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Cancer branched chain amino acid

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https://www.readbyqxmd.com/read/29650854/-a-case-of-hyperammonemia-induced-by-chemotherapy-with-5-fluorouracil-for-metastatic-colon-cancer
#1
Shinji Tokuyama, Mutsumi Fukunaga, Ken Konishi, Shoko Honda, Ryohei Yukimoto, Aoi Okamoto, Akina Saito, Kazuyuki Okada, Hideo Ota, Shigekazu Yokoyama, Hirofumi Miki, Kenji Kobayashi
Systemic chemotherapy based on 5-fluorouracil(5-FU)is a standard treatment for unresectable or recurrent colon cancers. Here, we report a case of hyperammonemia induced by chemotherapy using 5-FU for metastatic colon cancer. An 84-yearold male patient with past histories of liver cirrhosis related to hepatitis C virus and renal dysfunction underwent an operation for the rectosigmoid colon cancer 8 years ago. Three years after that operation, a local recurrence of the colon cancer was diagnosed, and chemotherapy using sLV5FU2 was initiated...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29650838/-two-cases-of-hepatic-encephalopathy-after-chemotherapy-for-metastatic-colorectal-cancer
#2
Tae Matsumura, Shingo Noura, Masaki Hirota, Yuki Ozato, Daiki Marukawa, Takashi Shuto, Arisa Muratsu, Akinobu Yasuyama, Akihiro Takata, Chikato Koga, Chizu Kameda, Masahiro Murakami, Ryohei Kawabata, Junzo Shimizu, Junichi Hasegawa
We reported 2 cases of hepatic encephalopathy after chemotherapy for advanced colorectal cancer. Case 1: A 49-year-old male was diagnosed advanced sigmoid colon cancer with peritoneal dissemination, multiple liver metastasis and multiple osseous metastasis. After resection of primary lesion, we administered mFOLFOX6 plus bevacizumab combination therapy. He was in comatose(Japan coma scale 200)3 days after 2 courses of administration of this regimen. Case 2: A 57-year-old female was diagnosed advanced rectal cancer with multiple huge liver metastasis and multiple osseous metastasis...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29570613/branched-chain-amino-acids-beyond-nutrition-metabolism
#3
REVIEW
Cunxi Nie, Ting He, Wenju Zhang, Guolong Zhang, Xi Ma
Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in the regulation of energy homeostasis, nutrition metabolism, gut health, immunity and disease in humans and animals. As the most abundant of essential amino acids (EAAs), BCAAs are not only the substrates for synthesis of nitrogenous compounds, they also serve as signaling molecules regulating metabolism of glucose, lipid, and protein synthesis, intestinal health, and immunity via special signaling network, especially phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29484373/metabolic-changes-associated-with-papillary-thyroid-carcinoma-a-nuclear-magnetic-resonance-based-metabolomics-study
#4
Yanyun Li, Minjian Chen, Cuiping Liu, Yankai Xia, Bo Xu, Yanhui Hu, Ting Chen, Meiping Shen, Wei Tang
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients...
February 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29483444/-significance-of-transcatheter-arterial-chemoembolization-for-bclc-stage-b-hepatocellular-carcinoma-with-mal-nutrition
#5
Shunichi Shiozawa, Takebumi Usui, Kotaro Kuhara, Akira Tsuchiya, Tatsuomi Miyauchi, Teppei Kono, Yukio Shimojima, Shinichi Asaka, Kentaro Yamaguchi, Hajime Yokomizo, Takeshi Shimakawa, Kazuhiko Yoshimatsu, Takao Katsube, Yoshihiko Naritaka
BackgroundandAim: The recommendedind ication of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)is Barcelona Clinic Liver Cancer(BCLC)stage B HCC. But there are some cases in which we do not perform TACE because of liver damage with malnutrition in stage B. So we examined whether branched-chain amino acid (BCAA)improve nutritional status and perform TACE to contribute the prolongation of HCC survival. METHODS: This study included8 8 patients treatedfor liver cirrhosis with HCC...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29447920/over-expression-of-bcat1-is-a-prognostic-marker-in-gastric-cancer
#6
Yuan Xu, Weiming Yu, Taotao Yang, Miaozun Zhang, Chao Liang, Xianlei Cai, Qinshu Shao
As one form of branched chain amino-acid transaminase(BCAT) enzymes, It has been found that up-regulation of BCAT1 is associated with poor prognosis in numerous types of tumors, but studies on the role of BCAT1 expression in gastric cancer(GC) are rare. The aim of this study was to detect BCAT1 expression in (GC) and to analyze its association with prognosis of GC patients. Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and mRNA levels of BCAT1 were validated by immunohistochemistry (IHC) and Real-Time quantitative PCR (RT-qPCR) in GC tissues and adjacent noncancerous tissues (ANCT)...
February 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/29441565/metabolomics-and-transcriptomics-profiles-reveal-the-dysregulation-of-the-tricarboxylic-acid-cycle-and-related-mechanisms-in-prostate-cancer
#7
Yaping Shao, Guozhu Ye, Shancheng Ren, Hai-Long Piao, Xinjie Zhao, Xin Lu, Fubo Wang, Ma Wang, Jia Li, Peiyuan Yin, Tian Xia, Chuanliang Xu, Jane J Yu, Yinghao Sun, Guowang Xu
Genetic alterations drive metabolic reprogramming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa...
February 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29311600/depdc5-deficiency-contributes-to-resistance-to-leucine-starvation-via-p62-accumulation-in-hepatocellular-carcinoma
#8
Yuki Mizuno, Shu Shimada, Yoshimitsu Akiyama, Shuichi Watanabe, Tomomi Aida, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Shoji Yamaoka, Minoru Tanabe, Shinji Tanaka
Decrease in blood concentration of branched-chain amino acids, especially leucine, is known to promote liver carcinogenesis in patients with chronic liver disease, but the mechanism is unclear. We herein established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout (DEPDC5-KO) cells was higher than that of the DEPDC5 wild-type (DEPDC5-WT) under leucine starvation. Considering that autophagy deficiency might be involved in acquired resistance to leucine deprivation, we observed reduction of LC3-II followed by accumulation of p62 in the DEPDC5-KO, which induced reactive oxygen species (ROS) tolerance...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29221133/endogenous-glutamine-decrease-is-associated-with-pancreatic-cancer-progression
#9
Cecilia Roux, Chiara Riganti, Sammy Ferri Borgogno, Roberta Curto, Claudia Curcio, Valeria Catanzaro, Giuseppe Digilio, Sergio Padovan, Maria Paola Puccinelli, Monica Isabello, Silvio Aime, Paola Cappello, Francesco Novelli
Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211698/branched-chain-amino-acid-metabolism-in-cancer
#10
Elitsa A Ananieva, Adam C Wilkinson
PURPOSE OF REVIEW: The current review aims to provide an update on the recent biomedical interest in oncogenic branched-chain amino acid (BCAA) metabolism, and discusses the advantages of using BCAAs and expression of BCAA-related enzymes in the treatment and diagnosis of cancers. RECENT FINDINGS: An accumulating body of evidence demonstrates that BCAAs are essential nutrients for cancer growth and are used by tumors in various biosynthetic pathways and as a source of energy...
January 2018: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#11
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29118705/oxaliplatin-induced-hyperammonemic-encephalopathy-in-a-patient-with-metastatic-pancreatic-cancer-a-case-report
#12
Takatsugu Ogata, Hironaga Satake, Misato Ogata, Yukimasa Hatachi, Hisateru Yasui
Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m2 ) and oxaliplatin (100 mg/m2 ) on day 1, repeated every 2 weeks...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29066459/branched-chain-ketoacids-secreted-by-glioblastoma-cells-via-mct1-modulate-macrophage-phenotype
#13
Lidia Santos Silva, Gernot Poschet, Yannic Nonnenmacher, Holger M Becker, Sean Sapcariu, Ann-Christin Gaupel, Magdalena Schlotter, Yonghe Wu, Niclas Kneisel, Martina Seiffert, Rüdiger Hell, Karsten Hiller, Peter Lichter, Bernhard Radlwimmer
Elevated amino acid catabolism is common to many cancers. Here, we show that glioblastoma are excreting large amounts of branched-chain ketoacids (BCKAs), metabolites of branched-chain amino acid (BCAA) catabolism. We show that efflux of BCKAs, as well as pyruvate, is mediated by the monocarboxylate transporter 1 (MCT1) in glioblastoma. MCT1 locates in close proximity to BCKA-generating branched-chain amino acid transaminase 1, suggesting possible functional interaction of the proteins. Using in vitro models, we demonstrate that tumor-excreted BCKAs can be taken up and re-aminated to BCAAs by tumor-associated macrophages...
December 2017: EMBO Reports
https://www.readbyqxmd.com/read/28878358/enoyl-coa-hydratase-1-regulates-mtor-signaling-and-apoptosis-by-sensing-nutrients
#14
Ya-Kun Zhang, Yuan-Yuan Qu, Yan Lin, Xiao-Hui Wu, Hou-Zao Chen, Xu Wang, Kai-Qiang Zhou, Yun Wei, Fushen Guo, Cui-Fang Yao, Xia-Di He, Li-Xia Liu, Chen Yang, Zong-Yuan Guan, Shi-Dong Wang, Jianyuan Zhao, De-Pei Liu, Shi-Min Zhao, Wei Xu
The oncogenic mechanisms of overnutrition, a confirmed independent cancer risk factor, remain poorly understood. Herein, we report that enoyl-CoA hydratase-1 (ECHS1), the enzyme involved in the oxidation of fatty acids (FAs) and branched-chain amino acids (BCAAs), senses nutrients and promotes mTOR activation and apoptotic resistance. Nutrients-promoted acetylation of lys101 of ECHS1 impedes ECHS1 activity by impairing enoyl-CoA binding, promoting ECHS1 degradation and blocking its mitochondrial translocation through inducing ubiquitination...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28804274/non-invasive-urinary-metabolomic-profiling-discriminates-prostate-cancer-from-benign-prostatic-hyperplasia
#15
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
#16
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
#17
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 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28562536/acute-hyperammonemic-encephalopathy-after-fluoropyrimidine-based-chemotherapy-a-case-series-and-review-of-the-literature
#18
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
#19
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
#20
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
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