Base de dados : MEDLINE
Pesquisa : G04.712 [Categoria DeCS]
Referências encontradas : 12617 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 1262 ir para página                         

  1 / 12617 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29431352
[Au] Autor:Popova OA; Khatuaev RO
[Ti] Título:[Radiosensitivity of morphoenzymological structural elements of the jejunum mucous membrane in chronodynamics of the impact of electromagnetic fields impulses].
[So] Source:Gig Sanit;95(10):974-6, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Results of numerous researches have revealed that most sensitive to electromagnetic radiations are the nervous, endocrine and cardiovascular systems of an organism, however, the analysis of literary data confirms also the direct involvement of organs of the intestinal system in physiological, and not seldom, and the pathological program of the response of an organism to the action of extreme factors. In the experiment executed on white laboratory male rats by ourselves there was studied the grade of the radiosensitivity of morphoenzymological structural elements of jejunum mucous membrane after 5, 7 and 10 months of chronic influence of electromagnetic fields impulses with a density of induced currents 0.37; 0.7; 0.8; 2.7 kA/m and frequency of impulses 50, 100 and 500 in a week irrespective of their divisibility of ultrashort duration of 15 a 40 ns. Scientific value and novelty of results is concluded in revealed multiple linear relationships between indices of electromagneticfields (duration of the impact, density of induced currents, periodicity of impulses and the dynamics of the studied indices of a morphofunctional condition of a jejunum mucous membrane). Besides that, there was found the critical population to indices of electromagneticfields impulses parameters - the jejunum mast cells differing in hypersensitivity and dependence on duration of influence and density of induced currents revealed, at that their bioeffects were unidirectional.
[Mh] Termos MeSH primário: Campos Eletromagnéticos/efeitos adversos
Mucosa Intestinal
Jejuno
[Mh] Termos MeSH secundário: Animais
Radiação Eletromagnética/classificação
Mucosa Intestinal/patologia
Mucosa Intestinal/fisiopatologia
Mucosa Intestinal/efeitos da radiação
Jejuno/patologia
Jejuno/fisiopatologia
Jejuno/efeitos da radiação
Masculino
Modelos Animais
Tolerância a Radiação
Ratos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE


  2 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28456783
[Au] Autor:Cai S; Li Y; Bai JY; Zhang ZQ; Wang Y; Qiao YB; Zhou XZ; Yang B; Tian Y; Cao C
[Ad] Endereço:Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
[Ti] Título:Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.
[So] Source:Oncotarget;8(21):35061-35068, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have previously shown that Gαi3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gαi3 could also be important for irradiation resistance. In A172 human glioma cells, Gαi3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gαi3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gαi3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gαi3 knockdown, depletion (using Gαi3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gαi3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gαi3 in irradiation-resistance in human glioma cells.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/metabolismo
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo
Glioma/metabolismo
Tolerância a Radiação
[Mh] Termos MeSH secundário: Neoplasias Encefálicas/genética
Neoplasias Encefálicas/radioterapia
Linhagem Celular Tumoral
Núcleo Celular/metabolismo
Dano ao DNA
Proteína Quinase Ativada por DNA/metabolismo
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Glioma/genética
Glioma/radioterapia
Seres Humanos
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 3.6.5.1 (GNAI3 protein, human); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17043


  3 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28453388
[Au] Autor:Ayars M; Eshleman J; Goggins M
[Ad] Endereço:a Department of Pathology , The Johns Hopkins University School of Medicine , Baltimore , MD, USA.
[Ti] Título:Susceptibility of ATM-deficient pancreatic cancer cells to radiation.
[So] Source:Cell Cycle;16(10):991-998, 2017 May 19.
[Is] ISSN:1551-4005
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.
[Mh] Termos MeSH primário: Adenocarcinoma/radioterapia
Proteínas Mutadas de Ataxia Telangiectasia/genética
Carcinoma Ductal Pancreático/radioterapia
Tolerância a Radiação/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/genética
Adenocarcinoma/patologia
Carcinoma Ductal Pancreático/genética
Carcinoma Ductal Pancreático/patologia
Linhagem Celular Tumoral
Quebras de DNA de Cadeia Dupla
Dano ao DNA/efeitos da radiação
Reparo do DNA/efeitos da radiação
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Seres Humanos
Fosforilação/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (ATM protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1080/15384101.2017.1312236


  4 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Roesler, Rafael
Texto completo
[PMID]:29305710
[Au] Autor:Dietrich F; Figueiró F; Filippi-Chiela EC; Cappellari AR; Rockenbach L; Tremblay A; de Paula PB; Roesler R; Filho AB; Sévigny J; Morrone FB; Battastini AMO
[Ad] Endereço:Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, CEP 90035-003, Brazil.
[Ti] Título:Ecto-5'-nucleotidase/CD73 contributes to the radiosensitivity of T24 human bladder cancer cell line.
[So] Source:J Cancer Res Clin Oncol;144(3):469-482, 2018 Mar.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Trimodal therapy is a reasonable bladder-preserving option to radical cystectomy. However, many tumors are radioresistive. In this sense, the identification of new prognostic and predictive biomarkers that allow the selection of patients with better responses to radiation therapy would improve outcomes. With the aim of using ecto-5'-nucleotidase/CD73 as a predictive biomarker, the role of this enzyme in the context of radiotherapy in T24 human bladder cancer cell line was investigated. METHODS: T24 cell line was exposure to a single dose of radiation (4 Gray) and trypan blue assay (pharmacological assays of viability/cumulative population doubling), flow cytometry (cell cycle/cell death/active caspase-3/ecto-5'-nucleotidase/CD73 protein staining), DAPI staining (nuclear morphometric assay), RT-PCR and real-time PCR, malachite green method (ectonucleotidase enzymatic assay), and HPLC (analysis of AMP metabolism) were carried out. T24 cell line in which ecto-5'-nucleotidase/CD73 has been completely silenced (5'KO) was also used. RESULTS: The exposure of T24 cell line to a single dose (4 Gray) of radiation-induced cell death and triggered a transitory increase in ecto-5'-nucleotidase/CD73 expression, increased ectonucleotidase activity, and led to adenosine and inosine accumulation in the extracellular medium. Pharmacological inhibition or knocking out ecto-5'-nucleotidase/CD73 rescued cells' proliferative capacity, reducing their sensitivity to radiation. CONCLUSION: Our findings show that the induction of ecto-5'-nucleotidase/CD73 by radiation contributes to the radiosensitivity of T24 cell line.
[Mh] Termos MeSH primário: 5´-Nucleotidase/fisiologia
Tolerância a Radiação/genética
Neoplasias da Bexiga Urinária/patologia
Neoplasias da Bexiga Urinária/radioterapia
[Mh] Termos MeSH secundário: 5'-Nucleotidase/genética
5'-Nucleotidase/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/genética
Proliferação Celular/efeitos da radiação
Proteínas Ligadas por GPI/genética
Proteínas Ligadas por GPI/metabolismo
Proteínas Ligadas por GPI/fisiologia
Regulação Enzimológica da Expressão Gênica/efeitos da radiação
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Técnicas de Silenciamento de Genes
Seres Humanos
Dose de Radiação
Neoplasias da Bexiga Urinária/genética
Neoplasias da Bexiga Urinária/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GPI-Linked Proteins); EC 3.1.3.5 (5'-Nucleotidase); EC 3.1.3.5 (NT5E protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2567-3


  5 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29284117
[Au] Autor:Murata Y; Hashimoto T; Urushihara Y; Shiga S; Takeda K; Jingu K; Hosoi Y
[Ad] Endereço:Department of Radiation Biology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan.
[Ti] Título:Knockdown of AMPKα decreases ATM expression and increases radiosensitivity under hypoxia and nutrient starvation in an SV40-transformed human fibroblast cell line, LM217.
[So] Source:Biochem Biophys Res Commun;495(4):2566-2572, 2018 01 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Presence of unperfused regions containing cells under hypoxia and nutrient starvation contributes to radioresistance in solid human tumors. It is well known that hypoxia causes cellular radioresistance, but little is known about the effects of nutrient starvation on radiosensitivity. We have reported that nutrient starvation induced decrease of mTORC1 activity and decrease of radiosensitivity in an SV40-transformed human fibroblast cell line, LM217, and that nutrient starvation induced increase of mTORC1 activity and increase of radiosensitivity in human liver cancer cell lines, HepG2 and HuH6 (Murata et al., BBRC 2015). Knockdown of mTOR using small interfering RNA (siRNA) for mTOR suppressed radiosensitivity under nutrient starvation alone in HepG2 cells, which suggests that mTORC1 pathway regulates radiosensitivity under nutrient starvation alone. In the present study, effects of hypoxia and nutrient starvation on radiosensitivity were investigated using the same cell lines. METHODS: LM217 and HepG2 cells were used to examine the effects of hypoxia and nutrient starvation on cellular radiosensitivity, mTORC1 pathway including AMPK, ATM, and HIF-1α, which are known as regulators of mTORC1 activity, and glycogen storage, which is induced by HIF-1 and HIF-2 under hypoxia and promotes cell survival. RESULTS: Under hypoxia and nutrient starvation, AMPK activity and ATM expression were increased in LM217 cells and decreased in HepG2 cells compared with AMPK activity under nutrient starvation alone or ATM expression under hypoxia alone. Under hypoxia and nutrient starvation, radiosensitivity was decreased in LM217 cells and increased in HepG2 cells compared with radiosensitivity under hypoxia alone. Under hypoxia and nutrient starvation, knockdown of AMPK decreased ATM activity and increased radiation sensitivity in LM217 cells. In both cell lines, mTORC1 activity was decreased under hypoxia and nutrient starvation. Under hypoxia alone, knockdown of mTOR slightly increased ATM expression but did not affect radiosensitivity in LM217. Under hypoxia and nutrient starvation, HIF-1α expression was suppressed and glycogen storage was reduced. CONCLUSION: Our data suggest that AMPK regulates ATM expression and partially regulates radiosensitivity under hypoxia and nutrient starvation. The molecular mechanism underlying the induction of ATM expression by AMPK remains to be elucidated.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Proteínas Mutadas de Ataxia Telangiectasia/genética
Hipóxia Celular/efeitos da radiação
Meios de Cultura/metabolismo
Regulação para Baixo/genética
Neoplasias Experimentais/radioterapia
Tolerância a Radiação
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Apoptose/efeitos da radiação
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Linhagem Celular
Relação Dose-Resposta à Radiação
Regulação para Baixo/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Vetores Genéticos/genética
Células Hep G2
Seres Humanos
Neoplasias Experimentais/metabolismo
Neoplasias Experimentais/patologia
Dose de Radiação
Vírus 40 dos Símios/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Culture Media); EC 2.7.11.1 (ATM protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171229
[St] Status:MEDLINE


  6 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27779109
[Au] Autor:Pan D; Chen Y; Du Y; Ren Z; Li X; Hu B
[Ad] Endereço:Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences & Key Laboratory of Space Radiobiology of Gansu Province, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
[Ti] Título:Methylation of promoter of RBL1 enhances the radioresistance of three dimensional cultured carcinoma cells.
[So] Source:Oncotarget;8(3):4422-4435, 2017 Jan 17.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Three dimensional (3D) culture in vitro is a new cell culture model that more closely mimics the physiology features of the in vivo environment and is being used widely in the field of medical and biological research. It has been demonstrated that cancer cells cultured in 3D matrices are more radioresistant compared with cells in monolayer (2D). However, the mechanisms causing this difference remain largely unclear. Here we found that the cell cycle distribution and expression of cell cycle regulation genes in 3D A549 cells are different from the 2D. The higher levels of the promotor methylation of cell cycle regulation genes such as RBL1 were observed in 3D A549 cells compared with cells in 2D. The treatments of irradiation or 5-Aza-CdR activated the demethylation of RBL1 promotor and resulted in the increased expression of RBL1 only in 3D A549 cells. Inhibition of RBL1 enhanced the radioresistance and decreased the G2/M phase arrest induced by irradiation in 2D A549 and MCF7 cells. Overexpression of RBL1 sensitized 3D cultured A549 and MCF7 cells to irradiation. Taken together, to our knowledge, it is the first time to revealthat the low expression of RBL1 due to itself promotor methylation in 3D cells enhances the radioresistance. Our finding sheds a new light on understanding the features of the 3D cultured cell model and its application in basic research into cancer radiotherapy and medcine development.
[Mh] Termos MeSH primário: Técnicas de Cultura de Células/métodos
Metilação de DNA
Neoplasias/genética
Tolerância a Radiação
Proteína p107 Retinoblastoma-Like/genética
[Mh] Termos MeSH secundário: Células A549
Ciclo Celular/efeitos da radiação
Epigênese Genética
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Seres Humanos
Células MCF-7
Neoplasias/radioterapia
Regiões Promotoras Genéticas
Células Tumorais Cultivadas
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RBL1 protein, human); 0 (Retinoblastoma-Like Protein p107)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12647


  7 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29298329
[Au] Autor:Abou-Antoun TJ; Nazarian J; Ghanem A; Vukmanovic S; Sandler AD
[Ad] Endereço:Department of Pharmaceutical Sciences, the School of Pharmacy, Lebanese American University, Byblos, Lebanon.
[Ti] Título:Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance.
[So] Source:PLoS One;13(1):e0189711, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRß led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRß abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRß, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI tumorspheres was enhanced when sutent treatment was combined with survivin knock-down. We conclude that AI tumorspheres have a differential protein expression compared to AD cancer cells that contribute to their malignant phenotype and radio-resistance. Specific targeting of both cellular phenotypes is needed to improve outcomes in neuroblastoma patients.
[Mh] Termos MeSH primário: Adesão Celular
Neuroblastoma/patologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular
Camundongos
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Neuroblastoma/metabolismo
Neuroblastoma/radioterapia
Proteômica
Tolerância a Radiação
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Neoplasm Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189711


  8 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29320576
[Au] Autor:Srivastava P; Sarma A; Chaturvedi CM
[Ad] Endereço:Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
[Ti] Título:Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation.
[So] Source:PLoS One;13(1):e0190516, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High linear energy transfer (LET) radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator. PNKP (polynucleotide kinase/phosphatase) is an enzyme which plays important role in the non-homologous end joining (NHEJ) DNA repair pathway. It is expected that inhibition of PNKP activity may enhance the efficacy of the charged particle irradiation in the radioresistant prostate cancer cell line PC-3. To test this hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16 MeV/nucleon) and with an entrance LET of 287 kev/µm was used for the present study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity were measured by DAPI staining, nuclear ladder assay and colorimetric caspase-3method. Cell cycle arrest was determined by FACS analysis. Cell death was enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor) to treat cells as compared to that seen for PNKPi untreated cells. A low concentration (10µM) of PNKPi effectively radiosensitized the PC-3 cells in terms of reduction of dose in achieving the same survival fraction. PC-3 cells underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M phase when carbon ion irradiation was combined with PNKPi treatment. Our findings suggest that combined treatment of carbon ion irradiation and PNKP inhibition could enhance cellular radiosensitivity in a radioresistant prostate cancer cell line PC-3. The synergistic effect of PNKPi and carbon ion irradiation could be used as a promising method for carbon-ion therapy in radioresistant cells.
[Mh] Termos MeSH primário: Reparo do DNA
Polinucleotídeo 5´-Hidroxiquinase/antagonistas & inibidores
Neoplasias da Próstata/radioterapia
Tolerância a Radiação
[Mh] Termos MeSH secundário: Relação Dose-Resposta à Radiação
Seres Humanos
Masculino
Neoplasias da Próstata/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.1.78 (Polynucleotide 5'-Hydroxyl-Kinase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190516


  9 / 12617 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28463588
[Au] Autor:Judge JL; Lacy SH; Ku WY; Owens KM; Hernady E; Thatcher TH; Williams JP; Phipps RP; Sime PJ; Kottmann RM
[Ad] Endereço:a Department of Environmental Medicine, University of Rochester, Rochester, New York.
[Ti] Título:The Lactate Dehydrogenase Inhibitor Gossypol Inhibits Radiation-Induced Pulmonary Fibrosis.
[So] Source:Radiat Res;188(1):35-43, 2017 07.
[Is] ISSN:1938-5404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exposure of the lung to ionizing radiation that occurs in radiotherapy, as well as after accidental or intentional mass casualty incident can result in pulmonary fibrosis, which has few treatment options. Pulmonary fibrosis is characterized by an accumulation of extracellular matrix proteins that create scar tissue. Although the mechanisms leading to radiation-induced pulmonary fibrosis remain poorly understood, one frequent observation is the activation of the profibrotic cytokine transforming growth factor-beta (TGF-ß). Our laboratory has shown that the metabolite lactate activates latent TGF-ß by a reduction in extracellular pH. We recently demonstrated that lactate dehydrogenase-A (LDHA), the enzyme that produces lactate, is upregulated in patients with radiation-induced pulmonary fibrosis. Furthermore, genetic silencing of LDHA or pharmacologic inhibition using the LDHA inhibitor gossypol prevented radiation-induced extracellular matrix secretion in vitro through inhibition of TGF-ß activation. In the current study, we hypothesized that LDHA inhibition in vivo prevents radiation-induced pulmonary fibrosis. To test this hypothesis, C57BL/6 mice received 5 Gy total-body irradiation plus 10 Gy thoracic irradiation from a Cs source to induce pulmonary fibrosis. Starting at 4 weeks postirradiation, mice were treated with 5 mg/kg of the LDHA inhibitor gossypol or vehicle daily until sacrifice at 26 weeks postirradiation. Exposure to radiation resulted in pulmonary fibrosis, characterized by an increase in collagen content, fibrosis area, extracellular matrix gene expression and TGF-ß activation. Irradiated mice treated with gossypol had significantly reduced fibrosis outcomes, including reduced collagen content in the lungs, reduced expression of active TGF-ß, LDHA and the transcription factor hypoxia-inducible factor-1 alpha (HIF-1α). These findings suggest that inhibition of LDHA protects against radiation-induced pulmonary fibrosis, and may be a novel therapeutic strategy for radiation-induced pulmonary fibrosis.
[Mh] Termos MeSH primário: Gossipol/administração & dosagem
L-Lactato Desidrogenase/antagonistas & inibidores
Fibrose Pulmonar/imunologia
Fibrose Pulmonar/prevenção & controle
Pneumonite por Radiação/imunologia
Pneumonite por Radiação/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Citocinas/imunologia
Relação Dose-Resposta a Droga
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fibrose Pulmonar/patologia
Dose de Radiação
Pneumonite por Radiação/patologia
Proteção Radiológica/métodos
Tolerância a Radiação/efeitos dos fármacos
Protetores contra Radiação/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytokines); 0 (Radiation-Protective Agents); EC 1.1.1.27 (L-Lactate Dehydrogenase); KAV15B369O (Gossypol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1667/RR14620.1


  10 / 12617 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28463025
[Au] Autor:Chen X; Wang P; Guo F; Wang X; Wang J; Xu J; Yuan D; Zhang J; Shao C
[Ad] Endereço:a Institute of Radiation Medicine , Fudan University , Shanghai , China.
[Ti] Título:Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition.
[So] Source:Int J Radiat Biol;93(8):764-770, 2017 08.
[Is] ISSN:1362-3095
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. MATERIALS AND METHODS: A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux. In some experiments, the A549 cells were respectively transfected with LC3 small interfering RNA (siRNA), or treated with Earle's Balanced Salt Solution (EBSS). RESULTS: We found that hypoxia enhanced cell radioresistance by increasing the induction of autophagy. And after hypoxia stress, the number of mitochondria was reduced but the cellular ROS level was enhanced. It was significant that autophagy may enhance cell radioresistance by reducing ROS during hypoxic treatment. CONCLUSIONS: We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors.
[Mh] Termos MeSH primário: Autofagia/efeitos da radiação
Carcinoma Pulmonar de Células não Pequenas/patologia
Neoplasias Pulmonares/patologia
Tolerância a Radiação/efeitos da radiação
Espécies Reativas de Oxigênio/metabolismo
Hipóxia Tumoral/efeitos da radiação
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
Tamanho Mitocondrial/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Reactive Oxygen Species)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180111
[Lr] Data última revisão:
180111
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1080/09553002.2017.1325025



página 1 de 1262 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