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The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

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Asian Journal of Andrology 2011年第6期13卷 798-805页

作者： Qi Jiang Bang-Min Han fu-jun zhao Yan Hong Shu-Jie Xia Department of Urology Shanghai First People＇s Hospital Institute of Urology Shanghai Jiao Tong University Shanghai 200080 China

It is well known that prostate cancer （PCa） occurs predominantly in the peripheral zone （PZ）, whereas benign prostatic hyperplasia （BPH） typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone （PZsc） and the transition zone （TZsc） on a PCa epithelial cell line （PC3） in the presence of sex hormones. First, we observed that androgen receptor （AR） mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone （DHT） and β-oestradiol （E2）（P〈0.05）. By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor （KGF） secretion increased with increasing concentrations of DHT （P〉0.01） and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 （TGF-β1） than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 （IGF-1） secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmoll^- 1 DHT plus 10 nmoll^-1 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

关键词： androgen growth factor oestrogen prostate cancer stromal cell

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Redundant prepuce increases the odds of chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）

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Asian Journal of Andrology 2014年第5期16卷 774-777,I0011页

作者： Yu-Yang zhao Dong-Liang Xu fu-jun zhao Bang-Min Han Yi Shao Wei zhao Shu-Jie Xia Department of Urology Shanghai First People's Hospital Institute of Urology Shanghai Jiao Tong University Shanghai China

Some published evidence has revealed that the dendritic cells can interact with pathogens that exist in the inner foreskin. This information provides a new vision that pathogens could play a role through the redundant prepuce; numerous studies have failed to find pathogens in prostates of patients who had chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）. However, no studies have reported an association between foreskin length and CP/CPPS. Hence, we conducted a retrospective case-control study of clinical data from 322 CP/CPPS patients （case group） and 341 nonCP/CPPS patients （control group）. Demographic characteristics, lifestyle factors, and foreskin lengths were collected and analyzed. Multivariate logistic regression was adopted to calculate the odds of foreskin length for CP/CPPS. According to the multivariate logistic regression results, when the foreskin length covered up more than half of the glans penis, the odds for CP/CPPS were higher with an increased foreskin （odds ratio （OR）： 1.66, 95% confidence interval （CI）： 1.04-2.66）. In comparison, when the glans penis was completely covered by the foreskin, the OR value increased to 1.86 （95% CI, 1.2-2.88）. The study results showed an association between foreskin length and the odds of CP/CPPS. When the foreskin length covered up more than half of the glans penis, there were greater odds for CP/CPPS. This possible mechanism might result from interaction between pathogens and DCs in the inner foreskin, consequently activating T-cells to mediate allergic inflammation in the prostate and producing the autoimmunizations causing CP/CPPS.

关键词： case control study chronic pelvic pain syndrome chronic prostatitis, prepuce

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Synthesis and Antioxidant Activity of Sapriparaquinone Analogues

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Chinese Chemical Letters 2006年第9期17卷 1177-1180页

作者： Fei DENG fu jun ZHANG Ming zhao Yi Ping WANG Jin Sheng ZHANG State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203

Twenty two sapriparaquinone derivatives were synthesized and their antioxidant activities were evaluated in vitro. Many of this kind of compounds demonstrated potent antioxidant activity against lipid peroxidation, especially compound 7 （IC50 = 3.7 μg/mL）. The preliminary structure-activity relationship of sapriparaquinone derivatives was discussed.

关键词： Synthesis sapriparaquinone antioxidant activity.

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Strata-pressure behavior of double-unit mining method combining fully-mechanized and mechanized coal face

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Journal of Coal Science & Engineering(China) 2013年第4期19卷 454-461页

作者： fu-jun zhao Yan-Fei XU Guo-Ju WANG School of Energy and Safety Engineering Hunan University of Science and Technology Xiangtan 411201 China Hunan Provincial Key Laboratory of Safe Mining Techniques of Coal Mines Hunan University of Science and Technology Xiangtan 411201 China

Based on the engineering background of double-unit face mining under complicated geological conditions and the lagging fully-mechanized face surpassing the fore mechanized face of double-unit face in Zhou Yuanshan coal mine, strata-pressure behavior in the process was analyzed based on FLAC3D and on-site measurement. The results show that the stress concentration factor of superposition abutment pressure and the alternate distance of double-unit face are meeting gauss function, the relationship between the depth of stress concentration point and alternate distance also meets gaussian function. When the alternate distance is larger than 24 m, the superimposition of pilot support pressure in the double-unit face is weak. When the alternate distance is more than 12-15 m, the changes of the roof subsidence coefficient and the depth of stress con- centration point are stabilized; when the alternate distance is 3-6 m, the fore working face end is in the greatest impact area of superposition abutment pressure, this area should be avoided in determining the reasonable alternate distance.

关键词： double-unit face alternate distance superposition abutment pressure stress concentration factor roof subsidencecoefficient

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Comparison of diagnostic efficacy between transrectal and transperineal prostate biopsy:a propensity score-matched study

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Asian Journal of Andrology 2019年第6期21卷 612-617页

作者： Chen-Yi Jiang Peng-Fei Shen Cheng Wang Hao-jun Gui Yuan Ruan Hao Zeng Shu-Jie Xia Qiang Wei fu-jun zhao Department of Urology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Urology West China HospitalSichuan UniversityWest China School of MedicineChengdu 610041China Department of Urology Shanghai General Hospital Affiliated to Nanjing Medical UniversityShanghai 200080China.

This study compared the diagnostic efficacy of transrectal ultrasound(TRUS)-guided prostate biopsy(TRBx)and transperineal prostate biopsy(TPBx)in patients with suspected prostate cancer(PCa).We enrolled 2962 men who underwent transrectal(n=1216)or transperineal(n=1746)systematic 12-core prostate *** data including age,prostate-specific antigen(PSA)level,and prostate volume(PV)were *** minimize confounding,we performed propensity score-matching analysis?We measured and compared PCa detection rates between TRBx and TPBx,which were stratified by clinical characteristics and Gleason *** effects of clinical characteristics on PCa detection rate were assessed by logistic *** all patients,TPBx detected a higher proportion of clinically significant PCa(P<0.001).Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with *** score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged≥80 years(80.4%vs 56.5%,P=0.004)and with PSA level 20.1-100.0 ng ml^-1(80.8%vs 69.1%,P=0.040).In conclusion,TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was;however,because of the high detection rate at certain ages and PSA levels,biopsy approaches should be optimized according to patents'clinical characteristics.

关键词： biopsy demography Gleason score propensity score prostatic neoplasms

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Two-micrometer thulium laser resection of the prostate-tangerine technique in benign prostatic hyperplasia patients with previously negative transrectal prostate biopsy

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Asian Journal of Andrology 2017年第2期19卷 244-247页

作者： Jian Zhuo Hai-Bin Wei Fei Zhang Hai-Tao Liu fu-jun zhao Bang-Min Han Xiao-Wen Sun jun-Lu Shu-Jie Xia Department of Urology Shanghai General Hospital of Nanjing Medical University Shanghai 200080 China Department of Urology Zhejiang Provincial People's Hospital Xiacheng District Hangzhou 310014 China

The 2-1μm thulium laser resection of the prostate-tangerine technique （TmLRP-TT） has been introduced as a minimally invasive treatment for benign prostatic hyperplasia （BPH）. This study was undertaken to assess the clinical efficacy and safety of TmLRP-TT for the treatment of BPH patients with previously negative transrectal prostate biopsy. A prospective analysis of 51 patients with previously negative transrectal prostate biopsy who underwent surgical treatment using TmLRP-TT was performed from December 2011 to December 2013. Preoperative status, surgical details, and perioperative complications were recorded. The follow-up outcome was evaluated with subjective and objective tests at I and 6 months. TmLRP-TT was successfully completed in all patients. Mean prostate volume, operative duration, and catheterization time were 93.3 ± 37.9 ml, 69.5 ± 39.5 min, and 6.5 ± 1.3 days, respectively. The mean International Prostate Symptom Score, quality of life score, maximum urinary flow rate, and post-void residual urine volume changed notably at 6-month follow-up （22.5 ± 6.9 vs 6.1 ± 3.2, 4.8 ± 1.3 vs 1.1 ± 0.9, 7.3 ± 4.5 vs 18.9 ± 7.1 ml s^-1, and 148.7 ± 168.7 vs 28.4 ± 17.9 ml）. Two （3.9%） patients required blood transfusion perioperatively, while 3 （5.9%） patients experienced transient hematuria postoperatively, and 2 （3.9%） patients received 3 days recatheterization due to clot retention. TmLRP-TT is a safe and effective minimally invasive technique for patients with previously negative transrectal prostate biopsy during the 6-month follow-up. This promising technology may be a feasible surgical method for previously negative transrectal prostate biopsy in the future.

关键词： 2-μm thulium laser resection of the prostate-tangerine technique benign prostatic hyperplasia laser surgery prostatebiopsy thulium laser

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The role of urethral pressure profile on treating premature ejaculation by tamsulosin

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Asian Journal of Andrology 2014年第5期16卷 792-793页

作者： Hui-Rong Chen fu-jun zhao Xiao-Hai Wang Qi Jiang Qi Zhang Ban-Ming Han jun Lu Shu-Jie Xia Department of Urology Shanghai First People's Hospital Shanghai Jiao Tong University Shanghai China

Dear Editor, I am Dr. Hui-Rong Chen, from the Department of Urology in Shanghai First People＇s Hospital at Shanghai Jiao Tong UnNersity, Shanghai, China. Premature ejaculation （PE） is a common sexual dysfunction, affecting approximately 20%-30% of sexually active men. According to intravaginal ejaculatory latency time （IELT） of l min, the incidence is approximately 1%-3%.1 PE is significantly associated with many personal and negative consequences, such as distress, frustration, and avoidance of sexual intimacy due to the inability of successful delayed ejaculation, α1-adrenergic blockers were effective in delaying ejaculation in approximately 50%-67% of the cases.2,3 Recently, abnormal ejaculation, an adverse infrequent side effect associated with the use of α1A-adrenergic blockers such as silodosin or tamsulosin, has drawn significant attention. Clinical studies suggested that this represents a relative anejaculation rather than a retrograde ejaculation. We present here the study to investigate the role of urethral pressure profile （UPP） on treating PE by tamsulosin.

关键词： The role urethral pressure

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Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression

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Asian Journal of Andrology 2013年第5期15卷 672-678页

作者： You-Yi Lu Bo Jian fu-jun zhao Di Cui Qi Jiang jun-Jie Yu En-Hui Li Xiao-Hai Wang Bang-Min Han Shu-Jie Xia Department of Urology The Affiliated First People's Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200080 China Department of Urology The Qingdao Municipal Hospital Qingdao 266071 China

Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors （ARs） by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA （shRNA）, matrix metalloproteinase （MMP） expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

关键词： age factors androgen receptor human metastasis prostate cancer

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Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells

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Asian Journal of Andrology 2011年第5期13卷 732-741页

作者： Yong-Chuan Wang Sheng-Qiang Yu Xiao-Hai Wang Bang-Min Han fu-jun zhao Guang-Hui Zhu Yan Hong Shu-Jie Xia Department of Urology The Affiliated First People＇s Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200080 China Department of Urology Yantai Yuhuangding Hospital Affiliated with the Medical College of Qingdao University Shandong 264000 China Department of General Surgery The Affiliated First People＇s Hospital of Shanghai Jiao Tong University Shanghai 200080 China

Prostate cancer （PCa） is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone （PZ） of donors of varying ages and found that cultured stromal cells from old donors （PZ-old） were more enlarged and polygonal than those from young donors （PZ-young）. furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage（〉100） and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor （HGF）, fibroblast growth factor 5 （FGF5）, insulin-like growth factor 2 （IGF2）, insulin-like growth factor-binding protein 4 （IGFBP4）, IGFBP5 and matrix metallopeptidase 1 （MMP1）. Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction （PCR）, Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epitheli

关键词： coculture gene expression peripheral zone phenotype prostate cancer stromal cells

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Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells

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Asian Journal of Andrology 2009年第1期11卷 119-126页

作者： Yue-Qing Tang Bang-Min Han Xin-Quan Yao Yan Hong Yan Wang fu-jun zhao Sheng-Qiang Yu Xiao-Wen Sun Shu-Jie Xia Department of Urology Shanghai First People＇s Hospital Institute of Urology Department of Urology Wujiang Third People＇s Hospital Suzhou 215228 China Department of Immunology Shanghai Jiao Tong University Shanghai 200025 China

Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules （dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]） to facilitate androgen receptor （AR） degradation via the ubiquitin-proteasome pathway （UPP） and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyl tetrazolium bromide （MTT） cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-（arg）8 peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-0 cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.

关键词： androgen receptor LNCaP prostate cancer proteolysis ubiquitin

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