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Lactate AND Cancer

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https://www.readbyqxmd.com/read/29236080/three-dimensional-analysis-of-the-interactions-between-hldh5-and-its-inhibitors
#1
REVIEW
Giulio Poli, Carlotta Granchi, Mohamed Aissaoui, Filippo Minutolo, Tiziano Tuccinardi
Inhibitors of human lactate dehydrogenase (hLDH5)-the enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD⁺-are promising therapeutic agents against cancer because this enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. Consequently, significant efforts have been made for the identification of small-molecule hLDH5 inhibitors displaying high inhibitory potencies. X-ray structure of hLDH5 complexes as well as molecular modeling studies contribute to identify and explain the main binding modes of hLDH5 inhibitors reported in literature...
December 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29235457/serum-metabolic-profile-alteration-reveals-response-to-platinum-based-combination-chemotherapy-for-lung-cancer-sensitive-patients-distinguished-from-insensitive-ones
#2
Shan Xu, Yanping Zhou, Hui Geng, Dandan Song, Jing Tang, Xianmin Zhu, Di Yu, Sheng Hu, Yanfang Cui
Most lung cancers are diagnosed at fairly advanced stages due to limited clinical symptoms. Platinum-based chemotherapy, either as single regimen or in combination with radiation, is one of the major recommendations for the patients. Earlier evaluation of the effectiveness of the chemotherapies is critical for developing better treatment plan given the toxicity of the chemotherapeutic reagents. Drug efficacy could be reflected in the systemic metabolism characteristics though knowledge about which remains scarce...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235008/oncological-assessment-of-stent-placement-for-obstructive-colorectal-cancer-from-circulating-cell-free-dna-and-circulating-tumor-dna-dynamics
#3
Goro Takahashi, Takeshi Yamada, Takuma Iwai, Kohki Takeda, Michihiro Koizumi, Seiichi Shinji, Eiji Uchida
BACKGROUND: The self-expanding metallic stent (SEMS) provides effective decompression for patients with malignant large bowel obstruction (MLBO); however, mechanical damage to malignant cells from insertion may negatively affect prognosis, similar to surgical manipulation, and its oncological safety is unclear. We examined mechanical damage from SEMS placement using circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA). METHODS: Between 1 November 2014 and 30 June 2017, 35 MLBO patients were analyzed, comprising 25 SEMS patients and 10 transanal decompression tube (TDT) patients (control)...
December 12, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29234547/testicular-cancer-presenting-as-gastric-variceal-hemorrhage
#4
Carlos Eduardo Salazar-Mejía, David Hernández-Barajas, Edio Llerena-Hernández, José Luis González-Vela, María Inés Contreras-Salcido, Adriana González-Gutiérrez, Omar David Borjas-Almaguer, Luis Alberto Pérez-Arredondo, Blanca Otilia Wimer-Castillo
Testicular cancer is the most common solid malignancy affecting males between the ages of 15 and 35. The symptomatology caused by this tumor varies according to the site of metastasis. We present the case of a 26-year-old male who arrived to the emergency department with hematemesis. He had no previous medical history. On arrival, we noted enlargement of the left scrotal sac. There was also a mass in the left scrotum which provoked displacement of the penis and right testis. The serum alpha-fetoprotein level was 17,090 ng/mL, lactate dehydrogenase was 1480 U/L, and human chorionic gonadotropin was 287...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/29229835/o-glcnacylation-destabilizes-the-active-tetrameric-pkm2-to-promote-the-warburg-effect
#5
Yang Wang, Jia Liu, Xin Jin, Dapeng Zhang, Dongxue Li, Fengqi Hao, Yunpeng Feng, Shan Gu, Fanlin Meng, Miaomiao Tian, Yi Zheng, Ling Xin, Xinbo Zhang, Xue Han, L Aravind, Min Wei
The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, O-GlcNAcylation, which specifically targets Thr405 and Ser406, residues of the region encoded by the alternatively spliced exon 10 in cancer cells...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29228690/cartilage-oligomeric-matrix-protein-promotes-prostate-cancer-progression-by-enhancing-invasion-and-disrupting-intracellular-calcium-homeostasis
#6
Emelie Englund, Giacomo Canesin, Konstantinos S Papadakos, Neelanjan Vishnu, Emma Persson, Bart Reitsma, Aseem Anand, Laila Jacobsson, Leszek Helczynski, Hindrik Mulder, Anders Bjartell, Anna M Blom
Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225342/differentiation-dynamics-of-mammary-epithelial-cells-revealed-by-single-cell-rna%C3%A2-sequencing
#7
Karsten Bach, Sara Pensa, Marta Grzelak, James Hadfield, David J Adams, John C Marioni, Walid T Khaled
Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells-especially in the luminal compartment-should rather be conceptualised as being part of a continuous spectrum of differentiation...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29225201/3-bromopyruvate-as-a-potential-pharmaceutical-in-the-light-of-experimental-data
#8
Izabela Szczuka, Andrzej Gamian, Grzegorz Terlecki
3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase)...
December 8, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#9
Annapoorna Sreedhar, Petra Petruska, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which is often upregulated in human cancers. However, how this anion transporter affects tumorigenesis is not well understood. Using the skin cell transformation JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase 2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In conjunction, upregulation of PFKFB2 expression correlated with elevated fructose 2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity, glucose uptake, and lactate production...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218237/increased-mir-21a-provides-metabolic-advantages-through-suppression-of-fbp1-expression-in-non-small-cell-lung-cancer-cells
#10
Qingchun Dai, Na Li, Xiaohong Zhou
Lung cancer is the most common solid tumor and the leading cause of cancer-related mortality worldwide. miR-21 is one of the most commonly observed aberrant miRNAs in human cancers. However, the biological roles of miR-21 in glucose metabolism of non-small cell lung cancer (NSCLC) cells remain unknown. In the present study, our findings demonstrated that miR-21 promoted glucose uptake and increased TXNIP expression. miR-21 increased lactate generation and decreased oxygen consumption in NSCLC cells. Moreover, we found that miR-21 promoted glycolysis and decreased OXPHOS...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#11
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29212305/cancer-energy-metabolism-shutting-power-off-cancer-factory
#12
REVIEW
Soo-Youl Kim
In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212301/convergence-of-cancer-metabolism-and-immunity-an-overview
#13
REVIEW
Chi Van Dang, Jung-Whan Kim
Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29211789/glycerol-3-phosphate-acyltransferase-2-expression-modulates-cell-roughness-and-membrane-permeability-an-atomic-force-microscopy-study
#14
Elizabeth R Cattaneo, Eduardo D Prieto, Maria B Garcia-Fabiani, Mauro A Montanaro, Herve Guillou, Maria R Gonzalez-Baro
In mammalian cells, de novo glycerolipid synthesis begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferases (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions, and overexpressed in several types of cancers and cancer-derived human cell lines where its expression contributes to the tumor phenotype. Using gene silencing and atomic force microscopy, we studied the correlation between GPAT2 expression and cell surface topography, roughness and membrane permeability in MDA-MB-231 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29207616/pkm2-activation-sensitizes-cancer-cells-to-growth-inhibition-by-2-deoxy-d-glucose
#15
Sui Seng Tee, Jae Mo Park, Ralph E Hurd, Kyle R Brimacombe, Matthew B Boxer, Tarik F Massoud, Brian K Rutt, Daniel M Spielman
Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207191/novel-evidence-that-pituitary-sex-hormones-regulate-migration-adhesion-and-proliferation-of-embryonic-stem-cells-and-teratocarcinoma-cells
#16
Zachariah Payne Sellers, Kamila Bujko, Gabriela Schneider, Magdalena Kucia, Mariusz Z Ratajczak
The pituitary sex hormones (SexHs): follicle‑stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) regulate several functions crucial for reproduction, including oogenesis, spermatogenesis, and lactation. An important source of prolactin-like hormones, known as lactogens, is the placenta, and lactogens bind to the PRL receptor (PRLR) with high affinity and thereby mimic the actions of PRL. Recently, it has been demonstrated that pituitary SexHs were involved in metastatic lung cancer, certain sarcomas, and leukemia...
November 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#17
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207019/stromal-epithelial-lactate-shuttle-induced-by-tumor%C3%A2-derived-interleukin%C3%A2-1%C3%AE-promotes-cell-proliferation-in-oral-squamous-cell-carcinoma
#18
Jie Wu, Yun Hong, Tong Wu, Juan Wang, Xiaobing Chen, Zhi Wang, Bin Cheng, Juan Xia
Stromal-epithelial lactate shuttle is an essential process to support fast‑growing tumor cells, however, the underlying mechanism remains ambiguous. Interleukin‑1β (IL‑1β), which is a key node gene in both stromal and epithelial cells of oral squamous cell carcinoma (OSCC), may participate in this metabolic reprogramming. In the present study, anaerobic glycolysis of cancer‑associated fibroblasts (CAFs) was evaluated and the role of IL‑1β in regulating stromal‑epithelial lactate shuttle was determined...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205754/preliminary-investigation-of-blood-concentrations-of-insulin-like-growth-factor-insulin-lactate-and-%C3%AE-hydroxybutyrate-in-dogs-with-lymphoma-as-compared-with-matched-controls
#19
B McQuown, K E Burgess, C R Heinze
It is well established that tumour cells have metabolic differences when compared with normal cells. This is particularly true for energy metabolism in which dogs with cancer have been reported to have higher blood insulin and lactate concentrations than control dogs. Moreover, some human and animal studies suggest that the insulin-like growth factor 1 (IGF-1) signalling pathway may play a role in tumorigenesis and tumour progression. At present, IGF-1 has not been evaluated in dogs with multicentric lymphoma...
December 4, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29205334/sodium-glucose-cotransporter-2-inhibitor-canagliflozin-attenuates-liver-cancer-cell-growth-and-angiogenic-activity-by-inhibiting-glucose-uptake
#20
Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Soichiro Saikawa, Keisuke Nakanishi, Masanori Furukawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi Yoshiji
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells...
December 4, 2017: International Journal of Cancer. Journal International du Cancer
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