Read by QxMD icon Read

Lactate AND MCT4

Raghavendra Rao, Motaz Nashawaty, Saher Fatima, Kathleen Ennis, Ivan Tkac
Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214...
March 13, 2018: NMR in Biomedicine
Hee Kyung Kim, InKyoung Lee, Heejin Bang, Hee Cheol Kim, Woo Yong Lee, Seong Hyeon Yun, Jeeyun Lee, Su Jin Lee, Young Suk Park, Kyoung-Mee Kim, Won Ki Kang
Monocarboxylate transporters (MCTs) are transmembrane proteins which control the lactate metabolism and associated with poor prognosis in solid tumors including colorectal cancer (CRC). Here we aimed to investigate the biological and clinical role of MCTs in CRC and to assess the potential of therapeutic application. A total of 16 human CRC cell lines, 11 patient-derived cells from malignant ascites (PDC), and 39 matched pairs of primary CRC and normal colorectal tissues were used to assess the role of MCT in vitro and in vivo...
February 26, 2018: Molecular Cancer Therapeutics
Anne Poder Andersen, Jacob Samsøe-Petersen, Eva Kjer Oernbo, Ebbe Boedtkjer, José M A Moreira, Marie Kveiborg, Stine Falsig Pedersen
High metabolic and proliferative rates in cancer cells lead to production of large amounts of H+ and CO2 , and as a result, net acid extruding transporters are essential for the function and survival of cancer cells. We assessed protein expression of the Na+ /H+ exchanger NHE1, the Na+ -HCO3- cotransporter NBCn1, and the lactate-H+ cotransporters MCT1 and -4 by immunohistochemical analysis of a large cohort of breast cancer samples. We found robust expression of these transporters in 20, 10, 4 and 11 percent of samples, respectively...
January 24, 2018: International Journal of Cancer. Journal International du Cancer
Maša Ždralević, Milica Vučetić, Boutaina Daher, Ibtissam Marchiq, Scott K Parks, Jacques Pouysségur
The evolution of life from extreme hypoxic environments to an oxygen-rich atmosphere has progressively selected for successful metabolic, enzymatic and bioenergetic networks through which a myriad of organisms survive the most extreme environmental conditions. From the two lethal environments anoxia/high O2, cells have developed survival strategies through expression of the transcriptional factors ATF4, HIF1 and NRF2. Cancer cells largely exploit these factors to thrive and resist therapies. In this review, we report and discuss the potential therapeutic benefit of disrupting the major Myc/Hypoxia-induced metabolic pathway, also known as fermentative glycolysis or "Warburg effect", in aggressive cancer cell lines...
December 28, 2017: Advances in Biological Regulation
Jieyun Cao, Michael Ng, Melanie A Felmlee
PURPOSE: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Daniel Monti, Federica Sotgia, Diana Whitaker-Menezes, Madalina Tuluc, Ruth Birbe, Adam Berger, Melissa Lazar, Paolo Cotzia, Rossitza Draganova-Tacheva, Zhao Lin, Marina Domingo-Vidal, Andrew Newberg, Michael P Lisanti, Ubaldo Martinez-Outschoorn
BACKGROUND: High oxidative stress as defined by hydroxyl and peroxyl activity is often found in the stroma of human breast cancers. Oxidative stress induces stromal catabolism, which promotes cancer aggressiveness. Stromal cells exposed to oxidative stress release catabolites such as lactate, which are up-taken by cancer cells to support mitochondrial oxidative phosphorylation. The transfer of catabolites between stromal and cancer cells leads to metabolic heterogeneity between these cells and increased cancer cell proliferation and reduced apoptosis in preclinical models...
June 2017: Seminars in Oncology
Lekha Mikkilineni, Diana Whitaker-Menezes, Marina Domingo-Vidal, John Sprandio, Paola Avena, Paolo Cotzia, Alina Dulau-Florea, Jerald Gong, Guldeep Uppal, Tingting Zhan, Benjamin Leiby, Zhao Lin, Barbara Pro, Federica Sotgia, Michael P Lisanti, Ubaldo Martinez-Outschoorn
BACKGROUND: Twenty percent of patients with classical Hodgkin Lymphoma (cHL) have aggressive disease defined as relapsed or refractory disease to initial therapy. At present we cannot identify these patients pre-treatment. The microenvironment is very important in cHL because non-cancer cells constitute the majority of the cells in these tumors. Non-cancer intra-tumoral cells, such as tumor-associated macrophages (TAMs) have been shown to promote tumor growth in cHL via crosstalk with the cancer cells...
June 2017: Seminars in Oncology
Mahasweta Gooptu, Diana Whitaker-Menezes, John Sprandio, Marina Domingo-Vidal, Zhao Lin, Guldeep Uppal, Jerald Gong, Roberto Fratamico, Benjamin Leiby, Alina Dulau-Florea, Jaime Caro, Ubaldo Martinez-Outschoorn
Metabolic heterogeneity between neoplastic cells and surrounding stroma has been described in several epithelial malignancies; however, the metabolic phenotypes of neoplastic lymphocytes and neighboring stroma in diffuse large B-cell lymphoma (DLBCL) is unknown. We investigated the metabolic phenotypes of human DLBCL tumors by using immunohistochemical markers of glycolytic and mitochondrial oxidative phosphorylation (OXPHOS) metabolism. The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism...
June 2017: Seminars in Oncology
Lindsay Wilde, Megan Roche, Marina Domingo-Vidal, Katherina Tanson, Nancy Philp, Joseph Curry, Ubaldo Martinez-Outschoorn
Glucose is a key metabolite used by cancer cells to generate ATP, maintain redox state and create biomass. Glucose can be catabolized to lactate in the cytoplasm, which is termed glycolysis, or alternatively can be catabolized to carbon dioxide and water in the mitochondria via oxidative phosphorylation. Metabolic heterogeneity exists in a subset of human tumors, with some cells maintaining a glycolytic phenotype while others predominantly utilize oxidative phosphorylation. Cells within tumors interact metabolically with transfer of catabolites from supporting stromal cells to adjacent cancer cells...
June 2017: Seminars in Oncology
Alan R Penheiter, Dinesh K Deelchand, Emily Kittelson, Sibel Erdogan Damgard, Stephen J Murphy, Daniel R O'Brien, William R Bamlet, Marie R Passow, Thomas C Smyrk, Fergus J Couch, George Vasmatzis, John D Port, Małgorzata Marjańska, Stephanie K Carlson
OBJECTIVE: We used transcriptomic profiling and immunohistochemistry (IHC) to search for a functional imaging strategy to resolve common problems with morphological imaging of cystic neoplasms and benign cystic lesions of the pancreas. METHODS: Resected pancreatic cancer (n = 21) and normal pancreas were laser-capture micro-dissected, and transcripts were quantified by RNAseq. Functional imaging targets were validated at the protein level by IHC on a pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated adenocarcinomas...
January 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Zheng-Wei Lee, Xin-Yi Teo, Zhi J Song, Dawn S Nin, Wisna Novera, Bok A Choo, Brian W Dymock, Philip K Moore, Ruby Y-J Huang, Lih-Wen Deng
Slow and continuous release of H2 S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2 S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active...
2017: Frontiers in Pharmacology
Nicola J Curtis, Lorraine Mooney, Lorna Hopcroft, Filippos Michopoulos, Nichola Whalley, Haihong Zhong, Clare Murray, Armelle Logie, Mitchell Revill, Kate F Byth, Amanda D Benjamin, Mike A Firth, Stephen Green, Paul D Smith, Susan E Critchlow
Tumors frequently display a glycolytic phenotype with increased flux through glycolysis and concomitant synthesis of lactate. To maintain glycolytic flux and prevent intracellular acidification, tumors efflux lactate via lactate transporters (MCT1-4). Inhibitors of lactate transport have the potential to inhibit glycolysis and tumor growth. We developed a small molecule inhibitor of MCT1 (AZD3965) and assessed its activity across a panel of cell lines. We explored its antitumor activity as monotherapy and in combination with doxorubicin or rituximab...
September 19, 2017: Oncotarget
Charlotte Petersen, Mette D Nielsen, Elise S Andersen, Astrid L Basse, Marie S Isidor, Lasse K Markussen, Birgitte M Viuff, Ian H Lambert, Jacob B Hansen, Stine F Pedersen
Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism...
October 12, 2017: Scientific Reports
Shiyu Tao, Ping Tian, Yanwen Luo, Jing Tian, Canfeng Hua, Yali Geng, Rihua Cong, Yingdong Ni, Ruqian Zhao
Studies on the effect of a high-concentrate (HC) diet on the hindgut microbiota and metabolome of ruminants are rarely reported. We used 454 pyrosequencing of 16S rDNA genes and gas chromatography-mass spectrometry to evaluate the effects of long-term feeding (HL) or short-term (HS) feeding of an HC diet on changes in bacterial microbiota and their metabolites in the hindgut, with Guanzhong goat as a ruminant model. Results indicated that an HC diet decreased bacterial diversity and induced metabolic disorder in the hindgut...
2017: Frontiers in Microbiology
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markella Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
November 1, 2017: Cancer Research
Silvia Lemma, Gemma Di Pompo, Paolo E Porporato, Martina Sboarina, Shonagh Russell, Robert J Gillies, Nicola Baldini, Pierre Sonveaux, Sofia Avnet
Recent progress in dissecting the molecular paracrine circuits of cancer and stromal cells in bone metastases (BM) are offering new options to improve current merely palliative approach. The study of tumor-stroma metabolic interplay may further ameliorate this scenario. In this context, we demonstrated that highly glycolytic MDA-MB-231 cancer cells, that form osteolytic BM in vivo, release a large amount of lactate at a significantly higher level than MCF7 cells. Thus, we speculated that lactate released from carcinoma cells is uptaken and metabolically used by osteoclasts, the key players of osteolysis associated with BM...
September 1, 2017: Biochimica et Biophysica Acta
Kazuo Yamagata, Natsumi Takahashi, Nozomi Akita, Toru Nabika
BACKGROUND: Astrocytes support a range of brain functions as well as neuronal survival, but their detailed relationship with stroke-related edema is not well understood. We previously demonstrated that the release of lactate from astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP/Izm) was attenuated under stroke conditions. The supply of lactate to neurons is regulated by astrocytic monocarboxylate transporters (MCTs). The purpose of this study was to examine the contributions of arginine vasopressin (AVP) and/or hypoxia and reoxygenation (H/R) to the regulation of MCTs and neurotrophic factor in astrocytes obtained from SHRSP/Izm and congenic SHRpch1_18 rats...
September 2, 2017: Journal of Neuroinflammation
K Diehl, L-A Dinges, O Helm, N Ammar, D Plundrich, A Arlt, C Röcken, S Sebens, H Schäfer
Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells...
August 28, 2017: Oncogene
Michel Bernier, Jonathan Catazaro, Nagendra S Singh, Artur Wnorowski, Anna Boguszewska-Czubara, Krzysztof Jozwiak, Robert Powers, Irving W Wainer
The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
Nicola J Curtis, Lorraine Mooney, Lorna Hopcroft, Filippos Michopoulos, Nichola Whalley, Haihong Zhong, Clare Murray, Armelle Logie, Mitchell Revill, Kate F Byth, Amanda D Benjamin, Mike A Firth, Stephen Green, Paul D Smith, Susan E Critchlow
Tumors frequently display a glycolytic phenotype with increased flux through glycolysis and concomitant synthesis of lactate. To maintain glycolytic flux and prevent intracellular acidification, tumors efflux lactate via lactate transporters (MCT1-4). Inhibitors of lactate transport have the potential to inhibit glycolysis and tumor growth. We developed a small molecule inhibitor of MCT1 (AZD3965) and assessed its activity across a panel of cell lines. We explored its antitumor activity as monotherapy and in combination with doxorubicin or rituximab...
May 25, 2017: Oncotarget
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"