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Cancer metabolism

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https://www.readbyqxmd.com/read/28230989/development-of-the-first-generation-of-disulfide-based-subtype-selective-and-potent-covalent-pyruvate-dehydrogenase-kinase-1-pdk1-inhibitors
#1
Yifu Liu, Zuoquan Xie, Dan Zhao, Jin Zhu, Fei Mao, Shuai Tang, Hui Xu, Cheng Luo, Mei-Yu Geng, Min Huang, Jian Li
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described Bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, based on the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analog, 3a, effectively inhibits PDK1 both at the molecular (kinact/Ki = 4.17×103M-1s-1) and the cellular level (down to 0.1 μM). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#2
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230822/disordered-redox-metabolism-of-brain-cells-in-rats-exposed-to-low-doses-of-ionizing-radiation-or-uhf-electromagnetic-radiation
#3
A P Burlaka, M O Druzhyna, A V Vovk, S М Lukin
AIM: To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. MATERIALS AND METHODS: The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#4
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230703/omics-and-cachexia
#5
Brigitte Twelkmeyer, Nicolas Tardif, Olav Rooyackers
PURPOSE OF REVIEW: The purpose of this review is to recapture recent advances in cachexia-related diseases, mainly cancer cachexia, and treatment using genomic, transcriptomics, proteomic, and metabolomics-related techniques. RECENT FINDINGS: From recent studies in the cancer cachexia field it is clear that the tumor has a direct effect on distant organs via its secretome. The affected pathways on the other hand were largely known from earlier studies with changes in energy-related pathways (mainly lipid metabolism) and the protein degradation pathways...
February 21, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28230171/impact-of-genetic-variation-on-human-camkk2-regulation-by-ca-2-calmodulin-and-multisite-phosphorylation
#6
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229591/ass1-is-a-metabolic-regulator-of-colorectal-cancer-pathogenicity
#7
Leslie A Bateman, Wan-Min Ku, Martin J Heslin, Carlo M Contreras, Christine F Skibola, Daniel K Nomura
Like many cancer types, colorectal cancers have dysregulated metabolism that promotes their pathogenic features. In this study, we used the activity-based protein profiling chemoproteomic platform to profile cysteine-reactive metabolic enzymes that are upregulated in primary human colorectal tumors. We identified argininosuccinate synthase 1 (ASS1) as an upregulated target in primary human colorectal tumors and show that pharmacological inhibition or genetic ablation of ASS1 impairs colorectal cancer colorectal pathogenicity...
February 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28229250/role-of-mirnas-in-human-disease-and-inborn-errors-of-metabolism
#8
Ana Rivera-Barahona, Belén Pérez, Eva Richard, Lourdes R Desviat
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression posttranscriptionally by base pairing with target messenger RNAs (mRNAs). They are estimated to target ∼60% of all human protein-coding genes and are involved in regulating key physiological processes and intracellular signaling pathways. They also exhibit tissue specificity, and their dysregulation is linked to the progression of pathology. Identifying disease associated miRNAs and their respective targets provides novel molecular insight into disease, enabling the design of new therapeutic strategies...
February 22, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28229171/potential-biomarkers-associated-with-oxidative-stress-for-risk-assessment-of-colorectal-cancer
#9
REVIEW
Paramita Mandal
Cells are continuously threatened by the damage caused by reactive oxygen/nitrogen species (ROS/RNS), which are produced during physiological oxygen metabolism. In our review, we will summarize the latest reports on the role of oxidative stress and oxidative stress-induced signaling pathways in the etiology of colorectal cancer. The differences in ROS generation may influence the levels of oxidized proteins, lipids, and DNA damage, thus contributing to the higher susceptibility of colon. Reactive species (RS) of various types are formed and are powerful oxidizing agents, capable of damaging DNA and other biomolecules...
February 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28228938/physical-activity-levels-in-locally-advanced-rectal-cancer-patients-following-neoadjuvant-chemoradiotherapy-and-an-exercise-training-programme-before-surgery-a-pilot-study
#10
Lisa Loughney, Malcolm A West, Borislav D Dimitrov, Graham J Kemp, Michael Pw Grocott, Sandy Jack
BACKGROUND: The aim of this pilot study was to measure changes in physical activity level (PAL) variables, as well as sleep duration and efficiency in people with locally advanced rectal cancer (1) before and after neoadjuvant chemoradiotherapy (CRT) and (2) after participating in a pre-operative 6-week in-hospital exercise training programme, following neoadjuvant CRT prior to major surgery, compared to a usual care control group. METHODS: We prospectively studied 39 consecutive participants (27 males)...
2017: Perioperative Medicine
https://www.readbyqxmd.com/read/28228780/the-relationship-between-vitamin-d-receptor-vdr-polymorphism-and-the-occurrence-of-osteoporosis-in-menopausal-iranian-women
#11
Raheleh Dabirnia, Sanaz Mahmazi, Amirhossein Taromchi, Masoum Nikzad, Ehsan Saburi
BACKGROUND: Osteoporosis, a multifactorial disease with reduced bone mineral density which increases the probability of bone fractures, is caused by calcium deficiency, and its incidence increases with age. It has been determined that mutations in functional regions of vitamin D receptor gene will affect the metabolism of minerals especially calcium and, therefore, bone density. The present study evaluates the relation between vitamin D receptor polymorphisms, TaqI (rs731236) and ApaI (rs7975232), and osteoporosis in menopausal Azari women in Zanjan province...
September 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/28228595/hepatitis-c-virus-specific-t-cell-receptor-mrna-engineered-human-t-cells-impact-of-antigen-specificity-on-functional-properties
#12
Anangi Balasiddaiah, Haleh Davanian, Soo Aleman, Anna Pasetto, Lars Frelin, Matti Sällberg, Volker Lohmann, Sarene Koh, Antonio Bertoletti, Margaret Chen
Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognising the HCV non-structural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBL) derived from healthy donors as well as chronically infected HCV patients...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228393/protein-turnover-provides-pancreatic-cancer-target
#13
(no author information available yet)
Decreased activity of the chromatin remodeling factor gene SMARCB1 drives a switch in pancreatic cancer cells toward a more aggressive, mesenchymal state. This change makes the tumors more susceptible to drugs that target protein metabolism and associated stress responses.
February 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28228357/activation-of-mtor-i%C3%AE%C2%BAb-%C3%AE-nf-%C3%AE%C2%BAb-pathway-contributes-to-lps-induced-hypotension-and-inflammation-in-rats
#14
Meryem Temiz-Resitoglu, Sefika Pinar Kucukkavruk, Demet Sinem Guden, Pelin Cecen, Ayse Nihal Sari, Bahar Tunctan, Aysegul Gorur, Lulufer Tamer-Gumus, Cuneyt Kemal Buharalioglu, Kafait U Malik, Seyhan Sahan-Firat
Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll-like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)-induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor-κB (NF-κB) p65, inhibitor κB (IκB)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)-α and activity of myeloperoxidase (MPO), which results in hypotension and inflammation...
February 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#15
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228010/selective-fusion-of-heterogeneous-classifiers-for-predicting-substrates-of-membrane-transporters
#16
Naeem Shaikh, Mahesh Sharma, Prabha Garg
Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic and toxicological profile. In the present study, predictive models for classifying small molecules into substrates and non-substrates of various pharmaceutically important membrane transporters are developed using QSAR and proteochemometric (PCM) approaches. For this purpose, 4575 substrate interactions for these transporters were collected from Metabolism and Transport Database (Metrabase) and literature...
February 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28227014/random-forests-to-predict-tumor-recurrence-following-cervical-cancer-therapy-using-pre-and-per-treatment-18-f-fdg-pet-parameters
#17
Geoffrey Roman-Jimenez, Oscar Acosta, Julie Leseur, Anne Devillers, Henri Der Sarkissian, Lina Guzman, Eloi'se Grossiord, Juan-David Ospina, Renaud De Crevoisier, Geoffrey Roman-Jimenez, Oscar Acosta, Julie Leseur, Anne Devillers, Henri Der Sarkissian, Lina Guzman, Eloi'se Grossiord, Juan-David Ospina, Renaud De Crevoisier, Oscar Acosta, Julie Leseur, Juan-David Ospina, Geoffrey Roman-Jimenez, Henri Der Sarkissian, Renaud De Crevoisier, Anne Devillers, Eloise Grossiord, Lina Guzman
The ability to predict tumor recurrence after chemoradiotherapy of locally advanced cervical cancer is a crucial clinical issue to intensify the treatment of the most high-risk patients. The objective of this study was to investigate tumor metabolism characteristics extracted from pre- and per-treatment (18)F-FDG PET images to predict 3-year overall recurrence (OR). A total of 53 locally advanced cervical cancer patients underwent pre- and per-treatment (18)F-FDG PET (respectively PET1 and PET2). Tumor metabolism was characterized through several delineations using different thresholds, based on a percentage of the maximum uptake, and applied by region-growing...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226339/current-concepts-of-phenylpiperidine-derivatives-use-in-the-treatment-of-acute-and-chronic-pain
#18
Nidal Elbaridi, Alan D Kaye, Stephanie Choi, Richard D Urman
Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. These agents have an important role in many aspects of medicine including anesthesia and pain medicine. After the development of meperidine, fentanyl, which is a second generation synthetic phenylpiperidine series opioid, was synthesized and introduced into clinical anesthesia practice as fentanyl citrate in 1968. Fentanyl-mediated or modulated responses involve action at the mu-opioid receptor as an agonist at the dorsal horn inhibiting ascending pain pathways in the rostral ventral medulla, increasing pain threshold, and producing both analgesic and sedative effects...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28225831/whole-body-staging-of-female-patients-with-recurrent-pelvic-malignancies-ultra-fast-18f-fdg-pet-mri-compared-to-18f-fdg-pet-ct-and-ct
#19
Julian Kirchner, Lino Morris Sawicki, Saravanabavaan Suntharalingam, Johannes Grueneisen, Verena Ruhlmann, Bahriye Aktas, Cornelius Deuschl, Ken Herrmann, Gerald Antoch, Michael Forsting, Lale Umutlu
OBJECTIVES: To evaluate the diagnostic feasibility of an ultra-fast 18F-FDG PET/MRI protocol, including T2-w and contrast-enhanced T1-w imaging as well as metabolic assessment (PET) in comparison to 18F-FDG PET/CT and CT for whole-body staging of female patients with suspected recurrence of pelvic malignancies. METHODS: 43 female patients with suspected tumor recurrence were included in this study. Suspicion was based on clinical follow-up and abnormal findings on imaging follow-up...
2017: PloS One
https://www.readbyqxmd.com/read/28225065/a-comprehensive-analysis-of-metabolomics-and-transcriptomics-in-cervical-cancer
#20
Kai Yang, Bairong Xia, Wenjie Wang, Jinlong Cheng, Mingzhu Yin, Hongyu Xie, Junnan Li, Libing Ma, Chunyan Yang, Ang Li, Xin Fan, Harman S Dhillon, Yan Hou, Ge Lou, Kang Li
Cervical cancer (CC) still remains a common and deadly malignancy among females in developing countries. More accurate and reliable diagnostic methods/biomarkers should be discovered. In this study, we performed a comprehensive analysis of metabolomics (285 samples) and transcriptomics (52 samples) on the potential diagnostic implication and metabolic characteristic description in cervical cancer. Sixty-two metabolites were different between CC and normal controls (NOR), in which 5 metabolites (bilirubin, LysoPC(17:0), n-oleoyl threonine, 12-hydroxydodecanoic acid and tetracosahexaenoic acid) were selected as candidate biomarkers for CC...
February 22, 2017: Scientific Reports
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