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Lung cancer metabolomics

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https://www.readbyqxmd.com/read/29093815/metabolomics-guided-pathway-analysis-reveals-link-between-cancer-metastasis-cholesterol-sulfate-and-phospholipids
#1
Caroline H Johnson, Antonio F Santidrian, Sarah E LeBoeuf, Michael E Kurczy, Nicholas J W Rattray, Zahra Rattray, Benedikt Warth, Melissa Ritland, Linh T Hoang, Celine Loriot, Jason Higa, James E Hansen, Brunhilde H Felding, Gary Siuzdak
Background: Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production. Methods: A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An "autonomous" mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP) tumors compared to microdissected paired lung metastases...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/29035945/the-functional-consequences-of-the-microbiome-in-hiv-insights-from-metabolomic-studies
#2
Sergio Serrano-Villar, Santiago Moreno, Manuel Ferrer
PURPOSE OF REVIEW: It is critical to gain insight into the metabolic pathways by which the microbiota might influence HIV immunopathogenesis to exploit host-microbiota interactions. The aim of this review is to sketch a very broad picture of recent advances in our knowledge of how HIV might affect the microbiota, with a focus on specific gene products, particularly, metabolites produced by the microbiota that may affect HIV immunopathogenesis. RECENT FINDINGS: First, we describe the different approaches used to explore imbalances in effector microbial products during HIV infection...
October 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28968813/metabolome-wide-association-study-identified-the-association-between-a-circulating-polyunsaturated-fatty-acids-variant-rs174548-and-lung-cancer
#3
Cheng Wang, Na Qin, Meng Zhu, Minjian Chen, Kaipeng Xie, Yang Cheng, Juncheng Dai, Jia Liu, Yankai Xia, Hongxia Ma, Guangfu Jin, Christopher I Amos, Zhibin Hu, Dongxin Lin, Hongbing Shen
Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s)...
October 26, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28967920/keap1-loss-promotes-kras-driven-lung-cancer-and-results-in-dependence-on-glutaminolysis
#4
Rodrigo Romero, Volkan I Sayin, Shawn M Davidson, Matthew R Bauer, Simranjit X Singh, Sarah E LeBoeuf, Triantafyllia R Karakousi, Donald C Ellis, Arjun Bhutkar, Francisco J Sánchez-Rivera, Lakshmipriya Subbaraj, Britney Martinez, Roderick T Bronson, Justin R Prigge, Edward E Schmidt, Craig J Thomas, Chandra Goparaju, Angela Davies, Igor Dolgalev, Adriana Heguy, Viola Allaj, John T Poirier, Andre L Moreira, Charles M Rudin, Harvey I Pass, Matthew G Vander Heiden, Tyler Jacks, Thales Papagiannakopoulos
Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1 (refs. 2, 3, 4), a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/28915902/development-and-clinical-application-of-radiomics-in-lung-cancer
#5
REVIEW
Bojiang Chen, Rui Zhang, Yuncui Gan, Lan Yang, Weimin Li
Since the discovery of X-rays at the end of the 19(th) century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics...
September 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28914192/current-trends-in-cancer-biomarker-discovery-using-urinary-metabolomics-achievements-and-new-challenges
#6
Casey Burton, Yinfa Ma
The development of effective screening methods for early cancer detection is one of the foremost challenges facing modern cancer research. Urinary metabolomics has recently emerged as a potentially transformative approach to cancer biomarker discovery owing to its noninvasive sampling characteristics and robust analytical feasibility. OBJECTIVE: To provide an overview of new developments in urinary metabolomics, cover the most promising aspects of hyphenated techniques in untargeted and targeted metabolomics, and to discuss technical and clinical limitations in addition to the emerging challenges in the field of urinary metabolomics and its application to cancer biomarker discovery...
September 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28871132/an-lc-ms-approach-to-quantitative-measurement-of-ammonia-isotopologues
#7
Jessica B Spinelli, Liam P Kelley, Marcia C Haigis
Ammonia is a fundamental aspect of metabolism spanning all of phylogeny. Metabolomics, including metabolic tracing studies, are an integral part of elucidating the role of ammonia in these systems. However, current methods for measurement of ammonia are spectrophotometric, and cannot distinguish isotopologues of ammonia, significantly limiting metabolic tracing studies. Here, we describe a novel LC-MS-based method that quantitatively assesses both (14)N-and (15)N-isotopologues of ammonia in polar metabolite extracts...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851999/benzo-a-pyrene-induced-metabolic-shift-from-glycolysis-to-pentose-phosphate-pathway-in-the-human-bladder-cancer-cell-line-rt4
#8
Nisha Verma, Mario Pink, Stefan Boland, Albert W Rettenmeier, Simone Schmitz-Spanke
Benzo[a]pyrene (B[a]P), a well-known polyaromatic hydrocarbon, is known for its lung carcinogenicity, however, its role in bladder cancer development is still discussed. Comparative two-dimensional blue native SDS-PAGE analysis of protein complexes isolated from subcellular fractions of 0.5 µM B[a]P-exposed cells indicated a differential regulation of proteins involved in carbohydrate, fatty acid, and nucleotide metabolism, suggesting a possible metabolic flux redistribution. It appeared that B[a]P exposure led to a repression of enzymes (fructose-bisphosphate aldolase A, glucose-6-phosphate isomerase, lactate dehydrogenase) involved in glycolysis, and an up-regulation of proteins (glucose-6-phosphate 1-dehydrogenase, 6-phosphogluconolactonase) catalyzing the pentose phosphate pathway and one carbon metabolism (10-formyltetrahydrofolate dehydrogenase, bifunctional purine biosynthesis protein)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28803255/panel-of-serum-metabolites-discriminates-cancer-patients-and-healthy-participants-of-lung-cancer-screening-a-pilot-study
#9
Małgorzata Roś-Mazurczyk, Anna Wojakowska, Łukasz Marczak, Krzysztof Polański, Monika Pietrowska, Joanna Polanska, Rafał Dziadziuszko, Jacek Jassem, Witold Rzyman, Piotr Widlak
INTRODUCTION: Blood biomarkers may support early diagnosis of lung cancer by enabling pre-selection of candidates for computed tomography screening or discrimination between benign and malignant screening-detected nodules. We aimed to identify features of serum metabolome distinguishing individuals with early-detected lung cancer from healthy participants of the lung cancer screening program. METHODS: Blood samples were collected in the course of a low-dose computed tomography screening program performed in the Gdansk district (Northern Poland)...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28783331/discovery-and-synthesis-of-caracolamide-a-an-ion-channel-modulating-dichlorovinylidene-containing-phenethylamide-from-a-panamanian-marine-cyanobacterium-cf-symploca-species
#10
C Benjamin Naman, Jehad Almaliti, Lorene Armstrong, Eduardo J Caro-Díaz, Marsha L Pierce, Evgenia Glukhov, Amanda Fenner, Carmenza Spadafora, Hosana M Debonsi, Pieter C Dorrestein, Thomas F Murray, William H Gerwick
A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target-directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gem-dichlorovinylidene moiety, caracolamide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three-step synthesis...
August 25, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28768294/measurement-of-metabolic-fluxes-using-stable-isotope-tracers-in-whole-animals-and-human-patients
#11
Julie A Reisz, Angelo D'Alessandro
PURPOSE OF REVIEW: Metabolic flux analysis using stable isotope labeled substrates allows for the tracing of carbon, nitrogen, and hydrogen atoms through metabolic pathways and is an invaluable tool for investigating dynamic metabolic changes occurring in health and disease. Studies of flux analysis in vivo are more technically challenging than in vitro or ex vivo but provide a highly detailed view of organ and/or systemic metabolism. We review here recent efforts in studies of diet and nutrition, non-small cell lung cancer, ischemia/reperfusion injury, and hemorrhagic shock where in vivo flux analysis was utilized to analyze metabolic modulation...
September 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28758372/metabolomic-profiling-of-long-term-weight-change-role-of-oxidative-stress-and-urate-levels-in-weight-gain
#12
Cristina Menni, Marie Migaud, Gabi Kastenmüller, Tess Pallister, Jonas Zierer, Annette Peters, Robert P Mohney, Tim D Spector, Vincenzo Bagnardi, Christian Gieger, Steve C Moore, Ana M Valdes
OBJECTIVE: To investigate the association between long-term weight change and blood metabolites. METHODS: Change in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3-79.6, baseline BMI: 25.11 ± 4.35) measured for 280 metabolites at follow-up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n = 1,760; age range: 25-70, baseline BMI: 27...
September 2017: Obesity
https://www.readbyqxmd.com/read/28729763/serum-and-plasma-metabolomic-biomarkers-for-lung-cancer
#13
Nishith Kumar, Md Shahjaman, Md Nurul Haque Mollah, S M Shahinul Islam, Md Aminul Hoque
In drug invention and early disease prediction of lung cancer, metabolomic biomarker detection is very important. Mortality rate can be decreased, if cancer is predicted at the earlier stage. Recent diagnostic techniques for lung cancer are not prognosis diagnostic techniques. However, if we know the name of the metabolites, whose intensity levels are considerably changing between cancer subject and control subject, then it will be easy to early diagnosis the disease as well as to discover the drug. Therefore, in this paper we have identified the influential plasma and serum blood sample metabolites for lung cancer and also identified the biomarkers that will be helpful for early disease prediction as well as for drug invention...
2017: Bioinformation
https://www.readbyqxmd.com/read/28659298/nutritional-metabolomics-and-breast-cancer-risk-in-a-prospective-study
#14
MULTICENTER STUDY
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...
August 2017: American Journal of Clinical Nutrition
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
#15
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...
September 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
#16
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit K 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. Because of 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 with matched treatment-naïve tumors...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28627685/metabolomic-analysis-based-on-1h-nuclear-magnetic-resonance-spectroscopy-metabolic-profiles-in-tuberculous-malignant-and-transudative-pleural-effusion
#17
Cheng Wang, Jingjin Peng, Yanling Kuang, Jiaqiang Zhang, Luming Dai
Pleural effusion is a common clinical manifestation with various causes. Current diagnostic and therapeutic methods have exhibited numerous limitations. By involving the analysis of dynamic changes in low molecular weight catabolites, metabolomics has been widely applied in various types of disease and have provided platforms to distinguish many novel biomarkers. However, to the best of our knowledge, there are few studies regarding the metabolic profiling for pleural effusion. In the current study, 58 pleural effusion samples were collected, among which 20 were malignant pleural effusions, 20 were tuberculous pleural effusions and 18 were transudative pleural effusions...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28576319/chloroformate-derivatization-for-tracing-the-fate-of-amino-acids-in-cells-and-tissues-by-multiple-stable-isotope-resolved-metabolomics-msirm
#18
Ye Yang, Teresa W-M Fan, Andrew N Lane, Richard M Higashi
Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment...
July 11, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28574715/development-of-a-data-independent-targeted-metabolomics-method-for-relative-quantification-using-liquid-chromatography-coupled-with-tandem-mass-spectrometry
#19
Yanhua Chen, Zhi Zhou, Wei Yang, Nan Bi, Jing Xu, Jiuming He, Ruiping Zhang, Lvhua Wang, Zeper Abliz
Quantitative metabolomics approaches can significantly improve the repeatability and reliability of metabolomics investigations but face critical technical challenges, owing to the vast number of unknown endogenous metabolites and the lack of authentic standards. The present study contributes to the development of a novel method known as "data-independent targeted quantitative metabolomics" (DITQM), which was used to investigate the label-free quantitative metabolomics of multiple known and unknown metabolites in biofluid samples...
June 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#20
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
June 1, 2017: Nature
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