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Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus-mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells. Additionally, APOC1 silencing decreased survivin, phospho-Rb, and p21 levels and increased cleaved caspase-3 expression. These data supported the procarcinogenic effects of APOC1 in the pathogenesis of PCa and suggested that targeting APOC1 may have applications in the treatment of PCa.
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OBJECTIVE: Genetic polymorphisms in ALDH2 and C12orf30 genes have been reported to increase the risk of developing esophageal squamous cell carcinoma (ESCC). This study aims to investigate the relationship between ALDH2 rs671 and c12orf30 rs4767364 polymorphisms in the chromosome 12q24 gene, and risk and prognosis of individuals developing esophageal cancer (ESCC) in Xinjiang Kazak and Han populations. METHODS: The case group consisted of 127 ESCC patients. The control group comprised of 125 healthy individuals. Subjects that were recruited all come from Xinjiang province. TaqMan and the Hardy-Weinberg equilibrium were the main methods employed to detect and examine the distribution of genotypes of rs671 and rs4767364. RESULTS: The genotype frequencies of ALDH2 rs671 between the Kazak case and control groups were statistically significant, while no significant difference was observed between the Han case and control groups (P>.05). Moreover, ALDH2 rs671 (G>A) was associated with poor prognosis of ESCC in both Kazak and Han populations, and c12orf30 rs4767364 (A>G) was also connected with poor prognosis of ESCC in Kazak but not in Han population. CONCLUSION: In the chromosome 12q24 locus, ALDH2 rs671 (G>A) is related to the susceptibility to ESCC in Kazak populations, and it is also associated with poor prognosis of EC in Kazak and Han populations. Furthermore, c12orf30 rs4767364 (A>G) may be correlated with poor ESCC prognosis in Kazak population.
Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença/genética , Idoso , Povo Asiático/estatística & dados numéricos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , PrognósticoRESUMO
This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4+/CD8+ T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4+T cells and CD8+T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates of Treg/CD4+T/CD8+T cells were decreased in the EBI3 mimics group, but the EBI3 inhibitors group exhibited an increase in apoptosis rate. In conclusion, over-expression of EBI3 could reduce the apoptosis of Treg/CD4+T/CD8+T cells and prevent radiation-induced immunosuppression of cervical cancer HeLa cells by inhibiting the activation of PD-1/PD-L1 signaling pathway.
Assuntos
Antígeno B7-H1/biossíntese , Interleucinas/biossíntese , Antígenos de Histocompatibilidade Menor/biossíntese , Neoplasias Experimentais/radioterapia , Receptor de Morte Celular Programada 1/biossíntese , Neoplasias do Colo do Útero/radioterapia , Animais , Antígeno B7-H1/genética , Proliferação de Células/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Células HeLa , Humanos , Imunofenotipagem , Terapia de Imunossupressão , Interleucinas/genética , Antígenos de Histocompatibilidade Menor/genética , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Receptor de Morte Celular Programada 1/genética , Ratos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transdução de Sinais/efeitos da radiação , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos da radiação , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVES: Evidence on the associations between short-term and long-term air temperature exposure and cognitive function in older adults, particularly those in Asia, is limited. We explored the relationships of short-term and long-term air temperature exposure with cognitive function in Taiwanese older adults through a repeated measures survey. DESIGN AND SETTING: We used data the ongoing Taiwan Longitudinal Study on Aging, a multiple-wave nationwide survey. PARTICIPANTS: We identified 1956, 1700, 1248 and 876 older adults in 1996, 1999, 2003 and 2007, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants' cognitive function assessment was based on the Short Portable Mental Status Questionnaire. We calculated the temperature moving average (TMA) for temperature exposure windows between 1993 and 2007 using data from air quality monitoring stations, depending on the administrative zone of each participant's residence. Generalised linear mixed models were used to examine the effects of short-term and long-term temperature changes on cognitive function. RESULTS: Short-term and long-term temperature exposure was significantly and positively associated with moderate-to-severe cognitive impairment, with the greatest increase in ORs found for 3-year TMAs (OR 1.247; 95% CI 1.107 to 1.404). The higher the quintiles of temperature exposure were, the higher were the ORs. The strongest association found was in long-term TMA exposure (OR 3.674; 95% CI 2.103 to 6.417) after covariates were controlled for. CONCLUSIONS: The risk of mild cognitive impairment increased with ambient temperature in community-dwelling older adults in Taiwan.