Base de dados : MEDLINE
Pesquisa : D12.776.157.530.450.074.500.400 [Categoria DeCS]
Referências encontradas : 1398 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 140 ir para página                         

  1 / 1398 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28448657
[Au] Autor:Drögemöller BI; Monzon JG; Bhavsar AP; Borrie AE; Brooks B; Wright GEB; Liu G; Renouf DJ; Kollmannsberger CK; Bedard PL; Aminkeng F; Amstutz U; Hildebrand CA; Gunaretnam EP; Critchley C; Chen Z; Brunham LR; Hayden MR; Ross CJD; Gelmon KA; Carleton BC
[Ad] Endereço:Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Título:Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer.
[So] Source:JAMA Oncol;3(11):1558-1562, 2017 Nov 01.
[Is] ISSN:2374-2445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects. Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients. Design, Setting, and Participants: This retrospective study was performed by the Canadian Pharmacogenomics Network for Drug Safety using patients recruited from 5 adult oncology treatment centers across Canada. Male patients who were 17 years or older, diagnosed with germ cell testicular cancer, and previously treated with cisplatin-based chemotherapy were recruited from July 2009 to April 2013 using active surveillance methodology. Cisplatin-induced ototoxic effects were independently diagnosed by 2 audiologists. Patients were genotyped for 7907 variants using a custom pharmacogenomic array. Logistic regression was used to identify genetic variants that were significantly associated with ototoxic effects. The validity of these findings was confirmed through independent replication and cell-based functional assays. Exposures: Cisplatin-based chemotherapy. Main Outcomes and Measures: Cisplatin-induced ototoxic effects. Results: After exclusions, 188 patients (median [interquartile range] age, 31 [24-39] years) were enrolled in this study to form the discovery and replication cohorts. Association and fine-mapping analyses identified a protein-coding variant, rs4788863 in SLC16A5, that was associated with protection against cisplatin-induced ototoxic effects in 2 independent cohorts (combined cohort: odds ratio, 0.06; 95% CI, 0.02-0.22; P = 2.17 × 10-7). Functional validation of this transporter gene revealed that in vitro SLC16A5-silencing altered cellular responses to cisplatin treatment, supporting a role for SLC16A5 in the development of cisplatin-induced ototoxic effects. These results were further supported by the literature, which provided confirmatory evidence for the role that SLC16A5 plays in hearing. Conclusions and Relevance: This study has identified a novel association between protein-coding variation in SLC16A5 and cisplatin-induced ototoxic effects. These findings have provided insight into the molecular mechanisms of this adverse drug reaction in adult patients with germ cell testicular cancer. Given that previous studies have shown that cimetidine, an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the findings from this study have important implications for otoprotectant strategies in humans.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Cisplatino/efeitos adversos
Perda Auditiva/induzido quimicamente
Perda Auditiva/genética
Transportadores de Ácidos Monocarboxílicos/genética
Variantes Farmacogenômicos
Neoplasias Testiculares/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Canadá
Relação Dose-Resposta a Droga
Predisposição Genética para Doença
Células HeLa
Perda Auditiva/diagnóstico
Perda Auditiva/metabolismo
Seres Humanos
Modelos Logísticos
Masculino
Transportadores de Ácidos Monocarboxílicos/efeitos dos fármacos
Transportadores de Ácidos Monocarboxílicos/metabolismo
Farmacogenética
Testes Farmacogenômicos
Fenótipo
Interferência de RNA
Estudos Retrospectivos
Fatores de Risco
Transfecção
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Monocarboxylic Acid Transporters); 0 (SLC16A5 protein, human); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1001/jamaoncol.2017.0502


  2 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29248133
[Au] Autor:Mikkilineni L; Whitaker-Menezes D; Domingo-Vidal M; Sprandio J; Avena P; Cotzia P; Dulau-Florea A; Gong J; Uppal G; Zhan T; Leiby B; Lin Z; Pro B; Sotgia F; Lisanti MP; Martinez-Outschoorn U
[Ad] Endereço:Department of Medical Oncology, National Cancer Institute, Bethesda, MD.
[Ti] Título:Hodgkin lymphoma: A complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment.
[So] Source:Semin Oncol;44(3):218-225, 2017 06.
[Is] ISSN:1532-8708
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. Metabolic heterogeneity is defined as high mitochondrial metabolism in some tumor cells and glycolysis in others. We hypothesized that there are metabolic differences between cancer cells and non-cancer tumor cells, such as TAMs and tumor-infiltrating lymphocytes in cHL and that greater metabolic differences between cancer cells and TAMs are associated with poor outcomes. METHODS: A case-control study was conducted with 22 tissue samples of cHL at diagnosis from a single institution. The case samples were from 11 patients with aggressive cHL who had relapsed after standard treatment with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or were refractory to this treatment. The control samples were from 11 patients with cHL who achieved a remission and never relapsed after ABVD. Reactive non-cancerous lymph nodes from four subjects served as additional controls. Samples were stained by immunohistochemistry for three metabolic markers: translocase of the outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 1 (MCT1), and monocarboxylate transporter 4 (MCT4). TOMM20 is a marker of mitochondrial oxidative phosphorylation (OXPHOS) metabolism. Monocarboxylate transporter 1 (MCT1) is the main importer of lactate into cells and is a marker of OXPHOS. Monocarboxylate transporter 4 (MCT4) is the main lactate exporter out of cells and is a marker of glycolysis. The immunoreactivity for TOMM20, MCT1, and MCT4 was scored based on staining intensity and percentage of positive cells, as follows: 0 for no detectable staining in > 50% of cells; 1+ for faint to moderate staining in > 50% of cells, and 2+ for high or strong staining in > 50% of cells. RESULTS: TOMM20, MCT1, and MCT4 expression was significantly different in Hodgkin and Reed Sternberg (HRS) cells, which are the cancerous cells in cHL compared with TAMs and tumor-associated lymphocytes. HRS have high expression of TOMM20 and MCT1, while TAMs have absent expression of TOMM20 and MCT1 in all but two cases. Tumor-infiltrating lymphocytes have low TOMM20 expression and absent MCT1 expression. Conversely, high MCT4 expression was found in TAMs, but absent in HRS cells in all but one case. Tumor-infiltrating lymphocytes had absent MCT4 expression. Reactive lymph nodes in contrast to cHL tumors had low TOMM20, MCT1, and MCT4 expression in lymphocytes and macrophages. High TOMM20 and MCT1 expression in cancer cells with high MCT4 expression in TAMs is a signature of high metabolic heterogeneity between cancer cells and the tumor microenvironment. A high metabolic heterogeneity signature was associated with relapsed or refractory cHL with a hazard ratio of 5.87 (1.16-29.71; two-sided P < .05) compared with the low metabolic heterogeneity signature. CONCLUSION: Aggressive cHL exhibits features of metabolic heterogeneity with high mitochondrial metabolism in cancer cells and high glycolysis in TAMs, which is not seen in reactive lymph nodes. Future studies will need to confirm the value of these markers as prognostic and predictive biomarkers in clinical practice. Treatment intensity may be tailored in the future to the metabolic profile of the tumor microenvironment and drugs that target metabolic heterogeneity may be valuable in this disease.
[Mh] Termos MeSH primário: Glicólise
Doença de Hodgkin/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Mitocôndrias/metabolismo
Transportadores de Ácidos Monocarboxílicos/metabolismo
Recidiva Local de Neoplasia/metabolismo
Fosforilação Oxidativa
Receptores de Superfície Celular/metabolismo
Células de Reed-Sternberg/metabolismo
Simportadores/metabolismo
Microambiente Tumoral
[Mh] Termos MeSH secundário: Adulto
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Bleomicina/administração & dosagem
Estudos de Casos e Controles
Dacarbazina/administração & dosagem
Doxorrubicina/administração & dosagem
Feminino
Doença de Hodgkin/tratamento farmacológico
Seres Humanos
Imuno-Histoquímica
Linfócitos do Interstício Tumoral/metabolismo
Macrófagos/metabolismo
Masculino
Meia-Idade
Proteínas Musculares/metabolismo
Indução de Remissão
Vimblastina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (Monocarboxylic Acid Transporters); 0 (Muscle Proteins); 0 (Receptors, Cell Surface); 0 (SLC16A4 protein, human); 0 (Symporters); 0 (TOMM20 protein, human); 0 (monocarboxylate transport protein 1); 11056-06-7 (Bleomycin); 5V9KLZ54CY (Vinblastine); 7GR28W0FJI (Dacarbazine); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  3 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29248134
[Au] Autor:Monti D; Sotgia F; Whitaker-Menezes D; Tuluc M; Birbe R; Berger A; Lazar M; Cotzia P; Draganova-Tacheva R; Lin Z; Domingo-Vidal M; Newberg A; Lisanti MP; Martinez-Outschoorn U
[Ad] Endereço:Marcus Institute of Integrative Health at Thomas Jefferson University, Philadelphia, PA.
[Ti] Título:Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.
[So] Source:Semin Oncol;44(3):226-232, 2017 06.
[Is] ISSN:1532-8708
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. N-Acetylcysteine (NAC) is an antioxidant that reduces oxidative stress and reverses stromal catabolism and stromal-carcinoma cell metabolic heterogeneity, resulting in reduced proliferation and increased apoptosis of cancer cells in experimental models of breast cancer. The purpose of this clinical trial was to determine if NAC could reduce markers of stromal-cancer metabolic heterogeneity and markers of cancer cell aggressiveness in human breast cancer. METHODS: Subjects with newly diagnosed stage 0 and I breast cancer who were not going to receive neoadjuvant therapy prior to surgical resection were treated with NAC before definitive surgery to assess intra-tumoral metabolic markers. NAC was administered once a week intravenously at a dose of 150 mg/kg and 600 mg twice daily orally on the days not receiving intravenous NAC. Histochemistry for the stromal metabolic markers monocarboxylate transporter 4 (MCT4) and caveolin-1 (CAV1) and the Ki67 proliferation assay and TUNEL apoptosis assay in carcinoma cells were performed in pre- and post-NAC specimens. RESULTS: The range of days on NAC was 14-27 and the mean was 19 days. Post-treatment biopsies showed significant decrease in stromal MCT4 and reduced Ki67 in carcinoma cells. NAC did not significantly change stromal CAV1 and carcinoma TUNEL staining. NAC was well tolerated. CONCLUSIONS: NAC as a single agent reduces MCT4 stromal expression, which is a marker of glycolysis in breast cancer with reduced carcinoma cell proliferation. This study suggests that modulating metabolism in the tumor microenvironment has the potential to impact breast cancer proliferation.
[Mh] Termos MeSH primário: Acetilcisteína/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Carcinoma Ductal de Mama/tratamento farmacológico
Carcinoma Intraductal não Infiltrante/tratamento farmacológico
Depuradores de Radicais Livres/uso terapêutico
Mastectomia
[Mh] Termos MeSH secundário: Adulto
Apoptose
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/metabolismo
Carcinoma Ductal de Mama/patologia
Carcinoma Intraductal não Infiltrante/metabolismo
Carcinoma Intraductal não Infiltrante/patologia
Carcinoma Papilar/tratamento farmacológico
Carcinoma Papilar/metabolismo
Carcinoma Papilar/patologia
Caveolina 1/metabolismo
Proliferação Celular
Feminino
Seres Humanos
Imuno-Histoquímica
Marcação In Situ das Extremidades Cortadas
Antígeno Ki-67/metabolismo
Meia-Idade
Transportadores de Ácidos Monocarboxílicos/metabolismo
Proteínas Musculares/metabolismo
Terapia Neoadjuvante
Estadiamento de Neoplasias
Projetos Piloto
Células Estromais/metabolismo
Resultado do Tratamento
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CAV1 protein, human); 0 (Caveolin 1); 0 (Free Radical Scavengers); 0 (Ki-67 Antigen); 0 (Monocarboxylic Acid Transporters); 0 (Muscle Proteins); 0 (SLC16A4 protein, human); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  4 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29248131
[Au] Autor:Wilde L; Roche M; Domingo-Vidal M; Tanson K; Philp N; Curry J; Martinez-Outschoorn U
[Ad] Endereço:Department of Medical Oncology Thomas Jefferson University, Philadelphia, PA.
[Ti] Título:Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development.
[So] Source:Semin Oncol;44(3):198-203, 2017 06.
[Is] ISSN:1532-8708
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. The Reverse Warburg Effect describes when glycolysis in the cancer-associated stroma metabolically supports adjacent cancer cells. This catabolite transfer, which induces stromal-cancer metabolic coupling, allows cancer cells to generate ATP, increase proliferation, and reduce cell death. Catabolites implicated in metabolic coupling include the monocarboxylates lactate, pyruvate, and ketone bodies. Monocarboxylate transporters (MCT) are critically necessary for release and uptake of these catabolites. MCT4 is involved in the release of monocarboxylates from cells, is regulated by catabolic transcription factors such as hypoxia inducible factor 1 alpha (HIF1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and is highly expressed in cancer-associated fibroblasts. Conversely, MCT1 is predominantly involved in the uptake of these catabolites and is highly expressed in a subgroup of cancer cells. MYC and TIGAR, which are genes involved in cellular proliferation and anabolism, are inducers of MCT1. Profiling human tumors on the basis of an altered redox balance and intra-tumoral metabolic interactions may have important biomarker and therapeutic implications. Alterations in the redox state and mitochondrial function of cells can induce metabolic coupling. Hence, there is interest in redox and metabolic modulators as anticancer agents. Also, markers of metabolic coupling have been associated with poor outcomes in numerous human malignancies and may be useful prognostic and predictive biomarkers.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo
Glucose/metabolismo
Neoplasias/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos
Proliferação Celular
Descoberta de Drogas
Fibroblastos/metabolismo
Glicólise
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Corpos Cetônicos/metabolismo
Ácido Láctico/metabolismo
Transportadores de Ácidos Monocarboxílicos/metabolismo
Proteínas Musculares/metabolismo
NF-kappa B/metabolismo
Neoplasias/tratamento farmacológico
Proteínas Proto-Oncogênicas c-myc/metabolismo
Ácido Pirúvico/metabolismo
Células Estromais/metabolismo
Simportadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (C12orf5 protein, human); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Intracellular Signaling Peptides and Proteins); 0 (Ketone Bodies); 0 (MYC protein, human); 0 (Monocarboxylic Acid Transporters); 0 (Muscle Proteins); 0 (NF-kappa B); 0 (Proto-Oncogene Proteins c-myc); 0 (SLC16A4 protein, human); 0 (Symporters); 0 (monocarboxylate transport protein 1); 33X04XA5AT (Lactic Acid); 8558G7RUTR (Pyruvic Acid); 8L70Q75FXE (Adenosine Triphosphate); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  5 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29248132
[Au] Autor:Gooptu M; Whitaker-Menezes D; Sprandio J; Domingo-Vidal M; Lin Z; Uppal G; Gong J; Fratamico R; Leiby B; Dulau-Florea A; Caro J; Martinez-Outschoorn U
[Ad] Endereço:Department of Medical Oncology, Dana Farber Cancer Institute, Harvard University Medical School, Boston, MA.
[Ti] Título:Mitochondrial and glycolytic metabolic compartmentalization in diffuse large B-cell lymphoma.
[So] Source:Semin Oncol;44(3):204-217, 2017 06.
[Is] ISSN:1532-8708
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. Staining patterns were assessed in 33 DLBCL samples as well as 18 control samples (non-neoplastic lymph nodes). TOMM20 and MCT1 were highly expressed in neoplastic lymphocytes, indicating an OXPHOS phenotype, whereas non-neoplastic lymphocytes in the control samples did not express these markers. Stromal cells in DLBCL samples strongly expressed MCT4, displaying a glycolytic phenotype, a feature not seen in stromal elements of non-neoplastic lymphatic tissue. Furthermore, the differential expression of lactate exporters (MCT4) on tumor-associated stroma and lactate importers (MCT1) on neoplastic lymphocytes support the hypothesis that neoplastic cells are metabolically linked to the stroma likely via mutually beneficial reprogramming. MCT4 is a marker of tumor-associated stroma in neoplastic tissue. Our findings suggest that disruption of neoplastic-stromal cell metabolic heterogeneity including MCT1 and MCT4 blockade should be studied to determine if it could represent a novel treatment target in DLBCL.
[Mh] Termos MeSH primário: Glicólise
Linfoma Difuso de Grandes Células B/metabolismo
Mitocôndrias/metabolismo
Fosforilação Oxidativa
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Estudos de Casos e Controles
Feminino
Seres Humanos
Imuno-Histoquímica
Linfócitos/metabolismo
Masculino
Proteínas de Membrana Transportadoras/metabolismo
Meia-Idade
Transportadores de Ácidos Monocarboxílicos/metabolismo
Proteínas Musculares/metabolismo
Receptores de Superfície Celular/metabolismo
Células Estromais/metabolismo
Simportadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (Monocarboxylic Acid Transporters); 0 (Muscle Proteins); 0 (Receptors, Cell Surface); 0 (SLC16A4 protein, human); 0 (Symporters); 0 (TOMM20 protein, human); 0 (monocarboxylate transport protein 1)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  6 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28471448
[Au] Autor:Xu W; Zhang Z; Zou K; Cheng Y; Yang M; Chen H; Wang H; Zhao J; Chen P; He L; Chen X; Geng L; Gong S
[Ad] Endereço:Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
[Ti] Título:MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis.
[So] Source:Cell Death Dis;8(5):e2761, 2017 May 04.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells. Overexpression of miR-1 mimics significantly decreased tumor glycolysis, including lactate production and glucose uptake, and cell proliferation, and these effects were reversed by ectopic expression of Smad3. Importantly, endogenous Smad3 regulated and interacted with HIF-1α, resulting in increasing activity of Smad3, and this interaction was dramatically abolished by addition of miR-1. We further demonstrated that Smad3 was central to the effects of miR-1 in colorectal cancer cells, establishing a previously unappreciated mechanism by which the miR-1/Smad3/HIF-1α axis facilitates the Warburg effect to promote cancer progression in vitro and in vivo. The results indicate that miR-1 may have an essential role as a tumor suppressor, suggesting its potential role in molecular therapy of patients with advanced colorectal cancer.
[Mh] Termos MeSH primário: Proteínas do Tecido Nervoso/metabolismo
Proteína Smad3/metabolismo
[Mh] Termos MeSH secundário: Animais
Antagomirs/metabolismo
Antagomirs/farmacologia
Antagomirs/uso terapêutico
Sequência de Bases
Peso Corporal/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Glicólise/efeitos dos fármacos
Células HCT116
Células HEK293
Células HT29
Hexoquinase/genética
Hexoquinase/metabolismo
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Camundongos
Camundongos Nus
Transportadores de Ácidos Monocarboxílicos/genética
Transportadores de Ácidos Monocarboxílicos/metabolismo
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Proteínas do Tecido Nervoso/antagonistas & inibidores
Proteínas do Tecido Nervoso/genética
Interferência de RNA
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antagomirs); 0 (FSD1 protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Monocarboxylic Acid Transporters); 0 (Muscle Proteins); 0 (Nerve Tissue Proteins); 0 (SLC16A4 protein, human); 0 (SMAD3 protein, human); 0 (Smad3 Protein); EC 2.7.1.1 (Hexokinase); EC 2.7.1.1 (hexokinase 2, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2017.60


  7 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27777899
[Au] Autor:Orellana-Manzano A; O'Ryan MG; Lagomarcino AJ; George S; Muñoz MS; Mamani N; Serrano CA; Harris PR; Ramilo O; Mejías A; Torres JP; Lucero Y; Quest AF
[Ad] Endereço:Host-Pathogen Interaction Laboratory, Microbiology and Mycology Program, Faculty of Medicine, University of ChileSantiago, Chile; Center for Molecular Studies of the Cell (CEMC), Faculty of Medicine, University of ChileSantiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medici
[Ti] Título: Infection Is Associated with Decreased Expression of SLC5A8, a Cancer Suppressor Gene, in Young Children.
[So] Source:Front Cell Infect Microbiol;6:121, 2016.
[Is] ISSN:2235-2988
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:infects half of the world's population and causes gastric cancer in a subset of infected adults. Previous blood microarray findings showed that apparently healthy children, persistently infected with have differential gene expression compared to age-matched, non-infected children. SLC5A8, a cancer suppressor gene with decreased expression among infected children, was chosen for further study based on bioinformatics analysis. A pilot study was conducted using specific qRT-PCR amplification of SLC5A8 in blood samples from infected and non-infected children, followed by a larger, blinded, case-control study. We then analyzed gastric tissue from infected and non-infected children undergoing endoscopy for clinical purposes. Demographics, clinical findings, and family history were similar between groups. SLC5A8 expression was decreased in infected vs. non-infected children in blood, 0.12 (IQR: 0-0.89) vs. 1.86 (IQR: 0-8.94, = 0.002), and in gastric tissue, 0.08 (IQR: 0.04-0.15) vs. 1.88 (IQR: 0.55-2.56; = 0.001). Children who were both stool positive and seropositive for had the lowest SLC5A8 expression levels. infection is associated with suppression of SCL5A8, a cancer suppressor gene, in both blood and tissue samples from young children. Young children, persistently infected with show decreased expression of SLC5A8 mRNA in both blood and tissue samples as compared to non-infected children.
[Mh] Termos MeSH primário: Genes Supressores de Tumor
Infecções por Helicobacter/patologia
Transportadores de Ácidos Monocarboxílicos/análise
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Criança
Pré-Escolar
Mucosa Gástrica/patologia
Seres Humanos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Monocarboxylic Acid Transporters); 0 (SLC5A8 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171224
[Lr] Data última revisão:
171224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  8 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28985563
[Au] Autor:Faubert B; Li KY; Cai L; Hensley CT; Kim J; Zacharias LG; Yang C; Do QN; Doucette S; Burguete D; Li H; Huet G; Yuan Q; Wigal T; Butt Y; Ni M; Torrealba J; Oliver D; Lenkinski RE; Malloy CR; Wachsmann JW; Young JD; Kernstine K; DeBerardinis RJ
[Ad] Endereço:Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
[Ti] Título:Lactate Metabolism in Human Lung Tumors.
[So] Source:Cell;171(2):358-371.e9, 2017 Oct 05.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Ácido Láctico/metabolismo
Neoplasias Pulmonares/metabolismo
[Mh] Termos MeSH secundário: Animais
Análise Química do Sangue
Linhagem Celular Tumoral
Ciclo do Ácido Cítrico
Modelos Animais de Doenças
Feminino
Ácidos Glicéricos/metabolismo
Xenoenxertos
Seres Humanos
Masculino
Camundongos
Transportadores de Ácidos Monocarboxílicos/genética
Transportadores de Ácidos Monocarboxílicos/metabolismo
Transplante de Neoplasias
Simportadores/genética
Simportadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glyceric Acids); 0 (Monocarboxylic Acid Transporters); 0 (Symporters); 0 (monocarboxylate transport protein 1); 33X04XA5AT (Lactic Acid); 820-11-1 (3-phosphoglycerate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


  9 / 1398 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28977587
[Au] Autor:Groeneweg S; Lima de Souza EC; Meima ME; Peeters RP; Visser WE; Visser TJ
[Ad] Endereço:The Rotterdam Thyroid Center & Department of Internal Medicine, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.
[Ti] Título:Outward-Open Model of Thyroid Hormone Transporter Monocarboxylate Transporter 8 Provides Novel Structural and Functional Insights.
[So] Source:Endocrinology;158(10):3292-3306, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monocarboxylate transporter 8 (MCT8) facilitates cellular uptake and efflux of thyroid hormone (TH). Mutations in MCT8 result in severe intellectual and motor disability known as the Allan-Herndon-Dudley syndrome (AHDS). Previous studies have provided valuable insights into the putative mechanism of substrate binding in the inward-open conformation, required for TH efflux. The current study aims to delineate the mechanism of substrate binding in the outward-open conformation, required for TH uptake. Extensive chemical modification and site-directed mutagenesis studies were used to guide protein homology modeling of MCT8 in the outward-open conformation. Arg271 and Arg445 were modified by phenylglyoxal, which was partially prevented in the presence of substrate. Substrate docking in our outward-open model suggested an important role for His192 and Arg445 in substrate binding. Interestingly, mutations affecting these residues have been identified in patients who have AHDS. In addition, our outward-open model predicted the location of Phe189, Met227, Phe279, Gly282, Phe287, and Phe501 at the substrate-binding center, and their Ala substitution differentially affected the apparent Vmax and Km of T3 transport, with F189A, F279A, and F287A showing the highest impact. Thus, here we present an MCT8 homology model in the outward-open conformation, which supports the important role of His192 and Arg445 in substrate docking and identifies critical residues at the putative substrate-binding center. Our findings provide insights into MCT8 structure and function, which add to our understanding of the pathogenic mechanism of mutations found in patients who have AHDS and can be used to screen for novel substrates and inhibitors.
[Mh] Termos MeSH primário: Transportadores de Ácidos Monocarboxílicos/química
Transportadores de Ácidos Monocarboxílicos/fisiologia
Hormônios Tireóideos/metabolismo
[Mh] Termos MeSH secundário: Animais
Arginina
Sítios de Ligação/genética
Sítios de Ligação/fisiologia
Transporte Biológico/fisiologia
Células COS
Linhagem Celular
Cercopithecus aethiops
Histidina
Seres Humanos
Retardo Mental Ligado ao Cromossomo X/genética
Modelos Moleculares
Estrutura Molecular
Transportadores de Ácidos Monocarboxílicos/genética
Hipotonia Muscular/genética
Atrofia Muscular/genética
Mutagênese Sítio-Dirigida
Mutação
Conformação Proteica
Transfecção
Tri-Iodotironina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Monocarboxylic Acid Transporters); 0 (SLC16A2 protein, human); 0 (Thyroid Hormones); 06LU7C9H1V (Triiodothyronine); 4QD397987E (Histidine); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00082


  10 / 1398 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28938430
[Au] Autor:Kersseboom S; van Gucht ALM; van Mullem A; Brigante G; Farina S; Carlsson B; Donkers JM; van de Graaf SFJ; Peeters RP; Visser TJ
[Ad] Endereço:Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
[Ti] Título:Role of the Bile Acid Transporter SLC10A1 in Liver Targeting of the Lipid-Lowering Thyroid Hormone Analog Eprotirome.
[So] Source:Endocrinology;158(10):3307-3318, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The thyroid hormone (TH) analog eprotirome (KB2115) was developed to lower cholesterol through selective activation of the TH receptor (TR) ß1 in the liver. Interestingly, eprotirome shows low uptake in nonhepatic tissues, explaining its lipid-lowering action without adverse extrahepatic thyromimetic effects. Clinical trials have shown marked decreases in serum cholesterol levels. We explored the transport of eprotirome across the plasma membrane by members of three TH transporter families: monocarboxylate transporters MCT8 and MCT10; Na-independent organic anion transporters 1A2, 1B1, 1B3, 1C1, 2A1, and 2B1; and Na-dependent organic anion transporters SLC10A1 to SLC10A7. Cellular transport was studied in transfected COS1 cells using [14C]eprotirome and [125I]TH analogs. Of the 15 transporters tested initially, the liver-specific bile acid transporter SLC10A1 showed the highest eprotirome uptake (greater than a sevenfold induction after 60 minutes) as well as TRß1-mediated transcriptional activity. Uptake of eprotirome by SLC10A1 was Na+ dependent and saturable with a Michaelis constant of 8 µM. Eprotirome transport was inhibited by known substrates for SLC10A1 (e.g., cholate and taurocholate), and by TH analogs such as triiodothyropropionic acid and triiodothyroacetic acid. However, no significant SLC10A1-mediated transport was observed of these [125I]TH analogs. We also studied the plasma disappearance and biliary excretion of [14C]eprotirome injected in control and Slc10a1 knockout mice. Although eprotirome is also transported by mouse Slc10a1, the pharmacokinetics of eprotirome were not affected by Slc10a1 deficiency. In conclusion, we have demonstrated that the liver-specific bile acid transporter SLC10A1 effectively transports eprotirome. However, Slc10a1 does not appear to be critical for the liver targeting of this TH analog in mice. Therefore, the importance of SLC10A1 for liver uptake of eprotirome in humans remains to be elucidated.
[Mh] Termos MeSH primário: Anilidas/farmacologia
Anilidas/farmacocinética
Anticolesterolemiantes
Fígado/efeitos dos fármacos
Transportadores de Ânions Orgânicos Dependentes de Sódio/fisiologia
Simportadores/fisiologia
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Células COS
Membrana Celular/metabolismo
Cercopithecus aethiops
Seres Humanos
Fígado/metabolismo
Camundongos
Camundongos Knockout
Terapia de Alvo Molecular
Transportadores de Ácidos Monocarboxílicos/metabolismo
Transportadores de Ânions Orgânicos/metabolismo
Transportadores de Ânions Orgânicos Dependentes de Sódio/deficiência
Transportadores de Ânions Orgânicos Dependentes de Sódio/genética
RNA Mensageiro/análise
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Sódio/farmacologia
Simportadores/deficiência
Simportadores/genética
Hormônios Tireóideos/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid); 0 (Anilides); 0 (Anticholesteremic Agents); 0 (Monocarboxylic Acid Transporters); 0 (Organic Anion Transporters); 0 (Organic Anion Transporters, Sodium-Dependent); 0 (RNA, Messenger); 0 (Symporters); 0 (Thyroid Hormones); 145420-23-1 (sodium-bile acid cotransporter); 9NEZ333N27 (Sodium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00433



página 1 de 140 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde