ABSTRACT
Androgen receptor (AR) plays a key regulatory role in the development of castration resistant prostate cancer (CRPC), and the level of constitutive active variants represented by androgen receptor variant 7 (AR-V7) is increasing during the progress of CRPC, which can be used as a molecular marker of disease progress and prognosis of patients with CRPC. It is an important target to overcome castration resistance and improve the quality of life and survival of patients. In this paper, the function of AR-V7 and its molecular regulation mechanism in CRPC are reviewed. The research shows that the generation of AR-V7 is related to the structural rearrangement of AR gene, gene amplification and the selective splicing of AR gene transcripts, and it is affected by the coordinated regulation of multiple signal pathway molecules such as TGF-β; AR-V7 changes the transport and nuclear localization mechanism of AR protein, and further affects the transcriptional expression of downstream target genes. AR-V7 antagonizes AR activity and blocks the differentiation process driven by AR and androgen, and inhibits the expression of tumor suppressor genes to stimulate the proliferation of tumor cells, thus promoting the progress of Pca. Related targeting studies have revealed AR-V7 targets and CRPC treatment strategies. Currently, they mainly focus on AR-V7 protein degradation, mRNA expression inhibition and N-terminal domain targeting intervention. With the development of in-depth research, the molecular mechanism of AR-V7 in the progress of Pca will be gradually clarified, which will certainly play a greater role in the prevention and treatment of CRPC.
ABSTRACT
Ovarian tumor-associated protease B1(OTUB1) is a member of the deubiquitinase family. Its highly specific recognition and cleavage function of polyubiquitinated chains has attracted widespread attention, and it can regulate a variety of important signaling pathways, such as the epithelial-mesenchymal transition (EMT) pathway, the MAPK signaling pathway, and the p53-related signaling pathway. In recent years, it has gradually become a new direction of oncology research. More and more studies have proved that OTUB1 is closely related to various tumors such as hepatocellular carcinoma, colorectal cancer, and breast cancer. It regulates the occurrence, development, and prognosis of tumors. OTUB1 could be a potential treatment for tumors. Urinary tract tumors mainly include prostate cancer, bladder cancer, and renal cell carcinoma. In this review, the research progress on the correlation between OTUB1 and urological tumors was reviewed, including its important role in the occurrence and development of urological tumors and the possibility of treating urological tumors with OTUB1.
ABSTRACT
Objective To investigate the expression of B7-H3 in muscle infiltration bladder transitional cell carcinoma and its clinical significance.Methods The clinical and pathological data of 115 patients with muscle infiltration bladder transitional cell carcinoma who underwent radical surgery were retrospectively analyzed.The expression of B7-H3 in bladder cancer tissues and corresponding paracancerous tissues was detected by immunohistochemical staining,and the relationship between B7-H3 and clinicopathological characteristics was analyzed.Results The positive expression of B7-H3 was mainly in the cytoplasm,presenting brownish yellow granules.B7-H3 had positive expression in all bladder cancer tissues but no expression in paracancerous tissues.The high positive rate of B7-H3 expression in bladder cancer was 68.7％.The abnormal expression of B7-H3 was correlated with the distant metastasis and intravascular tumor thrombi (all P＜0.05),but not with gender,age,tumor stage and grade,lymph node metastasis and recurrence (all P＞0.05).The survival analysis result showed that the survival time of the patients with high expression of B7-H3 in the bladder cancer tissues was significantly lower than that of patients with low expression of B7-H3,and the difference was statistically significant (P＜0.05).Conclusion The expression of B7-H3 in muscle infiltration bladder cancer tissues is up-regulated and is positively associated with the distant metastasis of bladder cancer and intravascular tumor thrombus.The expression of B7-H3 may indicate poor prognosis of the patients with bladder cancer.
ABSTRACT
Objective To investigate the expression of adenylate kinase 4 (AK4) in prostate cancer and its clinical significance.Methods The clinical data of 85 patients with prostate cancer who have underwent radical surgery were retrospectively analyzed.The expression of AK4 in prostate cancer tissues and corresponding paracancerous tissues was detected by immunohistochemistry to analyze the relationship with clinicopathological features.Results The positive rates of AK4 in prostate cancer and paracancerous tissues were 85.9％ and 38.8％ respectively,and the difference was statistically significant (P＜0.05).The abnormal expression of AK4 was correlated with recurrence and distant metastasis (all P＜0.05).The survival time of AK4-overexpressing patients with prostate cancer was significantly lower than that of AK4 low-expression patients,and the difference was statistically significant (P＜0.05).Conclusions The expression of AK4 in prostate cancer tissues is up-regulated,which is related to the distant metastasis of carcinoma and vascular tumor thrombus,which suggests that the expression of AK4 may indicate the poor prognosis of patients with prostate cancer.
ABSTRACT
Objective To evaluate the effect of child obesity intervention comprehensive program on the improvement of overweight,obese control and knowledge-attitude-practice.Methods The study design was under cluster-randomized controlled trial,with 965 children in the intervention and 895 children in the control groups.Repeated measurement data on child obesity was analyzed through Generalized Estimating Equation models.Results The risk of becoming overweight or obesity in the intervention group was 0.824 times more than children in the control group,showing a reduction of 17.6％ the risk of being overweight or obese (P=0.031).In addition,the possibility of increasing one unit of correct rate on obesity related knowledge,children in the intervention group children was 1.044 times (P=0.001) than in the control group.On the mean obesity related correct attitude rate,it was 1.023 times (P=0.001) in the intervention group of the control group.Regarding the possibility of increasing one unit om the mean obesity related behavior score,children in the intervention group was 1.522 times (P=0.001) than those in the control group (P=0.046).Conclusion The comprehensive child obesity intervention program could effectively reduce the risk of developing overweight or obeseity and improving the obesity related knowledge,attitude and behavior in children.