1.Androgen biosynthesis in castration-resistant prostate cancer: Advances in studies.
Bo CHEN ; De-Hong CAO ; Jian-Bing GUO ; Liang-Ren LIU ; Qiang WEI
National Journal of Andrology 2019;25(3):265-271
Prostate cancer is a most common malignant tumor in the male urogenital system. Currently, castration-resistant prostate cancer (CRPC) is a bottleneck in the treatment of prostate cancer, which has a very poor prognosis, with a median survival of merely 12 months. Although androgen-deprivation therapy eliminates the majority of the androgens in circulation, CRPC patients adapt to low-level androgens by synthesizing intratumoral androgens or altering androgen receptors. This review summarizes the main ways of synthesizing testosterone and dihydrotestosterone (DHT), the enzymes involved, and changes of the androgen level in different stages of CRPC. Blocking any one of the pathways of androgen biosynthesis is likely to upregulate another and lead to incomplete androgen elimination and consequently drug resistance. Therefore, identifying the pathways of androgen biosynthesis may provide an opportunity for the development of the drugs for blocking the major pathways of androgen and introtumoral androgen biosynthesis and antagonizing androgen receptors.
2.Efficacy and safety of low-intensity extracorporeal shock wave therapy in the treatment of ED: A meta-analysis of randomized controlled trials.
Dun-Sheng MO ; Xu-Xin ZHAN ; Hong-Wei SHI ; Hong-Cai CAI ; Jun MENG ; Jing ZHAO ; Xue-Jun SHANG
National Journal of Andrology 2019;25(3):257-264
Objective:
To evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of ED based on the available clinical evidence.
METHODS:
We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to June 2018 for published randomized controlled trials on the treatment of ED by LI-ESWT. We performed literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria, and conducted a meta-analysis of the data obtained using the RevMan 5.3 software.
RESULTS:
A total of 595 ED cases in 8 double-blind randomized controlled trials (RCT) were included in this study, 362 in the LI-ESWT and 233 in the control group. Compared with the controls, the patients treated by LI-ESWT showed significantly improved IIEF (WMD = 1.70, 95% CI: 0.44-2.96, P = 0.008) and erection hardness score (EHS) (RR = 11.72, 95% CI: 5.13-26.80, P < 0.01). The IIEF scores of the patients were markedly increased at 4 and 24 weeks after LI-ESWT (WMD = 1.43, 95% CI: 0.10-2.75, P = 0.03; WMD = 3.09, 95% CI: 1.49-4.68, P = 0.0002), as well as after the 10th to 12th treatment (WMD = 1.81, 95% CI: 0.31-3.31, P = 0.02) though not after the 5th to 6th (WMD = 1.88, 95% CI: -2.10 to 5.86, P = 0.35). LI-ESWT also significantly increased the IIEF scores in the patients with the baseline IIEF ≥12 (WMD = 2.13, 95% CI: 0.51-3.75, P = 0.01) but not in those with the baseline IIEF ≤11 (WMD = 1.04, 95% CI: -0.96 to 3.03, P = 0.31). No significant adverse events were reported in the 8 RCTs.
CONCLUSIONS
As a non-invasive treatment, LI-ESWT is safe and effective and can significantly improve IIEF and EHS in ED patients.
3.Reproduction-related proteins differentially expressed in the testes of the mice with kidney-yang or kidney-yin deficiency.
Chang-Bo CHEN ; Jing MA ; Jian JIA ; Ying-Qi LI ; A-Qing LIU ; Hai-Jun DONG
National Journal of Andrology 2019;25(3):248-256
Objective:
To compare the differentially expressed proteins in mice with kidney-yang deficiency and those with kidney-yin deficiency induced by hydrocortisone, and explore the similar and different material bases of male infertility caused by the two types of kidney deficiency.
METHODS:
Thirty Kunming mice were equally randomized into a normal control, a kidney-yang deficiency and a kidney-yin deficiency group. The animals of the normal control group were injected intraperitoneally with normal saline at 0.2 ml qd for 7 days, while those of the latter two groups with hydrocortisone at 25 mg/kg/d for 10 days and 50 mg/kg/d for 7 days, respectively, for establishment of kidney-yang deficiency and kidney-yin deficiency models. Then the pathological changes in the testicular tissue of the mice were observed by HE staining and the differentially expressed proteins were compared among different groups using isobaric tags for relative and absolute quantitation (iTRAQ) and the bioinformatics method.
RESULTS:
Sod1 was found to be a reproduction-related node protein differentially expressed in the testis tissues of the two types of kidney-deficiency mice, more highly expressed in the kidney-yin than in the kidney-yang deficiency group (P < 0.05). Five reproduction-associated node proteins were co-expressed in the testes of the two groups of kidney-deficiency mice, with significantly up-regulated expression of Rps28 and down-regulated expressions of Rpl11, Rplp2, Svs2 and Svs3a (P < 0.01).
CONCLUSIONS
Sod1 may be one of the key material bases for the differentiation of male infertility caused by kidney-yang deficiency from that induced by kidney-yin deficiency, while Rps28, Rpl11, Rplp2, Svs2 and Svs3a may be the common material bases of male infertility caused by the two types of kidney deficiency.
4.Glans-preserving surgery for superficial penile squamous cell carcinoma ≥2 cm in diameter.
Xiang ZHOU ; Shang-Qian WANG ; Ya-Min WANG ; Yi-Chun WANG ; Yi WANG ; Qi-Jie ZHANG ; Rong CONG ; Cheng-Jian JI ; Chao QIN ; Ning-Hong SONG
National Journal of Andrology 2019;25(3):243-247
Objective:
To explore the feasibility of glans-preserving surgery (GPS) in the treatment of superficial penile squamous cell carcinoma (PSCC) with the lesion diameter of ≥2 cm.
METHODS:
We retrospectively analyzed the clinical data on 69 cases of superficial PSCC (≤T1aN0) treated by GPS (n = 36) or radical surgery (total or partial penectomy, n = 33) from July 2007 to July 2017.
RESULTS:
The mean tumor diameter and depth of invasion were 3.16 (2.0-6.0) cm and 0.89 (0.5-2.0) cm in the GPS group and 3.56 (2.0-6.0) cm and 1.89 (0.6-4.0) cm respectively in the radical surgery group. The patients were followed up for 10-102 (mean 42) months, during which, 5 patients in the GPS group developed local recurrence at 40 days and 2, 4, 7 and 9 months postoperatively, again underwent gansectomy, partial penectomy or GPS, and experienced no more recurrence during the follow-up of 54, 34, 39, 66 and 70 months. No local recurrence was observed in the radical surgery group, and none of the 69 patients experienced lymph node metastasis or died during the follow-up.
CONCLUSIONS
GPS is safe and efficient for the treatment of superficial PSCC with the lesion diameter of ≥2 cm.
5.Application of superb microvascular imaging in manifesting the blood flow of the penile cavernous artery in vascular ED patients.
Xiao-Feng LAN ; Fan JIANG ; Mei PENG ; Ting-Ting WU ; Xiang XIE ; Jun WU ; Rui HU ; Wei TAN
National Journal of Andrology 2019;25(3):238-242
Objective:
To investigate the application value of superb microvascular imaging (SMI) in the diagnosis of penile vascular ED.
METHODS:
Seventy-two ED patients underwent SMI and color Doppler flow imaging (CDFI), all ultrasonographically diagnosed with penile vascular ED. We compared SMI and CDFI in detecting the grades of blood flow in the cavernous artery and the lengths of time needed to obtain satisfactory blood flow spectrum from the patients.
RESULTS:
SMI mainly revealed grades Ⅲ and Ⅳ blood flow, in 43 and 20 of the 72 patients (87.5%), while CDFI chiefly manifested grades Ⅰ and Ⅱ blood flow, in 26 and 32 cases respectively (80.6%). The former showed significantly better manifestations of the penile cavernous artery than the latter. It took less time to obtain the spectrums of grades Ⅲ and Ⅳ blood flow ([1.52 ± 0.18] and [1.21 ± 0.11] min) than grades Ⅰ and Ⅱ ([5.23 ± 0.44] and [4.46 ± 0.65] min), and SIM took significantly less time than CDFI ([1.32 ± 0.42] vs [4.53 ± 0.67] min, P < 0.05).
CONCLUSIONS
SMI is superior to CDFI in better manifesting the blood flow of the penile cavernous artery and shortening the examination time, and therefore deserves a wide application in the diagnosis of vascular ED.
6.Correlation between CFTR 5T polymorphisms and the risk of congenital bilateral absence of the vas deferens.
Guo-Guo ZHAO ; Hong-Bo SUN ; Hui-Jie ZHI ; Fan WANG ; Qiu-Yue WU ; Xin-Yi XIA ; Xiao-Feng XU
National Journal of Andrology 2019;25(3):231-237
Objective:
To investigate the association between the 5T site polymorphism of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the risk of congenital bilateral absence of the vas deferens (CBAVD).
METHODS:
This case-control study included 40 male patients with isolated CBAVD in the experimental group and 104 healthy men as controls. We used the Sanger sequencing method to encode the CFTR gene intron 9 (TG) m-n(T) and type the haplotypes, followed by a review and meta-analysis of the data obtained from the experiment and relevant literature from the PubMed, Web of science, Medline, CNKI and an exploration of the correlation between 5T mutation and the risk of CBAVD.
RESULTS:
Sanger sequencing revealed 6 genotypes in the CBAVD patients, including TG11-5T, TG12-5T, TG13-5T, TG11-7T, TG12-7T and TG11-9T, and 7 in the healthy controls, which were TG11-5T, TG12-5T, TG10-7T, TG11-7T, TG12-7T, TG13-7T and TG11-9T. Compared with the controls, the CBAVD patients showed obviously increased rates of the TG12-5T haplotype (4.81% [10/208] vs 16.25% [13/80]) and the TG13-5T haplotype (0% vs 7.5% [6/80]), but no significant difference in the TG11-5T haplotype (1.92% [4/208] vs 2.50% [2/80]). There was a statistically significant difference between the experimental and control groups in the TG12_13-5T haplotype (OR = 7.40, 95% CI: 4.83-11.34, P < 0.01). The TG12_13-5T haplotype was found to be highly correlated with CBAVD.
CONCLUSIONS
The haplotype of TG12_13-5T increases the risk of CBAVD in men, which has provided a theoretical basis for male reproduction.
7.Chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in males undergoing IVF/ICSI.
Xian-Bao MAO ; Lin-Tao XUE ; Wei-Ying MO ; Yao-Xi MO ; Jun-Ping CHENG ; Shi-Kai WANG ; Yue-Yue HUANG ; Zheng-da LI ; Xiao-Hui ZHANG ; Ting-Ting ZHOU ; Ping-Pin WEI ; Wei-Hong TAN
National Journal of Andrology 2019;25(3):223-230
Objective:
To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).
METHODS:
We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes.
RESULTS:
Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% [34/2 370], 22.08% [34/154]), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% [82/2 370], 53.25% [82/154]), 26 cases of interbrachial inversion of chromosome 9 (1.10% [26/2 370], 16.88% [26/154]), 10 cases of Y chromosome polymorphisms (0.42% [10/2 370], 6.50% [10/154]), and 2 cases of mixed chromosome polymorphisms (0.08% [2/2 370], 1.42% [2/154]). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05).
CONCLUSIONS
Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.
8.Down-regulated PTTG1 expression promotes the senescence of human prostate cancer LNCaP-AI.
Yang-Yang WEI ; Xiao-Ming SONG ; Zhao-Hui XIONG ; Ke-Quan LU ; Lu ZHENG ; Xi-Liang CAO
National Journal of Andrology 2019;25(3):216-222
Objective:
To investigate the effect of the down-regulated expression of pituitary tumor-transforming gene 1 (PTTG1) on the senescence of human castration-resistant prostate cancer LNCaP-AI cells.
METHODS:
Human castration-resistant prostate cancer LNCaP-AI cells were induced in vitro and transfected with siRNA targeting PTTG1 (the siRNA-PTTG1 group), the reagent lip3000 only (the mock group) or siRNA negative control vector (the NC group). All the cells were cultured in fetal bovine serum (FBS) or charcoal-stripped bovine serum (CSS) and counted with the cell counting chamber. The senescence characteristics of the transfected LNCaP-AI cells were examined by senescence-associated β-galactosidase (SA-β-Gal) staining, and the expressions of the senescence-related β-galactosidase-1-like proteins (Glb1), the cyclin-dependent kinase inhibitors p-21CIP1 and p-27Kip1, and the chromatin-regulating heterochromatin protein 1γ (HP1γ) were detected by Western blot.
RESULTS:
The expression of PTTG1 in the human prostate cancer LNCaP-AI cells was significantly reduced in the siRNA-PTTG1 group compared with those in the mock and NC groups (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05). Culture with FBS markedly increased while that with CSS decreased the number of LNCaP-AI cells transfected with siRNA, but both FBS and CSS enhanced the proliferation of the LNCaP-AI cells in the mock and NC groups. SA-β-Gal staining revealed that reducing the expression of PTTG1 induced a remarkably higher positive rate of the LNCaP-AI cells in the siRNA-PTTG1 than in the mock and NC groups ([63.5 ± 2.35]% vs [11.3 ± 1.24]% and [12.4 ± 1.15]%, P < 0.05). The siRNA-PTTG1 group, in comparison with the mock and NC groups, showed a significantly down-regulated expression of PTTG1 (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05), but up-regulated expressions of p-21CIP1 (0.32 ± 0.03 vs 0.20 ± 0.02 and 0.21 ± 0.03, P < 0.05), p-27Kip1 (0.38 ± 0.02 vs 0.20 ± 0.03 and 0.22 ± 0.01, P < 0.05), Glb1 (0.24 ± 0.01 vs 0.13 ± 0.01 and 0.15 ± 0.01, P < 0.05), and HP1γ (0.41 ± 0.01 vs 0.26 ± 0.01 and 0.27 ± 0.02, P < 0.05) in the LNCaP-AI cells.
CONCLUSIONS
Down-regulated expression of PTTG1 induces senescence of human castration-resistant prostate cancer LNCaP-AI cells.
9.Effects of long non-coding RNA RP1-90L14.1 on the biological behaviors of cancer prostate LNCaP cells and its regulating mechanisms.
Pin-Geng WU ; Yu-Xi ZHANG ; Zhe ZHANG ; Chui-Ze KONG
National Journal of Andrology 2019;25(3):209-215
Objective:
To investigate the effects of long non-coding RNA RP1-90L14.1 on the proliferation, migration and invasion of prostate cancer LNCaP cells and the expressions of GRIN2A and BACE2.
METHODS:
Using RT-PCR, we detected the expression of RP1-90L14.1 in LNCaP and LNCaP-AI cells, transiently transfected the RP1-90L14.1 overexpression plasmid (the RP1-90L14.1 group) and vector plasmid (the LNCaP-NC group) into the LNCaP cells, and cultured the two groups of cells with ordinary medium and phenol red-free activated carbon adsorption medium (PRF-ACA). Then we examined the proliferation, migration and invasiveness of the cells by CCK-8 and Transwell, and determined the mRNA and protein expressions of GRIN2A and BACE2 by RT-PCR and Western blot.
RESULTS:
The expression of RP1-90L14.1 was significantly higher in the LNCaP-AI than in the LNCaP cells (8.49 ± 0.43 vs 2.53 ± 0.95, P < 0.05), and so was that of LNCaP-RP1-90L14.1 in the RP1-90L14.1 than in the LNCaP-NC group after transfection (0.71 ± 0.22 vs 0.02 ± 0.01, P < 0.05). The optical densities (OD) of the cells were 51.95% and 50.69% higher in the RP1-90L14.1 than in the LNCaP-NC group after 72 hours of culture with ordinary medium and phenol red-free ACA (1.22 ± 0.08 vs 0.08 ± 0.05, P < 0.05; 0.79 ± 0.02 vs 0.53 ± 0.05, P < 0.05), and 51.72% and 60.23% higher in the former than in the latter after 96 hours (1.72 ± 0.07 vs 1.13 ± 0.05, P < 0.05; 1.18 ± 0.05 vs 0.73 ± 0.08, P < 0.05). The numbers of the migrating cells cultured with common medium and PRF-ACA were markedly higher in the RP1-90L14.1 than in the LNCaP-NC group after transfection (682.0 ± 42.7 vs 422.0 ± 37.1, P < 0.05; 419.0 ± 42.9 vs 251.0 ± 25.9, P < 0.05), and so were those of the invading cells (507.0 ± 22.2 vs 274.0 ± 19.6, P < 0.05; 352.0 ± 14.1 vs 216.0 ± 14.3, P < 0.05). Statistically significant differences were observed between the RP1-90L14.1 and LNCaP-NC groups in the mRNA and protein expressions of GRIN2A (5.13 ± 0.89 vs 2.09 ± 0.54, P < 0.05; 5.88 ± 0.29 vs 2.03 ± 0.22, P < 0.05) and BACE2 (5.82 ± 0.50 vs 2.53 ± 0.30, P < 0.05; 4.89 ± 0.19 vs 3.37 ± 0.13, P < 0.05).
CONCLUSIONS
lncRNA RP1-90L14.1 may play important roles in the proliferation, migration and invasiveness of prostate cancer cells. RP1-90L14.1 can promote the expressions of GRIN2A and BACE2 and may have an endogenous competitive relation with GRIN2A and BACE2.
10.The role of SPAG6/SPINK2 protein complex in the formation of sperm acrosome in mice.
Hong-Wei ZHANG ; Ling ZHANG ; Ya-Meng CHEN ; Xin SHEN ; Heng-Qi WANG ; Yun-Hao LIU ; Zhi-Bing ZHANG
National Journal of Andrology 2019;25(3):202-208
Objective:
To explore the expression and regulatory function of sperm-associated antigen 6 (SPAG6) in the formation of the sperm acrosome in mice.
METHODS:
The expression of SPAG6 during the first wave of spermatogenesis on postnatal days (PN) 8, 12, 16, 20, 24, 28, 30 and 35 was examined by Western blot and the localization of SPAG6 in the testicular germ cells was determined by immunofluorescence. The expression plasmids of SPAG6 and serine protease inhibitor Kazal-type 2 (SPINK2) were constructed, the interaction between SPAG6 and SPINK2 in the AH109 and CHO cells examined by yeast two-hybrid and co-localization assays, and the expression and localization of SPINK2 in the testicular germ cells of the SPAG6-knockout (SPAG6 KO) mice detected by immunofluorescence.
RESULTS:
SPAG6 was highly expressed between PN 16 and 28 and localized in the acrosome of the round spermatids. Yeast two-hybrid assay showed the growth of SPAG6 and SPINK2 in the selective culture medium SD/-Leu/-Trp/-His, and the transfection of the CHO cells revealed the co-localization of SPAG6 and SPINK2 around the nuclei. The expression and acrosomal localization of SPINK2 were not found in the testicular germ cells of the SPAG6-KO mice.
CONCLUSIONS
SPAG6 interacts with SPINK2 and probably participates in the formation of the sperm acrosome by stabilizing the expression of SPINK2 during spermatogenesis.