Human Reproduction Vol. 20, No.3 pp. 782-788, 2005
Messenger RNA Transcripts of the Meiotic Regulator BOULE in the Testis of Azoospermic Men and Their Application in Predicting the Success of Sperm Retrieval
Yung Ming Lin1,5, Pao Lin Kuo2, Ying Hung Lin3, Yen Ni Teng4 and Johnny Shinn Nan Lin1
Departments of 1 Urology, 2 Obstetrics & Gynecology and 3 Institute of Basic Medical Science, National Cheng Kung University, College of Medicine, Tainan, Taiwan and Department of 4 Early Childhood Education and Nursery, Chia Nan University of Pharmacy and Science, Tainan, Taiwan 5 To whom correspondence should be addressed at: Department of Urology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan, Taiwan 704.
BACKGROUND: Testicular sperm retrieval can lead to paternity for azoospermic patients with spermatogenic failure. The human BOULE gene, a meiotic regulator of germ cells, is a gene whose altered expression may be associated with sterility. We determined the levels of BOULE transcripts in the testes of azoospermic patients, and evaluated the relationship between BOULE transcript levels and patients' testicular phenotypes, clinical parameters and sperm retrieval results.
METHODS and RESULTS: BOULE transcript levels in the testes of 41 azoospermic patients were examined by quantitative competitive-reverse transcription–polymerase chain reaction. A significant decrease in BOULE transcript levels was detected in patients with spermatogenic failure, and BOULE transcript levels progressively decreased with increasing severity of testicular failure. BOULE transcript levels did not correlate with the serum hormone parameters measured. Significantly higher BOULE transcript levels were detected in 19 patients with successful sperm retrieval than in 12 patients with failed sperm retrieval. When using a cut-off value of 0.5 for BOULE transcript ratio to predict the success of sperm retrieval, both the sensitivity and specificity value were 100%.
CONCLUSIONS: We suggest the BOULE transcript plays an important role in human spermatogenesis and that the levels may predict the presence of testicular sperm in patients with spermatogenic failure.
Key words: azoospermia / BOULE / testis
男性學論文獎基礎組
Cancer Research 2005; 65: (6) March 15, 2005
Emodin Down-regulates Androgen Receptor and Inhibits Prostate Cancer Cell Growth
1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center and 2Graduate School of Biomedical Science, The University of Texas Health Science Center at Houston, Houston, Texas and 3Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Hormone-refractory relapse is an inevitable and lethal event for advanced prostate cancer patients after hormone deprivation. A growing body of evidence indicates that hormone deprivation may promote this aggressive prostate cancer phenotype. Notably, androgen receptor (AR) not only mediates the effect of androgen on the tumor initiation but also plays the major role in the relapse transition. This provides a strong rationale for searching new effective agents targeting the down-regulation of AR to treat or prevent advanced prostate cancer progression. Here, we show that emodin, a natural compound, can directly target AR to suppress prostate cancer cell growth in vitro and prolong the survival of C3(1)/SV40 transgenic mice in vivo. Emodin treatment resulted in repressing androgen-dependent transactivation of AR by inhibiting AR nuclear translocation. Emodin decreased the association of AR and heat shock protein 90 and increased the association of AR and MDM2, which in turn induced AR degradation through proteasomemediated pathway in a ligand-independent manner. Our work indicates a new mechanism for the emodin-mediated anticancer effect and justifies further investigation of emodin as a therapeutic and preventive agent for prostate cancer.
(Cancer Res 2005; 65(6): 2287-95)
輝瑞論文獎臨床組
The Journal of Urology Vol. 173, 1361-1363, April 2005
Highly Potent and Moderately Potent Topical Steroids are Effective in Treating Phimosis: A Prospective Randomized Study
Stephen Shei Dei Yang, Yao Chou Tsai, Chia Chang Wu, Shih Ping Liu, and From the Department of Urology, En Chu Kong Hospital, Taipei Medical University and Department of Urology, College of Medicine (SPL), National Taiwan University, Taipei, Taiwan.
Purpose: We report a prospective randomized study comparing the effects of highly potent and moderately potent topical steroids in treating pediatric phimosis.
Materials and Methods: A total of 70 boys 1 to 12 years old with phimosis were randomly assigned to receive topical application of either betamethasone valerate 0.06% (a highly potent steroid) or clobetasone butyrate 0.05% (a moderately potent steroid). Parents of the boys were instructed to retract the foreskin gently without causing pain, and to apply the topical steroids over the stenotic opening of the prepuce twice daily for 4 weeks, then for another 4 weeks if no improvement was achieved. Retractability of the prepuce was graded from 0 to 5. Response to treatment was arbitrarily defined as improvement in the retractability score for more than 2 points.
Results: Mean medication and followup periods were 4.3 and 19.1 weeks, respectively. The response rates in boys treated with betamethasone valerate and clobetasone butyrate were 81.3% and 77.4%, respectively (p=0.63). Mean retractibility score decreased from 3.9 ± 1.0 to 1.7 ± 1.1 and 4.2 ± 1.0 to 1.9 ± 1.0 in the betamethasone and clobetasone groups, respectively. Both steroids were effective in all age groups. Pretreatment retractability score did not affect treatment outcomes. No adverse effect was encountered.
Conclusions: Highly potent and moderately potent topical steroids are of comparable effectiveness in treating phimosis. A less potent steroid may be considered first to decrease the risk of the potential adverse effects.
輝瑞論文獎基礎組
The Journal of Urology Vol. 172, 2035-2039, November 2004
Down-Regulation of the Prostate Specific Antigen Promoter by p53 in Human Prostate Cancer Cells
Ke-Hung Tsui, Phei-Lang Chang, Han-Tze Lin and Horng-Heng Juang* From the Department of Urology, Chang Gung Memorial Hospital (K-HT, P-LC) and Departments of Nursing andBiomed icine,
Chang Gung Institute of Technology, School of Medicine (K-HT, P-LC) and Department of Anatomy (H-TC, H-HJ), Chang Gung University, Taiwan, Republic of China.
Purpose: The WT p53 gene appears to have a broad role in suppressing prostatic tumorigenesis. We identified the mechanisms responsible for the effect of p53 on prostate specific antigen (PSA) expression by prostate cancer cell lines in vitro and investigated the role of a putative p53 response element in the PSA promoter region in prostate cancer cells.
Materials and Methods: LNCaP cells were used to determine the effect of doxorubicin on p53 and PSA expression. The putative p53 response element in the human PSA promoter was identified by transient gene expression with site direct mutagenesis assays using a PSA reporter vector. Quantitative PSA secretions were assessed using enzyme-linked immunosorbent assays.
Results: Enzyme-linked immunosorbent and immunoblot assays indicated that doxorubicin treatment increased p53 expression but inhibited PSA levels in LNCaP cells. Transient gene expression assays showed that human PSA promoter activity was blocked by doxorubicin treatment. Mutation of the p53 response element GGGCATGTCT to GGGAGGATCT abolished the blocking effects of doxorubicin on PSA gene promoter activity.
Conclusions: Results demonstrate that p53 regulates PSA gene expression through a putative p53 response element in the PSA promoter within human prostate cancer cells.
男性學論文獎
