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1.
Cancer Med ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464090

RESUMO

RIG-I is associated with the occurrence and development of many tumors. However, the role of RIG-I in radiotherapy and chemotherapy in NPC has not been reported to date. In our study, RIG-I expression was significantly reduced in chemoradiotherapy-resistant NPC tissues and cells compared with that in therapy-sensitive tissues and cells. RIG-I expression increased in nonresistant NPC cells, including CNE1 and CNE2, in a dose-dependent manner with increasing chemotherapy drug concentration or radiotherapy dose. RIG-I overexpression promoted radiotherapy and chemotherapy sensitivity in NPC cells, leading to cellular apoptosis and increased expression of the proapoptotic factors BAX and caspase-3. Similarly, RIG-I knockdown in NPC cells promoted chemoradiotherapy resistance and reduced apoptosis. Analysis of microarray data indicated that the expression of IFN/JAK2 and endoplasmic reticulum (ER) stress response markers, such as JAK2, STAT1, IRF9, IFNB1, IRF3, p-IRF3, XBP1, ATF6, IFIT2, and ISG15, was inhibited in chemoradiotherapy-resistant cells compared with that in sensitive cells. Conversely, activation of IFN/JAK2 and ER stress response pathways in NPC cells reduced paclitaxel resistance and increased apoptosis. RIG-I promotes IFN/JAK2 and ER stress response-mediated apoptosis to inhibit chemoradiation resistance in nasopharyngeal carcinoma.

2.
Kaohsiung J Med Sci ; 35(8): 474-485, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271505

RESUMO

Radiation therapy is the primary treatment for primary nasopharyngeal carcinoma (NPC). The aim of this study is to identify the effect of the Numb/Notch signaling pathway on radiation sensitivity in human NPC cells. NPC tissues and normal nasopharyngeal tissues were collected. To evaluate the regulatory effects of the Numb/Notch signaling pathway, NPC cells were subjected to radiotherapy and various doses of the Numb/Notch signaling pathway inhibitor gamma secretase inhibitor (GSI). Next, the expression of Notch and Numb proteins was determined in NPC tissues and normal nasopharyngeal tissues, and the correlation of Notch and Numb protein expression with the clinicopathological features of NPC tissues was analyzed. Then, the effect of radiotherapy on NPC cell survival rate, survival fraction, apoptosis rate, proliferation, migration, and invasion as well as Numb/Notch signaling pathway-related molecules was detected. The results demonstrated that the Numb/Notch signaling pathway was activated in NPC tissues. Following treatment with radiotherapy and GSI, the Numb/Notch signaling pathway was inhibited. In addition, the NPC cell survival rate, survival fraction, cell proliferation, migration, and invasion were decreased, whereas the colony number and apoptosis rate were increased. Following radiotherapy and GSI treatment, Numb expression was increased, whereas Notch1, Hes1, Jagged1, and c-Myc expression was decreased. However, the greatest difference was noted upon treatment with radiotherapy +15 µM GSI. The results reported in this study suggest that a high dose of the inhibitor of the Numb/Notch signaling pathway GSI increased the radiation sensitivity in human NPC cells.

3.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31092699

RESUMO

Introduction: The treatment strategy for low-grade gliomas (LGGs) is still controversial, and there are no standardized criteria to predict the prognosis of patients with LGGs. Magnetic resonance imaging (MRI) is a routine test for preoperative diagnosis for LGG and can reflect the destructive features for the tumor. In the present study, we aimed to explore the relationship between the MRI features and prognosis in patients with LGG.Methods: Clinical data of 80 patients with pathologically proved LGGs between January 2010 and December 2016 were analyzed retrospectively. MRI features were classified as contrast enhancement pattern (focal enhancement, diffuse enhancement and ring-like enhancement), necrosis and cysts based on the preoperative MR images. Kaplan-Meier method and multivariate analysis were performed on the data by SPSS software to explore the prognostic significance of MRI features.Results: Patients with cystic LGG had a significantly longer 5-year progression-free survival (PFS) than that with no cyst (90.9 ± 8.7 vs 65.7 ± 9.1%, P=0.045). Multivariate analysis further verified cyst as an independent prognosis factor for PFS (P=0.027, hazard ratio [HR] = 0.084). Additionally, patients with ring-like enhancement exhibited significantly longer 5-year PFS time in the Kaplan-Meier survival curves (100 vs 67.2 ± 7.7%, P=0.049). There was no significant difference in PFS and overall survival (OS) between patients with or without necrosis.Conclusion: Our study suggests that cyst formation and ring-like enhancement on preoperative MR images can be useful to predict a favorable prognosis in patients with LGGs.

4.
Oncotarget ; 8(59): 100657-100667, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29246010

RESUMO

Biliary tract cancer (BTC) is the second common cancer in liver cancer. Chemotherapy is the mainstay of treatments for patients with advanced or metastatic disease, while fluorouracil (FU)-based and gemcitabine (GEM)-based treatments are most widely applied. This NMA aimed to figure out whether the addition of platinum (PLA) and target agents (TAR) can influence the efficacy and safety of standard chemotherapy. Network meta-analysis (NMA) was conducted based on the records from PubMed, Embase and Cochrane. Eligible data was extracted from available qualified trials and outcomes. Software R 3.2.3 and STATA 13.0 were used to conduct the Bayesian NMA, calculating odds ratios (ORs) and hazard ratios (HRs) with 95% credible interval (CrI) to evaluate different treatments.Almost all treatments were superior to best supportive care (BSC) and FU in terms of 1-OS, 2-OS and 1-PFS. GEM+PLA and GEM+PLA+TAR exhibited better efficacy than most treatments in 1-OS, 2-OS and 1-PFS, and yielded better results than BSC and GEM+FU in terms of 2-PFS. Most drug-containing treatments reported higher overall response rate (ORR) than BSC. GEM and GEM+FU were associated with a higher risk of neutropenia and thrombocytopenia compared to FU, FU+PLA and GEM+PLA. No statistical difference was detected in terms of nausea and vomiting.GEM+PLA and GEM+PLA+TAR were both efficacious and were associated with fewer adverse events. In conclusion, the addition of PLA can significantly improve the efficacy of FU and GEM-based treatments, and the addition of TAR to GEM+PLA can contribute to further improvement, but with a mild increase of adverse events.

5.
Onco Targets Ther ; 9: 3633-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27382301

RESUMO

OBJECTIVE: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC.

6.
Tumour Biol ; 37(7): 9875-86, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26812694

RESUMO

The objective of this study was to investigate the expression, proliferation, and apoptosis function of long-chain non-coding RNA maternally expressed gene 3 (MEG3) and antisense non-coding RNA at the INK4 locus (ANRIL) in gallbladder cancer (GBC) tissues. GBC tissues and adjacent normal samples were collected from 84 patients from January 2008 to June 2010. Empty vector, pcDNA-MEG3, and pcDNA-ANRIL vectors were transfected into GBC-SD and QBC939 cells. An MTT assay, real-time quantitative polymerase chain reaction (RT-qPCR), flow cytometry, Western blotting, and immunohistochemistry were applied. The effects of MEG3 and ANRIL were also verified in mice. Compared with normal tissues, the expression of MEG3 was significantly lower in GBC tissues, whereas the expression of ANRIL was significantly higher (both P < 0.05). The overexpression of MEG3 and underexpression of ANRIL were significantly associated with GBC prognosis (both P < 0.05). The expressions of MEG3 and ANRIL were higher in pcDNA-MEG3 and pcDNA-ANRIL-transfected cells than in empty vector-transfected cells in vitro (both P < 0.05). Most of the pcDNA-MEG3-transfected cells were in the G0-G1 phase, which showed reduced cell activity and clone counts and increased p53 and decreased cyclin D1, whereas the pcDNA-ANRIL-transfected cells were mostly in the S phase and showed contrasting behavior. Mice injected with pcDNA-MEG3-transfected cells had smaller and lighter tumors, decreased ki-67 levels, and increased caspase 3 levels, whereas those injected with pcDNA-ANRIL showed contrasting results (all P < 0.05). MEG3 can inhibit the proliferation of GBC cells and promote apoptosis, whereas ANRIL can improve the proliferation of gallbladder cells and inhibit apoptosis. Collectively, our results suggest that therapeutic strategies directed toward upregulating MEG3 and downregulating ANRIL may be clinically relevant for the inhibition of GBC deterioration.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias da Vesícula Biliar/genética , RNA Longo não Codificante/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proliferação de Células , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Lipids Health Dis ; 14: 44, 2015 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-25980409

RESUMO

BACKGROUND: Recent studies implicate adipokines in the pathogenesis of inflammatory diseases, including psoriasis. In this study we evaluated the significance of serum resistin levels in psoriasis patients using a meta-analysis approach.223 METHODS: Relevant articles were retrieved by searching the following English and Chinese databases: Cochrane Library, PubMed, Springer Link, Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI). The retrieved studies were subjected to a thorough screening procedure to identify case-control studies that contained the required data. Data was extracted from each study and Version 12.0 STATA statistical software was employed for statistical analyses. RESULTS: Nine case-control studies, containing 421 psoriasis patients and 348 healthy controls, were included in this study. The major result of the meta-analysis revealed a statistically significant association between serum resistin levels and psoriasis (SMD=2.22, 95%CI: 1.14-3.29, P<0.001). Subgroup analysis based on ethnicity showed that, compared to the healthy controls, serum resistin levels were markedly higher in psoriasis patients in both Asian and Caucasian populations (Asians: SMD=3.27, 95%CI=1.62~4.91, P<0.001; Caucasians: SMD=0.91, 95%CI=0.28~1.54, P<0.001). CONCLUSIONS: Based on our results, we conclude that serum resistin level in psoriasis patients is higher than healthy controls, and raises the possibility that elevated serum resistin levels may be a novel diagnostic marker in psoriasis and may predict the occurrence of co-morbidities in psoriasis patients.


Assuntos
Psoríase/sangue , Resistina/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/etiologia
8.
Tumour Biol ; 35(3): 2529-35, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24254302

RESUMO

BACKGROUND: Published data regarding the association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. MATERIALS AND METHODS: We systematically searched PubMed, Embase, and Web of Science with a time limit of August 19, 2013. Summary odds ratios (ORs) with 95% CIs were used to assess the strength of association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility using random-effects model. RESULTS: A total of eight case-control studies including 2,597 cases and 3,063 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility for GG vs TT (OR = 1.00, 95% CI = 0.73-1.36, p = 0.00 for heterogeneity), TG vs TT (OR = 1.17, 95% CI = 0.88-1.55, p = 0.00 for heterogeneity), the dominant model GG + TG vs TT (OR = 1.21, 95% CI = 0.91-1.60, p = 0.00 for heterogeneity) nor the recessive model GG vs TG + TT(OR = 0.95, 95% CI = 0.75-1.20, p = 0.02 for heterogeneity). In subgroup analysis, no significant associations were found in the Asian or Caucasian populations. CONCLUSION: This meta-analysis suggested that the APE1 Asp148Glu polymorphism was not associated with colorectal cancer susceptibility among Asians or Caucasians.


Assuntos
Neoplasias Colorretais/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Humanos , Razão de Chances
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