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[PMID]:27771434
[Au] Autor:James MO; Jahn SC; Zhong G; Smeltz MG; Hu Z; Stacpoole PW
[Ad] Endereço:Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610-0485, United States. Electronic address: mojames@ufl.edu.
[Ti] Título:Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.
[So] Source:Pharmacol Ther;170:166-180, 2017 Feb.
[Is] ISSN:1879-016X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen. In all studied species, including humans, DCA has the interesting property of inhibiting its own metabolism upon repeat dosing, resulting in alteration of its pharmacokinetics. The first step in DCA metabolism is conversion to glyoxylate catalyzed by glutathione transferase zeta 1 (GSTZ1), for which DCA is a mechanism-based inactivator. The rate of GSTZ1 inactivation by DCA is influenced by age, GSTZ1 haplotype and cellular concentrations of chloride. The effect of DCA on its own metabolism complicates the selection of an effective dose with minimal side effects.
[Mh] Termos MeSH primário: Ácido Dicloroacético/administração & dosagem
Glutationa Transferase/metabolismo
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Ácido Dicloroacético/efeitos adversos
Ácido Dicloroacético/farmacologia
Relação Dose-Resposta a Droga
Seres Humanos
Hipertensão Pulmonar/tratamento farmacológico
Doenças Mitocondriais/tratamento farmacológico
Neoplasias/tratamento farmacológico
Neoplasias/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9LSH52S3LQ (Dichloroacetic Acid); EC 2.5.1.- (GSTZ1 protein, human); EC 2.5.1.18 (Glutathione Transferase); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.2 (pyruvate dehydrogenase (acetyl-transferring) kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:29059435
[Au] Autor:Stacpoole PW
[Ad] Endereço:Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL.
[Ti] Título:Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer.
[So] Source:J Natl Cancer Inst;109(11), 2017 Nov 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mitochondrial pyruvate dehydrogenase complex (PDC) irreversibly decarboxylates pyruvate to acetyl coenzyme A, thereby linking glycolysis to the tricarboxylic acid cycle and defining a critical step in cellular bioenergetics. Inhibition of PDC activity by pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation has been associated with the pathobiology of many disorders of metabolic integration, including cancer. Consequently, the PDC/PDK axis has long been a therapeutic target. The most common underlying mechanism accounting for PDC inhibition in these conditions is post-transcriptional upregulation of one or more PDK isoforms, leading to phosphorylation of the E1α subunit of PDC. Such perturbations of the PDC/PDK axis induce a "glycolytic shift," whereby affected cells favor adenosine triphosphate production by glycolysis over mitochondrial oxidative phosphorylation and cellular proliferation over cellular quiescence. Dichloroacetate is the prototypic xenobiotic inhibitor of PDK, thereby maintaining PDC in its unphosphorylated, catalytically active form. However, recent interest in the therapeutic targeting of the PDC/PDK axis for the treatment of cancer has yielded a new generation of small molecule PDK inhibitors. Ongoing investigations of the central role of PDC in cellular energy metabolism and its regulation by pharmacological effectors of PDKs promise to open multiple exciting vistas into the biochemical understanding and treatment of cancer and other diseases.
[Mh] Termos MeSH primário: Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Complexo Piruvato Desidrogenase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Acetilcoenzima A/metabolismo
Trifosfato de Adenosina/biossíntese
Biomimética
Ciclo do Ácido Cítrico/fisiologia
Ácido Dicloroacético/farmacologia
Metabolismo Energético
Glicólise
Seres Humanos
Isoenzimas/metabolismo
Mitocôndrias/metabolismo
NAD/metabolismo
Fosforilação Oxidativa
Proteínas Serina-Treonina Quinases/metabolismo
Complexo Piruvato Desidrogenase/metabolismo
Ácido Pirúvico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Pyruvate Dehydrogenase Complex); 0U46U6E8UK (NAD); 72-89-9 (Acetyl Coenzyme A); 8558G7RUTR (Pyruvic Acid); 8L70Q75FXE (Adenosine Triphosphate); 9LSH52S3LQ (Dichloroacetic Acid); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.2 (pyruvate dehydrogenase (acetyl-transferring) kinase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx071


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[PMID]:28934276
[Au] Autor:Piao L; Fang YH; Kubler MM; Donnino MW; Sharp WW
[Ad] Endereço:Section of Emergency Medicine; Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
[Ti] Título:Enhanced pyruvate dehydrogenase activity improves cardiac outcomes in a murine model of cardiac arrest.
[So] Source:PLoS One;12(9):e0185046, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA) hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown. We hypothesized that therapeutic hypothermia (TH) following CA is associated with the inhibition of PDK activity and increased PDH activity. We further hypothesized that an inhibitor of PDK activity, dichloroacetate (DCA), would improve PDH activity and post-CA outcomes. METHODS AND RESULTS: Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 12-minute KCl-induced CA followed by cardiopulmonary resuscitation. Compared to normothermic (37°C) CA controls, administering TH (30°C) improved overall survival (72-hour survival rate: 62.5% vs. 28.6%, P<0.001), post-resuscitation myocardial function (ejection fraction: 50.9±3.1% vs. 27.2±2.0%, P<0.001; aorta systolic pressure: 132.7±7.3 vs. 72.3±3.0 mmHg, P<0.001), and neurological scores at 72-hour post CA (9.5±1.3 vs. 5.4±1.3, P<0.05). In both heart and brain, CA increased lactate concentrations (1.9-fold and 3.1-fold increase, respectively, P<0.01), decreased PDH enzyme activity (24% and 50% reduction, respectively, P<0.01), and increased PDK protein expressions (1.2-fold and 1.9-fold, respectively, P<0.01). In contrast, post-CA treatment with TH normalized lactate concentrations (P<0.01 and P<0.05) and PDK expressions (P<0.001 and P<0.05), while increasing PDH activity (P<0.01 and P<0.01) in both the heart and brain. Additionally, treatment with DCA (0.2 mg/g body weight) 30 min prior to CA improved both myocardial hemodynamics 2 hours post-CA (aortic systolic pressure: 123±3 vs. 96±4 mmHg, P<0.001) and 72-hour survival rates (50% vs. 19%, P<0.05) in normothermic animals. CONCLUSIONS: Enhanced PDH activity in the setting of TH or DCA administration is associated with improved post-CA resuscitation outcomes. PDH is a promising therapeutic target for improving post-CA outcomes.
[Mh] Termos MeSH primário: Ácido Dicloroacético/uso terapêutico
Parada Cardíaca/terapia
Hipotermia Induzida
Complexo Piruvato Desidrogenase/metabolismo
[Mh] Termos MeSH secundário: Animais
Reanimação Cardiopulmonar
Terapia Combinada
Feminino
Parada Cardíaca/enzimologia
Parada Cardíaca/mortalidade
Hemodinâmica
Camundongos
Camundongos Endogâmicos C57BL
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pyruvate Dehydrogenase Complex); 9LSH52S3LQ (Dichloroacetic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185046


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[PMID]:28644886
[Au] Autor:Ward NP; Poff AM; Koutnik AP; D'Agostino DP
[Ad] Endereço:Department of Molecular Pharmacology & Physiology, University of South Florida, Tampa, FL, United States of America.
[Ti] Título:Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells.
[So] Source:PLoS One;12(6):e0180061, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination. Similarly, rotenone enhanced oxidative stress resultant from DCA treatment and this too was required for the noted augmentation of cytotoxicity. Adenosine monophosphate kinase (AMPK) activation was not observed with the concentration of metformin required to enhance DCA activity. Moreover, addition of an activator of AMPK did not enhance DCA cytotoxicity, whereas an inhibitor of AMPK heightened the cytotoxicity of the combination. Our data indicate that metformin enhancement of DCA cytotoxicity is dependent on complex I inhibition. Particularly, that complex I inhibition cooperates with DCA-induction of glucose oxidation to enhance cytotoxic oxidative stress in VM-M3 GBM cells.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Ácido Dicloroacético/toxicidade
Complexo I de Transporte de Elétrons/antagonistas & inibidores
Glioblastoma/tratamento farmacológico
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/metabolismo
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/fisiologia
Glioblastoma/metabolismo
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Potencial da Membrana Mitocondrial/fisiologia
Metformina/farmacologia
Camundongos
Estresse Oxidativo/fisiologia
Rotenona/farmacologia
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 03L9OT429T (Rotenone); 11062-77-4 (Superoxides); 9100L32L2N (Metformin); 9LSH52S3LQ (Dichloroacetic Acid); EC 1.6.5.3 (Electron Transport Complex I); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180061


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[PMID]:28591165
[Au] Autor:Harting TP; Stubbendorff M; Hammer SC; Schadzek P; Ngezahayo A; Murua Escobar H; Nolte I
[Ad] Endereço:Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
[Ti] Título:Dichloroacetate affects proliferation but not apoptosis in canine mammary cell lines.
[So] Source:PLoS One;12(6):e0178744, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Targeting mitochondrial energy metabolism is a novel approach in cancer research and can be traced back to the description of the Warburg effect. Dichloroacetate, a controversially discussed subject of many studies in cancer research, is a pyruvate dehydrogenase kinase inhibitor. Dichloroacetate causes metabolic changes in cancerous glycolysis towards oxidative phosphorylation via indirect activation of pyruvate dehydrogenase in mitochondria. Canine mammary cancer is frequently diagnosed but after therapy prognosis still remains poor. In this study, canine mammary carcinoma, adenoma and non-neoplastic mammary gland cell lines were treated using 10 mM Dichloroacetate. The effect on cell number, lactate release and PDH expression and cell respiration was investigated. Further, the effect on apoptosis and several apoptotic proteins, proliferation, and microRNA expression was evaluated. Dichloroacetate was found to reduce cell proliferation without inducing apoptosis in all examined cell lines.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Ácido Dicloroacético/farmacologia
Glândulas Mamárias Animais/citologia
[Mh] Termos MeSH secundário: Animais
Contagem de Células
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Respiração Celular/efeitos dos fármacos
Cães
Feminino
Proteínas Inibidoras de Apoptose/metabolismo
Ácido Láctico/metabolismo
MicroRNAs/genética
MicroRNAs/metabolismo
Microscopia de Fluorescência
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Serina-Treonina Quinases/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inhibitor of Apoptosis Proteins); 0 (MicroRNAs); 33X04XA5AT (Lactic Acid); 9LSH52S3LQ (Dichloroacetic Acid); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.2 (pyruvate dehydrogenase (acetyl-transferring) kinase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178744


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[PMID]:28528979
[Au] Autor:Wang M; Liao C; Hu Y; Qinwen Pan; Jiang J
[Ad] Endereço:Center of Breast Disease, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, China.
[Ti] Título:Sensitization of breast cancer cells to paclitaxel by dichloroacetate through inhibiting autophagy.
[So] Source:Biochem Biophys Res Commun;489(2):103-108, 2017 Jul 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro. But the sensitization to Dox of DCA was significantly reduced through induction of autophagy by rapamycin. Moreover, the combined therapy of Dox and DCA could significantly inhibit tumor growth in vivo and prolong mouse survival time. Taken together, we demonstrate that DCA could inhibit doxorubicin-inducing autophagy and provide a novel strategy for improving the anti-cancer efficacy of chemotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Autofagia/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Ácido Dicloroacético/farmacologia
Paclitaxel/farmacologia
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Doxorrubicina/antagonistas & inibidores
Doxorrubicina/farmacologia
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Seres Humanos
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 80168379AG (Doxorubicin); 9LSH52S3LQ (Dichloroacetic Acid); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE


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[PMID]:28505181
[Au] Autor:Sradhanjali S; Tripathy D; Rath S; Mittal R; Reddy MM
[Ad] Endereço:The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Bhubaneswar, India.
[Ti] Título:Overexpression of pyruvate dehydrogenase kinase 1 in retinoblastoma: A potential therapeutic opportunity for targeting vitreous seeds and hypoxic regions.
[So] Source:PLoS One;12(5):e0177744, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR. Our results further demonstrate that inhibition of PDK1 using small molecule inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in reduced cell growth and increased apoptosis. We also confirm that combination treatment of DCA with chemotherapeutic agent carboplatin further enhanced the therapeutic efficacy compared to single drug treatment. In addition, we observed changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as well as decreased cell migration in response to PDK1 inhibition. Additionally, we show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a novel therapeutic strategy for RB.
[Mh] Termos MeSH primário: Expressão Gênica
Proteínas Serina-Treonina Quinases/genética
Retinoblastoma/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Ácido Dicloroacético/farmacologia
Sinergismo Farmacológico
Seres Humanos
Hipóxia/genética
Hipóxia/metabolismo
Imuno-Histoquímica
Ácido Láctico/biossíntese
Terapia de Alvo Molecular
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Retinoblastoma/tratamento farmacológico
Retinoblastoma/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Reactive Oxygen Species); 33X04XA5AT (Lactic Acid); 9LSH52S3LQ (Dichloroacetic Acid); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.2 (pyruvate dehydrogenase (acetyl-transferring) kinase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177744


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[PMID]:28426747
[Au] Autor:Sun L; Moritake T; Ito K; Matsumoto Y; Yasui H; Nakagawa H; Hirayama A; Inanami O; Tsuboi K
[Ad] Endereço:Department of Radiological Health Science, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan.
[Ti] Título:Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets.
[So] Source:PLoS One;12(4):e0176162, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS) production, mitochondria function, oxygen consumption rate (OCR), energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma.
[Mh] Termos MeSH primário: Neoplasias Cerebelares/patologia
Meduloblastoma/patologia
Células-Tronco Neoplásicas/patologia
Tolerância a Radiação
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Neoplasias Cerebelares/metabolismo
Ácido Dicloroacético/farmacologia
Glicólise
Seres Humanos
Meduloblastoma/metabolismo
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Consumo de Oxigênio
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 9LSH52S3LQ (Dichloroacetic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176162


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[PMID]:28362670
[Au] Autor:Terzi E; Guvenc U; Tursen B; Tursen U; Kaya TI
[Ad] Endereço:*Department of Dermatology, Orhangazi State Hospital, Bursa, Turkey; †Department of Dermatology, Yenisehir Hospital, Mersin, Turkey; ‡Department of Dermatology, Sistem Hospital, Mersin, Turkey; §Department of Dermatology, Mersin University, School of Medicine, Mersin, Turkey.
[Ti] Título:The Effectiveness of Matrix Cauterization With Bichloracetic Acid in the Treatment of Ingrown Toenails.
[So] Source:Dermatol Surg;43(5):728-733, 2017 May.
[Is] ISSN:1524-4725
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chemical matricectomy is performed mainly by 2 agents, phenol and sodium hydroxide. Chemical matricectomy with phenol has a low recurrence rate and good cosmetic results, but it produces extensive tissue destruction and can result in drainage and a delayed healing time. These adverse effects have brought forward the use of chemical agents such as sodium hydroxide and trichloroacetic acid for matricectomy. OBJECTIVE: This prospective study aimed mainly to evaluate the efficacy of partial nail avulsion and selective chemical cauterization of the matrix using 90% bichloracetic acid (BCA) in the treatment of the ingrown nails. MATERIALS AND METHODS: A total of 30 patients with 58 ingrown toenail edges were included in this study. All of the patients underwent chemical matricectomy with 90% BCA after partial nail avulsion. Adverse effects such as postoperative pain and drainage were minimal in most of the patients. RESULTS: One patient who underwent matricectomy had recurrence in a single nail edge (1.8%) at the 12th month of the follow-up. No recurrence was observed in 29 patients during mean follow-up period. This was considered to be statistically significant (p < .001). CONCLUSION: This is the first study to use BCA for the treatment of ingrown toenail. Partial nail avulsion followed by BCA matricectomy is a safe, simple, and effective method with low rates of postoperative morbidity and high rates of success. Therefore, partial nail avulsion and BCA matricectomy can be used as an alternative treatment method for the treatment of ingrown toenails.
[Mh] Termos MeSH primário: Cauterização/métodos
Ácido Dicloroacético/administração & dosagem
Unhas Encravadas/cirurgia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Cauterização/efeitos adversos
Criança
Pré-Escolar
Feminino
Seres Humanos
Masculino
Meia-Idade
Complicações Pós-Operatórias
Estudos Prospectivos
Recidiva
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9LSH52S3LQ (Dichloroacetic Acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1097/DSS.0000000000000696


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[PMID]:27760379
[Au] Autor:Pandey T; Shukla R; Shukla H; Sonkar A; Tripathi T; Singh AK
[Ad] Endereço:Molecular & Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, Meghalaya, India.
[Ti] Título:A combined biochemical and computational studies of the rho-class glutathione s-transferase sll1545 of Synechocystis PCC 6803.
[So] Source:Int J Biol Macromol;94(Pt A):378-385, 2017 Jan.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Peroxides are one of the most important radicals that cause oxidative stress. Certain Glutathione S-transferases (GSTs) have been reported to show peroxidase activity. We report a novel peroxidase activity of Synechocystis GST- sll1545. The recombinant protein was purified to homogeneity and characterized. Low Km (0.109µM) and high Vmax (0.663µmolmin ) values suggest a high preference of sll1545 for cumenehydroperoxide. Disc inhibition assay confirmed the ability of the enzyme to protect cells against peroxide-induced damage. sll1545 has very low sequence and structural similarity with theta and alpha class GSTs that exhibit glutathione-dependent peroxidase activity. Recent data from our laboratory shows that sll1545 is also strongly active against dichloroacetate (DCA), which is a characteristic of zeta class GST. Interestingly, sll1545 shows less than 20% sequence identity with zeta class GST. Molecular dynamic simulation results show that sll1545 was much more structurally different from alpha/theta classes. Our results suggest that sll1545 shows structural variation from zeta, theta/alpha classes of GSTs but have related enzymatic activity. Phylogenetic analysis reveal that sll1545 is evolutionally very distinct from the known GSTs. Overall, the data suggest that Synechocystis sll1545 does not belong to any known GST class and represent a novel GST class, which we have named rho.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Glutationa Transferase/química
Peroxidase/química
Synechocystis/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Derivados de Benzeno/química
Domínio Catalítico
Sequência Conservada
Ácido Dicloroacético/química
Ligações de Hidrogênio
Cinética
Simulação de Dinâmica Molecular
Oxirredução
Filogenia
Estrutura Secundária de Proteína
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Benzene Derivatives); 9LSH52S3LQ (Dichloroacetic Acid); EC 1.11.1.7 (Peroxidase); EC 2.5.1.18 (Glutathione Transferase); PG7JD54X4I (cumene hydroperoxide)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170612
[Lr] Data última revisão:
170612
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE



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