, Jianwei Zhou, Hongchuan Jin
Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548481/isolation-of-phenotypically-distinct-cancer-cells-using-nanoparticle-mediated-sorting
#14
Brenda Green, Leyla Kermanshah, Mahmoud Labib, Sharif Ahmed, Pamuditha Silva, Laili Mahmoudian, I-Hsin Chang, Reza M Mohamadi, Jonathan V Rocheleau, Shana O Kelley
Isolating subpopulations of heterogeneous cancer cells is an important capability for the meaningful characterization of circulating tumor cells at different stages of tumor progression and during epithelial to mesenchymal transition (EMT). Here, we describe a two-dimensional separation approach that yields phenotypically-distinct subpopulations of cancer cells. Magnetic nanoparticles coated with antibodies against the epithelial cell adhesion molecule (EpCAM) are used to enrich cancer cells in a microfluidic platform...
May 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#15
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28548388/epithelial-mesenchymal-plasticity-how-have-quantitative-mathematical-models-helped-improve-our-understanding
#16
REVIEW
Mohit Kumar Jolly, Satyendra C Tripathi, Jason A Somarelli, Samir M Hanash, Herbert Levine
Phenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colonize distant organs. As a result, phenotypic plasticity can accelerate tumor progression. A well-studied example of phenotypic plasticity is the bidirectional conversions among epithelial, mesenchymal, and hybrid epithelial/mesenchymal phenotype(s). These conversions can alter a repertoire of cellular traits associated with multiple hallmarks of cancer, such as metabolism, immune-evasion, invasion and metastasis...
May 26, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28548184/obesity-and-kidney-disease-hidden-consequences-of-the-epidemic
#17
Csaba P Kovesdy, Susan Furth, Carmine Zoccali
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset Chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic kidney disease in the long-term...
March 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28548125/next-generation-sequencing-based-molecular-characterization-of-primary-urinary-bladder-adenocarcinoma
#18
Somak Roy, Dinesh Pradhan, Wayne L Ernst, Stephanie Mercurio, Yana Najjar, Rahul Parikh, Anil V Parwani, Reetesh K Pai, Rajiv Dhir, Marina N Nikiforova
Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28548104/genomic-analysis-of-oesophageal-squamous-cell-carcinoma-identifies-alcohol-drinking-related-mutation-signature-and-genomic-alterations
#19
Jiang Chang, Wenle Tan, Zhiqiang Ling, Ruibin Xi, Mingming Shao, Mengjie Chen, Yingying Luo, Yanjie Zhao, Yun Liu, Xiancong Huang, Yuchao Xia, Jinlin Hu, Joel S Parker, David Marron, Qionghua Cui, Linna Peng, Jiahui Chu, Hongmin Li, Zhongli Du, Yaling Han, Wen Tan, Zhihua Liu, Qimin Zhan, Yun Li, Weimin Mao, Chen Wu, Dongxin Lin
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548087/the-distinct-metabolic-phenotype-of-lung-squamous-cell-carcinoma-defines-selective-vulnerability-to-glycolytic-inhibition
#20
Justin Goodwin, Michael L Neugent, Shin Yup Lee, Joshua H Choe, Hyunsung Choi, Dana M R Jenkins, Robin J Ruthenborg, Maddox W Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D Minna, Kristi L Helke, Pankaj K Singh, David B Shackelford, Jung-Whan Kim
Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux...
May 26, 2017: Nature Communications
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