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Cancer branched chain amino acid

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https://www.readbyqxmd.com/read/28804274/non-invasive-urinary-metabolomic-profiling-discriminates-prostate-cancer-from-benign-prostatic-hyperplasia
#1
Clara Pérez-Rambla, Leonor Puchades-Carrasco, María García-Flores, José Rubio-Briones, José Antonio López-Guerrero, Antonio Pineda-Lucena
INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. OBJECTIVES: In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28798381/transcriptional-hallmarks-of-cancer-cell-lines-reveal-an-emerging-role-of-branched-chain-amino-acid-catabolism
#2
Ieva Antanavičiūtė, Valeryia Mikalayeva, Ieva Ceslevičienė, Gintarė Milašiūtė, Vytenis Arvydas Skeberdis, Sergio Bordel
A comparative analysis between cancer cell lines and healthy dividing cells was performed using data (289 microarrays and 50 RNA-seq samples) from 100 different cancer cell lines and 6 types of healthy stem cells. The analysis revealed two large-scale transcriptional events that characterize cancer cell lines. The first event was a large-scale up-regulation pattern associated to epithelial-mesenchymal transition, putatively driven by the interplay of the SP1 transcription factor and the canonical Wnt signaling pathway; the second event was the failure to overexpress a diverse set of genes coding membrane and extracellular proteins...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28584183/nature-and-nurture-what-determines-tumor-metabolic-phenotypes
#3
REVIEW
Jared R Mayers, Matthew G Vander Heiden
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein...
June 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28562536/acute-hyperammonemic-encephalopathy-after-fluoropyrimidine-based-chemotherapy-a-case-series-and-review-of-the-literature
#4
REVIEW
Seiichiro Mitani, Shigenori Kadowaki, Azusa Komori, Keiji Sugiyama, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando, Yozo Sato, Hidekazu Yamaura, Yoshitaka Inaba, Makoto Ishihara, Tsutomu Tanaka, Masahiro Tajika, Kei Muro
Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28516268/gpna-inhibits-the-sodium-independent-transport-system-l-for-neutral-amino-acids
#5
Martina Chiu, Cosimo Sabino, Giuseppe Taurino, Massimiliano G Bianchi, Roberta Andreoli, Nicola Giuliani, Ovidio Bussolati
L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine...
May 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28514443/cancer-progression-by-reprogrammed-bcaa-metabolism-in-myeloid-leukaemia
#6
Ayuna Hattori, Makoto Tsunoda, Takaaki Konuma, Masayuki Kobayashi, Tamas Nagy, John Glushka, Fariba Tayyari, Daniel McSkimming, Natarajan Kannan, Arinobu Tojo, Arthur S Edison, Takahiro Ito
Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28501528/bckdk-of-bcaa-catabolism-cross-talking-with-the-mapk-pathway-promotes-tumorigenesis-of-colorectal-cancer
#7
Peipei Xue, Fanfan Zeng, Qiuhong Duan, Juanjuan Xiao, Lin Liu, Ping Yuan, Linni Fan, Huimin Sun, Olesya S Malyarenko, Hui Lu, Ruijuan Xiu, Shaoqing Liu, Chen Shao, Jianmin Zhang, Wei Yan, Zhe Wang, Jianyong Zheng, Feng Zhu
Branched-chain amino acids catabolism plays an important role in human cancers. Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, and the new global incidence is over 1.2 million cases. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting enzyme in branched-chain amino acids catabolism, which plays an important role in many serious human diseases. Here we investigated that abnormal branched-chain amino acids catabolism in colorectal cancer is a result of the disease process, with no role in disease initiation; BCKDK is widely expressed in colorectal cancer patients, and those patients that express higher levels of BCKDK have shorter survival times than those with lower levels; BCKDK promotes cell transformation or colorectal cancer ex vivo or in vivo...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28422839/unexpected-side-effect-in-mcrc-a-care-compliant-case-report-of-regorafenib-induced-hyperammonemic-encephalopathy
#8
Michela Quirino, Sabrina Rossi, Giovanni Schinzari, Michele Basso, Antonia Strippoli, Alessandra Cassano, Carlo Barone
RATIONALE: Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable. PATIENT CONCERNS: A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28319069/the-branched-chain-amino-acid-transaminase-1-sustains-growth-of-antiestrogen-resistant-and-er%C3%AE-negative-breast-cancer
#9
V Thewes, R Simon, M Hlevnjak, M Schlotter, P Schroeter, K Schmidt, Y Wu, T Anzeneder, W Wang, P Windisch, M Kirchgäßner, N Melling, N Kneisel, R Büttner, U Deuschle, H P Sinn, A Schneeweiss, S Heck, S Kaulfuss, H Hess-Stumpp, J G Okun, G Sauter, A E Lykkesfeldt, M Zapatka, B Radlwimmer, P Lichter, M Tönjes
Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells...
July 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28245795/in-search-of-druggable-targets-for-gbm-amino-acid-metabolism
#10
Eduard H Panosyan, Henry J Lin, Jan Koster, Joseph L Lasky
BACKGROUND: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. METHODS: First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas...
February 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28235484/branched-chain-amino-acid-transaminase-1-bcat1-promotes-the-growth-of-breast-cancer-cells-through-improving-mtor-mediated-mitochondrial-biogenesis-and-function
#11
Ling Zhang, Junqing Han
Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. BCAA catabolism is a conserved regulator of physiological aging and participates in diverse physiological and pathological processes, including carcinoma development. The roles of BCAA catabolism in human breast cancer remains unknown. Here we provide evidence that BCAA catabolism is involved in human breast cancer. The plasma and tissue levels of BCAAs are increased in breast cancer, which is accompanied by the elevated expression of the catabolic enzymes, including branched-chain amino acid transaminase 1 (BCAT1)...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28179968/the-effectiveness-of-a-liver-disease-education-class-for-providing-information-to-patients-and-their-families
#12
Yukio Kadokawa, Kazuhiro Katayama, Kozo Takahashi, Nobuhisa Fukushima, Setsu Tanaka, Yuko Taniguchi, Takatoshi Nawa, Mitsuru Sakakibara, Kazuyoshi Ohkawa
BACKGROUND: We have been conducting liver disease education classes regularly in our hospital for the purpose of providing health information to patients and their families. METHODS: In order to evaluate the effectiveness of these classes, we conducted a questionnaire survey of patients and family members who attended the classes held three times in 2012. The cumulative total number of participants was 80 (49 patients, 26 family members, and five others). The classes focused on the following areas: 1) prevention of hepatic cancer; 2) treatment of hepatic cancer; 3) iron restriction diet for hepatitis C patients; and 4) importance of branched-chain amino acid preparations...
March 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28138303/amino-acid-profiles-of-serum-and-urine-in-search-for-prostate-cancer-biomarkers-a-pilot-study
#13
Paweł Dereziński, Agnieszka Klupczynska, Wojciech Sawicki, Jerzy A Pałka, Zenon J Kokot
There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28099419/genomic-deletion-of-malic-enzyme-2-confers-collateral-lethality-in-pancreatic-cancer
#14
Prasenjit Dey, Joelle Baddour, Florian Muller, Chia Chin Wu, Huamin Wang, Wen-Ting Liao, Zangdao Lan, Alina Chen, Tony Gutschner, Yaan Kang, Jason Fleming, Nikunj Satani, Di Zhao, Abhinav Achreja, Lifeng Yang, Jiyoon Lee, Edward Chang, Giannicola Genovese, Andrea Viale, Haoqiang Ying, Giulio Draetta, Anirban Maitra, Y Alan Wang, Deepak Nagrath, Ronald A DePinho
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis...
February 2, 2017: Nature
https://www.readbyqxmd.com/read/28095274/protein-intake-and-breast-cancer-survival-in-the-nurses-health-study
#15
Michelle D Holmes, Jun Wang, Susan E Hankinson, Rulla M Tamimi, Wendy E Chen
Purpose Greater protein intake has been associated with better breast cancer survival in several prospective studies, including among 1,982 women in the Nurses' Health Study. We proposed to extend this previous finding. We hypothesized that protein, essential amino acid, branched-chain amino acid, and leucine intakes are associated with improved survival and that these associations are stronger in tumors expressing insulin receptor (IR). Patients and Methods We included 6,348 women diagnosed with stage I to III breast cancer between 1976 and 2004...
January 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28052414/microrna-218-inhibits-tumor-growth-and-increases-chemosensitivity-to-cddp-treatment-by-targeting-bcat1-in-prostate-cancer
#16
Wenjing Zhu, Yiqun Shao, Yu Peng
MicroRNAs have been reported to be associated with chemosensitivity of several types of cancers. However, the underlying molecular mechanisms are poorly understood. In this study, we explored miR-218 increased the chemosensitivity to cis-diaminedichloroplatinum treatment of prostate cancer. We found that the expression level of miR-218 was down-regulated in the human prostate cancer specimens. Moreover, overexpression of miR-218 inhibited cell viability, migration, and invasion in PC3 and DU145 cells. Furthermore, we demonstrated that the tumor suppressive role of miR-218 was mediated by negatively regulating branched-chain amino acid transaminase 1 (BCAT1) protein expression...
June 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28011449/association-of-plasma-concentrations-of-branched-chain-amino-acids-with-risk-of-colorectal-adenoma-in-a-large-japanese-population
#17
S Budhathoki, M Iwasaki, T Yamaji, H Yamamoto, Y Kato, S Tsugane
Background: Available evidence from animal studies suggests that branched-chain amino acids (BCAAs) may have a protective effect against colorectal carcinogenesis. However, a possible effect of BCAAs against colorectal neoplasia has not been evaluated in humans. Here, we aimed to evaluate whether plasma concentrations of BCAA are associated with the risk of colorectal adenoma (CRA), a precursor lesion of colorectal cancer. Patients and methods: CRA cases and controls were identified from examinees who underwent total colonoscopy as part of a cancer screening program between 2004 and 2005 and responded to self-administered dietary and lifestyle questionnaires...
April 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#18
Sen Peng, Harshil Dhruv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
Background: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). Methods: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
June 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/27872968/new-functions-and-potential-applications-of-amino-acids
#19
Hisayuki Uneyama, Hisamine Kobayashi, Naoto Tonouchi
Currently, several types of amino acids are being produced and used worldwide. Nevertheless, several new functions of amino acids have been recently discovered that could result in other applications. For example, oral stimulation by glutamate triggers the cephalic phase response to prepare for food digestion. Further, the stomach and intestines have specific glutamate-recognizing systems in their epithelial mucosa. Regarding clinical applications, addition of monosodium glutamate to the medicinal diet has been shown to markedly enhance gastric secretion in a vagus-dependent manner...
2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27770143/-1-h-nuclear-magnetic-resonance-nmr-based-serum-metabolomics-of-human-gallbladder-inflammation
#20
Raj Kumar Sharma, Kumudesh Mishra, Alvina Farooqui, Anu Behari, Vinay Kumar Kapoor, Neeraj Sinha
OBJECTIVE AND DESIGN: We present in this article (1)H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). MATERIAL/METHODS: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). (1)H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation...
January 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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