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Lactate AND Cancer

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https://www.readbyqxmd.com/read/29033844/syngeneic-b16f10-melanoma-causes-cachexia-and-impaired-skeletal-muscle-strength-and-locomotor-activity-in-mice
#1
Fabrício A Voltarelli, Fernando T Frajacomo, Camila de Souza Padilha, Mayra T J Testa, Paola S Cella, Diogo F Ribeiro, Donizete X de Oliveira, Luciana C Veronez, Gabriela S Bisson, Felipe A Moura, Rafael Deminice
Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 10(4) B16F10 melanoma cells or PBS as a Sham negative control...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29031720/brown-adipocytes-can-display-a-mammary-basal-myoepithelial-cell-phenotype-in%C3%A2-vivo
#2
Li Li, Baoguo Li, Min Li, Chaoqun Niu, Guanlin Wang, Ting Li, Elżbieta Król, Wanzhu Jin, John R Speakman
OBJECTIVE: Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS: To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030348/lactate-fuels-the-tca-cycle-in-non-small-cell-lung-cancer
#3
(no author information available yet)
In many patients with NSCLC, lactate is a major fuel source for the tumor TCA cycle.
October 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29029484/ybx1-promotes-tumor-growth-by-elevating-glycolysis-in-human-bladder-cancer
#4
Liuyu Xu, Hongyun Li, Longchao Wu, Shiming Huang
Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028110/melanoma-staging-evidence-based-changes-in-the-american-joint-committee-on-cancer-eighth-edition-cancer-staging-manual
#5
Jeffrey E Gershenwald, Richard A Scolyer, Kenneth R Hess, Vernon K Sondak, Georgina V Long, Merrick I Ross, Alexander J Lazar, Mark B Faries, John M Kirkwood, Grant A McArthur, Lauren E Haydu, Alexander M M Eggermont, Keith T Flaherty, Charles M Balch, John F Thompson
Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria...
October 13, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/29026946/psma-targeted-radioligandtherapy-in-metastatic-castration-resistant-prostate-cancer-after-chemotherapy-abiraterone-and-or-enzalutamide-a-retrospective-analysis-of-overall-survival
#6
K Rahbar, M Boegemann, A Yordanova, M Eveslage, M Schäfers, M Essler, H Ahmadzadehfar
AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with (177)Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of (177)Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle...
October 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29024608/erastin-like-anti-warburg-agents-prevent-mitochondrial-depolarization-induced-by-free-tubulin-and-decrease-lactate-formation-in-cancer-cells
#7
David N DeHart, John J Lemasters, Eduardo N Maldonado
In Warburg metabolism, suppression of mitochondrial metabolism contributes to a low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of metabolites across the mitochondrial outer membrane occurs through voltage-dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces VDAC closure and dynamically regulates mitochondrial membrane potential (ΔΨ). Erastin, a small molecule that binds to VDAC, antagonizes the inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact cells...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29018777/rationale-feasibility-and-acceptability-of-ketogenic-diet-for-cancer-treatment
#8
REVIEW
Hae-Yun Chung, Yoo Kyoung Park
Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients...
September 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29017161/prognostic-factors-for-survival-in-patients-with-advanced-intrahepatic-cholangiocarcinoma-treated-with-gemcitabine-plus-cisplatin-as-first-line-treatment
#9
Utako Ishimoto, Shunsuke Kondo, Akihiro Ohba, Mitsuhito Sasaki, Yasunari Sakamoto, Chigusa Morizane, Hideki Ueno, Takuji Okusaka
OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. METHODS: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016...
October 11, 2017: Oncology
https://www.readbyqxmd.com/read/28993194/identification-of-a-selective-inhibitor-of-human-monocarboxylate-transporter-4
#10
Yuya Futagi, Masaki Kobayashi, Katsuya Narumi, Ayako Furugen, Ken Iseki
The human monocarboxylate transporters (hMCTs/SLC16As) mediate the uptake of various monocarboxylates. Several isoforms of hMCTs are expressed in cancerous tissue as well as in normal tissue. In cancerous tissue, hypoxia induces the expression of hMCT4, which transports the energetic metabolite l-lactate across the plasma membrane. Since hMCT4 is involved in pH regulation and the transport of l-lactate in cancer cells, an hMCT4 inhibitor could function as an anticancer agent. Although several non specific hMCT inhibitors have been developed, a selective hMCT4 inhibitor has not yet been identified...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28992664/-clinical-study-on-the-efficacy-and-continuous-docetaxel-based-chemotherapy-treatment-for-castration-resistant-prostate-cancer
#11
Ippei Chikazawa, Shinya Inoue, Yusuke Nakazawa, Dan Nakai, Nobuyo Morita, Tatsuro Tanaka, Yoshiharu Motoo, Katsuhito Miyazawa
We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level...
September 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28985563/lactate-metabolism-in-human-lung-tumors
#12
Brandon Faubert, Kevin Y Li, Ling Cai, Christopher T Hensley, Jiyeon Kim, Lauren G Zacharias, Chendong Yang, Quyen N Do, Sarah Doucette, Daniel Burguete, Hong Li, Giselle Huet, Qing Yuan, Trevor Wigal, Yasmeen Butt, Min Ni, Jose Torrealba, Dwight Oliver, Robert E Lenkinski, Craig R Malloy, Jason W Wachsmann, Jamey D Young, Kemp Kernstine, Ralph J DeBerardinis
Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high (18)fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with (13)C-lactate revealed extensive labeling of TCA cycle metabolites...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28983605/ldha-promotes-tumor-metastasis-by-facilitating-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma
#13
Juping Zhao, Xin Huang, Zhaoping Xu, Jun Dai, Hongchao He, Yu Zhu, Haofei Wang
Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay...
September 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28982912/predictive-factors-for-poor-progression-free-survival-in-patients-with-non-small-cell-lung-cancer-treated-with-nivolumab
#14
MULTICENTER STUDY
Yoshihiko Taniguchi, Akihiro Tamiya, Syun-Ichi Isa, Kenji Nakahama, Kyoichi Okishio, Takayuki Shiroyama, Hidekazu Suzuki, Takako Inoue, Motohiro Tamiya, Tomonori Hirashima, Fumio Imamura, Shinji Atagi
BACKGROUND: Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. MATERIALS AND METHODS: In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28982111/the-characteristics-and-outcomes-of-small-bowel-adenocarcinoma-a-multicentre-retrospective-observational-study
#15
Hiroyuki Sakae, Hiromitsu Kanzaki, Junichiro Nasu, Yutaka Akimoto, Kazuhiro Matsueda, Masao Yoshioka, Masahiro Nakagawa, Shinichiro Hori, Masafumi Inoue, Tomoki Inaba, Atsushi Imagawa, Masahiro Takatani, Ryuta Takenaka, Seiyu Suzuki, Toshiyoshi Fujiwara, Hiroyuki Okada
BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy that accounts for 1-2% of gastrointestinal tumours. We investigated the clinical characteristics, outcomes, and prognostic factors of primary SBA. METHODS: We retrospectively analysed the characteristics and clinical courses of 205 SBA patients from 11 institutions in Japan between June 2002 and August 2013. RESULTS: The primary tumour was in the duodenum and jejunum/ileum in 149 (72...
October 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28979765/micrornas-in-the-development-and-neoplasia-of-the-mammary-gland
#16
REVIEW
Manoj Kumar Jena
Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation...
2017: F1000Research
https://www.readbyqxmd.com/read/28978906/energy-stress-induced-lncrna-filnc1-represses-c-myc-mediated-energy-metabolism-and-inhibits-renal-tumor-development
#17
Zhen-Dong Xiao, Leng Han, Hyemin Lee, Li Zhuang, Yilei Zhang, Joelle Baddour, Deepak Nagrath, Christopher G Wood, Jian Gu, Xifeng Wu, Han Liang, Boyi Gan
The roles of long non-coding RNAs in cancer metabolism remain largely unexplored. Here we identify FILNC1 (FoxO-induced long non-coding RNA 1) as an energy stress-induced long non-coding RNA by FoxO transcription factors. FILNC1 deficiency in renal cancer cells alleviates energy stress-induced apoptosis and markedly promotes renal tumor development. We show that FILNC1 deficiency leads to enhanced glucose uptake and lactate production through upregulation of c-Myc. Upon energy stress, FILNC1 interacts with AUF1, a c-Myc mRNA-binding protein, and sequesters AUF1 from binding c-Myc mRNA, leading to downregulation of c-Myc protein...
October 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28978646/lactate-mediated-mitoribosomal-defects-impair-mitochondrial-oxidative-phosphorylation-and-promote-hepatoma-cell-invasiveness
#18
Young-Kyoung Lee, Jin J Lim, Un-Woo Jeoun, Seongki Min, Eun-Beom Lee, So Mee Kwon, Changhan Lee, Gyesoon Yoon
Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal defect...
October 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28978072/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#19
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978061/mir-200c-inhibits-bladder-cancer-progression-by-targeting-lactate-dehydrogenase-a
#20
Daozhang Yuan, Shunsheng Zheng, Liyan Wang, Jing Li, Jianan Yang, Bin Wang, Xiong Chen, Xiaobo Zhang
Lactate dehydrogenase A (LDHA) is overexpressed in various cancers. We investigated LDHA expression and function in bladder cancer. We demonstrate that LDHA is up-regulated in bladder cancer cells and promotes proliferation, invasion, and glycolysis. Additionally, we found that microRNA (miR)-200c directly targets LDHA in bladder cancer cells. Ectopic expression of miR-200c inhibited LDHA-induced glycolysis, cell proliferation, and invasion. Thus, targeting LDHA through miR-200c is a potential therapeutic strategy in bladder cancer...
September 15, 2017: Oncotarget
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