Summary: To study the expression of hypoxia inducible factor-1α (HIF-1α) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1α was assayed by means of immunohistochemical techni...Summary: To study the expression of hypoxia inducible factor-1α (HIF-1α) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1α was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1α in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1α expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1α was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1α in NP. The level of HIF-1α in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1α is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.展开更多
Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in ter...Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in terms of erectile dysfunction.This systematic review and meta-analysis aimed to evaluate the preservation of erectile function following robotic-assisted and laparoscopic radical prostatectomy,with a separate analysis of randomized clinical trials and non-randomized studies.Methods:This review was carried out using randomized and non-randomized studies involving adult patients diagnosed with localized prostate cancer undergoing radical prostatectomy,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO.Applicable literature from PubMed,Cochrane,Embase,and the Latin American and Caribbean Health Sciences Literature database was analysed.The bias in randomized clinical trials was assessed using the Cochrane Risk of Bias 2.0 tool,and observational studies were evaluated via the Newcastle-Ottawa Scale.The statistical analysis was performed using Review Manager version 5.4.Results:Our analysis included 13 studies involving 6281 patients.Comparative meta-analysis of non-randomized studies demonstrated that robotic techniques were significantly more effective in preserving erectile function at 3 months(risk difference[RD]0.05,95%confidence interval[CI]0.00-0.11;p=0.040),6 months(RD 0.10,95%CI 0.03-0.17;p=0.006),and 12 months postoperatively(RD 0.06,95%CI 0.02-0.10;p=0.002).Conclusion:Robotic-assisted surgery showed greater preservation of erectile function 3 months,6 months,and 12 months after radical prostatectomy.However,additional studies with meticulous methodological criteria are necessary for future analysis.展开更多
Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-ca...Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-called 'bystander effect' mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis. mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by re- verse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malig- nant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. As- sessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was ab- normally located and markedly diminished as compared with normal prostatic epithelial ones, dis- playing a negative correlation to the pathological grade (χ2=4.025, P<0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indi- cated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein par- ticipated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of 'bystander effect', but also to initiation and progression of prostatic neoplasm.展开更多
Several studies have revealed that the preoperative serum testosterone and percent tumor volume （PTV） predict extra-prostatic extension （EPE） and biochemical recurrence （BCR） after radical prostatectomy. This st...Several studies have revealed that the preoperative serum testosterone and percent tumor volume （PTV） predict extra-prostatic extension （EPE） and biochemical recurrence （BCR） after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy （LRP）. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen （PSA） 〉0.2 ng ml^-1. The threshold for serum total testosterone was 3.0 ng ml^-1, Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone （〈3.0 ng ml^-1） was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone （〈3.0 ng ml^-1, adjusted OR, 8.52; 95% CI, 5.04-14.4, P = 0.001） predicted EPE and PTV （adjusted OR, 1.02; 95% CI, 1.01-1.05, P = 0.046） predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.展开更多
BACKGROUND Prostate cancer(PCa)is one of the most common cancers among men.Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy ...BACKGROUND Prostate cancer(PCa)is one of the most common cancers among men.Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy of detecting clinically significant PCa in recent years.AIM To investigate the diagnostic efficiency of a template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa.METHODS Data from patients with an increasing prostate-specific antigen(PSA)level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed.All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area.A total of 127 patients with complete data were included in the final analysis.A multivariable logistic regression analysis was conducted,and a two-sided P<0.05 was considered statistically significant.RESULTS PCa was detected in 66 of 127 patients,and 56 cases presented clinically significant PCa.Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa,specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa.A randomized biopsy detected seven cases of PCa negative on targeted biopsy,and four cases had clinically significant PCa.PSA density(OR:1.008,95%CI:1.003-1.012,P=0.001;OR:1.006,95%CI:1.002-1.010,P=0.004)and Prostate Imaging-Reporting and Data System(PI-RADS)scores(both P<0.001)were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone.CONCLUSION This single-centered study proposed a feasible template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy.Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.展开更多
In order to screen the genes differentially expressed in two human prostate cancer cells with different metastasis potentials, suppression subtractive hybridization （SSH） was done twice on human prostate cancer cell...In order to screen the genes differentially expressed in two human prostate cancer cells with different metastasis potentials, suppression subtractive hybridization （SSH） was done twice on human prostate cancer cell line with high potential of metastasis PC3M-IE8 and its synogenetic cell line PC3M-2B4 with low metastasis potential. In the first subtraction PC3M-2B4 was used as tester and PC3M-1E8 as driver and the forward subtractive library was constructed. In the second one the tester and driver were interchanged and the reverse subtractive library was constructed. The screened clones of both libraries were sequenced and Gene Bank homology search was performed. Some clones were confirmed by quantitative real-time PCR. The results showed that two subtractive libraries containing 238 positive clones were constructed. Analysis of 16 sequenced clones randomly picked from two libraries showed that 4 differentially expressed gene fragments were identified as new EST with unknown functions. It was concluded that two subtractive libraries of human prostate cancer cell lines with different metastasis potentials were constructed successfully.展开更多
Aim： To examine the impact and prognostic significance of α-tocopherol associated protein （TAP） expression in a series of prostate cancer patients. Methods： Tissues from 87 patients underwent radical prostatectom...Aim： To examine the impact and prognostic significance of α-tocopherol associated protein （TAP） expression in a series of prostate cancer patients. Methods： Tissues from 87 patients underwent radical prostatectomy were examined for TAP expression by immunohistochemistry. The relationships of the staining results, the clinic pathological characteristics and the recurrence times were analyzed. Results： Compared with the adjacent areas of normal and benign glands, immunoreactivity of TAP was reduced in areas of prostate cancer. A lower TAP-positive cell number per mm^2 of the largest cancer area （defined as TAP-PN） was associated with higher clinical stage （r = -0.248, P = 0.0322）. Inverse associations were found among the TAP-PN and positive lymph nodes （r = -0.231, P = 0.0325）, preoperative prostatespecific antigen （PSA） levels （r = -0.423, P = 0.0043）, tumor size （r = -0.315, P = 0.0210） and elevated tumor cell proliferation, which was indicated by the staining of Ki-67 （r = -0.308, P = 0.0026）. TAP-PN was a significant predictor of recurrence univariately （P = 0.0006）, as well as multivariately, adjusted for known markers including preoperative PSA, clinical stage, Gleason score, surgical margin, extra-prostatic extension, seminal vesicle invasion and lymph node metastasis （P = 0.0012）. Conclusion： Reduced expression of TAP was associated with the cell proliferation status of prostate cancer, adverse pathological parameters and the increased risk of recurrence.展开更多
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 ...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.展开更多
Prostate cancer is one of the major health care problems, but the molecular pathogenesis has been relatively insufficiently elucidated. Recently, whole exome sequencing of prostate cancer identified recurrent mutation...Prostate cancer is one of the major health care problems, but the molecular pathogenesis has been relatively insufficiently elucidated. Recently, whole exome sequencing of prostate cancer identified recurrent mutations involving MED12 in Caucasian patients, which finding was not reproduced in one subsequent study by Sanger sequencing. Thus, we investigated mutation status of MED12 in exons 2 and 26 by Sanger sequencing in 102 radical prostatectomy cases from Korean patients. The analysis found the mutation in none of the cases. Therefore, MED12 mutation does not appear to represent a significant molecular alteration in this cohort of patients according to the analysis by the traditional ＂gold standard.＂展开更多
Objective: To explore the possible mechanisms of growth regression of human androgen dependent prostate carcinoma cells caused by androgen withdrawal. Methods: After 24 h of treatment with 1 × 10-9 mol/L dihydrot...Objective: To explore the possible mechanisms of growth regression of human androgen dependent prostate carcinoma cells caused by androgen withdrawal. Methods: After 24 h of treatment with 1 × 10-9 mol/L dihydrotestosterone (DHT), the expression of phosphorylated ERK proteins and cell cycle regulation molecules including CDK2, CDK4, CDK6 and P27kip1 in human androgen dependent prostate carcinoma cell line LNCaP was measured by Western blot analysis 0 h, 8 h and 24 h of after androgen withdrawal. Human androgen independent prostate carcinoma cell line PC-3 was also examined as control. Results: Down-regulation of phosphorylated ERK, CDK2, CDK4 and CDK6 and up-regulation of P27kip1 were found initially in LNCaP cell line 8 h after androgen withdrawal. The levels of phosphorylated ERK and CDKs decreased continuously and reached the lowest after 24 h, while continuous elevation of P27kip1 was detected thereafter to 24 h. No expression change of phosphorylated ERK, CDKs and P27kip1 were detected in PC-3 cell line. Conclusion: The androgen withdrawal can cause ERKs activation decrease and cell cycle regulation molecules changes, which may be one of the mechanisms for inhibited growth of androgen dependent prostate carcinoma after androgen ablation by either operative or medicine methods.展开更多
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...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展开更多
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 ...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）展开更多
Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng ml-1, False-positives lead to unnecessary biopsies with...Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng ml-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA between 4.0 and 10 ng m1-1. We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1, Thirty （19.1%） were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHh The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity （95% CI） of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 （49%） unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHi levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1.Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng m1-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA between 4.0 and 10 ng mI-L We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng mI-L Thirty （19.1%） were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity （95% CI） of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 （49%） unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHi levels also correspond to increasing the risk of detecting GS 〉7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 nR ml-1.展开更多
This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer dia...This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineurat invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis （P 〈 0.05）. Gleason score （odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P= 0.001）, perineural invasion （OR = 4.961, 95% CI = 2.656-9.270, P〈 0.001）, and number of positive cores （OR = 4.403, 95% CI = 1.878-10.325, P = 0.001） were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion （49.5%） was much higher than that with localized disease （17.8%）. In contrast, prostate volume showed a protective effect against positive surgical margin （OR = 0.572, 95% CI = 0.346-0.945, P = 0.029）. Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin.展开更多
The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted...The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-J3, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-l, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor （AR）, and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.展开更多
We report the overall rate, locations and predictive factors of positive surgical margins （PSMs） in 271 patients with high-risk prostate cancer. Between April 2008 and October 2011, we prospectively collected data f...We report the overall rate, locations and predictive factors of positive surgical margins （PSMs） in 271 patients with high-risk prostate cancer. Between April 2008 and October 2011, we prospectively collected data from patients classified as D＇Amico high-risk who underwent robot-assisted laparoscopic radical prostatectomy. Overall rate and location of PSMs were reported. Stepwise logistic regression models were fitted to assess predictive factors of PSM. The overall rate of PSMs was 25.1% （68 of 271 patients）. Of these PSM, 38.2% （26 of 68） were posterolateral （PL）, 26.5% （18 of 68） multifocal, 16.2% （11 of 68） in the apex, 14.7% （10 of 68） in the bladder neck, and 4.4% （3/68） in other locations. The PSM rate of patients with pathological stage pT2 was 8.6% （12 of 140）, 26.6% （17 of 64） of pT3a, 53.3% （32/60） of pT3b, and 100% （7 of 7） of pT4. In a logistic regression model including pre-, intra-, and post-operative parameters, body mass index （odds ratio [OR]. 1.09; 95% confidence interval [CI]： 1.01-1.19, P = 0.029）, pathological stage （pT3b or higher vs pT2; OR： 5.14; 95% Ch 1.92-13.78; P = 0.001） and percentage of the tumor （OR： 46.71; 95% CI： 6.37-342.57; P 〈 0.001） were independent predictive factors for PSMs. The most common location of PSMs in patients at high-risk was the PL aspect, which reflects the reported tumor aggressiveness. The only significant predictive factors of PSMs were pathological outcomes, such as percentage of the tumor in the specimen and pathological stage.展开更多
Prostate cancer antigen 3 （PCA3） is a biomarker for diagnosing prostate cancer （PCa） identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 me...Prostate cancer antigen 3 （PCA3） is a biomarker for diagnosing prostate cancer （PCa） identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic （ROC） curve （AUC） and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA （0.750 vs 0.622, P = 0.046） in patients with a PSA of 4.0-10.0 ng ml-I, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1. However, the AUC of the PCA3 score （0.712） is not superior to %fPSA （0.698） or PSAD （0.773） in patients with a PSA 〉10.0 ng ml-1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1.展开更多
The skeleton is the most common metastatic organ in patients with prostate cancer （PCa）. Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed ...The skeleton is the most common metastatic organ in patients with prostate cancer （PCa）. Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia （BPH）, 20 with localized PCa and 30 with bone-metastatic PCa （10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa）. A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis （P〈O.O01）. There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall＇s bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels （P=0.012 and P〈O.O01, respectively）. The serum miR-141 level was found to be positively correlated with alkaline phosphatase （ALP） level in patients with skeletal metastasis, using Pearson＇s bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen （PSA） level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.展开更多
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 ...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.展开更多
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 w...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.展开更多
文摘Summary: To study the expression of hypoxia inducible factor-1α (HIF-1α) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1α was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1α in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1α expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1α was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1α in NP. The level of HIF-1α in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1α is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.
文摘Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in terms of erectile dysfunction.This systematic review and meta-analysis aimed to evaluate the preservation of erectile function following robotic-assisted and laparoscopic radical prostatectomy,with a separate analysis of randomized clinical trials and non-randomized studies.Methods:This review was carried out using randomized and non-randomized studies involving adult patients diagnosed with localized prostate cancer undergoing radical prostatectomy,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO.Applicable literature from PubMed,Cochrane,Embase,and the Latin American and Caribbean Health Sciences Literature database was analysed.The bias in randomized clinical trials was assessed using the Cochrane Risk of Bias 2.0 tool,and observational studies were evaluated via the Newcastle-Ottawa Scale.The statistical analysis was performed using Review Manager version 5.4.Results:Our analysis included 13 studies involving 6281 patients.Comparative meta-analysis of non-randomized studies demonstrated that robotic techniques were significantly more effective in preserving erectile function at 3 months(risk difference[RD]0.05,95%confidence interval[CI]0.00-0.11;p=0.040),6 months(RD 0.10,95%CI 0.03-0.17;p=0.006),and 12 months postoperatively(RD 0.06,95%CI 0.02-0.10;p=0.002).Conclusion:Robotic-assisted surgery showed greater preservation of erectile function 3 months,6 months,and 12 months after radical prostatectomy.However,additional studies with meticulous methodological criteria are necessary for future analysis.
文摘Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-called 'bystander effect' mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis. mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by re- verse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malig- nant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. As- sessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was ab- normally located and markedly diminished as compared with normal prostatic epithelial ones, dis- playing a negative correlation to the pathological grade (χ2=4.025, P<0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indi- cated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein par- ticipated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of 'bystander effect', but also to initiation and progression of prostatic neoplasm.
文摘Several studies have revealed that the preoperative serum testosterone and percent tumor volume （PTV） predict extra-prostatic extension （EPE） and biochemical recurrence （BCR） after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy （LRP）. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen （PSA） 〉0.2 ng ml^-1. The threshold for serum total testosterone was 3.0 ng ml^-1, Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone （〈3.0 ng ml^-1） was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone （〈3.0 ng ml^-1, adjusted OR, 8.52; 95% CI, 5.04-14.4, P = 0.001） predicted EPE and PTV （adjusted OR, 1.02; 95% CI, 1.01-1.05, P = 0.046） predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.
基金the Beijing Hospital Clinical Research 121 Project(BJ-2018-090 to Ming Liu).
文摘BACKGROUND Prostate cancer(PCa)is one of the most common cancers among men.Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy of detecting clinically significant PCa in recent years.AIM To investigate the diagnostic efficiency of a template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa.METHODS Data from patients with an increasing prostate-specific antigen(PSA)level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed.All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area.A total of 127 patients with complete data were included in the final analysis.A multivariable logistic regression analysis was conducted,and a two-sided P<0.05 was considered statistically significant.RESULTS PCa was detected in 66 of 127 patients,and 56 cases presented clinically significant PCa.Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa,specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa.A randomized biopsy detected seven cases of PCa negative on targeted biopsy,and four cases had clinically significant PCa.PSA density(OR:1.008,95%CI:1.003-1.012,P=0.001;OR:1.006,95%CI:1.002-1.010,P=0.004)and Prostate Imaging-Reporting and Data System(PI-RADS)scores(both P<0.001)were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone.CONCLUSION This single-centered study proposed a feasible template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy.Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.
基金This project was supported by grants from National Basic Research Program "973" (No 2002CB513207)National Natural Sciences Foundation (No 30571950) of China
文摘In order to screen the genes differentially expressed in two human prostate cancer cells with different metastasis potentials, suppression subtractive hybridization （SSH） was done twice on human prostate cancer cell line with high potential of metastasis PC3M-IE8 and its synogenetic cell line PC3M-2B4 with low metastasis potential. In the first subtraction PC3M-2B4 was used as tester and PC3M-1E8 as driver and the forward subtractive library was constructed. In the second one the tester and driver were interchanged and the reverse subtractive library was constructed. The screened clones of both libraries were sequenced and Gene Bank homology search was performed. Some clones were confirmed by quantitative real-time PCR. The results showed that two subtractive libraries containing 238 positive clones were constructed. Analysis of 16 sequenced clones randomly picked from two libraries showed that 4 differentially expressed gene fragments were identified as new EST with unknown functions. It was concluded that two subtractive libraries of human prostate cancer cell lines with different metastasis potentials were constructed successfully.
文摘Aim： To examine the impact and prognostic significance of α-tocopherol associated protein （TAP） expression in a series of prostate cancer patients. Methods： Tissues from 87 patients underwent radical prostatectomy were examined for TAP expression by immunohistochemistry. The relationships of the staining results, the clinic pathological characteristics and the recurrence times were analyzed. Results： Compared with the adjacent areas of normal and benign glands, immunoreactivity of TAP was reduced in areas of prostate cancer. A lower TAP-positive cell number per mm^2 of the largest cancer area （defined as TAP-PN） was associated with higher clinical stage （r = -0.248, P = 0.0322）. Inverse associations were found among the TAP-PN and positive lymph nodes （r = -0.231, P = 0.0325）, preoperative prostatespecific antigen （PSA） levels （r = -0.423, P = 0.0043）, tumor size （r = -0.315, P = 0.0210） and elevated tumor cell proliferation, which was indicated by the staining of Ki-67 （r = -0.308, P = 0.0026）. TAP-PN was a significant predictor of recurrence univariately （P = 0.0006）, as well as multivariately, adjusted for known markers including preoperative PSA, clinical stage, Gleason score, surgical margin, extra-prostatic extension, seminal vesicle invasion and lymph node metastasis （P = 0.0012）. Conclusion： Reduced expression of TAP was associated with the cell proliferation status of prostate cancer, adverse pathological parameters and the increased risk of recurrence.
文摘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.
文摘Prostate cancer is one of the major health care problems, but the molecular pathogenesis has been relatively insufficiently elucidated. Recently, whole exome sequencing of prostate cancer identified recurrent mutations involving MED12 in Caucasian patients, which finding was not reproduced in one subsequent study by Sanger sequencing. Thus, we investigated mutation status of MED12 in exons 2 and 26 by Sanger sequencing in 102 radical prostatectomy cases from Korean patients. The analysis found the mutation in none of the cases. Therefore, MED12 mutation does not appear to represent a significant molecular alteration in this cohort of patients according to the analysis by the traditional ＂gold standard.＂
文摘Objective: To explore the possible mechanisms of growth regression of human androgen dependent prostate carcinoma cells caused by androgen withdrawal. Methods: After 24 h of treatment with 1 × 10-9 mol/L dihydrotestosterone (DHT), the expression of phosphorylated ERK proteins and cell cycle regulation molecules including CDK2, CDK4, CDK6 and P27kip1 in human androgen dependent prostate carcinoma cell line LNCaP was measured by Western blot analysis 0 h, 8 h and 24 h of after androgen withdrawal. Human androgen independent prostate carcinoma cell line PC-3 was also examined as control. Results: Down-regulation of phosphorylated ERK, CDK2, CDK4 and CDK6 and up-regulation of P27kip1 were found initially in LNCaP cell line 8 h after androgen withdrawal. The levels of phosphorylated ERK and CDKs decreased continuously and reached the lowest after 24 h, while continuous elevation of P27kip1 was detected thereafter to 24 h. No expression change of phosphorylated ERK, CDKs and P27kip1 were detected in PC-3 cell line. Conclusion: The androgen withdrawal can cause ERKs activation decrease and cell cycle regulation molecules changes, which may be one of the mechanisms for inhibited growth of androgen dependent prostate carcinoma after androgen ablation by either operative or medicine methods.
文摘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
文摘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）
文摘Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng ml-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA between 4.0 and 10 ng m1-1. We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1, Thirty （19.1%） were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHh The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity （95% CI） of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 （49%） unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHi levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1.Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng m1-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA between 4.0 and 10 ng mI-L We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng mI-L Thirty （19.1%） were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity （95% CI） of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 （49%） unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHi levels also correspond to increasing the risk of detecting GS 〉7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 nR ml-1.
文摘This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineurat invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis （P 〈 0.05）. Gleason score （odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P= 0.001）, perineural invasion （OR = 4.961, 95% CI = 2.656-9.270, P〈 0.001）, and number of positive cores （OR = 4.403, 95% CI = 1.878-10.325, P = 0.001） were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion （49.5%） was much higher than that with localized disease （17.8%）. In contrast, prostate volume showed a protective effect against positive surgical margin （OR = 0.572, 95% CI = 0.346-0.945, P = 0.029）. Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin.
文摘The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-J3, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-l, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor （AR）, and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.
文摘We report the overall rate, locations and predictive factors of positive surgical margins （PSMs） in 271 patients with high-risk prostate cancer. Between April 2008 and October 2011, we prospectively collected data from patients classified as D＇Amico high-risk who underwent robot-assisted laparoscopic radical prostatectomy. Overall rate and location of PSMs were reported. Stepwise logistic regression models were fitted to assess predictive factors of PSM. The overall rate of PSMs was 25.1% （68 of 271 patients）. Of these PSM, 38.2% （26 of 68） were posterolateral （PL）, 26.5% （18 of 68） multifocal, 16.2% （11 of 68） in the apex, 14.7% （10 of 68） in the bladder neck, and 4.4% （3/68） in other locations. The PSM rate of patients with pathological stage pT2 was 8.6% （12 of 140）, 26.6% （17 of 64） of pT3a, 53.3% （32/60） of pT3b, and 100% （7 of 7） of pT4. In a logistic regression model including pre-, intra-, and post-operative parameters, body mass index （odds ratio [OR]. 1.09; 95% confidence interval [CI]： 1.01-1.19, P = 0.029）, pathological stage （pT3b or higher vs pT2; OR： 5.14; 95% Ch 1.92-13.78; P = 0.001） and percentage of the tumor （OR： 46.71; 95% CI： 6.37-342.57; P 〈 0.001） were independent predictive factors for PSMs. The most common location of PSMs in patients at high-risk was the PL aspect, which reflects the reported tumor aggressiveness. The only significant predictive factors of PSMs were pathological outcomes, such as percentage of the tumor in the specimen and pathological stage.
文摘Prostate cancer antigen 3 （PCA3） is a biomarker for diagnosing prostate cancer （PCa） identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic （ROC） curve （AUC） and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA （0.750 vs 0.622, P = 0.046） in patients with a PSA of 4.0-10.0 ng ml-I, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1. However, the AUC of the PCA3 score （0.712） is not superior to %fPSA （0.698） or PSAD （0.773） in patients with a PSA 〉10.0 ng ml-1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1.
文摘The skeleton is the most common metastatic organ in patients with prostate cancer （PCa）. Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia （BPH）, 20 with localized PCa and 30 with bone-metastatic PCa （10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa）. A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis （P〈O.O01）. There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall＇s bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels （P=0.012 and P〈O.O01, respectively）. The serum miR-141 level was found to be positively correlated with alkaline phosphatase （ALP） level in patients with skeletal metastasis, using Pearson＇s bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen （PSA） level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.
文摘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.
基金The work was supported by a grant from the Guangdong Scientfic and Technologic Committee(No 970750)
文摘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.
