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Cancer metabolism

Alexandrine Robert, Irvin R Schultz, Nicolas Hucher, Tiphaine Monsinjon, Thomas Knigge
The disposition and metabolism of fluoxetine in the European shore crab and the Dungeness crab were assessed. Crabs received intracardiac doses of either 0.13 μg/kg or 0.5 mg/kg fluoxetine, respectively. In addition, fluoxetine was administered to Metacarcinus cancer by oral gavage at 7.8 mg/kg. The distribution of fluoxetine was quantified in haemolymph and digestive gland for both crabs, as well as brain, muscle, and testis of Carcinus maenas, over 12 days. The metabolite norfluoxetine, was also measured in C...
August 9, 2017: Chemosphere
Saoirse O Dolly, Mark D Gurden, Konstantinos Drosopoulos, Paul Clarke, Johann de Bono, Stan Kaye, Paul Workman, Spiros Linardopoulos
BACKGROUND: F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in multiple cancers through genetic deletion and mutations in a broad range of tumours. Loss of FBXW7 functionality results in the stabilisation of multiple major oncoproteins, culminating in increased cellular proliferation and pro-survival pathways, cell cycle deregulation, chromosomal instability and altered metabolism...
August 22, 2017: British Journal of Cancer
Theodore M Brasky, Emily White, Chi-Ling Chen
Purpose Inconsistent findings have been reported of a link between the use of one-carbon metabolism-related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplement use relative to cancer risk...
August 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Shuhua Shan, Jiangying Shi, Peng Yang, Bin Jia, Haili Wu, Xiaoli Zhang, Zhuoyu Li
Apigenin (AP), as an anti-cancer agent, has been widely explored. However, the molecular targets of apigenin on tumor metabolism are unclear. Currently, we found that AP could block the cellular glycolysis through restraining the tumor-specific pyruvate kinase M2 (PKM2) activity and expression, and further significantly induce the anti-colon cancer effects. The IC50 values of AP against HCT116, HT29 and DLD1 cells respectively were 27.9 ± 2.45, 48.2 ± 3.01 and 89.5 ± 4.89 μM. Fluorescence spectra and solid-phase AP extraction assays proved that AP could directly bind to PKM2 and markedly inhibit PKM2 activity in vitro and in HCT116 cells...
August 22, 2017: Journal of Agricultural and Food Chemistry
Showkat Ahmad Bhawani, Ahmad Husaini, Fasihuddin Badruddin Ahmad, Mohd Razip Asaruddin
Proteins have played avery important role in the drug industry for developing treatments of various diseases such as auto-immune diseases, cancer, diabetes, mental disorder, metabolic disease, and others. Therapeutic proteins have high activity and specificity but they have some limitations such as short half-life, poor stability, low solubility and immunogenicity, so they cannot prolong their therapeutic activity. These shortcomings have been rectified by using polymers for the conjugation with proteins. The conjugates of protein-polymer improves the half-lives, stability and makes them non-immunogenic...
August 21, 2017: Current Protein & Peptide Science
Kyoichi Kaira, Tetsuya Higuchi, Ichiro Naruse, Yukiko Arisaka, Azusa Tokue, Bolag Altan, Satoshi Suda, Akira Mogi, Kimihiro Shimizu, Noriaki Sunaga, Takeshi Hisada, Shigehisa Kitano, Hideru Obinata, Takehiko Yokobori, Keita Mori, Masahiko Nishiyama, Yoshihito Tsushima, Takayuki Asao
BACKGROUND: Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether (18)F-FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase. METHODS: Twenty-four patients were enrolled in this study. (18)F-FDG-PET/CT was carried out before and 1 month after nivolumab therapy...
August 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
Wun-Jae Kim, Jayoung Kim
Abnormal metabolism is a widely accepted biological signature of prostatic diseases, including prostate cancer and benign prostate hyperplasia. Recently accumulated epidemiological and experimental evidence illustrate that the metabolic syndrome, impaired mitochondrial function, and prostatic pathological conditions intersect. The perturbed metabolism and metabolic mediates influence key signaling pathways in various prostatic pathological conditions. This short review article aids to highlight recent findings on metabolism, metabolic mechanisms, and mitochondrial metabolism as a possible route to finding a cure for prostate diseases, including prostate cancer...
September 2017: Prostate International
Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X Zeng, Hua Lu
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63...
August 21, 2017: Scientific Reports
Evangelos C Tatsis, Inês Carqueijeiro, Thomas Dugé de Bernonville, Jakob Franke, Thu-Thuy T Dang, Audrey Oudin, Arnaud Lanoue, Florent Lafontaine, Anna K Stavrinides, Marc Clastre, Vincent Courdavault, Sarah E O'Connor
Monoterpene indole alkaloids comprise a diverse family of over 2000 plant-produced natural products. This pathway provides an outstanding example of how nature creates chemical diversity from a single precursor, in this case from the intermediate strictosidine. The enzymes that elicit these seemingly disparate products from strictosidine have hitherto been elusive. Here we show that the concerted action of two enzymes commonly involved in natural product metabolism-an alcohol dehydrogenase and a cytochrome P450-produces unexpected rearrangements in strictosidine when assayed simultaneously...
August 22, 2017: Nature Communications
Itziar M D Posada, Benoit Lectez, Farid A Siddiqui, Christina Oetken-Lindholm, Mukund Sharma, Daniel Abankwa
As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator...
August 21, 2017: Scientific Reports
Marina V Shirmanova, Irina N Druzhkova, Maria M Lukina, Varvara V Dudenkova, Nadezhda I Ignatova, Ludmila B Snopova, Vladislav I Shcheslavskiy, Vsevolod V Belousov, Elena V Zagaynova
Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi was measured using genetically encoded sensor SypHer2 and metabolic state was accessed by fluorescence intensities and lifetimes of endogenous cofactors NAD(P)H and FAD. Our data support the notion that cisplatin induces acidification of the cytoplasm early after the treatment...
August 21, 2017: Scientific Reports
Sanjeev Kumar, Elizabhet Cruz Gomez, Mounira Chalabi-Dchar, Cong Rong, Sadhan Das, Iva Ugrinova, Xavier Gaume, Karine Monier, Fabien Mongelard, Philippe Bouvet
Nucleolin is an essential protein that plays important roles in the regulation of cell cycle and cell proliferation. Its expression is up regulated in many cancer cells but its molecular functions are not well characterized. Nucleolin is present in the nucleus where it regulates gene expression at the transcriptional and post-transcriptional levels. Using HeLa cells depleted in nucleolin we performed an mRNA and miRNA transcriptomics analysis to identify biological pathways involving nucleolin. Bioinformatic analysis strongly points to a role of nucleolin in lipid metabolism, and in many signaling pathways...
August 21, 2017: Scientific Reports
James Kinross, Reza Mirnezami, James Alexander, Richard Brown, Alasdair Scott, Dieter Galea, Kirill Veselkov, Rob Goldin, Ara Darzi, Jeremy Nicholson, Julian R Marchesi
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis...
August 21, 2017: Scientific Reports
Valéry L Payen, Myriam Y Hsu, Kristin S Rädecke, Elisabeth Wyart, Thibaut Vazeille, Caroline Bouzin, Paolo E Porporato, Pierre Sonveaux
Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion and metastasis. While host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small molecule drugs to prevent metastasis...
August 21, 2017: Cancer Research
Wen Zhang, Manman Zhang, Chao Gao, Yipeng Zhang, Yongsheng Ge, Shiting Guo, Xiaoting Guo, Zikang Zhou, Qiuyuan Liu, Yingxin Zhang, Cuiqing Ma, Fei Tao, Ping Xu
l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Tianyi Zhang, Fu-Ning Hsu, Xiao-Jun Xie, Xiao Li, Mengmeng Liu, Xinsheng Gao, Xun Pei, Yang Liao, Wei Du, Jun-Yuan Ji
Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a Drosophila model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The Axin mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of β-catenin transcriptional activities. We demonstrate pharmacologic mitigation of these phenotypes in Axin mutants by identifying bortezomib and additional peptide boronic acids...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Jae Ho Lee, Yong Geun Jeon, Kyoung-Hwa Lee, Hye Won Lee, Jeu Park, Hagoon Jang, Minyong Kang, Hye Sun Lee, Hee Jin Cho, Do-Hyun Nam, Cheol Kwak, Jae Bum Kim
Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. However, the relationship between aberrant lipid metabolism and tumorigenesis in ccRCC is not thoroughly understood. Here, we demonstrate that ring finger protein 20 (RNF20) acts as a tumor suppressor in ccRCC. RNF20 overexpression repressed lipogenesis and cell proliferation by inhibiting sterol regulatory element-binding protein 1c (SREBP1c), and SREBP1 suppression by either knockdown or the pharmacological inhibitor betulin attenuated proliferation and cell cycle progression in ccRCC cells...
August 21, 2017: Molecular and Cellular Biology
Wei-Wen Sung, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells...
August 4, 2017: Experimental Cell Research
RoJenia N Jones, Stephanie A Erhard, Mark R Malham, Ayaz Y Gen, Kyle Sullivan, Kenneth W Olsen, Rodney M Dale
It has been well established that many types of rapidly dividing normal and diseased cells require an increased amount of folate for DNA replication and repair as well as cellular metabolism. Thus one of folate's cognate receptors, Folate Receptor 1 (FOLR1) is usually up-regulated in rapidly dividing cells, including many types of cancerous tumors. Because zebrafish have become a model organism for understanding conserved vertebrate cellular pathways and human disease, there has been an increased need to identify and elucidate orthologous zebrafish genes that are central to known human maladies...
August 18, 2017: Gene Expression Patterns: GEP
Kiel Neumann, Robert Flavell, David M Wilson
Cancer and other diseases are increasingly understood in terms of their metabolic disturbances. This thinking has revolutionized the field of ex vivo metabolomics and motivated new approaches to detect metabolites in living systems, including proton magnetic resonance spectroscopy ((1)H-MRS), hyperpolarized (13)C MRS, and PET. For PET, imaging abnormal metabolism in vivo is hardly new. Positron-labeled small-molecule metabolites have been used for decades in humans, including (18)F-FDG, which is used frequently to detect upregulated glycolysis in tumors...
September 2017: Seminars in Nuclear Medicine
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