ABSTRACT
Autophagy is a basic cellular mechanism, which not only acts as a " housekeeper" in the normal physiological and biochemical processes of cells, but also participates in the occurrence and development of many diseases. Many studies have shown that autophagy is closely related to prostatitis, benign prostatic hyperplasia and prostate cancer. Autophagy plays an important role both in the onset of the disease and in the treatment of the disease. This article expounds the influence and mechanism of autophagy in prostate diseases, and provides new ideas and methods for the diagnosis and treatment of prostate diseases.
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Objective:To evaluate the prognostic value of the ratio of androgen receptor splice variant 7 (AR-V7) and androgen receptor (AR) in prostate cancer.Methods:One hundred and five prostate cancer patients treated by castration therapy were selected in this study in People′s Hospital of Gaozhou City, Guangdong Province from March 2013 to March 2018. The expression of AR and AR-V7 in biopsy specimens was detected by immunohistochemistry. The relationship between AR, AR-V7, AR-V7/AR and prognosis of patients was analyzed. Cox regression was used to analyze the related factors affecting prognosis of prostate cancer.Results:The positive rate of AR expression was 59.0% (62/105), and the positive rate of AR-V7 expression was 19.0% (20/105). The patients were followed up for 15 to 61 (44.8 ± 10.1) months. The progression free survival (PFS) and overall survival (OS) in AR-V7 positive patients were significantly shorter than those in AR-V7 negative patients: (10.8 ± 2.2) months vs. (25.0 ± 3.4) months and (20.3 ± 5.1) months vs. (42.8 ± 7.4) months, and there were statistical differences ( P<0.01). The PFS and OS in high AR-V7/AR expression patients were significantly shorter than those in low AR-V7/AR expression patients: (12.5 ± 3.2) months vs. (24.9 ± 5.5) months and (22.5 ± 4.6) months vs. (42.1 ± 8.3) months, and there were statistical differences ( P<0.01). In multivariate Cox regression analyses, T4 stage (HR = 2.618, 95% CI 1.362 to 4.986, P<0.01) and high AR-V7/AR ( HR = 5.799, 95% CI 2.541 to 13.253, P<0.01) could effectively and independently predict the prognosis of hormonal therapy. Conclusions:AR-V7 positive and high AR-V7/AR prostate cancer patients treated by castration therapy may have shorter PFS and OS, compared with AR-V7 negative and low AR-V7/AR patients. High AR-V7/AR is the independent predictor of the prognosis of prostate cancer.
ABSTRACT
Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC). Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib, sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate (ORR) than IFN (47% versus 12%, P<0.000001). Bevacizumab plus IFN produced a superior PFS [risk ratio (RR): 0.86, 95% confidence interval (CI): 0.76-0.97; P=0.01] and ORR (RR: 2.19; 95% CI: 1.72-2.78; P<0.00001) in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects (RR: 1.31; 95% CI: 1.20-1.43; P<0.00001) as compared with IFN. The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months). It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.
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OBJECTIVE: To summarize advances in clinical application of ureter stent and its biocompatibility. METHODS: A computer-based online search of CNKI (1989/2009) and Medline (1989/2009) was performed with the key words of "ureter, biocompatibility, stent, treatment, complications" in Chinese and English respectively. A total of 51 articles were collected. and 21 were included. The treatment advances and its biocompatibility of ureter stent were summarized, and clinical application advances, biocompatibility and complication prevention of ureter stent were explored. RESULTS: Ureter stent includes polymerizer, metal and degradable material stents. As the common implants in treatment of upper urinary tract diseases, ureter stent functions as stent and internal drainage, and relieve ureteral obstruction, prevent leakage of urine postoperatively and ureterostenosis. Complications following ureter stent implantation include stent shifting, urine reflux, irdtative symptoms of bladder, fouling and stone formation as well as infection. However, these complications can be relieved through positive treatment. CONCLUSION: Ureter stent is an effective approach to treat urologic disease, but the biocompatibility required improvement. Rigorous operation during stent implantation and positive treatment of complication can effectively prevent complications.
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BACKGROUND: The morbility of rheumatoid arthritis is closely associated with cell apoptosis process. Hyperplasia of synoviocyte lies in the relatively insufficiency of synoviocyte apoptosis. Therefore, induction of synoviocyte apoptosis has clinical significance in the treatment of rheumatoid arthritis. Arteannuin and its derivatives can induce the apoptosis of various cells. OBJECTIVE: To observe the effect of artesunate on the expression of Fas/FasL and Bcl-2/Bax, which are correlated with apoptosis in synoviocyte of adjuvant arthritis. DESIGN: Randomized and controlled observation. SETTING: First College of Clinical Medical Science, Three Gorges UniversityMATERIALS: The experiment was conducted in the laboratories of Immunology and Morphology, Three Gorges University from September 2005 to November 2005. Fifty 8-week-old male Wistar rats of clean grade and (150±21) g were provided by the Animal Experimental Center of Tongji Medical College, Huazhong University of Science and Technology; Complete Freud adjuvant by SIGMA, U.S., and artesunate solution by Guilin Pharmaceutical Corporation.rabbit anti-mouse Fas (SC-716), rabbit anti-mouse FasL and Technology (No. SCXK 2004-2007).Complete Freud adjuvant (SIGMA, U.S. No. 093K8932); artesunate solution (Guilin Pharmaceutical Cor); rabbit anti-mouse Fas (SC-716), rabbit anti-mouse FasL multi-antibody (SC-834), goat anti-mouse IgG-HRP multimer, rabbit anti-mouse P53 (M3566) multi-antibody, Bcl-2 (sc-7382) multi-antibody, rabbit anti-mouse Bax (sc-7480) multi-antibody, ABC compound reagent kit and DAB coloring reagent all acquired from Santa Cruz biotechnology (Santa Cruz, USA); methotrexate (MTX) purchased from Shanghai Hualian Pharmaceutical Co., Ltd.; microscope and image analysis system obtained from Leica (Leica,Germany); microtome (Leica, Germany).METHODS: Fifty rats were randomly divided into six groups: normal group (n =8), model group (n =8), high dose artesunate group (n =8), low dose artesunate group (n =8), artesunate plus methotrexate (MTX) group (n =8), and MTX group (n =8). ①Model construction was referred to literature: Except the normal group with 0.1 mL normal saline, all rats were injected with 0.1 mL complete Freund's adjuvant into the right voix pedis to establish the models of adjuvant arthritis. Since the 13th day after modeling, high and low dose artesunate groups were intraperitoneally injected with 40 and 20 mg/kg artesunate, respectively everyday; artesunate plus MTX group was intraperitoneally injected with 20 mg/kg artesunate everyday and 0.4 mg/kg MTX every three days; MTX group with 0.4 mg/kg MTX solution every three days;model group with 1 mL normal group everyday. ②The arthrosis index (Al) of each group was evaluated before and 13 days after administration; the expressions of Fas/FasL, Bcl-2, and Bax in synovial membrane tissue were examined by immunohistochemistry.MAIN OUTCOME MEASURES : Al and the expression of Fas/FasL, Bcl-2, and Bax in synovial membrane tissue of each group.RESULTS: Fifty rats were involved in the result analysis. ①Thirteen days after administration, the Al of each experiment group (including model control) was remarkably lower than that before treating (P ＜ 0.01). The Al of eachexperiment group was significantly lower than that in model control group (P ＜ 0.01). ②The expression of Fas/FasL in high and low dose artesunate groups and artesunate plus MTX group was up-regulated significantly compared with that in model group (P ＜ 0.01). There was no statistically significant difference in the expression between MTX group and model group (P ＞ 0.05); the expression of Bcl-2 was significantly down-regulated but Bax up-regulated in two artesunate groups,artesunate plus MTX group and MTX group compared with that in model group (P ＜ 0.05).CONCLUSION: The findings suggest that artesunate could alleviate adjuvant arthritis, up-regulate the expression of Fas/FasL and Bax, but down-regulate that of Bcl-2, in which the induction of synoviocyte apoptosis may be one of the mechanisms.