Base de dados : MEDLINE
Pesquisa : D06.472.699.327.740.860.780 [Categoria DeCS]
Referências encontradas : 274 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 28 ir para página                         

  1 / 274 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
[PMID]:26917260
[Au] Autor:Liu AX; Zhang D; Zhu YM; Gao HJ; Jiang JY; Hu XL; Lv PP; Leung PC; Huang HF
[Ti] Título:Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line.
[So] Source:Curr Mol Med;16(3):299-311, 2016.
[Is] ISSN:1875-5666
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental and JEG-3 cell function. Furthermore, we aim to investigate the downstream pathways of GHRH/GHRH-R axis in the control of the JEG-3 cell viability and apoptosis. In this study, we detected the expression pattern of GHRH-R in human chorionic villous tissues and JEG-3 cell. Then, we evaluated the effects of GHRH/GHRH-R and the downstream pathways by using GHRH antagonist (JMR-132) on JEG-3 cell. Our present study found the expressions of GHRH-R in placental villous tissues and JEG-3 cell, and the expression levels of GHRH-R was significantly lower in villous tissues of early pregnancy loss when compared to normal controls. JMR-132 inhibited cellular viability and induced apoptosis in JEG-3 cell in a time and dosedependent manners through activation of caspase-3, p38, and p53, as well as inhibition of phosphorylation of Akt. Interestingly, ER stress markers such as GRP78, ubiquitinated proteins and phospho-eIF2α were significantly increased in JEG-3 cell after being treated with JMR-132. Conversely, pretreated with salubrinal (a selective inhibition of protein phosphatase 1-mediated eIF2α dephosphorylation), JEG-3 cells were rescued from JMR-132-mediated cell growth inhibition, and abolished JMR-132-induced cleaved caspase-3, CHOP, phospho-p53, and ubiquitinated proteins accumulation. Knockdown of endogenous GHRH-R significantly abolished the JMR-132-induced cleaved caspase-3 and activation of p38. In conclusion, our results, for the first time, demonstrated the expression levels of GHRH-R were closely related to the placental function. Inhibition of GHRH-R by using GHRH antagonist in JEG-3 cell may reduce cell viability and induce apoptosis through inactivation of Akt and ER stress via phosphorylation of eIF2α. These observations have enriched our understanding on the function of GHRH/GHRH-R axis and the downstream pathways in the control of the placental development. The Most Important Aspect of the Paper: Our present study for the first time provided evidences that GHRH and GHRH-R loops involve in JEG-3 cell viability and apoptosis through Akt and eIF2α pathways.
[Mh] Termos MeSH primário: Vilosidades Coriônicas/metabolismo
Fator de Iniciação 2 em Eucariotos/genética
Hormônio Liberador de Hormônio do Crescimento/genética
Proteínas Proto-Oncogênicas c-akt/genética
Receptores de Neuropeptídeos/genética
Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética
Trofoblastos/metabolismo
[Mh] Termos MeSH secundário: Aborto Espontâneo/genética
Aborto Espontâneo/metabolismo
Aborto Espontâneo/patologia
Adulto
Apoptose
Estudos de Casos e Controles
Caspase 3/genética
Caspase 3/metabolismo
Linhagem Celular Tumoral
Sobrevivência Celular
Vilosidades Coriônicas/efeitos dos fármacos
Vilosidades Coriônicas/patologia
Cinamatos/farmacologia
Fator de Iniciação 2 em Eucariotos/metabolismo
Feminino
Regulação da Expressão Gênica
Hormônio Liberador de Hormônio do Crescimento/metabolismo
Seres Humanos
Gravidez
Proteínas Proto-Oncogênicas c-akt/metabolismo
Receptores de Neuropeptídeos/metabolismo
Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo
Sermorelina/análogos & derivados
Sermorelina/antagonistas & inibidores
Sermorelina/farmacologia
Transdução de Sinais
Tioureia/análogos & derivados
Tioureia/farmacologia
Trofoblastos/efeitos dos fármacos
Trofoblastos/patologia
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/genética
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cinnamates); 0 (Eukaryotic Initiation Factor-2); 0 (GHRH(1-29)NH2, PhAcTyr(1)-Arg(2)-P(H)e(4-CL)(6)-Ala(8)-Tyr(Me)(10)-His(11)-Abu(15)-His(20)-Nle(27)-Arg(28)-HLCr(29)-); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (Tumor Suppressor Protein p53); 0 (salubrinal); 0 (somatotropin releasing hormone receptor); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160227
[St] Status:MEDLINE


  2 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25827134
[Au] Autor:Bagno LL; Kanashiro-Takeuchi RM; Suncion VY; Golpanian S; Karantalis V; Wolf A; Wang B; Premer C; Balkan W; Rodriguez J; Valdes D; Rosado M; Block NL; Goldstein P; Morales A; Cai RZ; Sha W; Schally AV; Hare JM
[Ad] Endereço:Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
[Ti] Título:Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy.
[So] Source:J Am Heart Assoc;4(4), 2015 Mar 31.
[Is] ISSN:2047-9980
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Growth hormone-releasing hormone agonists (GHRH-As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-As prevents ventricular remodeling in a swine subacute MI model. METHODS AND RESULTS: Twelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending coronary artery (MI). Two weeks post MI, swine were randomized to receive injections of either 30 µg/kg GHRH-A (MR-409) (GHRH-A group; n=6) or vehicle (placebo group; n=6). Cardiac magnetic resonance imaging and pressure-volume loops were obtained at multiple time points. Infarct, border, and remote (noninfarcted) zones were assessed for GHRH receptor by immunohistochemistry. Four weeks of GHRH-A treatment resulted in reduced scar mass (GHRH-A: -21.9 ± 6.42%; P=0.02; placebo: 10.9 ± 5.88%; P=0.25; 2-way ANOVA; P=0.003), and scar size (percentage of left ventricular mass) (GHRH-A: -38.38 ± 4.63; P=0.0002; placebo: -14.56 ± 6.92; P=0.16; 2-way ANOVA; P=0.02). This was accompanied by improved diastolic strain. Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure-volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH-A group compared with the placebo group. CONCLUSIONS: Daily subcutaneous administration of GHRH-A is feasible and safe in a large animal model of subacute ischemic cardiomyopathy. Furthermore, GHRH-A therapy significantly reduced infarct size and improved diastolic strain, suggesting a local activation of the GHRH pathway leading to the reparative process.
[Mh] Termos MeSH primário: Cicatriz/tratamento farmacológico
Hormônio Liberador de Hormônio do Crescimento/agonistas
Infarto do Miocárdio/complicações
Isquemia Miocárdica/tratamento farmacológico
Sermorelina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Cicatriz/patologia
Creatina Quinase Forma MB/sangue
Creatina Quinase Forma MM/sangue
Feminino
Hormônio Liberador de Hormônio do Crescimento/uso terapêutico
Imagem por Ressonância Magnética
Infarto do Miocárdio/tratamento farmacológico
Miocárdio/patologia
Sermorelina/uso terapêutico
Suínos
Troponina I/sangue
Remodelação Ventricular/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (GHRH(1-29)N-CH3, N-Me-Tyr(1)-Ala(2)-Orn(12)-Abu(15)-Orn(21)-Nle(27)-Asp(28)-); 0 (Troponin I); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); EC 2.7.3.2 (Creatine Kinase, MB Form); EC 2.7.3.2 (Creatine Kinase, MM Form)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150402
[St] Status:MEDLINE


  3 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
[PMID]:25797248
[Au] Autor:Kanashiro-Takeuchi RM; Szalontay L; Schally AV; Takeuchi LM; Popovics P; Jaszberenyi M; Vidaurre I; Zarandi M; Cai RZ; Block NL; Hare JM; Rick FG
[Ad] Endereço:Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
[Ti] Título:New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor.
[So] Source:Oncotarget;6(12):9728-39, 2015.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We previously showed that growth hormone-releasing hormone (GHRH) agonists are cardioprotective following myocardial infarction (MI). Here, our aim was to evaluate the in vitro and in vivo activities of highly potent new GHRH agonists, and elucidate their mechanisms of action in promoting cardiac repair. METHODS AND RESULTS: H9c2 cells were cultured in serum-free medium, mimicking nutritional deprivation. GHRH agonists decreased calcium influx and significantly improved cell survival. Rats with cardiac infarction were treated with GHRH agonists or placebo for four weeks. MI size was reduced by selected GHRH agonists (JI-38, MR-356, MR-409); this accompanied an increased number of cardiac c-kit+ cells, cellular mitotic divisions, and vascular density. One week post-MI, MR-409 significantly reduced plasma levels of IL-2, IL-6, IL-10 and TNF-α compared to placebo. Gene expression studies revealed favorable outcomes of MR-409 treatment partially result from inhibitory activity on pro-apoptotic molecules and pro-fibrotic systems, and by elevation of bone morphogenetic proteins. CONCLUSIONS: Treatment with GHRH agonists appears to reduce the inflammatory responses post-MI and may consequently improve mechanisms of healing and cardiac remodeling by regulating pathways involved in fibrosis, apoptosis and cardiac repair. Patients with cardiac dysfunction could benefit from treatment with novel GHRH agonists.
[Mh] Termos MeSH primário: Insuficiência Cardíaca/tratamento farmacológico
Infarto do Miocárdio/tratamento farmacológico
Receptores de Neuropeptídeos/agonistas
Receptores de Neuropeptídeos/química
Receptores de Hormônios Reguladores de Hormônio Hipofisário/agonistas
Receptores de Hormônios Reguladores de Hormônio Hipofisário/química
[Mh] Termos MeSH secundário: Alprostadil/análogos & derivados
Alprostadil/química
Animais
Linhagem Celular
Ensaio de Imunoadsorção Enzimática
Perfilação da Expressão Gênica
Regulação da Expressão Gênica
Hormônio Liberador de Hormônio do Crescimento/análogos & derivados
Hormônio Liberador de Hormônio do Crescimento/química
Seres Humanos
Inflamação
Interleucina-10/sangue
Interleucina-2/sangue
Interleucina-6/sangue
Microscopia de Fluorescência
Mitose
Ratos
Sermorelina/análogos & derivados
Sermorelina/química
Fator de Necrose Tumoral alfa/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Interleukin-2); 0 (Interleukin-6); 0 (JI-38); 0 (N-Me-Tyr1,D-Ala2,Asn8,Arg29-NHCH3-JI-38); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (Tumor Necrosis Factor-alpha); 0 (somatotropin releasing hormone receptor); 120146-92-1 (MR 356); 130068-27-8 (Interleukin-10); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); F5TD010360 (Alprostadil)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150324
[St] Status:MEDLINE


  4 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25752763
[Au] Autor:Catanuto P; Tashiro J; Rick FG; Sanchez P; Solorzano CC; Glassberg MK; Block NL; Lew JI; Elliot SJ; Schally AV
[Ad] Endereço:Laboratory on Sex and Gender Differences in Health and Disease, University of Miami Miller School of Medicine, 1550 NW 10th Avenue, Suite 411, Miami, FL, 33136, USA.
[Ti] Título:Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on Matrix Metalloproteinase-2.
[So] Source:Horm Cancer;6(2-3):100-6, 2015 Jun.
[Is] ISSN:1868-8500
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Papillary thyroid cancer (PTC) is the most prevalent of all endocrine cancers. In recent studies, the presence of receptors for pituitary-type growth hormone-releasing hormone (pGHRH-R) has been demonstrated in various human cancers, including human prostate, brain, and other cancer lines. Thyroid malignancies, however, have not yet been investigated in this regard. In this study, we found that pGHRH-R and its functional splice variant, SV1, are present in normal thyroid and PTC cells. We also treated seven normal and PTC tumor thyroid cells in vitro with a GHRH antagonist, MIA-602, to compare its anti-proliferation and anti-invasion potential against vehicle-treated cells. We found that treatment with GHRH antagonist increases the expression of SV1 and pGHRH-R in tumor cells compared to tumor cells exposed to vehicle only, a response which may alter the sensitivity of signaling kinases within the cells. GHRH antagonist treatment of tumor cells also reduced activity of the tumor invasion marker, matrix metalloproteinase (MMP)-2, compared to tumor cells exposed to vehicle only. The expression of pGHRH-R and SV1, as well as MMP-2 activity, in normal thyroid cells remained unaffected by GHRH antagonist treatment. Similarly, cell proliferation rates for tumor or normal thyroid cells were not affected by GHRH antagonist treatment. Our findings have important implications for the therapeutic use of GHRH antagonist in cases of aggressive PTC refractory to conventional treatment modalities, and in which protein expression and MMP-2 activity in normal thyroid tissue is left unaltered.
[Mh] Termos MeSH primário: Carcinoma/metabolismo
Metaloproteinase 2 da Matriz/metabolismo
Receptores de Neuropeptídeos/biossíntese
Receptores de Hormônios Reguladores de Hormônio Hipofisário/biossíntese
Neoplasias da Glândula Tireoide/metabolismo
[Mh] Termos MeSH secundário: Western Blotting
Carcinoma Papilar
Proliferação Celular
Feminino
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Seres Humanos
Meia-Idade
Sermorelina/análogos & derivados
Sermorelina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (somatotropin releasing hormone receptor); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); EC 3.4.24.24 (MMP2 protein, human); EC 3.4.24.24 (Matrix Metalloproteinase 2)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150311
[St] Status:MEDLINE
[do] DOI:10.1007/s12672-015-0217-2


  5 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25489106
[Au] Autor:Qin YJ; Chan SO; Chong KK; Li BF; Ng TK; Yip YW; Chen H; Zhang M; Block NL; Cheung HS; Schally AV; Pang CP
[Ad] Endereço:Department of Ophthalmology & Visual Sciences and.
[Ti] Título:Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation.
[So] Source:Proc Natl Acad Sci U S A;111(51):18303-8, 2014 Dec 23.
[Is] ISSN:1091-6490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disruptions in immunity and occurrence of inflammation cause many eye diseases. The growth hormone-releasing hormone-growth hormone-insulin-like growth factor-1 (GHRH-GH-IGF1) axis exerts regulatory effects on the immune system. Its involvement in ocular inflammation remains to be investigated. Here we studied this signaling in endotoxin-induced uveitis (EIU) generated by LPS. The increase in GHRH receptor (GHRH-R) protein levels was parallel to the increase in mRNA levels of pituitary-specific transcription factor-1, GHRH-R splice variant 1, GHRH, and GH following LPS insult. Elevation of GHRH-R and GH receptor was localized on the epithelium of the iris and ciliary body, and GHRH-R was confined to the infiltrating macrophages and leukocytes in aqueous humor but not to those in stroma. Treatment with GHRH-R antagonist decreased LPS-stimulated surges of GH and IGF1 in aqueous humor and alleviated inflammation by reducing the infiltration of macrophages and leukocytes and the production of TNF-α, IL-1ß, and monocyte chemotactic protein-1. Our results indicate that inflammation in the iris and ciliary body involves the activation of GHRH signaling, which affects the recruitment of immune cells and the production of proinflammatory mediators that contribute to EIU pathogenesis. Moreover, the results suggest that GHRH-R antagonists are potential therapeutic agents for the treatment of acute ocular inflammation.
[Mh] Termos MeSH primário: Hormônio Liberador de Hormônio do Crescimento/uso terapêutico
Receptores de Neuropeptídeos/antagonistas & inibidores
Receptores de Hormônios Reguladores de Hormônio Hipofisário/antagonistas & inibidores
Sermorelina/análogos & derivados
Uveíte/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Ensaio de Imunoadsorção Enzimática
Hormônio do Crescimento/sangue
Fator de Crescimento Insulin-Like I/metabolismo
Ratos
Ratos Sprague-Dawley
Sermorelina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (somatotropin releasing hormone receptor); 67763-96-6 (Insulin-Like Growth Factor I); 86168-78-7 (Sermorelin); 9002-72-6 (Growth Hormone); 9034-39-3 (Growth Hormone-Releasing Hormone)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:151028
[Lr] Data última revisão:
151028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141210
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1421815112


  6 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25486366
[Au] Autor:Szalontay L; Schally AV; Popovics P; Vidaurre I; Krishan A; Zarandi M; Cai RZ; Klukovits A; Block NL; Rick FG
[Ad] Endereço:a Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education ; Miami , FL USA.
[Ti] Título:Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function.
[So] Source:Cell Cycle;13(17):2790-7, 2014.
[Is] ISSN:1551-4005
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malignant melanoma is the deadliest form of skin cancer; the treatment of advanced and recurrent forms remains a challenge. It has recently been reported that growth hormone-releasing hormone (GHRH) receptor is involved in the pathogenesis of melanoma. Therefore, we investigated the effects of our new GHRH antagonists on a human melanoma cancer cell line. Antiproliferative effects of GHRH antagonists, MIA-602, MIA-606 and MIA-690, on the human melanoma cell line, A-375, were studied in vitro using the MTS assay. The effect of MIA-690 (5 µg/day 28 d) was further evaluated in vivo in nude mice bearing xenografts of A-375. Subcellular localization of p27 was detected with Western blot and immunofluorescent staining. MIA-690 inhibited the proliferation of A-375 cells in a dose-dependent manner (33% at 10 µM, and 19.2% at 5 µM, P < 0 .05 vs. control), and suppressed the growth of xenografted tumors by 70.45% (P < 0.05). Flow cytometric analysis of cell cycle effects following the administration of MIA-690 revealed a decrease in the number of cells in G2/M phase (from 19.7% to 12.9%, P < 0.001). Additionally, Western blot and immunofluorescent studies showed that exposure of A-375 cells to MIA-690 triggered the nuclear accumulation of p27. MIA-690 inhibited tumor growth in vitro and in vivo, and increased the translocation of p27 into the nucleus thus inhibiting progression of the cell cycle. Our findings indicate that patients with malignant melanoma could benefit from treatment regimens, which combine existing chemotherapy agents and novel GHRH-antagonists.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Inibidor de Quinase Dependente de Ciclina p27/metabolismo
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Melanoma/patologia
[Mh] Termos MeSH secundário: Animais
Ciclo Celular/efeitos dos fármacos
Ciclo Celular/genética
Linhagem Celular Tumoral
Núcleo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Hormônio Liberador de Hormônio do Crescimento/metabolismo
Seres Humanos
Melanoma/genética
Camundongos Nus
Receptores de Neuropeptídeos/metabolismo
Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo
Sermorelina/análogos & derivados
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
Neoplasias Cutâneas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (somatotropin releasing hormone receptor); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141209
[St] Status:MEDLINE
[do] DOI:10.4161/15384101.2015.945879


  7 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25000999
[Au] Autor:Muñoz-Moreno L; Arenas MI; Carmena MJ; Schally AV; Prieto JC; Bajo AM
[Ad] Endereço:Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, 28871, Alcalá de Henares, Spain.
[Ti] Título:Growth hormone-releasing hormone antagonists abolish the transactivation of human epidermal growth factor receptors in advanced prostate cancer models.
[So] Source:Invest New Drugs;32(5):871-82, 2014 Oct.
[Is] ISSN:1573-0646
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in a variety of cellular phenotypes related with tumorigenesis process. Human epidermal growth factor receptor family members (HER) such as EGFR and HER2 are involved in mitogenic signaling pathways implicated in the progression of prostate cancer. We analyzed the cross-talk between GHRH and EGF receptors in prostate cancer. The effects of GHRH in HER signaling were evaluated on human androgen-independent PC3 prostate cancer cells in vitro and GHRH antagonist in vitro and in nude mice xenografts of PC3 prostate cancer. Time-course studies indicated that GHRH had a stimulatory activity on both the expression of EGFR and HER2. GHRH analogues, JMR-132 and JV-1-38, endowed with antagonistic activity for GHRH receptors, abrogated the response to GHRH in PC3 cells. GHRH stimulated a rapid ligand-independent activation of EGFR and HER2 involving at least cAMP/PKA and Src family signaling pathways. GHRH also stimulated a slow ligand-dependent activation of EGFR and HER2 involving an extracellular pathway with an important role for ADAM. Preliminary results also revealed an increase of mRNA for GHRH and GHRH receptor induced by EGF. The inhibition of tumor growth, in vivo, was associated with a substantial reduction in the expression of mRNA and protein levels of EGFR and HER2 in the tumors. GHRH antagonist JV-1-38, significantly decreased the phosphorylated Src levels. The cross-talk between HER and GHRH-R may be impeded by combining drugs acting upon GHRH receptors and HER family members in human advanced prostate cancer.
[Mh] Termos MeSH primário: Hormônio Liberador de Hormônio do Crescimento/análogos & derivados
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Neoplasias da Próstata/metabolismo
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Sermorelina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Fator de Crescimento Epidérmico/farmacologia
Hormônio Liberador de Hormônio do Crescimento/farmacologia
Seres Humanos
Masculino
Camundongos Nus
RNA Mensageiro/metabolismo
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptor ErbB-2/antagonistas & inibidores
Receptor ErbB-2/genética
Receptor ErbB-2/metabolismo
Receptores de Neuropeptídeos/genética
Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética
Sermorelina/farmacologia
Quinases da Família src/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, PhAcTyr(1)-Arg(2)-P(H)e(4-CL)(6)-Ala(8)-Tyr(Me)(10)-His(11)-Abu(15)-His(20)-Nle(27)-Arg(28)-HLCr(29)-); 0 (JV 1-38); 0 (RNA, Messenger); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (somatotropin releasing hormone receptor); 62229-50-9 (Epidermal Growth Factor); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.2 (src-Family Kinases)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140709
[St] Status:MEDLINE
[do] DOI:10.1007/s10637-014-0131-4


  8 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:23815362
[Au] Autor:Nair D; Ramesh V; Li RC; Schally AV; Gozal D
[Ad] Endereço:Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
[Ti] Título:Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.
[So] Source:J Neurochem;127(4):531-40, 2013 Nov.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep.
[Mh] Termos MeSH primário: Transtornos Cognitivos/psicologia
Hormônio Liberador de Hormônio do Crescimento/metabolismo
Hipóxia/metabolismo
Estresse Oxidativo
[Mh] Termos MeSH secundário: Animais
Transtornos Cognitivos/etiologia
Desoxiguanosina/análogos & derivados
Desoxiguanosina/metabolismo
Depressão/etiologia
Depressão/psicologia
Eritropoetina/metabolismo
Hormônio Liberador de Hormônio do Crescimento/agonistas
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Hipóxia/complicações
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Transtornos de Aprendizagem/etiologia
Transtornos de Aprendizagem/psicologia
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Aprendizagem em Labirinto
Camundongos
Camundongos Endogâmicos C57BL
Receptor IGF Tipo 1/metabolismo
Sermorelina/análogos & derivados
Sermorelina/farmacologia
Transdução de Sinais
Sono
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-); 0 (Hif1a protein, mouse); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 11096-26-7 (Erythropoietin); 86168-78-7 (Sermorelin); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); 9034-39-3 (Growth Hormone-Releasing Hormone); EC 2.7.10.1 (Receptor, IGF Type 1); G9481N71RO (Deoxyguanosine)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130703
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.12360


  9 / 274 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23624870
[Au] Autor:Seitz S; Rick FG; Schally AV; Treszl A; Hohla F; Szalontay L; Zarandi M; Ortmann O; Engel JB; Buchholz S
[Ad] Endereço:Department of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, Germany. stephan_seitz@gmx.de
[Ti] Título:Combination of GHRH antagonists and docetaxel shows experimental effectiveness for the treatment of triple-negative breast cancers.
[So] Source:Oncol Rep;30(1):413-8, 2013 Jul.
[Is] ISSN:1791-2431
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:In preclinical studies, antagonists of growth hormone-releasing hormone (GHRH) have demonstrated inhibitory effects on the growth of various types of cancers expressing the pituitary type of GHRH receptors (pGHRH-R) and/or its active splice variant 1 (SV1). In this study, we investigated the effectiveness of the treatment of MDA-MB-231 human triple-negative breast cancer (TNBC) with GHRH antagonist JMR-132 alone or in combination with docetaxel. Receptor expression in the MDA-MB-231 human breast cancer cell line was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Cell viability assays were performed on MDA-MB-231 cells treated with JMR-132, docetaxel or in combination. For studies in vivo, a subcutaneous nude mouse xenograft model was used. JMR-132 was administered s.c. at a dose of 10 µg/day and docetaxel at a dose of 10 mg/kg i.p. given on day 1 and 5. Similar regimens were used for the combination of both substances. At the end of the experiment, an mRNA-based human cancer pathway array including 84 major genes was performed on the tumor tissue of mice treated with JMR-132 to elucidate the mechanism of action of GHRH antagonists in vivo. The in vitro proliferation studies revealed that JMR-132 and docetaxel decreased the cell viability in a dose-dependent manner. The combination of both treatments produced a significantly greater inhibition of cell viability compared to the single agents. Treatment of nude mice bearing MDA-MB-231 xenografts with JMR-132 and docetaxel significantly (p<0.05) inhibited tumor growth by 46 and 50%, respectively. Treatment with the combination of JMR-132 and docetaxel led to an inhibition of tumor volume by 71.6% (p<0.001). Polymerase chain reaction array analysis revealed that JMR-132 interacts with signal transduction pathways involved in proliferation, apoptosis and angiogenesis. Our results suggest that GHRH antagonists in combination with taxanes may enhance the efficacy of treatment for patients with TNBC expressing the SV1 and/or the pGHRH receptor.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Sermorelina/análogos & derivados
Taxoides/uso terapêutico
Neoplasias de Mama Triplo Negativas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular
Sobrevivência Celular/efeitos dos fármacos
Feminino
Seres Humanos
Camundongos
Camundongos Nus
Transplante de Neoplasias
Neovascularização Patológica/tratamento farmacológico
Receptores de Neuropeptídeos/metabolismo
Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo
Sermorelina/uso terapêutico
Neoplasias de Mama Triplo Negativas/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (GHRH(1-29)NH2, PhAcTyr(1)-Arg(2)-P(H)e(4-CL)(6)-Ala(8)-Tyr(Me)(10)-His(11)-Abu(15)-His(20)-Nle(27)-Arg(28)-HLCr(29)-); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (Taxoids); 0 (somatotropin releasing hormone receptor); 15H5577CQD (docetaxel); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:130522
[Lr] Data última revisão:
130522
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130430
[St] Status:MEDLINE
[do] DOI:10.3892/or.2013.2435


  10 / 274 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:23280565
[Au] Autor:Rick FG; Schally AV; Block NL; Abi-Chaker A; Krishan A; Szalontay L
[Ad] Endereço:Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, Florida 33125, USA. ferencrick@gmail.com
[Ti] Título:Mechanisms of synergism between antagonists of growth hormone-releasing hormone and antagonists of luteinizing hormone-releasing hormone in shrinking experimental benign prostatic hyperplasia.
[So] Source:Prostate;73(8):873-83, 2013 Jun.
[Is] ISSN:1097-0045
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Benign prostatic hyperplasia (BPH) affects aging men. Combined therapy with antagonists of growth hormone-releasing hormone (GHRH) and of luteinizing hormone-releasing hormone (LHRH or GnRH) induces prostate shrinkage in rat models. We investigated the mechanisms of action of this combination on cell cycle traverse and expression of prostatic genes. METHODS: Effects of GHRH antagonist, JMR-132 (40 µg/day), the LHRH antagonist, cetrorelix (0.625 mg/kg), and their combination were evaluated on testosterone-induced benign prostatic hyperplasia in male Wistar rats. Influence of JMR-132, cetrorelix, and their combinations on cell viability was assessed by MTS assay in BPH-1 human prostate epithelial cells and WPMY-1 normal prostate stromal cells. Cell cycle was analyzed by laser flow cytometry. Real-time PCR arrays were performed. RESULTS: The combination of antagonists caused marked shrinkage of rat prostate (29.5%). In vitro, JMR-132 plus cetrorelix (both 5µM) produced synergistic (57.4%) inhibition of growth of BPH-1 cells, but a lesser inhibition (46%) of WPMY-1 cells. Co-treatment of with JMR-132 plus cetrorelix induced a significant increase of BPH-1 cells blocked in S-phase plus cells with lower G0 /G1 and G2 /M DNA content. Significant changes in expression of >40 gene transcripts related to growth factors, inflammatory cytokines, and signal transduction were identified. CONCLUSIONS: GHRH antagonist and LHRH antagonist combination potentiates rat prostate weight reduction and synergistically inhibits of growth of BPH-1 leading to cell cycle arrest in S-phase. These effects were lesser in normal stromal prostate cell line, WPMY-1. Our findings suggest that GHRH antagonists could be useful for BPH therapy, possibly in combination with LHRH antagonists.
[Mh] Termos MeSH primário: Pontos de Checagem do Ciclo Celular/fisiologia
Hormônio Liberador de Gonadotropina/análogos & derivados
Hormônio Liberador de Gonadotropina/antagonistas & inibidores
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores
Hiperplasia Prostática/tratamento farmacológico
Sermorelina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Regulação para Baixo/efeitos dos fármacos
Sinergismo Farmacológico
Perfilação da Expressão Gênica
Hormônio Liberador de Gonadotropina/farmacologia
Seres Humanos
Masculino
Tamanho do Órgão
Hiperplasia Prostática/patologia
Ratos
Ratos Wistar
Sermorelina/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (GHRH(1-29)NH2, PhAcTyr(1)-Arg(2)-P(H)e(4-CL)(6)-Ala(8)-Tyr(Me)(10)-His(11)-Abu(15)-His(20)-Nle(27)-Arg(28)-HLCr(29)-); 33515-09-2 (Gonadotropin-Releasing Hormone); 86168-78-7 (Sermorelin); 9034-39-3 (Growth Hormone-Releasing Hormone); OON1HFZ4BA (cetrorelix)
[Em] Mês de entrada:1307
[Cu] Atualização por classe:130426
[Lr] Data última revisão:
130426
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130103
[St] Status:MEDLINE
[do] DOI:10.1002/pros.22633



página 1 de 28 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