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Glutamine cancer

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https://www.readbyqxmd.com/read/28814091/the-effect-of-vitamin-d-on-mcf-7-breast-cancer-cell-metabolism
#1
B Saracligil, B Ozturk, A Unlu, S Abusoglu, G Tekin
The role of vitamin D in calcium absorption and bone health is known. The studies revealed that vitamin D modulates breast cancer cell growth and it is also associated with a reduced breast cancer risk. The primary objective of this study was to highlight the metabolic effect of Vitamin D on MCF-7 breast cancer cell line. For that purpose, we checked the apoptosis, energy, amino-acid and acylcarnitine levels in cancer cells, that the study propose, that 1α, 25(OH)2D3 could inhibit cell growth in a dose and time dependent manner...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#2
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#3
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#4
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrate that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation accompanied with a relative decrease in the proliferation of MUC1-overexpressing cells compared to steady state conditions...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#5
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28804556/anti-tumor-efficacy-evaluation-of-a-novel-monoclonal-antibody-targeting-neutral-amino-acid-transporter-asct2-using-patient-derived-xenograft-mouse-models-of-gastric-cancer
#6
Noriyuki Kasai, Aya Sasakawa, Kenta Hosomi, Tze Wei Poh, Bernadette Lynn Chua, Wei Peng Yong, Jimmy So, Shing Leng Chan, Richie Soong, Koji Kono, Toshihiko Ishii, Kazuya Yamano
ASC amino acid transporter 2 (ASCT2), also known as solute linked carrier family 1 member A5 (SLC1A5) is a Na+-dependent glutamine/neutral amino acid transporter. ASCT2 acts as a high-affinity transporter of L-glutamine (Gln) and has been reported to be up-regulated in a variety of cancerous tissues including stomach, liver, and kidney. In this study, we evaluated anti-tumor efficacy of a novel anti-ASCT2 humanized monoclonal antibody, KM8094, which has a neutralizing activity against glutamine uptake, as a therapeutic antibody against gastric cancer and explored clinical predictive biomarker candidates by utilizing patient-derived xenograft (PDX) mouse models...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#7
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28801576/disrupting-glutamine-metabolic-pathways-to-sensitize-gemcitabine-resistant-pancreatic-cancer
#8
Ru Chen, Lisa A Lai, Yumi Sullivan, Melissa Wong, Lei Wang, Jonah Riddell, Linda Jung, Venu G Pillarisetty, Teresa A Brentnall, Sheng Pan
Pancreatic cancer is a lethal disease with poor prognosis. Gemcitabine has been the first line systemic treatment for pancreatic cancer. However, the rapid development of drug resistance has been a major hurdle in gemcitabine therapy leading to unsatisfactory patient outcomes. With the recent renewed understanding of glutamine metabolism involvement in drug resistance and immuno-response, we investigated the anti-tumor effect of a glutamine analog (6-diazo-5-oxo-L-norleucine) as an adjuvant treatment to sensitize chemoresistant pancreatic cancer cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800318/mir-513c-suppresses-neuroblastoma-cell-migration-invasion-and-proliferation-through-direct-targeting-glutaminase-gls
#9
Hong-Liang Xia, Yao Lv, Chun-Wei Xu, Ming-Cui Fu, Ting Zhang, Xiang-Ming Yan, Shu Dai, Qian-Wei Xiong, Yun Zhou, Jian Wang, Xu Cao
Neuroblastoma is a brain malignancy of childhood and accounts for 7-10% of childhood cancers, leading to approximately 15% of pediatric cancer deaths. MicroRNAs (miRNAs) are a family of short (about 18-25 nucleotides), noncoding and single stranded endogenous RNAs, which complementarily bind to the 3' untranslated regions of their target genes. Recently, glutamine metabolism has been recognized as an important nutrition source for tumor cells, and hence targeting glutamine metabolism could benefit to development of anti-cancer agents...
July 2, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28782227/short-androgen-receptor-poly-glutamine-promoted-endometrial-cancer-is-associated-with-benzo-a-pyrene-mediated-aryl-hydrocarbon-receptor-activation
#10
Lumin Chen, Bo-Ying Bao, Wei-Chun Chang, Jason Yen-Ping Ho, Bi-Hua Cheng, Chung-Lin Wang, Qifeng Tang, Wei-Chung Cheng, Hui-Wen Chang, Yao-Ching Hung, Wen-Lung Ma
The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28771772/altered-glutamine-metabolism-in-breast-cancer-subtype-dependencies-and-alternative-adaptations
#11
REVIEW
Rokaya El Ansari, Alan McIntyre, Madeleine L Craze, Ian O Ellis, Emad A Rakha, Andrew R Green
Cancer cells must alter their metabolism in order to satisfy the demands of necessary energy and cellular building blocks. These metabolic alterations are mediated by many oncogenic changes that affect cellular signalling pathways, which result in sustained cell growth and proliferation. Recently, metabolomics, has received great attention in the field of cancer research and as the essential metabolic pathways that drive tumour growth and progression are determined, the possibilities of new targets for therapeutic intervention are opened...
August 3, 2017: Histopathology
https://www.readbyqxmd.com/read/28770610/amino-acid-profiles-as-potential-biomarkers-for-pediatric-cancers-a-preliminary-communication
#12
Anna Synakiewicz, Malgorzata Sawicka-Zukowska, Natalia Adrianowska, Grazyna Galezowska, Joanna Ratajczyk, Anna Owczarzak, Lucyna Konieczna, Teresa Stachowicz-Stencel
AIM: Childhood cancer remains one of the main cause of death in the pediatric population. Amino acids (AAs) level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease. METHODS: Seventy-seven children with cancer, including 47 with hematological and 30 with solid tumors were enrolled in this study and compared with healthy children. Twenty-two plasma-free AAs were determined by HPLC with fluorometric detection. RESULTS: The results revealed significant decrease in glutamine levels for oncological patients and significant increase in aspartic acid, glutamic acid, asparagine, serine, citrulline, alanine, GABA, tryptophan, methionine, valine, phenylalanine and isoleucine levels in cancer children versus control...
August 3, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28768294/measurement-of-metabolic-fluxes-using-stable-isotope-tracers-in-whole-animals-and-human-patients
#13
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/28759021/asct2-regulates-glutamine-uptake-and-cell-growth-in-endometrial-carcinoma
#14
A D Marshall, M van Geldermalsen, N J Otte, T Lum, M Vellozzi, A Thoeng, A Pang, R Nagarajah, B Zhang, Q Wang, L Anderson, J E J Rasko, J Holst
Glutamine commonly becomes a conditionally essential amino acid in cancer. Glutamine is supplied to the cell by transporters such as ASCT2 (SLC1A5), which is frequently upregulated in multiple cancers. Here we investigated the expression of ASCT2 in endometrial carcinoma, and evaluated the contribution of ASCT2 to glutamine uptake and endometrial cancer cell growth. Analysis of human gene expression data showed that ASCT2 was significantly upregulated in both endometrioid and serous subtypes of endometrial carcinoma, compared to normal, age-matched endometrium...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28750681/drug-induced-amino-acid-deprivation-as-strategy-for-cancer-therapy
#15
REVIEW
Marcus Kwong Lam Fung, Godfrey Chi-Fung Chan
Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers...
July 27, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28749408/clinical-role-of-asct2-slc1a5-in-kras-mutated-colorectal-cancer
#16
Kosuke Toda, Gen Nishikawa, Masayoshi Iwamoto, Yoshiro Itatani, Ryo Takahashi, Yoshiharu Sakai, Kenji Kawada
Mutation in the KRAS gene induces prominent metabolic changes. We have recently reported that KRAS mutations in colorectal cancer (CRC) cause alterations in amino acid metabolism. However, it remains to be investigated which amino acid transporter can be regulated by mutated KRAS in CRC. Here, we performed a screening of amino acid transporters using quantitative reverse-transcription polymerase chain reaction (RT-PCR) and then identified that ASCT2 (SLC1A5) was up-regulated through KRAS signaling. Next, immunohistochemical analysis of 93 primary CRC specimens revealed that there was a significant correlation between KRAS mutational status and ASCT2 expression...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28743736/sfpq-a-multifunctional-nuclear-protein-regulates-the-transcription-of-pde3a
#17
Dong Keun Rhee, Steven C Hockman, Sun-Kyung Choi, Yong-Eun Kim, Chungoo Park, Vincent C Manganiello, Kee Kwang Kim
Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of PDE3A , and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE)...
July 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28733531/dual-inhibition-of-glycolysis-and-glutaminolysis-as-a-therapeutic-strategy-in-the-treatment-of-ovarian-cancer
#18
Li Sun, Yajie Yin, Leslie H Clark, Wenchuan Sun, Stephanie A Sullivan, Arthur-Quan Tran, Jianjun Han, Lu Zhang, Hui Guo, Esther Madugu, Tommy Pan, Amanda L Jackson, Joshua Kilgore, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729763/serum-and-plasma-metabolomic-biomarkers-for-lung-cancer
#19
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/28726641/a-plant-fungal-type-phosphoenolpyruvate-carboxykinase-located-in-the-parasite-mitochondrion-ensures-glucose-independent-survival-of-toxoplasma-gondii
#20
Richard Nitzsche, Özlem Günay-Esiyok, Maximilian Tischer, Vyacheslav Zagoriy, Nishith Gupta
Toxoplasma gondii is considered as one of the most successful intracellular pathogens, because it can reproduce in varied nutritional milieus, encountered in diverse host-cell types of essentially any warm-blooded organism. Our earlier work has demonstrated that the acute (tachyzoite) stage of T. gondii depends on cooperativity of glucose and glutamine catabolism to meet biosynthetic demands. Either of these two nutrients can sustain the parasite survival; however, what determines the metabolic plasticity has not been resolved yet...
July 18, 2017: Journal of Biological Chemistry
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