[Comparison of efficacy and safety of transurethral thulium laser vapoenucleation of prostate and transurethral thulium laser enucleation of prostate in the treatment of benign prostatic hyperplasia].

Objective: To compare early outcomes between transurethral thulium laser vapoenucleation of prostate and transurethral thulium laser enucleation of prostate for the treatment of benign prostatic hyperplasia (BPH). Methods: Retrospective analysis was conducted on the clinical data of 1 638 BPH patients admitted to the Department of Urology of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021. There were 916 patients underwent transurethral thulium laser vapoenucleation of prostate (ThuVEP group) and 722 patients underwent transurethral thulium laser enucleation of prostate (ThuLEP group). The operation time, eliminated tissue weight, surgical complications, duration of post-operative catheter implantation were compared between the two groups. The improvement of International Prostate Symptom Score (IPSS), Quality of Life Index (QoL), maximum uroflow rate (Qmax) and post-void residual urine volume (PVR) at 1 month after operation was compared between the two groups. Results: There were no significant differences in age, preoperative and 1-month postoperative prostate volume, IPSS score, QoL score, Qmax, and PVR between the ThuVEP and ThuLEP group (all P>0.05). There were no significant differences in perioperative indicators such as operation time, cutting or enucleation time, tissue crushing time, tissue weight, hemoglobin change, catheter indwelling time, and postoperative hospital stay between ThuVEP group and ThuLEP group (all P>0.05). The incidence of minor gross hematuria after extubation in the ThuVEP group was 7.8% (56/916), which was lower than 9.4% (65/722) in the ThuLEP group (P=0.026); the incidence of temporary incontinence at 1 month after surgery was 5.2% (38/916) in ThuVEP group, lower than 11.9% (86/722) in ThuLEP group (P<0.001). A total of 3 patients (0.4%) in ThuLEP group required operative intervention for severe post-operation bleeding, but none of ThuVEP group suffered from this kind of surgical complications. Conclusions: ThuVEP has similar efficacy with ThuLEP for the treatment of BPH. ThuVEP can significantly reduce the incidence of post-operation temporary urine incontinence, and has much superiority in stanching bleeding.

[Laser treatment of benign prostate hyperplasia and its related problems after operation].

Benign prostate hyperplasia (BPH) is the main cause of lower urinary tract symptoms in elder man. As the progression of aging society, the number of BPH patient is getting larger, while there are some patient needs surgical interventions. Regarding as the main surgical intervention, trans-urethral resection of the prostate is gradually developing and focusing on minimal invasive, safety and long-term sustainability. As the surgical energy medium developing, the traditional electronic heat energy has been replaced by laser. Laser has different wavelength which suit for different operational ways separately, and it was applied on more and more surgical ways. Although the revolution of operational techniques and equipment make choices of surgeons diverse, the prevention and treatment of BPH post-surgical problems is still the clinical key points. We concluded the laser treatment on BPH and its post-surgical problem, and try to provide methods and idea for the application of clinical laser applications.

[A new understanding of wound repair after surgery for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. Transurethral resection of prostate (TURP), as an important BPH treatment, is also the most effective way to relieve prostatic obstruction. However, postoperative complications, such as lower urinary tract symptoms (LUTS), infection, hematuria and bladder neck contracture, may still occur, which seriously impact the therapeutic effect and patients' quality of life. The wound healing after BPH surgery is closely associated with the occurrence of postoperative complications. Therefore, comprehensively understanding the influencing factors of wound healing and designing tailored interventions will be particularly important for reducing postoperative complications of BPH.

[Effects of androgen deprivation therapy for prostate cancer on gut microbiota and treatment].

Androgen deprivation therapy is widely regarded as the first-line therapy for advanced prostate cancer. Although the initial efficacy is significant, clinical complications that arise after the therapy can reduce the patient's life quality, affect the efficacy, and even endanger their health or life due to the progression to castration-resistant prostate cancer (CRPC). The gut microbiota is associated not only with local diseases of the intestinal tract but also with systemic diseases such as liver or neurological diseases, but its relationship with prostate cancer is less frequently studied. Androgen deprivation therapy for prostate cancer affects the gut microbiota of prostate cancer patients, thereby inducing relevant complications and promoting CRPC formation. In this review, we present the microecological effects of androgen deprivation therapy for prostate cancer on gut microbiota from the perspectives of gut microbiota diversity, intestinal microbiota structure, and functional pathways. We also propose corresponding countermeasures, such as fecal microbiota transplantation, oral antibiotics, and oral probiotics, to improve the efficacy and outcome of androgen deprivation therapy for prostate cancer by regulating gut microbiota, and provide new ideas for the diagnosis and treatment of advanced prostate cancer.

[Overview of risk factors for stress urinary incontinence and strategies in its prevention and treatment].

Stress urinary incontinence is a medical problem that afflicts women worldwide. The causes can be mainly divided into 4 parts: increased abdominal pressure and chronic ischemia of pelvic floor muscles, endocrine changes, pelvic structural damages, inflammatory and consumptive states. The choice of prevention and treatment should also be based on a comprehensive assessment of individualized factors. Treatment techniques which are more minimally invasive or even non-invasive than surgery are currently a hot topic of research in the field of pelvic floor and urinary control, including laser and radiofrequency therapy, periurethral injection therapy, exogenous stem cell therapy and technology for activation of endogenous stem cells. They are expected to solve the clinical problem of stress urinary incontinence with a wider scope of application, lower trauma and fewer complications in the future.

[Risk factors for recurrent hospitalizations of patients with atrial fibrillation].

Objective: To determine the predictors of recurrent hospitalizations among atrial fibrillation (AF) patients. Methods: We analyzed data from the Chinese Atrial Fibrillation Registry (CAFR), a prospective cohort study involving non-valvular atrial fibrillation (NVAF) patients from Augest 2011 to December 2017. A total of 5 349 NVAF patients with a minimum of 48 months follow-up were included for analysis. Data including patient demographics, complications, medical and ablation history were collected. The maximum number of all-cause hospitalizations within one-year for each patient served as the primary endpoint. Patients hospitalized less than twice within one-year were defined as non-recurrent hospitalizations group, those hospitalized at least twice within one-year were definned as recurrent hospitalizations group. Logistic regression model was used to identify associated risk factors for recurrent hospitalizations. Results: Of 5 349 NVAF patients, those hospitalized for 0, 1, 2, 3, 4 and at least 5 times within one-year was 2 703 (50.5%), 1 776 (33.2%), 642 (12.0%), 161(3.0), 52 (1.0%), 15 (0.3%), respectively. Eight hundred and seventy (16.3%) patients were included in recurrent hospitalizations group, 4 479 (83.7%) patients were included in non-recurrent hospitalizations group. Compare with non-recurrent hospitalizations group, patients in recurrent hospitalizations group was more likely to be older and female, more frequently had a history of hypertension, heart failure, coronary heart disesase, ischaemic stroke/transient ischaemic attack, diabetes mellitus, peptic ulcer, a AF duration for more than 1 year, medication including drugs for ventricular rate control, statin, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocker (ARB) and higher CHA(2)DS(2)-VASc scores (P<0.05), but less frequently had higher education, a history of drinking, smoking and ablation (P<0.05). Multivariable analysis showed that age 50-64 (OR=1.47, 95%CI 1.20-1.80), age≥65 (OR=1.89, 95%CI 1.50-2.38), female (OR=1.21, 95%CI 1.01-1.46), hypertension history (OR=1.42, 95%CI 1.16-1.74), heart failure history (OR=1.73, 95%CI 1.37-2.18), coronary heart disease history (OR=1.63, 95%CI 1.31-2.03), peptic ulcer history (OR=2.00, 95%CI 1.18-3.39) were independent risk factors for recurrent hospitalizations, while higher education (college or above) (OR=0.82, 95%CI 0.69-0.99) was the protective factor for recurrent hospitalizations. Conclusions: Nearly 1 in 6 of AF patients were admitted to hospital more than once within one year in this NVAF cohort. Age≥50, female, hypertension history, heart failure history, coronary heart disease history, peptic ulcer history are associated with an increased risk of recurrent hospitalizations.

[Efficacy and safety of low-intensity pulsed ultrasound at different intervals by mechanical force in treating erectile dysfunction: a preliminary study].

Objective: To study the efficacy and safety of low-intensity pulsed ultrasound (LIPUS) at different intervals by mechanical force in treating erectile dysfunction (ED). Method: Forty patients with mild to moderate ED were randomized in a 1∶1 ratio to receive 16-treatment sessions of LIPUS in group A and group B, applied 3 times per week and 2 times per week, respectively. End-point assessments were made at 8th week after treatment. Efficacy were evaluated using International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Erectile Hardness Score (EHS), Self-Esteem and Relationship Questionnaire (SEAR), Sexual Encounter Profile (SEP), Global Assessment Question (GAQ), and pain were assessed by Visual Analogue Score (VAS).Treatment response was confirmed by a minimal clinically importance difference (MCID) at 8th week. Results: Compared with baseline, IIEF-EF score [(17.1±5.48 vs 23.4±3.75, P<0.05) and (18.9±4.34 vs 24.1±4.32, P<0.05)], proportion of EHS 4 [(0 vs 40%, P<0.05) and (16.7% vs 55.6%, P<0.05)], and Overall Relationship score [(50.6 vs 67.5, P<0.05) and (44.4 vs 70.1, P<0.05)] were significantly improved at 8th week in two groups, respectively. Compared with baseline, the positive responses to SEP-3 increased significantly at 8th week in two groups (50.0% vs 80.0%,P<0.05) and (44.4% vs 88.9%, P<0.05), respectively. The positive responses to GAQ-2 were 90.0% and 88.9% at 8th week in two groups, respectively. There were no significant differences in IIEF-EF, EHS, SEAR, SEP and GAQ at 8th week between two groups. There was no significant difference in treatment response using MCID between two groups at end-point (80.5% vs 77.5%). The treatment duration for full sessions were 2.5 weeks less in group A than group B. No adverse effects were reported in all cases. Conclusion: LIPUS at two different intervals is effective and safe for mild to moderate ED, and the regimen at 3 times per week can achieve quite good effect in relatively short duration,while the long-term effects is still be clarified in further study.

[Comparative observation of thulium laser resection of the prostate-tangerine technique and transurethral resection of the prostate for the treatment of benign prostatic hyperplasia of various sizes].

Objective: To compare the efficiency and safety of thulium laser resection of the prostate-tangerine technique (TmLRP-TT) and transurethral resection of the prostate (TURP) for the treatment of benign prostatic hyperplasia (BPH) of various sizes. Methods: Clinical data of 249 BPH patients received TmLRP-TT or TURP were retrospectively collected. Patients were divided into small prostate group [prostate volume (PV)<40 ml], medium prostate group (40 ml≤PV<80 ml) and large prostate group (PV ≥ 80 ml) based on transrectal ultrasound (TRUS) results. Age, PV, Prostate-specific antigen (PSA), International prostate symptom score (IPSS), Quality of life (QoL), maximum of flow rate (Q(max)) and post-void residual urine (PVR) of patients received TmLRP-TT or TURP in each group were analyzed, as well as the perioperative data including operation time, hemoglobin and serum sodium level, transfusion, postoperative length of indwelling catheter and postoperative hospital stay. Furthermore, the postoperative complication rates of patients received the two operative methods in each group up to follow-up of 6 months were compared. Results: As for baseline indicators, there were no significant differences regarding age, prostate volume, PSA, IPSS, QoL, Qmax and PVR of patients received TmLRP-TT or TURP in each group (all P>0.05). In the small prostate group, there were no significant differences with operation time, hemoglobin and serum sodium level, transfusion, postoperative length of indwelling catheter and postoperative hospital stay received TmLRP-TT or TURP (all P>0.05). For the medium prostate group, patients received TmLRP-TT underwent longer operation time [(67.4±15.1) vs (57.5±11.5) min, P<0.001], but shorter length of indwelling catheter [(1.5±0.6) vs (3.1±0.9) d, P<0.001] and postoperative hospital stay [(3.5±0.9) vs (5.6±1.0) d, P<0.001], and there were no significant differences regarding transfusion rate (3/73 vs 1/78, P=0.280), hemoglobin [(9.8±9.0) vs (12.2±9.6) g/L, P=0.107] and serum sodium decrease [(2.07±3.65) vs (2.97±3.35) mmol/L, P=0.373]. In the large prostate group, patients received TmLRP-TT also underwent longer operation time [(86.5±14.3) vs (76.7±14.6) min, P=0.022], but less hemoglobin [(11.3±13.8) vs (23.3±15.0) g/L, P=0.006] and serum sodium decrease [(2.41±2.67) vs (4.00±6.22) mmol/L, P=0.042], lower transfusion rate (5/27 vs 0/24, P=0.026), and shorter length of indwelling catheter [(1.8±0.7) vs (4.3±1.5) d, P<0.001] as well as postoperative hospital stay [(3.7±1.1) vs (6.1±1.7) d, P<0.001]. Less overall complications were encountered in the medium (38/73 vs 24/78, P=0.008) and large (26/27 vs 10/24, P<0.001) prostate group who received TmLRP-TT, which was not seen in the small prostate group (P=0.589). Conclusions: TmLRP-TT and TURP are similarly efficient for the treatment of BPH of various sizes. For BPH patients with medium and large prostate, TmLRP-TT demonstrated significant advantages in reducing the overall complications, although the operation time was slightly longer.

Treatment for residual stones using flexible ureteroscopy and holmium laser lithotripsy after the management of complex calculi with single-tract percutaneous nephrolithotomy.

This study validated the effectiveness and safety of the treatment for residual stones using flexible ureteroscopy (fURS) and holmium laser (0.6-1.2 J, 20-30 Hz) lithotripsy via a fiber with a 200-µm core diameter and 0.22 numerical aperture (NA) after the management of complex calculi with single-tract percutaneous nephrolithotomy (PCNL). Between January 2014 and June 2016, 27 consecutive patients with complex calculi underwent fURS and holmium laser lithotripsy after a planned single-tract PCNL. Among the 27 patients with complex calculi, 9 had full staghorn calculi, 7 had partial staghorn calculi, and 11 had multiple calculi. After the first single-tract PCNL session, the mean stone size and mean stone surface area were 18.0 ± 10.7 mm and 181.9 ± 172.2 mm2, respectively. Treatment for residual stones with fURS and holmium laser lithotripsy was successfully completed and was performed without intraoperative complications. The mean operative time of the fURS procedure was 69.1 ± 23.6 min, and the mean hospital stay was 5.3 ± 2.4 days. The mean decrease in the hemoglobin level was 7.3 ± 6.5 g/l. After the fURS procedure, the overall stone-free rate was 88.9%. The overall postoperative complication rate was 14.8% (Clavien grade I 11.1%; Clavien grade II 3.7%). The current approach tested here combines the advantages of both PCNL and fURS and effectively manages complex calculi with a high stone-free rate (SFR) (88.9%). This approach also reduced the number of treatment sessions, the number of percutaneous access tracts, and the blood loss and potential morbidity associated with multiple tracts.

[Effectiveness of microsurgical crossover anastomosis in treating complicated obstructive azoospermia].

Objective: To evaluate the efficacy and safety of microsurgical crossover vasovasostomy in treating complicated obstructive azoospermia. Methods: The data of 14 patients with complicated obstructive azoospermia treated with microsurgical crossover vasovasostomy were reviewed from October 2012 to March 2016.Ten of them underwent microsurgical crossover vasovasostomy. Intraoperative exploration revealed that 2 patients had vas deferens injury and contralateral testicular atrophy or epididymal obstruction due to previous hernia repair; 7 patients had obstruction of intracorporeal vas deferens on one side and epididymal obstruction on the other side; the other 1 patient had unilateral vasal obstruction with contralateral epididymal obstruction. Furthermore, 4 patients underwent microsurgical crossover vasoepididymostomy, including 3 patients who had obstruction at caput epididymis on one side, and obstruction at cauda epididymis and distal vas deferens on the other side; the other patient had absence of vas deferens in the scrotum on one side, and testicular atrophy on the other side. Regular follow-up visits were conducted after the surgery. Results: Two patients were lost to follow-up; the other 12 patients were follow-up for an average of 11 (range: 2-23) months. In the 10 cases receiving microsurgical crossover vasovasostomy (including 2 patients lost to follow-up), 1 has not undergone semen re-analysis, 6 were confirmed patent, including 3 reporting spontaneous pregnancy. The patency rate in the 4 patients receiving microsurgical crosseover vasoepididymostomy was 2/4, with 1 patient reporting spontaneous pregnancy. There was no complaint of discomfort or complications following the surgery. Conclusions: Microsurgical crossover anastomosis may be effective and safe for patients with complicated obstructive azoospermia, according to preoperative assessment and intraoperative exploration. It allows natural conception for patients with refractory infertility. The microsurgical crossover anastomosis could be an effective therapy to achieve satisfactory patency of vas deferens.

[Effect of prostate peripheral zones stromal cells on the proliferation of prostate cells by overexpression of LMO2 gene].

OBJECTIVE: To explore the biological effect of prostate peripheral zones (PZs) stromal cells on the proliferation of prostate cells by overexpression of LMO2 gene. METHODS: Genes expressional distinction of different prostate stromal cells was screened by gene expression arrays. To validate the microarray data, real time-polymerase chain reaction (RT-PCR), Western blotting analysis were used to check the over expression of LMO2 in PZs cells.To compare the effect of stromal cells which overexpressed LMO2 gene on in vitro proliferation ability of BPH-1 and PC3 cell lines, cell proliferation was measured by CCK-8 and EdU assay. Cytokines chip was used to screen expression of cytokines in WPMY-1-LMO2 conditioned medium. The changes of BPH-1 and PC3 proliferation associated proteins were assessed by Western blotting. RESULTS: A total of 512 genes were identified as markedly differentially expressed in stromal cells originated from different zones. Among these genes, LMO2 gene was overexpression in peripheral zones stromal cells, and confirmed by RT-PCR and Western blotting. Expression level of LMO2 gene was significantly up-regulated in peripheral zones stromal cells compared with transitional zones stromal cells, increased by 3.36 folds on average (P<0.01). The proliferation of both PC3 and BPH-1 were found increased and STAT3 phosphorylation and CCND1 expression were increased after cultured in conditioned medium from stromal cells which stably expressed LMO2. Cytokines chip found increased FGF-9 and IL-11 expression in the medium supernatant reserved from LMO2-overexpressed stromal cell line. CONCLUSIONS: Distinct gene expression exists among prostate stromal cells originated from different zones. LMO2 overexpressed stromal cells can induce prostate epithelial cell growth via paracrine of FGF-9, IL-11 or other cytokines.

Thulium: YAG 2 mum cw laser prostatectomy: where do we stand?

INTRODUCTION: Tm:YAG 2 mum cw laser prostatectomy was introduced in the treatment of benign ptostatic obstruction (BPO). Since then numerous studies have been published proving efficacy during follow-up. However, different surgical techniques were introduced with different names for similar techniques that complicate comparison. This reviews aim was to compare published data and break down surgical techniques to core points. The authors define validate appellations for different surgical techniques and propose further use of these names to ensure homogenous nomenclature. MATERIALS AND METHODS: All publications on Thulium:YAG prostatectomy have been included in this review. Articles were reviewed and associated due to the nature of the surgical approach. A systematic review of published data was performed. RESULTS: Sixteen peer-reviewed publications dealing with Tm:YAG laser prostatectomy were printed since 2005. Four different surgical principles are described, including vaporization, resection and enucleation. Follow-up, up to 24 months, showed durable functional results. CONCLUSION: Efficacy of Tm:YAG prostatectomy was shown. Surgical techniques include "Tm:YAG Vaporization of the prostate (ThuVAP)", "Tm:YAG VapoResection of the prostate (ThuVaRP)" and "Tm:YAG VapoEnucleation of the prostate (ThuVEP)". The almost blunt enucleation is introduced as "Tm:YAG laser enucleation of the prostate (ThuLEP)". The authors recommend the use of this neologism in the future. Further, large-scale prospective studies are needed to prove long-term durability. To initiate and canalize these upcoming studies, the Urothulium Study Group was founded, combining international experts on Thulium:YAG laser prostatectomy under its roof.

Specific targeting of prostate cancer cells in vitro by the suicide gene/prodrug system, uracil phosphoribosyltransferase/5-fluorouracil, under the control of prostate-specific membrane antigen promoter/enhancer.

This study was designed to investigate the prostate cancer-specific tumoricidal effect of the suicide gene, Escherichia coli uracil phosphoribosyltransferase (UPRT), driven by the human prostate-specific membrane antigen promoter/enhancer (PSMA(E/P)) in vitro. When transfected with PSMA(E/P)-EGFP (enhanced green fluorescence protein) (a plasmid construct with the green fluorescence protein gene driven by the PSMA(E/P)), only the androgen-responsive and PSMA-positive prostate cancer cell line, LNCaP, expressed GFP, indicating the specificity of the PSMA(E/P) activity in androgen-sensitive and PSMA-positive prostate cancer cells. Taking advantage of this prostate cancer-specific property of PSMA(E/P), we successfully introduced bacterial UPRT into LNCaP cells where the tumoricidal effect of 5-fluorouracil (5-FU) was significantly increased when compared with the cells without the exogenous UPRT. We conclude that the efficacy of 5-FU-based chemotherapy in prostate cancers can be significantly improved by targeted expression of the suicide gene UPRT under the control of PSMA(E/P).

Androgen receptor isoforms in human prostatic cancer tissue and LNCaP cell line.

AIM: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaP cell line. METHODS: With high resolution isoelectric focusing (IEF) method we demonstrated the different expressions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. RESULTS: Data were obtained from three prostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the second specimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressed all the three AR isoforms. Binding of 3H-dihydrotestosterone (3H-DHT) to these three isoforms was inhibited by the addition of 100-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. CONCLUSION: The expression of AR isoforms is different in different prostate cancer tissues, which may be related to the difference in the effect of anti-androgen therapy in different patients.

Apoptosis and hormonal milieu in ductal system of normal prostate and benign prostatic hyperplasia.

AIM: To study the apoptotic rate (AR) and the androgen and estrogen milieu in the proximal and distal ductal systems of prostate, in order to help exploring the effects of these factors on prostatic growth and the pathogenesis of benign prostatic hypertrophy (BPH). METHODS: The proximal and distal ends of the ductal system were incised from 20 normal prostate as well as the hypertrophic prostate tissue from 20 patients with BPH. The AR was determined by the DNA end-labeling method and dihydrotestosterone (DHT) and estrodiol (E2), by radioimmunoassay. RESULTS: There was no significant difference in DHT and E2 density between the proximal and distal ends of the ductal systems in normal prostate. E2 appeared to be higher in BPH than in normal prostatic tissues, but the difference was statistically insignificant. In normal prostatic tissue, the AR was significantly higher in the distal than in the proximal ends of the ductal system (P < 0.05), while the AR of the proximal ends was significantly higher (P < 0.01) than that in the BPH tissue. No significant correlation was noted between the DHT and E2 density and the AR both in the normal prostate and BPH tissues. CONCLUSION: The paper is the first time describing a difference in AR in different regions of the ductal system of normal prostate, while the hormonal milieu is similar, indicating a functional inhomogeneity of these regions. A low AR in the proximal duct, where BPH originates, and an even lower AR in the BPH tissue, suggesting the participation of apoptosis in the BPH pathogenesis.

Androgen receptor isoforms in human and rat prostate.

AIM: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatic tissues. METHODS: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from patients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPH specimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4 degrees C, the tissues were examined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. RESULTS: From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In human BPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 isoforms at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 isoforms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at different combinations. Binding of 3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-fold excess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. CONCLUSION: AR isoforms are different in different patients. Although their genesis is not clear, the therapeutic implication of the present observation appears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.

Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase.

Normal diploid cells have a limited replicative potential in culture, with progressively increasing interdivision time. Rarely, cell lines arise which can divide indefinitely; like tumor cells, such "immortal" lines display frequent chromosomal aberrations which may reflect high rates of recombination. Recombination frequencies within a plasmid substrate were 3.5-fold higher in nine immortal human cell lines than in six untransformed cell strains. Expression of HsRAD51, a human homolog of the yeast RAD51 and Escherichia coli recA recombinase genes, was 4.5-fold higher in immortal cell lines than in mortal cells. Stable transformation of human fibroblasts with simian virus 40 large T antigen prior to cell immortalization increased both chromosomal recombination and the level of HsRAD51 transcripts by two- to fivefold. T-antigen induction of recombination was efficiently blocked by introduction of HsRAD51 antisense (but not control) oligonucleotides spanning the initiation codon, implying that HsRAD51 expression mediates augmented recombination. Since p53 binds and inactivates HsRAD51, T-antigen-p53 association may block such inactivation and liberate HsRAD51. Upregulation of HsRAD51 transcripts in T-antigen-transformed and other immortal cells suggests that recombinase activation can also occur at the RNA level and may facilitate cell transformation to immortality.

Induction of duplication reversion in human fibroblasts, by wild-type and mutated SV40 T antigen, covaries with the ability to induce host DNA synthesis.

Intrachromosomal homologous recombination, manifest as reversion of a 14-kbp duplication in the hypoxanthine phosphoribosyl transferase (HPRT) gene, is elevated in human cells either stably transformed or transiently transfected by the SV40 (simian virus 40) large T antigen gene. Following introduction of wild-type SV40, or any of several T-antigen point mutations in a constant SV40 background, we observed a strong correlation between the stimulation of chromosomal recombination and induction of host-cell DNA synthesis. Moreover, inhibitors of DNA replication (aphidicolin and hydroxyurea) suppress SV40-induced homologous recombination to the extent that they suppress DNA synthesis. Stable integration of plasmids encoding T antigen also augments homologous recombination, which is suppressed by aphidicolin. We infer that the mechanism by which T antigen stimulates homologous recombination in human fibroblasts involves DNA replicative synthesis.