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1.
Zhonghua Nan Ke Xue ; 25(6): 566-571, 2019 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32223095

RESUMO

Transurethral enucleation of the prostate allows more complete excision of the proliferative glands at the anatomical level, and has its unique advantages over the traditional surgical procedures, such as better results of surgery, lower recurrence rate, and higher satisfaction of the patients. At present, transurethral laser enucleation of the prostate has a limited application in many grass-root hospitals for the high price of laser and plasma equipment and a high incidence rate of postoperative urinary incontinence. In this context, monopolar transurethral enucleation and resection of the prostate (mTUERP) has come into the attention of clinicians, which can be performed with the equipment for transurethral resection of the prostate (TURP) and may become a real alternative of TURP. This paper presents an overview on the development and present status of mTUERP.


Assuntos
Próstata/cirurgia , Ressecção Transuretral da Próstata/métodos , Humanos , Masculino , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Incontinência Urinária/etiologia
2.
Tumour Biol ; 35(6): 5481-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24532432

RESUMO

Altered expression of transmembrane protease/serine 4 (TMPRSS4) is observed in various types of human cancers. However, the clinical significance of TMPRSS4 expression in gallbladder cancer (GBC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of TMPRSS4 in GBC. The levels of TMPRSS4 mRNA and protein in GBC tissues and adjacent noncancerous tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry. To investigate the correlations between TMPRSS4 and the clinicopathological features of GBC, the expression of TMPRSS4 in 97 patients with GBC were detected by immunohistochemistry. The correlation of TMPRSS4 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of TMPRSS4 mRNA and protein in GBC tissues were both significantly higher than those in adjacent noncancerous tissues. Immunohistochemical staining revealed that high TMPRSS4 expression was closely correlated with tumor size (P=0.032), histological grade (P=0.002), pathologic T stage (P=0.005), clinical stage (P=0.013), and lymph node metastasis (P=0.003). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of TMPRSS4 resulted in a significantly poor prognosis of GBC patients. Multivariate analysis showed that the status of TMPRSS4 expression was an independent prognostic factor for GBC patients. Our results showed that TMPRSS4 plays a key role in GBC and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in GBC.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Proteínas de Membrana/fisiologia , Serina Endopeptidases/fisiologia , Adulto , Idoso , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/análise , Serina Endopeptidases/análise , Serina Endopeptidases/genética , Taxa de Sobrevida
3.
Front Microbiol ; 15: 1312286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414777

RESUMO

Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+-N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3--N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.

4.
Lab Invest ; 93(7): 844-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23752129

RESUMO

M2-polarized tumor-associated macrophages (TAMs) are key regulators of the link between inflammation and cancer. A negative correlation between infiltration intensity of M2-polarized TAMs and prognosis of pancreatic cancer has been reported. Epithelial-mesenchymal transition (EMT) is an important biological process in the progression of primary tumors toward metastasis. Inflammation-induced EMT has been previously shown, therefore, we hypothesized M2-polarized TAMs could induce EMT in pancreatic cancer. Toll-like receptor 4 (TLR4) signaling has an active role in tumor progression during chronic inflammation and the receptor is primarily expressed on macrophages. Activation of TLR4 on M2-polarized TAMs stimulates an increase in the cytokine interleukin-10 (IL-10); consequently, another aim was to investigate the potential role of TLR4/IL-10 signaling in the EMT of pancreatic cancer. Treatment with IL-4 (20 ng/ml) for 24 h successfully induced the polarization of macrophage cell line RAW 264.7 to M2 phenotype, IL-10(high), IL-12(low), and IL-23(low), and high expression of CD204 and CD206. A coculture system allowed investigation of the roles of M2-polarized TAMs and TLR4/IL-10 signaling in the EMT of Panc-1 and BxPC-3 pancreatic cancer cell lines. Our results showed that coculture with M2-polarized TAMs increased fibroblastic morphology, upregulated mesenchymal markers vimentin and snail at the mRNA and protein levels, and increased proliferation, migration, and metalloproteinase (MMP)2 and MMP9 proteolytic activity in pancreatic cancer cells. Simultaneously, coculture with M2-polarized TAMs decreased the expression of the epithelial marker E-cadherin. Coculture with pancreatic cancer cells increased TLR4 mRNA and protein expression in M2-polarized TAMs. Application of TLR4 siRNA and neutralizing antibodies against TLR4 and IL-10 markedly inhibited E-cadherin reduction and the upregulation of snail and vimentin. Furthermore, activation of TLR4 signaling by lipopolysaccharide profoundly increased the EMT of pancreatic cancer cells. In conclusion, M2-polarized TAMs promoted EMT in pancreatic cancer cells partially through TLR4/IL-10 signaling, suggesting novel therapeutic strategies and enhancing our understanding of M2-polarized TAMs.


Assuntos
Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal , Interleucina-10/metabolismo , Macrófagos/fisiologia , Neoplasias Pancreáticas/patologia , Receptor 4 Toll-Like/metabolismo , Adenocarcinoma/imunologia , Adenocarcinoma/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Fibroblastos/patologia , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais
5.
Tumour Biol ; 34(2): 853-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23242609

RESUMO

Accumulating evidence for overexpression of FOXC1 in various types of human cancer suggests that it plays a key role in tumor biology. However, little is known about the function of FOXC1 in pancreatic ductal adenocarcinoma (PDA). This study was to investigate the expression profile of FOXC1 in PDA and its clinical significance. We detected the expression profile of FOXC1 mRNA and protein in PDA tissue and in corresponding normal tissue by quantitative reverse-transcriptase polymerase chain reaction and western blotting. Immunohistochemistry was also used in the detection of FOXC1 protein expression. The clinicopathological implications of these proteins were analyzed statistically. Survival analysis was performed to assess prognostic significance. FOXC1 mRNA was overexpressed in PDA tissue when compared with corresponding normal tissue, so was FOXC1 protein. The overexpression of FOXC1 was significantly associated with the degree of clinical stage (p < 0.001), histological differentiation (p = 0.002), and lymph node metastases (p < 0.001). Survival analysis revealed that overexpression of FOXC1 is associated with a poorer prognosis. These observations suggest that FOXC1 plays a key role in PDA and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in PDA.


Assuntos
Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
6.
Int J Cancer ; 131(11): 2487-98, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22438101

RESUMO

Our study shows that coadministration of curcumin and an orally bioactive alkylphospholipid perifosine results in a significant increase in colorectal cancer cell apoptosis and a marked inhibition of cell growth both in vitro and in vivo. This novel combinatorial regimen leads to changes of multiple cell signaling pathways including inactivation of Akt and nuclear factor-κB as well as activation of c-Jun N-terminal kinases and endoplasmic reticulum stress. Further, perifosine and curcumin synergistically increase intracellular level of reactive oxygen species and ceramide, and downregulate the expression of cyclin D1 and Bcl-2 in colorectal cancer cells. These changes at molecular level together account for the cancer cell apoptosis and growth inhibition. We conclude that perifosine sensitizes colorectal cancer cells to curcumin by modulating multiple signaling pathways. Adding perifosine with curcumin may represent an effective therapy regimen against colorectal cancers, and possible other aggressive tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Curcumina/farmacologia , Fosforilcolina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células CACO-2 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ceramidas/metabolismo , Neoplasias Colorretais/patologia , Curcumina/administração & dosagem , Ciclina D1/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Retículo Endoplasmático/efeitos dos fármacos , Feminino , Células HCT116 , Células HT29 , Humanos , Proteínas I-kappa B/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos SCID , Complexos Multiproteicos , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilcolina/administração & dosagem , Fosforilcolina/farmacologia , Proteínas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Zhonghua Nan Ke Xue ; 18(7): 635-8, 2012 Jul.
Artigo em Zh | MEDLINE | ID: mdl-22994052

RESUMO

For lack of the biomarker, early diagnosis of prostate cancer is often difficult. Caveolin-1 (Cav-1) is an important oncogene and a major structural coat protein of caveolae, which is involved in multiple cellular functions including molecular transport, cell adhesion, and signal transduction, as well as in the development and progression of prostate cancer. Cav-1 is secreted as a biologically active molecule that promotes cell survival and angiogenesis within the tumor microenvironment, and is overexpressed in the metastatic and primary sites of human prostate cancer. Secreted Cav-1 can be detected in the peripheral blood, and its expression level has an indicative value in the diagnosis and prognosis of prostate cancer. This review focuses on the structure and biological characteristics of Cav-1 and its correlation with prostate cancer.


Assuntos
Biomarcadores Tumorais , Caveolina 1 , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico
8.
Pancreas ; 48(7): 904-912, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31268976

RESUMO

OBJECTIVES: Tumor-associated macrophages are dominant players in establishing the inmmunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC). Immune checkpoint inhibitor monotherapy has achieved limited clinical effectiveness. To date, the interaction of macrophages and checkpoint regulators and their correlation with clinicopathologic characteristics in PDAC have been largely unavailable. METHODS: Macrophages and immune checkpoint expression were assessed by immunohistochemistry from 80 PDAC samples. Clinicopathologic features and the prognostic value of each marker were evaluated. In vitro changes in the expression of immune markers in cocultured macrophages and PDAC cells were detected by Western blot and immunosorbance assays. RESULTS: The macrophages marker CD163 and the checkpoint marker programmed death-ligand 1 (PD-L1) remained as the independent prognostic factors for overall survival (hazard ratio, 2.543; P = 0.017 and hazard ratio, 2.389; P = 0.021). Furthermore, integrated analysis of CD163 and PD-L1 served as more optimal indicators of survival (P = 0.000). In vitro coculture of macrophages and PDAC cells significantly increased the expression of CD163 and PD-L1, compared with monocultured counterpart (P < 0.05). CONCLUSIONS: Combined analysis of CD163 and PD-L1 was enhanced indicators of survival in PDAC patients. The interaction of macrophages and immune checkpoints implied the value of the combination therapy.


Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Carcinoma Ductal Pancreático/imunologia , Macrófagos/imunologia , Neoplasias Pancreáticas/imunologia , Receptores de Superfície Celular/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Receptores de Superfície Celular/metabolismo , Microambiente Tumoral/imunologia
9.
Sci Rep ; 7(1): 4223, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28652617

RESUMO

CD146, also known as melanoma cell adhesion molecule, was initially identified as a marker of melanoma progression and metastasis. Recently many clinical studies investigated overexpression of CD146 predict poor prognosis of solid tumor, however, the results was inconclusive, partly due to small numbers of patients included. This present meta-analysis was therefore performed utilizing the results of all clinical studies concerned to determine the prognostic value of CD146 expression in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. In this meta-analysis, 12 studies involving 2,694 participants were included, and we drew the conclusion that strong significant associations between CD146 expression and all endpoints: overall survival (OS) [hazard ratio (HR) = 2.496, 95% confidence interval (95% CI) 2.115-2.946], time to progression (TTP) (HR = 2.445, 95% CI 1.975-3.027). Furthermore, the subgroup analysis revealed that the associations between CD146 overexpression and the outcome endpoints (OS or TTP) were significant in Mongoloid patients and Caucasian patients, as well in patients with lung cancer and digestive system cancer. In conclusion, these results showed that high CD146 was associated with poor survival in human solid tumors. CD146 may be a valuable prognosis predictive biomarker; nevertheless, whether CD146 could be a potential therapeutic target in human solid tumors needs to be further studied.


Assuntos
Biomarcadores Tumorais/análise , Antígeno CD146/análise , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias do Sistema Digestório/diagnóstico , Neoplasias do Sistema Digestório/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Melanoma/diagnóstico , Melanoma/metabolismo , Prognóstico , Análise de Sobrevida
10.
Oncotarget ; 8(14): 22800-22810, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28206952

RESUMO

Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm. We aim to explore the anti-HCC activity by a natural prenylflavonoid icaritin. Icaritin was cytotoxic and pro-apoptotic when added to established (HepG2, KYN-2 and Huh-7 lines) and primary human HCC cells. At the signaling level, icaritin inhibited sphingosine kinase 1 (SphK1) activity in HCC cells, which led to pro-apoptotic ceramide production and JNK1 activation. SphK1 inhibition or silence (by shRNA/microRNA) mimicked icaritin-mediated cytotoxicity, and almost nullified icaritin's activity in HepG2 cells. Reversely, exogenous over-expression of SphK1 sensitized icaritin-induced HepG2 cell apoptosis. In vivo, oral administration of icaritin dramatically inhibited HepG2 xenograft growth in SCID mice. Further, SphK1 activity in icaritin-treated tumors was largely inhibited. In summary, icaritin exerts potent anti-HCC activity in vitro and in vivo. SphK1 inhibition could be the primary mechanism of its actions in HCC cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/enzimologia , Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Ceramidas/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Sci Rep ; 6: 33658, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27645103

RESUMO

Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS). In this meta-analysis, 16 studies involving 2,569 participants were included, and we drew the conclusion that TROP2 overexpression was significantly associated with poor OS (pooled HR = 1.896, 95% CI = 1.599-2.247, P < 0.001) and short DFS (pooled HR = 2.336, 95% CI = 1.596-3.419, P < 0.001). Furthermore, the subgroup analysis revealed that the associations between TROP2 overexpression and the outcome endpoints (OS or DFS) were significant in in patients with female genital system neoplasms, as well in gastrointestine neoplasms. In addition, subgroup analysis found no difference HR across populations of different descent.Taken together, TROP2 overexpression was associated with poor survival in human solid tumors. TROP2 may be a valuable prognosis predictive biomarker and a potential therapeutic target in human solid tumors.


Assuntos
Antígenos de Neoplasias/genética , Biomarcadores Tumorais , Moléculas de Adesão Celular/genética , Expressão Gênica , Neoplasias/genética , Neoplasias/mortalidade , Humanos , Neoplasias/diagnóstico , Prognóstico , Viés de Publicação , Análise de Sobrevida
12.
Addict Behav ; 42: 1-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25462646

RESUMO

OBJECTIVE: Internet addiction is one of the most common problems among adolescents and effective treatment is needed. This research aims to test the effectiveness and underlying mechanism of multi-family group therapy (MFGT) to reduce Internet addiction among adolescents. METHOD: A total of 92 participants consisting of 46 adolescents with Internet addiction, aged 12-18years, and 46 their parents, aged 35-46years, were assigned to the experimental group (six-session MFGT intervention) or a waiting-list control. Structured questionnaires were administered at pre-intervention (T1), post-intervention (T2) and a three-month follow-up (T3). RESULTS: There was a significant difference in the decline both in the average score and proportion of adolescents with Internet addiction in MFGT group at post-intervention (MT1=3.40, MT2=2.46, p<0.001; 100 versus 4.8%, p<0.001) maintained for three months (MT3=2.06, p<0.001; 100 versus 11.1%, p<0.001). Reports from both adolescents and parents were significantly better than those in the control group. Further explorations of the underlying mechanisms of effectiveness based on the changed values of measured variables showed that the improvement in adolescent Internet use was partially explained by the satisfaction of their psychological needs and improved parent-adolescent communication and closeness. CONCLUSIONS: The six-session multi-family group therapy was effective in reducing Internet addiction behaviors among adolescents and could be implemented as part of routine primary care clinic services in similar populations. As family support system is critical in maintaining the intervention effect, fostering positive parent-adolescent interaction and addressing adolescents' psychological needs should be included in preventive programs for Internet addiction in the future.


Assuntos
Comportamento Aditivo/terapia , Terapia Familiar/métodos , Internet , Relações Pais-Filho , Pais , Psicoterapia de Grupo/métodos , Adolescente , Adulto , Comportamento Aditivo/psicologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Neural Regen Res ; 10(3): 438-44, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25878593

RESUMO

Previous studies have shown that up-regulation of transforming growth factor ß1 results in neuroprotective effects. However, the role of the transforming growth factor ß1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1ß mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

14.
Cancer Biol Ther ; 16(1): 34-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25692620

RESUMO

The colorectal cancer is the leading contributor of cancer-related mortality. Mammalian target of rapamycin (mTOR), existing in 2 complexes (mTORC1/2), is frequently dysregulated and constitutively activated in colorectal cancers. It represents an important drug target. Here we found that INK-128, the novel ATP-competitive kinase inhibitor of mTOR, blocked both mTORC1 and mTORC2 activation in colorectal cancer cells (both primary and transformed cells). The immunoprecipitation results showed that the assembly of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-Sin1 association) was also disrupted by INK-128. INK-128 inhibited colorectal cancer cell growth and survival, and induced both apoptotic and non-apoptotic cancer cell death. Further, INK-128 showed no effect on Erk/MAPK activation, while MEK/Erk inhibition by MEK-162 enhanced INK-128-induced cytotoxicity in colorectal cancer cells. Meanwhile, INK-128 downregulated Fascin1 (FSCN1)/E-Cadherin expressions and inhibited HT-29 cell in vitro migration. In vivo, daily INK-128 oral administration inhibited HT-29 xenograft growth in mice, which was further enhanced by MEK-162 administration. Finally, we found that INK-128 sensitized 5-fluorouracil-(5-FU)-mediated anti-HT-29 activity in vivo and in vitro. Thus, our preclinical studies strongly suggest that INK-128 might be investigated for colorectal cancer treatment in clinical trials.


Assuntos
Antineoplásicos/farmacologia , Benzoxazóis/farmacologia , Neoplasias Colorretais/metabolismo , Complexos Multiproteicos/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Benzoxazóis/administração & dosagem , Caderinas/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Fluoruracila/farmacologia , Células HT29 , Humanos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Proteínas dos Microfilamentos/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
15.
World J Gastroenterol ; 10(21): 3201-4, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15457575

RESUMO

AIM: To study the pathway of apoptosis in chronic liver disease and the role of mitochondria in programmed cell death. METHODS: Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied. The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2, Bcl-x(L), Bcl-2 alpha were studied immunohistochemically by SP method. Specimens from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for their ultramicrostructures with special attention to their mitochondrial changes. Specimens from 3 normal adults (demised in traffic accidents) were used as control. RESULTS: The expression of proapoptotic proteins (Fas, FasL, Bax) in hepatocytes was significantly higher in the chronic hepatitis group than in the cirrhosis group (P<0.001). In the study of ultramicrostructure 364 hepatocytes were examined, from 12 cases of chronic hepatitis (including 10 mild cases, 1 moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes were found with various kinds of destruction in their mitochondria. Rupture of the outer membrane of mitochondria and the leakage of matrix from the intermembrane space were definitely demonstrated. The ultramicrostructural changes of mitochondria in the chronic hepatitis group were statistically higher than that in normal adults control group (chi(2)=4.32, P<0.05). CONCLUSION: The result of the study was in support of the current view that the apoptotic process in chronic hepatitis patients were largely along the intrinsic pathway (mitochondrial pathway), given that the intrinsic and extrinsic pathways could interlinked (converged) at some point on their progression, also it is impossible at present to exclude the possibility that the two pathways could be chosen by hepatocytes in parallel simultaneously.


Assuntos
Apoptose/fisiologia , Hepatite Crônica/patologia , Fígado/patologia , Proteína Ligante Fas , Hepatite Crônica/fisiopatologia , Humanos , Imuno-Histoquímica , Fígado/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Microscopia Eletrônica , Mitocôndrias/fisiologia , Mitocôndrias/ultraestrutura , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2 , Receptor fas/metabolismo
16.
Zhonghua Gan Zang Bing Za Zhi ; 12(5): 290-2, 2004 May.
Artigo em Zh | MEDLINE | ID: mdl-15161506

RESUMO

OBJECTIVE: To explore the effect and mechanism on HBV replication in C gene truncated mutant. METHODS: Protein expression of C gene truncated vector and wild C gene vector were assay by SDS-PAGE Western blot. Constructed C gene truncated expression vector was cotransfected with wild HBV genome; virus load was detected by PCR in the culture medium and the cell. The formation of core particle was assay by Native western blot. RESULTS: The recombinant vectors can efficiently express. Virus load of the cotransfected group by pcDNA3-deltaC and adwR9 was lower than that of control group in the culture medium and the cell. Protein band of the co-expressed group by pcDNA3-deltaC and pcDNA3-C showed slightly weaker than that of the co-expressed group by pcDNA3 and pcDNA3-C. CONCLUSION: C gene truncated mutant could interfere with the formation of core particle and reduce of HBV replication


Assuntos
Terapia Genética , Hepatite B/terapia , Proteínas do Core Viral/genética , Linhagem Celular , Humanos , Mutação , Transfecção , Replicação Viral
17.
Zhonghua Gan Zang Bing Za Zhi ; 11(6): 344-6, 2003 Jun.
Artigo em Zh | MEDLINE | ID: mdl-12837212

RESUMO

OBJECTIVE: To evaluate the possibility of hepatitis B virus (HBV) as a vector in liver-targeting gene therapy. METHODS: A fragment containing the small envelope gene of HBV was replaced with the reporter gene green fluorescent protein (GFP) to construct the recombinant HBV vector, which was transfected into HepG2 cells with liposome. The expression of GFP was observed with fluorescence microscope. The HBV cccDNA was testified using semi-nest PCR. The viral particles of the recombinant HBV in culture medium were detected by PCR as well as Southern blot. RESULTS: The HBV vector carrying the interesting gene of GFP could express the functional protein in the transfected hepatocytes. However, the recombinant HBV vector was replication-deficient, which could not be packed and replicated in the hepatocytes to secrete mature recombinant HBV particles carrying the interesting gene of GFP when transfected solely but could when cotransfected with the recombinant and helper construct which lacked part of 5'-proximal HBV RNA packaging signal epsilon. CONCLUSION: It is possible that HBV is reconstructed as a liver-targeting vector for gene therapy.


Assuntos
Transformação Celular Viral , Terapia Genética , Vírus da Hepatite B/genética , Hepatócitos/virologia , Células Cultivadas , Técnicas de Transferência de Genes , Genes Reporter , Terapia Genética/métodos , Vetores Genéticos/genética , Vetores Genéticos/fisiologia , Vírus da Hepatite B/fisiologia , Hepatócitos/citologia , Humanos , Fígado/citologia , Fígado/virologia , Proteínas Recombinantes/genética , Transfecção , Replicação Viral
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 26(2): 131-2, 143, 2002 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16104180

RESUMO

It's known to all that the refractory ascites treatment has so far been a very difficult clinical problem. We have extracted much experience from the practical techniques used in the refractory ascites treatments of more than 1,000 cases, and have developed the ascites ultrafiltration & concentration therapeutic instrument--FSCLZLY-A. The clinical applications show that it is very effective. Its effective rate is about 72.08%. Therefore, it is a very useful and important medical device for refractory ascites, for the improvement of renal function, and for the prevention of the infection of abdominal cavity.


Assuntos
Ascite/terapia , Ultrafiltração/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrafiltração/métodos
19.
J Exp Clin Cancer Res ; 32: 105, 2013 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-24370277

RESUMO

BACKGROUND: Numerous studies have yielded inconclusive results regarding the relationship between anti-apoptotic protein Bcl-2 expression and the sensitivity to chemotherapy in the patients with breast cancer. The purpose of the current study was therefore to elaborate their relationship. METHODS, FINDINGS: A total of 23 previously published eligible studies involving 2,467 cases were identified and included in this meta-analysis. Negative Bcl-2 expression was associated with good chemotherapy response in breast cancer patients (total objective response [OR]: risk ratio [RR] = 1.16, 95% confidence interval [CI] = 1.02-1.32, p = 0.026; total complete response [CR]: RR = 1.67, 95% CI = 1.24-2.24, p = 0.001; pathological CR: RR = 1.92, 95% CI = 1.38-2.69, p < 0.001). In further stratified analyses, this association remained for sub-groups of response in neoadjuvant chemotherapy setting, especially pathological CR. Besides, negative Bcl-2 expression was significantly associated with good OR and pathological CR in anthracycline-based chemotherapy subgroup. Furthermore, there were significant links between negative Bcl-2 expression and taxane-based chemotherapy with pathological CR, but not OR. CONCLUSION: The results of the present meta-analysis suggest that Bcl-2 expression is a predictive factor for chemotherapy sensitivity in breast cancer patients. They could also potentially benefit further clinical treatment for breast cancers.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Humanos , Terapia Neoadjuvante , Taxoides/uso terapêutico , Resultado do Tratamento
20.
Nutrition ; 28(5): 504-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22178002

RESUMO

OBJECTIVE: There is substantial evidence that the low intake of fruit and vegetables (FV) is a major risk factor for many nutrition-related non-communicable diseases. The purpose of our study was to assess FV consumption and the variables that influence FV consumption among Chinese people age 60 and older. METHODS: Twenty-four-hour dietary recall data from the 1991, 1993, 1997, 2000, 2004, 2006, and 2009 China Health and Nutrition Surveys were used to collect the FV intake and sociodemographic variables examined in this article. Data were analyzed using t tests, χ(2) tests, and logistic regression. RESULTS: Between 1991 and 2009, elderly Chinese adults experienced an improvement in dietary FV intake. The FV consumption increased from 325.7 g/d in 1991 to 379.0 g/d in 2009. During this 18-y period, the proportion of daily consumers increased from 11.0% to 32.5% for fruit and remained over 95% for vegetables. Age, gender, educational attainment, community, activity level, marital status, and drinking were significantly associated with FV consumption. CONCLUSION: The findings of this study indicated that FV intake among elderly adults in China was lower than the minimum of 400 g/d recommended by the World Health Organization. Greater public health efforts and approaches are needed to promote FV consumption in elderly Chinese adults.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar , Frutas , Verduras , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas , Povo Asiático , Índice de Massa Corporal , China , Análise por Conglomerados , Escolaridade , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Inquéritos Nutricionais , População Rural , Fumar , Fatores Socioeconômicos , Inquéritos e Questionários , População Urbana
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