KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate cancer in Chinese

Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 withCaP (adenocarcinoma clinical stage C and D) were analyzed by means of immunohistochemical methods. Results:The KAII/CD82 expression in BPH tissue was all positive, which was uniformly located on the glandular cell mem-brane at the cell-to-cell borders, but KAII/CD82 expression in metastasis CaP tissues was either significantly lower thanthat of BPH or negative, and the immunostaining pattern was not continuous. In late-stage CAP KAII/CD82 expressionwas correlated inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P > 0.05). Conclusion:The authors believe that decreased and negative KAII/CD82 expression in late-stage CaP may be related to tumor pro-gression and metastasis, and appears to be a prognostic marker.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Undescended epididymo-testicular metastasis from prostatic carcinoma

Dear Sir, Metastasis of prostatic carcinoma to testis is un- common in the clinical situation, and the involvement of the epididymis is even rarer. Heidrich et al. [1] found only 80 cases of testicular involvement in prostate cancer in published reports. In 1993, Wiebe et al. [2] found only 14 previous cases of epididymal metastasis from prostatic carcinoma in published work. The simulta- neous involvement of testis and epididymis was reported by Suhler and Blanchard in 1980 [3]. To our knowledge, this was the first documented case of a prostatic carcinoma metastasizing to undescended testis and epididymis.

Analysis on chromosome 8 heterozygosity loss in humanprostate carcinoma and high grade prostaticintraepithelial neoplasia

Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. The chromosome 8 heterozygosity loss was detected by PCR based micro-satellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade prostatic intraepithelial neoplasia. Results: There were different frequencies of chromosome 8 heterozygosity loss in 10 samples of prostate carcinoma. 8p23.1-p23.2 and p21-p22 were two high frequency heterozygosity loss regions. Chromosome 8 heterozygosity loss was detected in 3 samples of high grade prostatic intraepithelial neoplasia. Conclusion: There were high frequency heterozygosity loss regions on chromosome 8 of prostate carcinoma, located at 8p23.1-p23.2 and p21-p22. The high grade prostatic intraepithelial neoplasia and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.

Diagnosis and treatment of primary seminoma of the prostate:A case report and review of literature

BACKGROUND Primary seminoma of the prostate(PSP)is a rare type of extragonadal germ cell tumour that is easily misdiagnosed,owing to the lack of specific clinical features.It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis.CASE SUMMARY A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital.A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy.Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles.Further radiotherapy treatment for the local lesion was performed,and the patient had a disease-free survival period of 96 mo.This case was analysed along with 13 other cases of PSP identified from the literature.Only four of the cases(28.6%)were initially confirmed by prostate biopsy.In these cases,imaging examinations showed an enlarged prostate(range 6-11 cm)involving the bladder neck(13/14).Of the 14 total cases,11(78.6%)presented typical pure seminoma cell features,staining strongly positive for placental alkaline phosphatase,CD117,and OCT4.The median age at diagnosis was 51(range 27-59)years,and patients had a median progression-free survival time of 48(range 6-156)mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy.The remaining three were cases of mixed embryonal tumours with focal seminoma,which had clinical features similar to those of pure PSP,in addition that they also had elevated serum alpha fetoprotein,beta-human chorionic gonadotropin,and lactose dehydrogenase.CONCLUSION PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck.Further prostate biopsies may aid in proper PSP diagnosis.Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Commentary on: Mobley AJ, Lam YW, Lau KM, Pais VM, Lesperance JO, Steadman B, et al. Monitoring the serological Proteome Colon, the latest modality in prostate cancer detection. J Urol 2004; 172: 331-7.

This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting

Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels

Aim： To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. Methods： The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific anitgen （PSA） levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. Results： The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% （6/90） in our patients （P 〈 0.05）. The increased cancer detection rates decreased significantly when the patient PSA level increased from 0-20 ng/mL to 20.1-50 ng/mL and 〉 50 ng/mL （P 〈 0.01）. The number of positive biopsy cores in prostate cancer patients increased significantly with increasing patient PSA level （P 〈 0.01）. The rate of organ-confined prostate cancer decreased significantly with increasing patient PSA level （P 〈 0.01）. Conclusion： The extended 10- core strategy is recommended for Chinese patients with PSA 〈 20 ng/mL and the sextant strategy is recommended for those with PSA〉 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy 〉 10 years and the sextant strategy should be applied in those with life expectancy 〈 10 years. （Asian J Androl 2008 Mar; 10： 325-331）

Radioiodine therapy for castration-resistant prostate cancer following prostate-specific membrane antigen promoter-mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Differences in reproductive endocrinology between Asian men and Caucasian men——a literature review

This review provides an overview of the literature on aspects of reproductive endocrinology wherein Asian menmay differ from Caucasian, notably, prostatic nioplasm and the sensivity to pharmacological regimens of male contra-ception. Both genetic and environmental factors, such as nutrition, might be relevant. Asian men residing in Asia seemto be relatively protected from clinical prostatic nioplasm while the prevalence of preclinical prostatic nioplasm is notdifferent. Migration to an area with a higher prevalence reduces this difference but does not undo it. With regard toprostatic nioplasm the following factors have been considered as relevant in Asian men: 1) a reduction in 5α-reductaselevel, 2) decreased levels of androgenic ketosteroid precursors of 5α-reduced androgen metabolites, 3) the decreasedpresence of a P53 mutation, 4) a higher CAG-repeat length of the androgen receptor, 5) a possible higher level ofphysical activity, 6) differences in sexual activity. Furthermore, Asian men respond to a higher degree with azoosper-mia in response to contraceptive steroids. Possible explanations offered for the more pronounced response to contracep-tive steroids are: 1) differences in testicular structure and decreased spermatogenic potential, 2) an earlier and moremarked suppression in LH secretion by exogenous androgens. The differences may be due to genetical and/or environ-mental factors influencing the peripheral testosterone metabolism. Dietary factors such as the higher intake of phytoe-strogens in Asians might exert effects on 5α-reductase activity and/or on sex hormone binding globulin (SHBG) levels,thus having an impact on the biological efficay of circulating androgens. ( Asian J Androl 2000; 2: 13 - 20)

Clinical significance of the leptin and leptin receptor expressions in prostate tissues

Aim： To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia （BPH） and prostate cancer （PCa）, and to investigate whether they are associated with the development and progression of PCa. Methods： hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups： localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index （BMI） and PCa. Results： The percentage of the leptin expression in PCa was significantly higher than that in BPH （P 〈 0.01）. For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa （P 〈 0.05）. Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa （Gleason score ≤6） and poorly differentiated PCa （Gleason score 8-10） （P 〈 0.05）. The relation between the leptin expression level in PCa and the BMI was not remarkable （P = 0.447）. Conclusion： Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.

Cyclooxygenase-2 expression is dependent upon epidermal growth factor receptor expression or activation in androgen independent prostate cancer

Aim： To investigate the expression of cyclooxygenase-2 （COX-2） and epidermal growth factor receptor （EGFR） and the possible mechanism in the development in androgen independent prostate cancer （AIPC）. Methods： Immunohistochemistry was performed on paraffin-embedded sections with goat polyclonal against COX-2 and mouse monoclonal antibody against EGFR in 30 AIPC and 18 androgen dependent prostate cancer （ADPC） specimens. The effect of epidermal growth factor （EGF） treatments on the expression of COX-2 and signal pathway in PC-3 and DU-145 cells was studied using reverse transcription-polymerase chain reaction （RT-PCR） and Western blot analysis. ELISA was used to measure prostaglandin E2 （PGE2） levels in the media of PC-3 and DU-145 incubated with EGF for 24 h. Results： COX-2 was positively expressed in AIPC and ADPC, which were predominantly in endochylema of prostate cancer （PCa） cells. Intense staining was seen in AIPC （80%） and in ADPC （55.5%）, but there was no significant association between the two groups. EGFR expression was also positive in the two groups （61.8% in ADPC and 90% in AIPC, P 〈 0.01）. A significant association was found between EGFR expression and a higher Gleason score （P 〈 0.05） or tumor stage （P 〈 0.05）. The expression of PGE2 was increased in PC-3 and DU-145 cells after being incubated with EGF. Both p38MAPK and PI-3K pathway were involved in the PC-3 cell COX-2 upregulation course. In DU- 145, only p38MAPK pathway was associated with COX-2 upregulation. Conclusion： EGFR activation induces COX-2 expression through PI-3K and/or p38MAPK pathways. COX-2 and EGFR inhibitors might have a cooperative anti-tumor effect in PCa.

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

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.

Oral microbiota in the oral-genitourinary axis:identifying periodontitis as a potential risk of genitourinary cancers

Periodontitis has been proposed as a novel risk factor of genitourinary cancers:although periodontitis and genitourinary cancers are two totally distinct types of disorders,epidemiological and clinical studies,have established associations between them.Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis.Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers.Therefore,oral microbiota provides the bridge between periodontitis and genitourinary cancers.We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers.We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer,and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Role of androgen receptor in prostate cancer

The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)

^(68)Ga-PSMA PET/CT versus CT and bone scan for investigation of PSA failure post radical prostatectomy

Objective:To evaluate the use of Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography(^(68)Ga-PSMA PET/CT),compared with conventional CT abdomen/pelvis(CTAP)and whole body single photon emission CT bone scan(BS),for detection of local or distant metastasis following biochemical failure/recurrence in post-prostatectomy patients.Methods:We conducted a review of our prospectively maintained,institutional database to identify 384 patients with post-prostatectomy biochemical failure/recurrence who underwent PSMA PET/CT,CTAP and BS from February 2015 to August 2017 in Nepean Hospital,tertiary referral centre.The results of the three imaging modalities were analysed for their ability to detect local recurrence and distant metastases.PSMA PET/CT and CTAP imaging were separately performed on the same day and the BS was performed within several days(mostly in 24 h).Difference in detection rates was determined between the modalities and the Chi square test was used to determine significance.Results:A total of 384 patients were identified with a median prostate-specific antigen(PSA)of 0.465 ng/mL(interquartile range =0.19-2.00 ng/mL).Overall,PSMA PET/CT was positive for 245(63.8%)patients whereas CTAP and BS were positive in 174 patients(45.3%).A total of 98 patients(25.5%)had local or distant metastasis detected on PSMA only,while 20 patients(5.2%)had recurrences detected on CTAP but not on PSMA PET/CT.Conclusion:The use of PSMA PET/CT has a higher detection rate of predicted local or distant metastasis compared to CTAP and BS in the staging of patients with biochemical recurrences after radical prostatectomy.

Prostate calculi in cancer and BPH in a cohort of Korean men：presence of calculi did not correlate with cancer risk

Prostatic calculi are common and are associated with inflammation of the prostate. Recently,it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer （PCa） in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography （TRUS） and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings,patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume.The correlations between PCa risk and age,serum total PSA levels,prostate volume,and prostatic calculi were analyzed. Patient age and PSA,as well as the frequency of prostatic calculi in the biopsy specimens,differed significantly between both the groups （P〈0.05）. In the PCa group,the Gleason scores （GSs） were higher in patients with prostatic calculi than in patients without prostatic calculi （P = 0.023）. Using multivariate logistic regression analysis,we found that patient age,serum total PSA and prostate volume were risk factors for PCa （P = 0.001）,but that the presence of prostatic calculi was not associated with an increased risk of PCa （P = 0.13）. In conclusion,although the presence of prostatic calculi was not shown to be a risk factor for PCa,prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.

Younger patients have poorer biochemical outcome after radical prostatectomy in high-risk prostate cancer

The aim of this study was to investigate the prognostic significance of patient age with respect to tumour aggressiveness in men who underwent radical prostatectomy （RP） for prostate cancer. In this study, we reviewed the records of 743 patients who received RP without neoadjuvant or adjuvant therapy at our institution and were followed up for 〉2 years postoperatively. For our analyses, the patients were divided into two groups according to age： younger （〈60 years） and older （≥ 60 years）. Through uni- and multivariate analyses, associations of various clinicopathological parameters, including biochemical recurrence-free survival, with patient age, were evaluated among all patients, and the patients were stratified according to their D＇Amico risk classification. Among all subjects, younger （n= 126） and older （n=617） patients showed no significant differences regarding pathological parameters and biochemical recurrence-free survival （P=0.288）. For the high-risk group （n= 206）, younger patients had a lower rate of biochemical recurrence-free survival following surgery than older patients （P=0.017）, despite the fact that no significant differences were observed regarding various known prognostic parameters between the two age groups. In addition, multivariate analysis revealed that age was an independent predictor of biochemical recurrence-free survival among the high-risk group （P=O.O03）. Our results showed that relatively younger patients have a comparable biochemical outcome compared with their older counterparts following RP performed for prostate cancer. However, among patients with high-risk disease, younger patients have a worse biochemical outcome following RP compared with older patients.

Genetic variation of the PSCA gene(rs2294008) is not associated with the risk of prostate cancer

Prostate stem cell antigen（PSCA） is a cell-membrane glycoprotein consisting of 123 amino acids and highly expressed in the prostate,but there have been few reports on the relationship between rs2294008 of PSCA and prostate cancer in the literature.Therefore,we evaluated the association between rs2294008 and the risk of prostate cancer.A total of 240 prostate cancer patients and 306 controls（patients with benign prostatic hyperplasia） were enrolled.Genotype analysis of rs2294008 of PSCA was performed using PCR.Logistic regression analysis was performed according to the genotype of PSCA rs2294008.We found that CT and TT genotypes were associated with an insignificant risk of prostate cancer compared with the CC genotype（P= 0.627 and 0.397,respectively）.In addition,there was no significant difference in rs2294008 according to clinicopathological parameters,such as age,Gleason score,prostate-specific antigen（PSA）,stage,and metastasis in prostate cancer（P 〉 0.05 for each）.Age,Gleason score,PSA,pathologic stage,and metastasis did not modify the association between PSCA and the risk of prostate cancer（each P 〉 0.05 for each）.Taken together,the genetic polymorphism of PSCA rs2294008 was not associated with the risk of prostate cancer.Our results suggest that rs2294008 may not play a role in prostate carcinogenesis.

Cooperative Therapeutic Effects of Herpes Simplex Virus Thymidine Kinase Gene/Ganciclovir System and Chemotherapeutic Agents on Prostate Cancer in vitro

The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir （HSV-tk/GCV） approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer （HRPC） cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction （RT-PCR） and strept avidin-biotin complex （SABC） im- munohistochemical method. The killing effect of GCV, cisplatin （CDDP）, etoposide （VP-16）, vincristine （VCR）, methotrexate （MTX）, 5-fluorouracil （5-Fu）, and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry （FCM）. The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38 % and 35.51%, and the proportion of necrosis being 33.05 % and 28.87 %, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment. Our results highlight the potential for such new combination therapies for future treatments of HRPC.

Biochemical recurrence of pathological T2+localized prostate cancer after robotic-assisted radical prostatectomy:A 10-year surveillance

BACKGROUND pT2+prostate cancer(PCa),a term first used in 2004,refers to organ-confined PCa characterized by a positive surgical margin(PSM)without extracapsular extension.Patients with a PSM are vulnerable to biochemical recurrence(BCR)following radical prostatectomy(RP);however,whether adjuvant radiotherapy(aRT)is imperative to PSM after RP remains controversial.This study had the longest follow-up on pT2+PCa after robotic-assisted RP since 2004.Moreover,we discussed our viewpoints on pT2+PCa based on real-world experiences.AIM To conclude a 10-year surveillance on pT2+PCa and compare our results with those of the published literature.METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled.Two serial tests of prostate specific antigen(PSA)≥0.2 ng/mL were defined as BCR.Various designed factors were analyzed using statistical tools for BCR risk.SAS 9.4 was applied and significance was defined as P<0.05.Univariate,multivariate,linear regression,and receiver operating characteristic(ROC)curve analyses were performed for statistical analyses.RESULTS With a median follow-up period of 9 years,25(52%)patients had BCR(BCR group),and the remaining 23(48%)patients did not(non-BCR group).The median time for BCR test was 4 years from the first postoperative PSA nadir.Preoperative PSA was significantly different between the BCR and non-BCR groups(P<0.001),and ROC curve analysis of preoperative PSA suggested a cutoff value of 19.09 ng/mL(sensitivity,0.600;specificity:0.739).The linear regression analysis showed no correlation between time to BCR and preoperative PSA(Pearson’s correlation,0.13;adjusted R2=0.026).CONCLUSION Robotic-assisted RP in pT2+PCa of worse conditions can provide better BCR-free survival.A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+PCa BCR rate.Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR.Based on our experiences and review of the literature,we do not recommend routine aRT for pT2+PCa.