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Cancer metabolomics

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https://www.readbyqxmd.com/read/28723573/proteomic-and-metabolomic-characterization-of-a-mammalian-cellular-transition-from-quiescence-to-proliferation
#1
Ho-Joon Lee, Mark P Jedrychowski, Arunachalam Vinayagam, Ning Wu, Ng Shyh-Chang, Yanhui Hu, Chua Min-Wen, Jodene K Moore, John M Asara, Costas A Lyssiotis, Norbert Perrimon, Steven P Gygi, Lewis C Cantley, Marc W Kirschner
There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720669/muc1-mediated-metabolic-alterations-regulate-response-to-radiotherapy-in-pancreatic-cancer
#2
Venugopal Gunda, Joshua J Souchek, Jaime Abrego, Surendra K Shukla, Gennifer D Goode, Enza Vernucci, Aneesha Dasgupta, Nina CHaika, Ryan J King, Sicong Li, Shuo Wang, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K Singh
Purpose: MUC1, an oncogene overexpressed in multiple solid tumors including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models. <p>Experimental design: We used MUC1 knockdown and overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response and metabolomic evaluations...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28711496/metabolomic-profiling-reveals-potential-biomarkers-in-esophageal-cancer-progression-using-liquid-chromatography-mass-spectrometry-platform
#3
Haiping Zhang, Lei Wang, Zhichao Hou, Hong Ma, Batur Mamtimin, Ayshamgul Hasim, Ilyar Sheyhidin
Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710076/opportunities-and-challenges-for-environmental-exposure-assessment-in-population-based-studies
#4
Chirag J Patel, Jacqueline Kerr, Duncan C Thomas, Bhramar Mukherjee, Beate Ritz, Nilanjan Chatterjee, Marta M Jankowska, Juliette Madan, Margaret R Karagas, Kimberly A McAllister, Leah E Mechanic, M Daniele Fallin, Christine Ladd-Acosta, Ian A Blair, Susan L Teiltelbaum, Christopher I Amos
BACKGROUND: A growing number and increasing diversity of factors are available for epidemiological studies. These measures provide new avenues for discovery and prevention yet they also raise many challenges for adoption in epidemiological investigations. METHODS: We evaluate 1) designs to investigate diseases that consider heterogeneous and multi-dimensional indicators of exposure and behavior, 2) the implementation of numerous methods to capture indicators of exposure, and 3) the analytical methods required for discovery and validation...
July 14, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28709411/rho-kinase-proteins-display-aberrant-upregulation-in-vascular-tumors-and-contribute-to-vascular-tumor-growth
#5
Clarissa N Amaya, Dianne C Mitchell, Brad A Bryan
BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells...
July 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28698610/tomatoes-protect-against-development-of-uv-induced-keratinocyte-carcinoma-via-metabolomic-alterations
#6
Jessica L Cooperstone, Kathleen L Tober, Ken M Riedl, Matthew D Teegarden, Morgan J Cichon, David M Francis, Steven J Schwartz, Tatiana M Oberyszyn
Prolonged tomato consumption can mitigate ultraviolet (UV) light induced sunburn via unknown mechanisms. Dietary carotenoids distributed to skin are hypothesized to protect skin against UV-induced damage, although other phytochemicals may play a role. We hypothesize that tomato consumption would protect against skin cancer. SKH-1 hairless and immunocompetent mice (n = 180) were fed AIN-93G or AIN-93G + 10% tangerine or red tomato powder for 35 weeks. From weeks 11-20, mice (n = 120) were exposed to 2240 J/m(2) UV-B light, 3x/week, and tumors were tracked weekly...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694488/outer-membrane-vesicles-secreted-by-pathogenic-and-nonpathogenic-bacteroides-fragilis-represent-different-metabolic-activities
#7
Natalya B Zakharzhevskaya, Anna A Vanyushkina, Ilya A Altukhov, Aleksey L Shavarda, Ivan O Butenko, Daria V Rakitina, Anastasia S Nikitina, Aleksandr I Manolov, Alina N Egorova, Eugene E Kulikov, Innokentii E Vishnyakov, Gleb Y Fisunov, Vadim M Govorun
Numerous studies are devoted to the intestinal microbiota and intercellular communication maintaining homeostasis. In this regard, vesicles secreted by bacteria represent one of the most popular topics for research. For example, the outer membrane vesicles (OMVs) of Bacteroides fragilis play an important nutritional role with respect to other microorganisms and promote anti-inflammatory effects on immune cells. However, toxigenic B. fragilis (ETBF) contributes to bowel disease, even causing colon cancer. If nontoxigenic B...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687010/longitudinal-serum-metabolomics-evaluation-of-trastuzumab-and-everolimus-combination-as-pre-operative-treatment-for-her-2-positive-breast-cancer-patients
#8
Elodie Jobard, Olivier Trédan, Thomas Bachelot, Arnaud M Vigneron, Céline Mahier Aït-Oukhatar, Monica Arnedos, Maria Rios, Jacques Bonneterre, Véronique Diéras, Marta Jimenez, Jean-Louis Merlin, Mario Campone, Bénédicte Elena-Herrmann
The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2.Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E)...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28686599/flux-balance-analysis-predicts-warburg-like-effects-of-mouse-hepatocyte-deficient-in-mir-122a
#9
Hua-Qing Wu, Mei-Ling Cheng, Jin-Mei Lai, Hsuan-Hui Wu, Meng-Chun Chen, Wen-Huan Liu, Wu-Hsiung Wu, Peter Mu-Hsin Chang, Chi-Ying F Huang, Ann-Ping Tsou, Ming-Shi Shiao, Feng-Sheng Wang
The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a-/-) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a-/-mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states...
July 7, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28685691/metabolomics-applications-in-precision-medicine-an-oncological-perspective
#10
Leonor Puchades-Carrasco, Antonio Pineda-Lucena
Nowadays, cancer therapy remains limited by the conventional one-size-fits-all approach. In this context, treatment decisions are based on the clinical stage of disease but fail to ascertain the individual´s underlying biology and its role in driving malignancy. The identification of better therapies for cancer treatment is thus limited by the lack of sufficient data regarding the characterization of specific biochemical signatures associated with each particular cancer patient or group of patients. Metabolomics approaches promise a better understanding of cancer, a disease characterized by significant alterations in bioenergetic metabolism, by identifying changes in the pattern of metabolite expression in addition to changes in the concentration of individual metabolites as well as alterations in biochemical pathways...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28677625/cytotoxic-effects-of-sarcophyton-sp-soft-corals-is-there-a-correlation-to-their-nmr-fingerprints
#11
Mohamed A Farag, Mostafa I Fekry, Montasser A Al-Hammady, Mohamed N Khalil, Hesham R El-Seedi, Achim Meyer, Andrea Porzel, Hildegard Westphal, Ludger A Wessjohann
Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues...
July 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28676459/shaping-functional-gut-microbiota-using-dietary-bioactives-to-reduce-colon-cancer-risk
#12
REVIEW
Derek V Seidel, M Andrea Azcárate-Peril, Robert S Chapkin, Nancy D Turner
Colon cancer is a multifactorial disease associated with a variety of lifestyle factors. Alterations in the gut microbiota and the intestinal metabolome are noted during colon carcinogenesis, implicating them as critical contributors or results of the disease process. Diet is a known determinant of health, and as a modifier of the gut microbiota and its metabolism, a critical element in maintenance of intestinal health. This review summarizes recent evidence demonstrating the role and responses of the intestinal microbiota during colon tumorigenesis and the ability of dietary bioactive compounds and probiotics to impact colon health from the intestinal lumen to the epithelium and systemically...
July 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28674522/desynchronization-of-circadian-clocks-in-cancer-a-metabolic-and-epigenetic-connection
#13
REVIEW
Kiran Padmanabhan, Marc Billaud
Circadian clocks are innate oscillators that drive daily rhythms in metabolism, physiology, and behavior. 24-h rhythms in gene expression, driven by core clock transcription factors, reflect the epigenetic state of the cell, which in turn is dictated by the metabolic environment. Cancer cells alter their metabolic state and gene expression and therefore are likely to tweak circadian clock function in their favor. Over the past decade, we have witnessed an extraordinary increase in systems-level studies that suggest intricate mechanistic links between the cellular metabolome and the circadian epigenome...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28671190/compensatory-metabolic-networks-in-pancreatic-cancers-upon-perturbation-of-glutamine-metabolism
#14
Douglas E Biancur, Joao A Paulo, Beata Małachowska, Maria Quiles Del Rey, Cristovão M Sousa, Xiaoxu Wang, Albert S W Sohn, Gerald C Chu, Steven P Gygi, J Wade Harper, Wojciech Fendler, Joseph D Mancias, Alec C Kimmelman
Pancreatic ductal adenocarcinoma is a notoriously difficult-to-treat cancer and patients are in need of novel therapies. We have shown previously that these tumours have altered metabolic requirements, making them highly reliant on a number of adaptations including a non-canonical glutamine (Gln) metabolic pathway and that inhibition of downstream components of Gln metabolism leads to a decrease in tumour growth. Here we test whether recently developed inhibitors of glutaminase (GLS), which mediates an early step in Gln metabolism, represent a viable therapeutic strategy...
July 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28665402/germline-bap1-mutations-induce-a-warburg-effect
#15
Angela Bononi, Haining Yang, Carlotta Giorgi, Simone Patergnani, Laura Pellegrini, Mingming Su, Guoxiang Xie, Valentina Signorato, Sandra Pastorino, Paul Morris, Greg Sakamoto, Shafi Kuchay, Giovanni Gaudino, Harvey I Pass, Andrea Napolitano, Paolo Pinton, Wei Jia, Michele Carbone
Carriers of heterozygous germline BAP1 mutations (BAP1(+/-)) develop cancer. We studied plasma from 16 BAP1(+/-) individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1(WT)) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1(WT) and BAP1(+/-) individuals...
June 30, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28659298/nutritional-metabolomics-and-breast-cancer-risk-in-a-prospective-study
#16
Mary C Playdon, Regina G Ziegler, Joshua N Sampson, Rachael Stolzenberg-Solomon, Henry J Thompson, Melinda L Irwin, Susan T Mayne, Robert N Hoover, Steven C Moore
Background: The epidemiologic evidence for associations between dietary factors and breast cancer is weak and etiologic mechanisms are often unclear. Exploring the role of dietary biomarkers with metabolomics can potentially facilitate objective dietary characterization, mitigate errors related to self-reported diet, agnostically test metabolic pathways, and identify mechanistic mediators.Objective: The aim of this study was to evaluate associations of diet-related metabolites with the risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial...
June 28, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28658205/mtorc1-dependent-amd1-regulation-sustains-polyamine-metabolism-in-prostate-cancer
#17
Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Natalia Martín-Martín, Sonia Fernandez-Ruiz, James D Sutherland, Michelle Clasquin, Julen Tomas-Cortazar, Jose Jimenez, Ines Torres, Phong Quang, Pilar Ximenez-Embun, Ruzica Bago, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Isabel Lacasa-Viscasillas, Miguel Unda, Verónica Torrano, Diana Cabrera, Sebastiaan M van Liempd, Ylenia Cendon, Elena Castro, Stuart Murray, Ajinkya Revandkar, Andrea Alimonti, Yinan Zhang, Amelia Barnett, Gina Lein, David Pirman, Ana R Cortazar, Leire Arreal, Ludmila Prudkin, Ianire Astobiza, Lorea Valcarcel-Jimenez, Patricia Zuñiga-García, Itziar Fernandez-Dominguez, Marco Piva, Alfredo Caro-Maldonado, Pilar Sánchez-Mosquera, Mireia Castillo-Martín, Violeta Serra, Naiara Beraza, Antonio Gentilella, George Thomas, Mikel Azkargorta, Felix Elortza, Rosa Farràs, David Olmos, Alejo Efeyan, Juan Anguita, Javier Muñoz, Juan M Falcón-Pérez, Rosa Barrio, Teresa Macarulla, Jose M Mato, Maria L Martinez-Chantar, Carlos Cordon-Cardo, Ana M Aransay, Kevin Marks, José Baselga, Josep Tabernero, Paolo Nuciforo, Brendan D Manning, Katya Marjon, Arkaitz Carracedo
Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28648284/common-molecular-subtypes-among-asian-hepatocellular-carcinoma-and-cholangiocarcinoma
#18
Jittiporn Chaisaingmongkol, Anuradha Budhu, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, So Mee Kwon, Marshonna Forgues, Yotsawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M Hewitt, Kris Ylaya, Xiaolin Wu, Jesper B Andersen, Snorri S Thorgeirsson, Joshua J Waterfall, Yuelin J Zhu, Jennifer Walling, Holly S Stevenson, Daniel Edelman, Paul S Meltzer, Christopher A Loffredo, Natsuko Hama, Tatsuhiro Shibata, Robert H Wiltrout, Curtis C Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W Wang
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28646744/systematic-biobanking-novel-imaging-techniques-and-advanced-molecular-analysis-for-precise-tumor-diagnosis-and-therapy-the-polish-mobit-project
#19
Jacek Niklinski, Adam Kretowski, Marcin Moniuszko, Joanna Reszec, Anna Michalska-Falkowska, Magdalena Niemira, Michal Ciborowski, Radoslaw Charkiewicz, Dorota Jurgilewicz, Miroslaw Kozlowski, Rodryg Ramlau, Cezary Piwkowski, Miroslaw Kwasniewski, Monika Kaczmarek, Andrzej Ciereszko, Tomasz Wasniewski, Robert Mroz, Wojciech Naumnik, Ewa Sierko, Magdalena Paczkowska, Joanna Kisluk, Anetta Sulewska, Adam Cybulski, Zenon Mariak, Boguslaw Kedra, Jacek Szamatowicz, Paweł Kurzawa, Lukasz Minarowski, Angelika Edyta Charkiewicz, Barbara Mroczko, Jolanta Malyszko, Christian Manegold, Lothar Pilz, Heike Allgayer, Mohammed L Abba, Hartmut Juhl, Frauke Koch
Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized...
June 21, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#20
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
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