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Asian Journal of Andrology 2008年第6期10卷 883-889页

作者： Jun Lu Qi Zhang Chun-Min Liang Shu-Jie Xia Cui-Ping Zhong Da-Wei Wang Department of Urology Shanghai Jiaotong University Affiliated First People＇s Hospital Shanghai 200080 China Department of Anatomy Histology and Embryology Shanghai Medical College Fudan University Shanghai 200080 China

Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine （SLC） cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC＋lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction （RT-PCR）. The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results： We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC＋lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos- phate buffer solution （PBS） counterparts （P 〈 0.01）. Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4＋, CD8＋ T cell and CD11c＋ DC within established tumor treated by SLC＋lysate-DC vaccine than other DC vaccines （P 〈 0.01）. Conclusion： DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4＋, CD8＋ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

关键词： dendritic cell secondary lymphoid chemokine prostate cancer tumor lysate

Intensity of stromal changes is associated with tumor relapse in clinically advanced prostate cancer after castration therapy

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Asian Journal of Andrology 2014年第5期16卷 710-714,I0007,I0008页

作者： Jian-Ping Wu Wen-Bin Huang Hui Zhou Lu-Wei Xu Jian-Hua Zhao Jia-Gen Zhu Jiang-Hao Su Hong-Bin Sun Department of Urology Nanjing Hospital Affiliated to Nanjing Medical University Nanjing China Department of Pathology Nanjing Hospital Affiliated to Nanjing Medical University Nanjing China

Reactive stromal changes in prostate cancer （PCa） are likely involved in the emergence of castration-resistant PCa （CRPC）. This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade （Masson stain 82.8% vs 45.6%, P 〈 0.001） and vimentin expression （P = 0.005） were significantly higher, and desmin expression （P = 0.004） significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 （P= 0.009）. Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse （hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012）. These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.

关键词： cancer-associated fibroblasts castration resistance prostate cancer reactive stroma vimentin

Vitamin D in prostate cancer

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Asian Journal of Andrology 2018年第3期20卷 244-252页

作者： Donald L Trump Jeanny B Aragon-Ching Inova Schar cancer Institute Inova Health System Fairfax VA 22037 USA.

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

关键词： androgens CYP24A1 inflammation prostate cancer vitamin D analogs

Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

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Asian Journal of Andrology 2004年第4期6卷 285-290页

作者： Sen-XiangYan YasuoEjima RyoheiSasaki Shu-SenZheng YusukeDemizu ToshinoriSoejima KazuroSugimura DepartmentofRadiology FirstAffiliatedHospitalCollegeofmedicineZhejiangUniversityHangzhou310003China DivisionofRadiology KobeGraduateSchoolofMedicineHyogo6500017Japan

Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This Gz/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21cipl levels with increasing genistein concentrations. Conclusion: Genistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.

关键词： prostate cancer genistein ionizing radiation (IR) apoptosis cell cycle

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

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Asian Journal of Andrology 2012年第2期14卷 204-221页

作者： Thomas W Storet Renee Miciek Thomas G Travison Section of Endocrinology Diabetes and Nutrition Boston University School of Medicine Boston MA 02118 USA

prostate cancer （PCa） is the most common visceral malignancy in men with androgen deprivation therapy （ADT） the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data （up to 2 years） for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

关键词： androgen deprivation therapy androgen suppression exercise prescription exercise training functional assessment lean body mass older men prostate cancer

Peripheral monocyte count： an independent diagnostic and prognostic biomarker for prostate cancer - a large Chinese cohort study

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Asian Journal of Andrology 2017年第5期19卷 579-585页

作者： Yan-Qing Wang Yin-Jie Zhu Jia-Hua Pan Fan Xu Xiao-Guang Shao Jian-Jun Sha Qiang Liu Yi-Ran Huang Bai-Jun Dong Wei Xue Department of Urology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China Department of Pathology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 x 109 1-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen （PSA）, free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival （hazard ratio = 2.244, P 〈 0.05） and overall survival （hazard ratio = 1.995, P 〈 0.05）, but not progression-free survival （P = 0.117）. Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

关键词： diagnosis monocyte prognosis prostate cancer

Impact of androgen-deprivation therapy on the outcome of dose-escalation prostate cancer radiotherapy without elective pelvic irradiation

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Asian Journal of Andrology 2017年第5期19卷 596-601页

作者： Wei-Hsien Hou Chao-Yuan Huang Chia-Chun Wang Keng-Hsueh Lan Chung-Hsin Chen Hong-Jen Yu Shih-Ping Liu Ming-Kuen Lai Yeong-Shau Pu Jason Chia-Hsien Cheng Division of Radiation Oncology Department of Oncology National Taiwan University Hospital Taipei Taiwan China Department of Urology National Taiwan University Hospital Taipei Taiwan China Department of Oncology National Taiwan University Hospital Taipei Taiwan China Graduate Institutes of Oncology National Taiwan University College of Medicine Taipei Taiwan China Graduate Institutes of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan China

The benefit of androgen-deprivation therapy （ADT） in combination with dose-escalated radiotherapy （DERT） for localized prostate cancer has not been determined in randomized studies. In this study, the benefit of ADT was assessed in patients uniformly treated with dose-escalated intensity-modulated radiation therapy （IMRT） to the prostate and seminal vesicles but not pelvis. In all, 419 patients with localized prostate adenocarcinoma underwent definitive IMRT （cumulative dose 78 Gy）, with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4 disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1% of patients. With a median follow-up of 60 months, 5-year biochemical failure-free, disease-free, and overall survival rates were 87%, 86%, and 87%, respectively. T stage was an independent predictor of all three rates. Five-year pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and disease-free survival but not overall survival. ADT showed benefit in high-risk disease but not intermediate-risk disease. Late gastrointestinal and genitourinary toxicities ≥ grade 2 occurred in 11.0% and 6.7%, respectively. In conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic nodal recurrence. ADT improves disease-free survival in patients with high-risk but not intermediate-risk disease.

关键词： androgen-deprivation therapy dose-escalation prostate cancer radiotherapy

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

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Asian Journal of Andrology 2008年第5期10卷 701-709页

作者： Bo Dai Yun-Yi Kong Ding-Wei Ye Chun-Guang Ma Xiao-Yan Zhou Xu-Dong Yao Department of Urology Cancer Hospital Fudan University Shanghai 200032 China Department of Pathology Cancer Hospital Fudan University Shanghai 200032 China Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋（P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

关键词： prostatic neoplasms human epidermal growth factor receptor type 2 immunohistochemistry gene amplification prostate cancer prognosis

Phytoestrogens Inhibiting Androgen Receptor Signal and prostate cancer Cell Proliferation

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Chemical Research in Chinese Universities 2013年第5期29卷 911-916页

作者： WU Jing LIU Shu SHEN Xiao-yan YANG Nan-yang LIU Ying TSUJI Ichiro YAMAMURA Takaki LI Jiang LI Xlao-meng Key Laboratory of Molecular Epigenetics Ministry of Education Institute of Genetics and Cytology Northeast Normal University Changchun 130024 P. R. China Dental Hospital Jilin University Changchun 130021 P. R. China Department of Public Health Tohoku University Sendai 980-8576 Japan Department of Nutritional Sciences Morioka University Morioka 020-0183 Japan

The androgen receptor（AR） signaling activated by dihydrotestosterone（DHT） plays critical roles in pros- tate cancer development and progression. Phytoestrogens, which are diphenolic compounds with estrogen and an- ti-estrogen effects, can bind to estrogen receptors. However, their function on AR signaling has not been fully eluci- dated. In this study, dual-luciferase reporter assay, immunobloting, docking system test, MTT assay, immunofluores- cence and chromatin immunoprecipitation（ChlP） assays were employed to examine the potential effects of three phytoestrogens（genistein, daidzein, flavone） on DHT-activated prostate specific antigen（PSA） activation, cell proli- feration and AR transactivation in lymph node carcinoma of prostate（LNCaP） cells. Phytoestrogens were detected to down-regulate DHT-activated AR-mediated PSA promoter transactivation by dual-luciferase reporter system. Fur- thermore, three phytoestrogens, especially genistein, were demonstrated to significantly decrease AR-activated PSA protein expression by Western blotting analysis. MTT experiment proves that phytoestrogens, especially genistein, remarkably inhibits the DHT-indueed cell proliferation in LNCaP cells. To provide reasonable explanations for expe- rimental phenomena mentioned above, we did docking system test and detected phytoestrogens to share the same AR-binding site with DHT. To further prove the competition between phytoestrogen and DHT on AR binding, we examined the effects of phytoestrogens on DHT-activated AR nuclear translocation and immunofluorescence analysis which confirms that phytoestrogens, especially genistein, inhibit DHT-activated androgen receptor nuclear transloca- tion. Results from ChIP show that phytoestrogens down-regulate DHT-induces AR binding to the androgen response elements（AREs, including AREI, AREII, and AREIII） in PSA promoter. Genistein remarkably down-regulates AR, binding to the AREI located in -250---39 bp and AREIII in --4170---3978 bp in the presence o

关键词： Androgen receptor Phytoestrogen prostate specific antigen(PSA) prostate cancer

Evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 342-349页

作者： Paul J Toren Martin E Gleave Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC V5Z 1M9 Canada

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

关键词： prostate cancer treatment resistance androgen receptor antagonists molecular targets