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Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
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OBJECTIVE@#To investigate the expression of DNMT3b in human bladder cancer tissues and its correlation with postoperative survival of patients with bladder cancer.@*METHODS@#Thirty-eight pairs of surgically resected human bladder cancer tissues and adjacent bladder tissues were detected by immunohistochemistry for DNMT3b expression, and the correlations of DNMT3b expression level were analyzed with the patients'age, gender, pathological grade, tumor size, T stage, lymph node metastasis and TNM stages. Kaplan-Meier survival analysis was performed to assess the effect of DNMT3b expression on survival outcomes of the patients.@*RESULTS@#High DNMT3b protein expression was detected in 63.16% of the bladder cancer tissues and in 13.16% of the adjacent tissues ( < 0.05). The expression level of DNMT3b was associated with the pathological grade (=0.002), tumor size ( < 0.001), T stage ( < 0.001), lymphatic metastasis (=0.039) and TNM stage ( < 0.001), but not with gender or age of the patients. Multivariate logistic regression analysis showed that the protein expression level of DNMT3b was correlated with tumor size (=0.008) and TNM grades of the tumor (=0.042). Kaplan-Meier analysis showed that the patients with a high DNMT3b expression had a significantly shorter overall survival than those with a low DNMT3b expression (=0.021).@*CONCLUSIONS@#DNMT3b overexpression in bladder cancer is closely related to such clinicopathological factors as pathological grade, tumor size, T stage, lymphatic metastasis, and TNM stage and a shorter overall survival of the patients, suggesting the potential value of DNMT3b as a prognostic marker and a new therapeutic target for bladder cancer.
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Objective@#To explore the effect of mindfulness traits on sleep quality of college students, and to investigate the mediating mechanism of cognitive emotion regulation and anxiety for mindfulness trait factors, and sleep quality in college students.@*Methods@#Totally 397 college students from five colleges were investigated using Five Facet Mindfulness Questionnaire, Cognitive Emotion Regulation Questionnaire, Self-Rating Anxiety Scale and Pittsburgh Sleep Quality Index.SPSS 22.0 version and Bootstrap method were used to analysis data and test intermediate effect.@*Results@#(1)The total score of mindfulness trait and the score of describe, act with awareness and non-judge factors in mindfulness traits were(118.44±9.38), (24.82±3.87), (27.41±5.53) and (25.07±4.60), respectively.The total score of sleep quality was (5.57±2.62), and it was negatively related to the above three factors (r=-0.13--0.37, all P<0.05). (2)Anxiety played a complete mediating role between describe factor and sleep quality.Negative cognitive emotion regulation and anxiety played multiple mediating roles between the total score of mindfulness trait, the act with awareness factor and sleep quality.Negative cognitive emotion regulation and anxiety played a complete chain mediated role between non-judge factor and sleep quality.@*Conclusion@#The describe, act with awareness and non-judge factors in mindfulness traits can affect sleep quality through mediation of negative cognitive emotion regulation and / or anxiety.
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Objective To explore the effect of mindfulness traits on sleep quality of college students,and to investigate the mediating mechanism of cognitive emotion regulation and anxiety for mindful-ness trait factors,and sleep quality in college students. Methods Totally 397 college students from five col-leges were investigated using Five Facet Mindfulness Questionnaire,Cognitive Emotion Regulation Question-naire,Self-Rating Anxiety Scale and Pittsburgh Sleep Quality Index. SPSS 22. 0 version and Bootstrap method were used to analysis data and test intermediate effect. Results (1)The total score of mindfulness trait and the score of describe,act with awareness and non-judge factors in mindfulness traits were(118. 44±9. 38), (24. 82± 3. 87),(27. 41± 5. 53) and ( 25. 07 ± 4. 60),respectively. The total score of sleep quality was (5. 57±2. 62),and it was negatively related to the above three factors (r=-0. 13--0. 37,all P<0. 05). (2) Anxiety played a complete mediating role between describe factor and sleep quality. Negative cognitive emo-tion regulation and anxiety played multiple mediating roles between the total score of mindfulness trait,the act with awareness factor and sleep quality. Negative cognitive emotion regulation and anxiety played a complete chain mediated role between non-judge factor and sleep quality. Conclusion The describe,act with aware-ness and non-judge factors in mindfulness traits can affect sleep quality through mediation of negative cogni-tive emotion regulation and / or anxiety.
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<p><b>OBJECTIVE</b>To investigate the effect of RNA interference of IgG gene on the radiosensitivity of the human prostate cancer PC3 cell line.</p><p><b>METHODS</b>PC3 cells were trasnfected via lipofectamine by the shRNA vector FCGR1AshRNA targeting the Fc segment of IgG, using NCshRNA as the negative control. Q-PCR and Western blotting were used to analyze the expression of IgG in the trasnfected cells. The cells were then exposed to ⁶⁰Co γ ray at 0, 2, 4, 6, 8, 10 Gy, and the cell proliferation was evaluated by MTS and the cells apoptosis estimated by flow cytometry at 12, 24 and 48 h.</p><p><b>RESULTS</b>MTS assay showed that ⁶⁰Co γ ray significantly inhibited the proliferation of PC3 cells transfected with FCGR1AshRNA as compared with NCshRNA-transfected and blank control cells (P<0.05). Flow cytometry showed that the cell apoptosis rate was significantly higher in FCGR1AshRNA group than in NCshRNA and blank control groups at 48 h after γ ray exposure (P<0.05). At 12, 24 and 48 h after 6 Gy radiation, the cells in FCGR1AshRNA group showed a significantly lowered proliferation rate and an increased apoptosis rate (P<0.05).</p><p><b>CONCLUSION</b>The shRNA targeting IgG gene can significantly enhance the sensitivity of PC3 cells to radiation. The combination of RNA interference targeting IgG gene with radiotherapy may be more effective in the treatment of prostate cancer.</p>
Subject(s)
Humans , Male , Apoptosis , Cell Line, Tumor , Radiation Effects , Cell Proliferation , Immunoglobulin G , Genetics , Prostatic Neoplasms , Pathology , RNA Interference , RNA, Small Interfering , Radiation Tolerance , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To study the expression of OCT4 protein in bladder cancer and its correlation to the clinicopathologic features and prognosis of bladder cancer.</p><p><b>METHODS</b>OCT4 mRNA and protein expression was detected in 5 bladder cancer cell lines (RT-4, Tcc-Sup, KK47, T24, and 5637) and 1 normal bladder cell lines by real-time PCR and Western blotting, respectively. Immunohistochemical analysis was used to detect the expression of OCT4 protein in 46 bladder cancer samples.</p><p><b>RESULTS</b>All the 5 bladder cancer cell lines expressed detectable levels of OCT4 mRNA and proteins, whereas the normal bladder cell line SV-HUC-1 was negative for OCT4 expression. The clinical bladder cancer tissues showed a high positivity rate of OCT4 expression (76.1%), which was not detected in normal bladder tissues. Specific OCT-4 signals were localized mainly in the nuclei of the cancer cells. The expression rate of OCT4 protein was significantly higher in bladder cancer tissue than in normal bladder epithelium (P<0.05), and showed a positive correlation to the grade of tumor differentiation and metastasis (P<0.05) but not to the patients' age, gender or TNM stage.</p><p><b>CONCLUSION</b>OCT4 protein expression is associated with tumor differentiation and metastasis in bladder cancer and may play an important role in the early diagnosis and prognostic evaluation of bladder cancer.</p>