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Lactate AND Cancer

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https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#1
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#2
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28207834/a-cyclin-dependent-kinase-inhibitor-dinaciclib-in-preclinical-treatment-models-of-thyroid-cancer
#3
Shu-Fu Lin, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, Richard J Wong
BACKGROUND: We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer. MATERIALS AND METHODS: Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28206968/intratumoral-lactate-metabolism-in-barrett-s-esophagus-and-adenocarcinoma
#4
Heikki Huhta, Olli Helminen, Sami Palomäki, Joonas H Kauppila, Juha Saarnio, Petri P Lehenkari, Tuomo J Karttunen
BACKGROUND: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. RESULTS: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205588/hypoxia-induced-angiotensin-ii-by-the-lactate-chymase-dependent-mechanism-mediates-radioresistance-of-hypoxic-tumor-cells
#5
Guozhu Xie, Ying Liu, Qiwei Yao, Rong Zheng, Lanfang Zhang, Jie Lin, Zhaoze Guo, Shasha Du, Chen Ren, Quan Yuan, Yawei Yuan
The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#6
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28198437/increased-nutrient-availability-in-dense-breast-tissue-of-postmenopausal-women-in-vivo
#7
Annelie Abrahamsson, Anna Rzepecka, Charlotta Dabrosin
Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193910/hif1-2%C3%AE-mediates-hypoxia-induced-ldha-expression-in-human-pancreatic-cancer-cells
#8
Xin-Gang Cui, Zhi-Tao Han, Shao-Hui He, Xing-da Wu, Tian-Rui Chen, Cheng-Hao Shao, Dan-Lei Chen, Ning Su, Yuan-Ming Chen, Ting Wang, Jing Wang, Dian-Wen Song, Wang-Jun Yan, Xing-Hai Yang, Tie-Long Liu, Hai-Feng Wei, Jianru Xiao
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages...
10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#9
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179998/phlpp-regulates-hexokinase-2-dependent-glucose-metabolism-in-colon-cancer-cells
#10
Xiaopeng Xiong, Yang-An Wen, Mihail I Mitov, Mary C Oaks, Shigeki Miyamoto, Tianyan Gao
Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28177758/differential-effect-of-hypoxia-and-acidity-on-lung-cancer-cell-and-fibroblast-metabolism
#11
Alexandra Giatromanolaki, Maria Liousia, Stella Arelaki, Dimitra Kalamida, Stamatia Pouliliou, Axilleas Mitrakas, Avgi Tsolou, Efthimios Sivridis, Michael I Koukourakis
This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA and LDH5 protein levels increased in the cancer cells but not in the fibroblasts. Acidity suppressed the above mentioned hypoxia effect. PDH-kinase-1 (PDK1 mRNA and protein) and inactive phosphorylated-PDH protein levels were induced under hypoxia in the cancer cells, whilst these were reduced in the MRC5 lung fibroblasts...
January 24, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28174256/a-time-for-myc-metabolism-and-therapy
#12
Chi V Dang
The MYC oncogene is frequently deregulated in human cancers, whereas the proto-oncogene is exquisitely, tightly regulated in normal cells. Deregulated MYC drives transcriptional imbalance, thereby altering metabolism and disrupting the circadian Bmal1-Clock E-box-dependent transcriptional circuitry. Sustained oncogenic MYC expression drives a constitutive growth program with mammalian target of rapamycin (mTOR) activation that renders cells dependent on nutrients, such that glucose or glutamine deprivation could trigger cell death and key enzymes such as lactate dehydrogenase A (LDHA) and glutaminase (GLS) amenable for targeting in cancers...
February 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28173667/-expression-of-hypoxia-inducible-factor-1%C3%AE-glucose-transporter-1-and-lactate-dehydrogenase-5-in-colorectal-cancer-and-clinicopathologic-significance
#13
T Y Yang, L S Hao, D Z Guo
Objective: To investigate the expression and clinicopathological significance of hypoxia-inducible factor 1 alpha (HIF-1α), glucose transporter 1(GLUT-1) and lactate dehydrogenase(LDH)-5 in colorectal cancer. Methods: The expression levels of HIF-1α, GLUT-1 and LDH-5 were detected by immunohistochemical staining in 142 specimens of human carcinoma in comparison with adjacent normal tissues. Results: The expression levels of HIF-1α(78.2%, 111/142), GLUT-1(75.4%, 107/142) and LDH-5(68.3%, 97/142) were higher in tumor tissues than in adjacent normal tissues(14...
February 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28170315/cytoplasmic-irradiation-induces-metabolic-shift-in-human-small-airway-epithelial-cells-via-activation-of-pim-1-kinase
#14
Jinhua Wu, Qin Zhang, Yen-Ruh Wuu, Sirui Zou, Tom K Hei
The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells...
February 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/28170295/after-chemotherapy-treatment-for-maternal-cancer-during-pregnancy-is-breastfeeding-possible
#15
Stephen Stopenski, Anum Aslam, Xinmin Zhang, Elyce Cardonick
OBJECTIVE: To report breastfeeding complaints of women diagnosed with cancer during pregnancy and correlate success with characteristics of their treatment. MATERIALS AND METHODS: This is a prospective cohort study of women diagnosed with cancer during pregnancy who attempted breastfeeding. We surveyed participants about breast engorgement, milk let down, and consistent breast milk production through mailed questionnaires. Treatment details, including the type and number of chemotherapy cycles given during pregnancy and antepartum or postpartum depression, were collected...
February 7, 2017: Breastfeeding Medicine: the Official Journal of the Academy of Breastfeeding Medicine
https://www.readbyqxmd.com/read/28160259/protein-malnutrition-during-fetal-programming-induces-fatty-liver-in-adult-male-offspring-rats
#16
Sabrina Edith Campisano, Stella Maris Echarte, Enrique Podaza, Andrea Nancy Chisari
We evaluated the effects of protein malnutrition on liver morphology and physiology in rats subjected to different malnutrition schemes. Pregnant rats were fed with a control diet or a low protein diet (LPD). Male offspring rats received a LPD during gestation, lactation, and until they were 60 days old (MM group), a late LPD that began after weaning (CM), or a LPD administrated only during the gestation-lactation period followed by a control diet (MC). On day 60, blood was collected and the liver was dissected out...
February 3, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28159922/base-excision-repair-imbalance-in-colorectal-cancer-has-prognostic-value-and-modulates-response-to-chemotherapy
#17
Natalia M Leguisamo, Helena C Gloria, Antonio N Kalil, Talita V Martins, Daniel B Azambuja, Lisiane B Meira, Jenifer Saffi
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients' clinical and pathological features...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159898/nlrx1-regulates-effector-and-metabolic-functions-of-cd4-t-cells
#18
Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Matthew Hulver, Ryan McMillan, Kristin Eden, Irving C Allen, Josep Bassaganya-Riera
Nucleotide oligomerization domain-like receptor X1 (NLRX1) has been implicated in viral response, cancer progression, and inflammatory disorders; however, its role as a dual modulator of CD4(+) T cell function and metabolism has not been defined. The loss of NLRX1 results in increased disease severity, populations of Th1 and Th17 cells, and inflammatory markers (IFN-γ, TNF-α, and IL-17) in mice with dextran sodium sulfate-induced colitis. To further characterize this phenotype, we used in vitro CD4(+) T cell-differentiation assays and show that NLRX1-deficient T cells have a greater ability to differentiate into an inflammatory phenotype and possess greater proliferation rates...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28141738/new-insights-into-the-mechanisms-of-the-ketogenic-diet
#19
Detlev Boison
PURPOSE OF REVIEW: High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood...
January 30, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28140518/metabonomics-by-proton-nuclear-magnetic-resonance-in-human-pleural-effusions-a-route-to-discriminate-between-benign-and-malignant-pleural-effusions-and-to-target-small-molecules-as-potential-cancer-biomarkers
#20
Lucio Zennaro, Paola Vanzani, Lorenzo Nicolè, Rocco Cappellesso, Ambrogio Fassina
BACKGROUND: Cytopathology is a noninvasive and cost-effective method for detecting cancer cells in pleural effusions (PEs), although in many cases, the diagnostic performance is hindered by the paucity of significant cells or the lack of clear morphological criteria. This study presents the results of an omics approach to improving the diagnostic performance of PE cytology. METHODS: Metabolic profiling with proton nuclear magnetic resonance ((1) H-NMR) was performed for 92 PEs (44 malignant cases of 8 different cancers and 48 benign cases of 7 nonneoplastic conditions)...
January 31, 2017: Cancer
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