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Cancer metabolomics

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https://www.readbyqxmd.com/read/28423651/succinate-dehydrogenase-b-deficient-cancer-cells-are-highly-sensitive-to-bromodomain-and-extra-terminal-inhibitors
#1
Satoshi Kitazawa, Shunsuke Ebara, Ayumi Ando, Yuji Baba, Yoshinori Satomi, Tomoyoshi Soga, Takahito Hara
Mutations in succinate dehydrogenase B (SDHB) gene are frequently observed in several tumors and associated with poor prognosis in these tumors. Therefore, drugs effective for SDHB-deficient tumors could fulfill an unmet medical need. In addition, such drugs would have an advantage in that selection of patients with SDHB-mutant cancer could increase the probability of success in clinical trials. Currently, however, the characteristics of SDHB-deficient cancers are not completely understood. Here, we established SDHB knockout cancer cell lines from human colon cancer HCT116 cells using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 knockout system, and clarified its metabolic characteristics...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423406/the-rise-of-radiomics-and-implications-for-oncologic-management
#2
Vivek Verma, Charles B Simone, Sunil Krishnan, Steven H Lin, Jinzhong Yang, Stephen M Hahn
Clinical medicine, particularly oncology, is progressing toward personalized care. Whereas the terms genomics, proteomics, transcriptomics, and metabolomics have dominated personalized medicine for the past couple decades, the concept of radiomics was first described in 2012. This nascent concept has major implications for personalized cancer care and involves extracting hundreds of standardized and quantifiable imaging characteristics from diagnostic computed tomography/magnetic resonance imaging images. The central hypothesis of radiomics is that these libraries of quantitative individual voxel-based variables are more sensitively associated with various clinical endpoints compared with the more qualitative radiologic, histopathologic, and clinical data more commonly utilized today...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28423352/prospective-serum-metabolomic-profile-of-prostate-cancer-by-size-and-extent-of-primary-tumor
#3
Jiaqi Huang, Alison M Mondul, Stephanie J Weinstein, Edward D Karoly, Joshua N Sampson, Demetrius Albanes
Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20)...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423060/phosphatidylcholine-specific-phospholipase-c-inhibition-down-regulates-cxcr4-expression-and-interferes-with-proliferation-invasion-and-glycolysis-in-glioma-cells
#4
Laura Mercurio, Serena Cecchetti, Alessandro Ricci, Aurora Pacella, Giovanni Cigliana, Giuseppina Bozzuto, Franca Podo, Egidio Iorio, Giulia Carpinelli
BACKGROUND: The chemokine receptor CXCR4 plays a crucial role in tumors, including glioblastoma multiforme (GBM), the most aggressive glioma. Phosphatidylcholine-specific phospholipase C (PC-PLC), a catabolic enzyme of PC metabolism, is involved in several aspects of cancer biology and its inhibition down-modulates the expression of growth factor membrane receptors interfering with their signaling pathways. In the present work we investigated the possible interplay between CXCR4 and PC-PLC in GBM cells...
2017: PloS One
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#5
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28420117/metabolomic-profiling-of-the-synergistic-effects-of-melittin-in-combination-with-cisplatin-on-ovarian-cancer-cells
#6
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin-Kyu Park, Jong-Woon Jeon, Valerie A Ferro, David G Watson
Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells...
April 14, 2017: Metabolites
https://www.readbyqxmd.com/read/28418859/serum-metabolomics-differentiating-pancreatic-cancer-from-new-onset-diabetes
#7
Xiangyi He, Jie Zhong, Shuwei Wang, Yufen Zhou, Lei Wang, Yongping Zhang, Yaozong Yuan
To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415762/metabonomics-studies-on-serum-and-urine-of-patients-with-breast-cancer-using-1h-nmr-spectroscopy
#8
Jianping Zhou, Yanxia Wang, Xinli Zhang
The aim of this study was to describe a metabolomic study of breast cancer using 1H-NMR combined with bioinformatics analysis. 1H-NMR spectroscopy combined with multi-variate pattern recognition analysis was used to cluster the groups (serum and urine samples from breast cancer patients and healthy controls) and establish a breast-cancer-specific metabolites phenotype. Orthogonalpartial least-squares discriminant analysis (OPLS-DA) was capable of distinguishing serum and urine samples from breast cancer patients and healthy controls and establishing a breast-cancer-specific metabolite profile...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415579/metabolite-marker-discovery-for-the-detection-of-bladder-cancer-by-comparative-metabolomics
#9
Chi-Hung Shao, Chien-Lun Chen, Jia-You Lin, Chao-Jung Chen, Shu-Hsuan Fu, Yi-Ting Chen, Yu-Sun Chang, Jau-Song Yu, Ke-Hung Tsui, Chiun-Gung Juo, Kun-Pin Wu
Bladder cancer is one of the most common urinary tract carcinomas in the world. Urine metabolomics is a promising approach for bladder cancer detection and marker discovery since urine is in direct contact with bladder epithelia cells; metabolites released from bladder cancer cells may be enriched in urine samples. In this study, we applied ultra-performance liquid chromatography time-of-flight mass spectrometry to profile metabolite profiles of 87 samples from bladder cancer patients and 65 samples from hernia patients...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413374/discrimination-of-pancreatic-cancer-and-pancreatitis-by-lc-ms-metabolomics
#10
Anna Lindahl, Rainer Heuchel, Jenny Forshed, Janne Lehtiö, Matthias Löhr, Anders Nordström
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available. OBJECTIVES: The aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS)...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28408240/intratumor-heterogeneity-in-primary-kidney-cancer-revealed-by-metabolic-profiling-of-multiple-spatially-separated-samples-within-tumors
#11
Takatsugu Okegawa, Megumi Morimoto, Satoru Nishizawa, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Toshiya Tamura, Ayumi Ando, Yoshinori Satomi, Kikuo Nutahara, Takahito Hara
Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here, we used global metabolomics analysis and tissue slice tracer studies to demonstrate that different portions of a human primary kidney tumor possess different metabolic characteristics and drug sensitivity...
April 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28404949/metabolomics-uncovers-a-link-between-inositol-metabolism-and-osteosarcoma-metastasis
#12
Ling Ren, Ellen S Hong, Arnulfo Mendoza, Sameer Issaq, Christine Tran Hoang, Michael Lizardo, Amy LeBlanc, Chand Khanna
Cancer development and progression are characterized by complex molecular events. The acquisition of these events is primarily believed to result from alterations in gene and protein expression/function. Recent studies have also suggested the role of metabolic alterations, or "metabolic reprogramming," that may similarly contribute to these events. Indeed, our previous investigations in osteosarcoma (OS) identified metabolic changes uniquely linked to metastasis. Based on those findings, here we sought to build a more detailed understanding of the specific alterations in metabolites or metabolic pathways that may be responsible for the observed metastasis-associated metabolic alterations, suggested by gene expression data...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#13
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28399896/glutaminase-1-plays-a-key-role-in-the-cell-growth-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis
#14
Soshi Takahashi, Jun Saegusa, Sho Sendo, Takaichi Okano, Kengo Akashi, Yasuhiro Irino, Akio Morinobu
BACKGROUND: The recent findings of cancer-specific metabolic changes, including increased glucose and glutamine consumption, have provided new therapeutic targets for consideration. Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients exhibit several tumor cell-like characteristics; however, the role of glucose and glutamine metabolism in the aberrant proliferation of these cells is unclear. Here, we evaluated the role of these metabolic pathways in RA-FLS proliferation and in autoimmune arthritis in SKG mice...
April 11, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28393905/metabolomic-characterisation-of-the-effects-of-oncogenic-pik3ca-transformation-in-a-breast-epithelial-cell-line
#15
Chung-Ho E Lau, Gregory D Tredwell, James K Ellis, Eric W-F Lam, Hector C Keun
Somatic mutations in PIK3CA are frequently found in a number of human cancers, including breast cancer, altering cellular physiology and tumour sensitivity to chemotherapy. This renders PIK3CA an attractive molecular target for early detection and personalised therapy. Using (1)H Nuclear Magnetic Resonance spectroscopy (NMR) and Gas Chromatography - Mass Spectrometery (GC-MS) together with (13)C stable isotope-labelled glucose and glutamine as metabolic tracers, we probed the phenotypic changes in metabolism following a single copy knock-in of mutant PIK3CA (H1047R) in the MCF10A cell line, an important cell model for studying oncogenic transformation in breast tissues...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393186/a-novel-5-fluorouracil-resistant-human-esophageal-squamous-cell-carcinoma-cell-line-eca-109-5-fu-with-significant-drug-resistance-related-characteristics
#16
Chi Zhang, Qunfeng Ma, Yinan Shi, Xue Li, Ming Wang, Junfeng Wang, Jianlin Ge, Zhinan Chen, Ziling Wang, Hong Jiang
5-Fluorouracil (5-FU) is used for the clinical treatment of esophageal squamous cell carcinomas (ESCCs), yet it also induces chemoresistant cancer cells during treatment, which leads to the failure of the therapy. To further explore the resistance mechanism of 5-FU in ESCC, we established the 5-FU-resistant ESCC cell line Eca-109/5-FU, which was prepared by the stepwise exposure to increasing 5-FU concentrations. MTT assay and nude mouse xenograft models were used to test the drug resistance and proliferation of Eca-109 and Eca-109/5-FU cells in vitro and in vivo...
March 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28389631/metabolic-profiling-and-novel-plasma-biomarkers-for-predicting-survival-in-epithelial-ovarian-cancer
#17
Hongyu Xie, Yan Hou, Jinlong Cheng, Margarita S Openkova, Bairong Xia, Wenjie Wang, Ang Li, Kai Yang, Junnan Li, Huan Xu, Chunyan Yang, Libing Ma, Zhenzi Li, Xin Fan, Kang Li, Ge Lou
Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies around the world, and patients with ovarian cancer always have an extremely poor chance of survival. Therefore, it is meaningful to develop a highly efficient model that can predict the overall survival for EOC. In order to investigate whether metabolites could be used to predict the survival of EOC, we performed a metabolic analysis of 98 plasma samples with follow-up information, based on the ultra-performance liquid chromatography mass spectrometry (UPLC/MS) systems in both positive (ESI+) and negative (ESI-) modes...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389626/metabolomics-for-biomarker-discovery-in-the-diagnosis-prognosis-survival-and-recurrence-of-colorectal-cancer-a-systematic-review
#18
Fan Zhang, Yuanyuan Zhang, Weiwei Zhao, Kui Deng, Zhuozhong Wang, Chunyan Yang, Libing Ma, Margarita S Openkova, Yan Hou, Kang Li
Colorectal cancer (CRC) remains an incurable disease. There are no effective noninvasive techniques that have achieved colorectal cancer (CRC) diagnosis, prognosis, survival and recurrence in clinic. To investigate colorectal cancer metabolism, we perform an electronic literature search, from 1998 to January 2016, for studies evaluating the metabolomic profile of patients with CRC regarding the diagnosis, recurrence, prognosis/survival, and systematically review the twenty-three literatures included. QUADOMICS tool was used to assess the quality of them...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388410/physiologic-medium-rewires-cellular-metabolism-and-reveals-uric-acid-as-an-endogenous-inhibitor-of-ump-synthase
#19
Jason R Cantor, Monther Abu-Remaileh, Naama Kanarek, Elizaveta Freinkman, Xin Gao, Abner Louissaint, Caroline A Lewis, David M Sabatini
A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28380457/the-integrative-metabolomic-transcriptomic-landscape-of-glioblastome-multiforme
#20
Dieter Henrik Heiland, Jakob Wörner, Jan Gerrit Haaker, Daniel Delev, Nils Pompe, Bianca Mercas, Pamela Franco, Annette Gäbelein, Sabrina Heynckes, Dietmar Pfeifer, Stefan Weber, Irina Mader, Oliver Schnell
The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs...
March 24, 2017: Oncotarget
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