This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers...This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.展开更多
The article ＂Cationic liposome-mediated transfection of CD40 ligand gene inhibits hepatic tumor growth of hepatocellular carcinoma in mice＂ [doi： 10. 1631/jzus.B0820178] by Jiang et al.（2009） in a recent issue of...The article ＂Cationic liposome-mediated transfection of CD40 ligand gene inhibits hepatic tumor growth of hepatocellular carcinoma in mice＂ [doi： 10. 1631/jzus.B0820178] by Jiang et al.（2009） in a recent issue of the Journal of Zhejiang University SCIENCE B was highly thought provoking. The authors have clearly demonstrated the efficacy of CD40 ligand gene therapy in inhibiting the growth of hepatocellular carcinomas. The findings of Jiang et al.（2009） are highly important as they further support and corroborate the rapidly expanding role of CD40 ligand gene therapy in the management of systemic malignancies besides hepatocellular carcinomas.展开更多
Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many c...Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many cases eventually progress to castration-resistant prostate cancer(CRPC),and led to treatment failure.To develop new therapeutic strategies to ameliorate the survival of PCa patients then has pressed the need on medicinal researchers.Of traditional Chinese medicinal herbs,Angelica gigas Naka(AGN),and its major pyranocoumarins were broadly reported on the effect of anti-PCa.However,existing reviews mainly focus on decursin(D),decursinol angelate(DA),and decursinol(DOH),without fully exploring other coumarins in AGN.Moreover,most reviews discuss general anticancer effects,with limited emphasis on PCa specifically.This review made a comprehensive summary of the coumarin components of AGN,and depicted the anti-PCa effects and mechanisms,giving a solid research support for drug discovery and development.This review also featured pharmacokinetic advantages and therapeutic potential of DOH,in order to suggest possibilities to overcome the in vivo transformation limitations of D and DA,and shed light on CRPC treatment.We also recommend future studies focus on more in vivo evidence,safety and toxicity evaluation,and clinical validation in humans.展开更多
We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Resea...We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.展开更多
Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is...Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer （PCa） and high-grade PCa （HGPCa） was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA （%fPSA ＋ PSA） was determined by the area under the receivers operating characteristic curve （AUC）. %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.展开更多
Recent evidence shows that certain microRNAs （miRNAs） play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence ...Recent evidence shows that certain microRNAs （miRNAs） play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases, miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios （HR） and 95% confidence intervals （95% CI） for recurrence free survival. A significantly （P=0.014） higher proportion of recurrent cases （78,6%） than non-recurrent cases （48.6%） had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese （HR=6.15, 95% CI= 1.04-36.48, P=-0.045）, but not in non-obese （HR= 1.28, 95% C1=0.30-5.49, P=0.74） cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.展开更多
Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m ce...Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.展开更多
Aim： To investigate the possible role of manganese in the regulation of mitochondrial aconitase （mACON） activity human prostate carcinoma cell line PC-3 cells. Methods： The mACON enzymatic activities of human pros...Aim： To investigate the possible role of manganese in the regulation of mitochondrial aconitase （mACON） activity human prostate carcinoma cell line PC-3 cells. Methods： The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays. Results： In vitro study revealed that manganese chloride （MnCI2） treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC- 3 cells. Although results from transient gene expression assays showed that MnCI2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by cotreatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCh on the gene expression of mACON. Conclusion： These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.展开更多
There are some current literatures describing the morphologic change of prostate carcinoma variants. Some subtypes do not respond to hormone deprivation therapy, for example adenosquamous and squamous cell carcinoma ...There are some current literatures describing the morphologic change of prostate carcinoma variants. Some subtypes do not respond to hormone deprivation therapy, for example adenosquamous and squamous cell carcinoma （SQCC）, basaloid and adenoid cystic carcinoma （ACC）, small cell carcinoma （SmCC）, sarcomatoid carcinoma, urothelial carcinoma; some are defined in special Gleason grade, some develop different prognosis. So, it is very important to identify these rare subtypes to avoid misdiagnosis. In this review, we aim to describe the typical clinicopathological features of the rare variants of prostate cancer, including prostate acinar adenocarcinoma morphologic variants.展开更多
The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in over...The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.展开更多
The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer （PCa）. In this study, a total of 31 patie...The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer （PCa）. In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% （4/31）. Serum prostate-specific antigen （PSA） was 8.9 ± 1.2μg L^-1 after the neoadjuvant therapy and 0.4±0.3μg L^-1 one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group （n = 12） and the radical prostatectomy group （n = 19, P 〈 0.01）. The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.展开更多
Intraductal carcinoma of the prostate(IDC-P)is an aggressive pathological pattern of prostate cancer(PCa).We investigated the association of IDC-P in prostate biopsy(PBx)with several pathological features after radica...Intraductal carcinoma of the prostate(IDC-P)is an aggressive pathological pattern of prostate cancer(PCa).We investigated the association of IDC-P in prostate biopsy(PBx)with several pathological features after radical prostatectomy(RP)and its prognostic value in high-risk PCa.A total of 418 patients with high-risk PCa after RP were included in this study.IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification.Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features.Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P.IDC-P was identified in PBx in 36/418(8.6%)patients.Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP,including Gleason score 8-10(P<0.001),seminal vesicular invasion(P<0.001),and pathological T(pT)3a(P=0.043).Patients with IDC-P in PBx manifested poorer biochemical-free survival(BFS)than those without IDC-P(37.47 months vs not reached,P<0.001).The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools.We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa.In addition,IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.展开更多
Objective:Small cell prostate carcinoma(SCPC)is a rare and highly malignant subtype of prostate cancer.SCPC frequently lacks androgen receptor(AR)and prostate-specific antigen(PSA)expression,and often responds poorly ...Objective:Small cell prostate carcinoma(SCPC)is a rare and highly malignant subtype of prostate cancer.SCPC frequently lacks androgen receptor(AR)and prostate-specific antigen(PSA)expression,and often responds poorly to androgen deprivation therapy(ADT).AR splice variant-7(AR-V7)is a truncated AR protein implicated in resistance to AR-targeting therapies.AR-V7 expression in castration-resistant prostate cancers has been evaluated extensively,and blood-based detection of AR-V7 has been associated with lack of response to abiraterone and enzalutamide.However,whether AR-V7 is expressed in SCPC is not known.Methods:Using validated antibodies,we performed immunohistochemistry(IHC)assay for the full-length AR(AR-FL)and(AR-V7)on post-ADT surgical SCPC specimens.Results:Seventy-five percent(9/12)of the specimens showed positive staining for the AR-FL with various intensities.Thirty-three percent(4/12)of the specimens showed positive staining for AR-V7.Among the specimens with positive AR-V7 staining,two samples displayed very weak staining,one sample showed weak-to-moderate staining,and one sample showed strong staining.All positive specimens displayed a heterogeneous pattern of AR-FL/AR-V7 staining.All specimens positive for AR-V7 were also positive for AR-FL.Conclusion:The study findings support the existence of measurable AR-FL and AR-V7 proteins in SCPC specimens.The results also have implications in detection of AR-V7 in specimens obtained through systemic sampling approaches such as circulating tumor cells.A positive AR-V7 finding by blood-based tests is not impossible in patients with SCPC who often demonstrate low PSA values.展开更多
Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were e...Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.展开更多
We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results b...We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative Study, We divided the patients into two groups using the Gleason score： an intermediate/high-grade group （≥7） and a low-grade group （〈6）. Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality （P〈 0.05）, and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation （P 〉 0.05）. Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer （PCa）. The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in Pca.展开更多
The concept of intraductal carcinoma of prostate （IDC-P） has evolved over the years and its clinieopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraducta...The concept of intraductal carcinoma of prostate （IDC-P） has evolved over the years and its clinieopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraductal lesions that represent earlier stages of the malignant process in other anatomic sites such as the breast, IDC-P has now been generally recognized as a prognostically unfavorable manifestation of later stage spreading of its invasive counterpart. We here briefly review the evolution of the IDC-P concept, the histological diagnostic criteria and differential diagnosis, the clinical significance, as well as recent molecular data of IDC-P.展开更多
Primary signet ring cell carcinoma(SRCC)of the prostate is a rare neoplasm.However,its potential tumorigenic mechanism,clinicopathological features,and prognostic outcome have not been systematically described.To dete...Primary signet ring cell carcinoma(SRCC)of the prostate is a rare neoplasm.However,its potential tumorigenic mechanism,clinicopathological features,and prognostic outcome have not been systematically described.To determine the pathogenic mechanism,we detected distributions of programmed cell death-ligand 1(PD-L1),programmed death 1(PD-1),and cellular components in the tumor microenvironment,including tumor-infiltrating lymphocytes(CD4 and CD8),tumor-associated macrophages(TAMs;CD163 and CD68),and tumor-associated fibroblasts(vimentin and alpha-smooth muscle actin[α-SMA]),in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma(PCa)by immunohistochemical staining.We found higher expression of PD-L1,CD163,and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores,indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate.For further analysis,we searched electronic journal databases and Surveillance,Epidemiology,and End Results(SEER)to identify 200 eligible patients including our four cases.According to Kaplan–Meier survival curve analysis,patients<68 years old,with radical prostatectomy(RP),Gleason score of 7–8,and lower clinical stage had longer overall survival(OS).Moreover,Cox multivariate analysis indicated that race(hazard ratio[HR]=1.422),surgical approach(HR=1.654),and Gleason score(HR=2.162)were independent prognostic factors for OS.Therefore,primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs,which warrants further clinical investigation.展开更多
We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate(IDC-P)for prognosis and the associations between IDC-P and clinicopathological parameters.Studies were identified in ...We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate(IDC-P)for prognosis and the associations between IDC-P and clinicopathological parameters.Studies were identified in PubMed,Cochrane Library,EMBASE,Web of Science,and SCOPUS up to December 1,2019.Hazard ratios(HRs)for survival data and odds ratios for clinicopathological data with 95%confidence intervals(CIs)were extracted.Heterogeneity was evaluated by the I2 value,and quality was assessed by the Newcastle-Ottawa Scale criteria.A total of 4179 patients from 13 studies were included.The results showed that IDC-P presence was significantly associated with poor progression-free survival(PFS;HR=2.31;95%Cl:1.96-2.73),cancer-specific survival(HR=1.89;95%Cl:1.28-2.77),and overall survival(HR=2.14;95%Cl:1.53-3.01).In the subgroup analysis,IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy(HR=2.48;95%Cl:2.05-3.00)and treated by radiotherapy(HR=2.83;95%Cl:1.65-4.85).Regarding clinicopathological characteristics,patients with IDC-P presence had significantly higher tumor clinical stages,Gleason scores,probabilities of lymph node invasion,positive surgical margins,and positive extraprostatic extension.Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics.Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination.These conclusions need further validation,and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.展开更多
To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were ...To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79%and 60% , respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P<0.01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.展开更多
The effect of Smac gene on the TRAIL-induced apoptosis of the prostate cancer cell line PC-3 and the molecular mechanism were investigated. The Smac gene was transfected into PC-3 cells under the induction of liposome...The effect of Smac gene on the TRAIL-induced apoptosis of the prostate cancer cell line PC-3 and the molecular mechanism were investigated. The Smac gene was transfected into PC-3 cells under the induction of liposome. The intrinsic Smac gene expression was detected by Western blotting. After treatment with TRAIL as an apoptosis inducer, in vitro cell growth activity was assayed by MTT colorimetry. The apoptosis rate of PC-3 cells was determined by annexin Ⅴ-FITC and propidium iodide staining flow cytometry. The expression of cellular XIAP and caspase-3 genes was examined by Western blotting. Smac-transfected cells (PC-3/Smac group) had significantly increased Smac protein level as compared with PC-3 controls (P<0.01). After induction with 100–200 ng/mL TRAIL for 12–36 h, cellular proliferation rate in PC-3/Smac group was significantly lower than in PC-3 controls (P<0.05). After induction with 100 ng/mL TRAIL for 24 h, the apoptosis rate in PC-3/Smac group was significantly enhanced as compared with that of PC-3 controls (P<0.05). Accordingly, the XIAP expression level was down-regulated significantly (P<0.05) and caspase-3 subunit P20 was up-regulated significantly (P<0.05). It is suggested that the over-expression of cellular Smac can inhibit inhibitor of apoptosis proteins (IAPs), enhance caspases activity and the apoptosis rate of PC-3 cells induced by TRAIL, which may provide a useful experimental basis for prostate cancer therapy.展开更多
文摘This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.
文摘The article ＂Cationic liposome-mediated transfection of CD40 ligand gene inhibits hepatic tumor growth of hepatocellular carcinoma in mice＂ [doi： 10. 1631/jzus.B0820178] by Jiang et al.（2009） in a recent issue of the Journal of Zhejiang University SCIENCE B was highly thought provoking. The authors have clearly demonstrated the efficacy of CD40 ligand gene therapy in inhibiting the growth of hepatocellular carcinomas. The findings of Jiang et al.（2009） are highly important as they further support and corroborate the rapidly expanding role of CD40 ligand gene therapy in the management of systemic malignancies besides hepatocellular carcinomas.
基金supported by the Natural Science Foundation of Guangdong Province(grant number 2021A1515011485)the Traditional Chinese Medicine Multidisciplinary Innovation Team Program of Liaoning Province(grant number LNZYYCXTD-JCCX-002)+1 种基金the Key Laboratory foundation of Ministry of Education for TCM Viscera State Theory and Applications of Liaoning University of Traditional Chinese Medicine(grant number.zyzx1807)“Three levels”Talent Construction Projects in Zhuhai College of Science and Technology.
文摘Prostatic carcinoma(PCa)has become one of the most common cancers among men worldwide,with both incidence and mortality rates steadily rising.Although current treatments are effective in the early stages of PCa,many cases eventually progress to castration-resistant prostate cancer(CRPC),and led to treatment failure.To develop new therapeutic strategies to ameliorate the survival of PCa patients then has pressed the need on medicinal researchers.Of traditional Chinese medicinal herbs,Angelica gigas Naka(AGN),and its major pyranocoumarins were broadly reported on the effect of anti-PCa.However,existing reviews mainly focus on decursin(D),decursinol angelate(DA),and decursinol(DOH),without fully exploring other coumarins in AGN.Moreover,most reviews discuss general anticancer effects,with limited emphasis on PCa specifically.This review made a comprehensive summary of the coumarin components of AGN,and depicted the anti-PCa effects and mechanisms,giving a solid research support for drug discovery and development.This review also featured pharmacokinetic advantages and therapeutic potential of DOH,in order to suggest possibilities to overcome the in vivo transformation limitations of D and DA,and shed light on CRPC treatment.We also recommend future studies focus on more in vivo evidence,safety and toxicity evaluation,and clinical validation in humans.
文摘We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.
文摘Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer （PCa） and high-grade PCa （HGPCa） was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA （%fPSA ＋ PSA） was determined by the area under the receivers operating characteristic curve （AUC）. %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.
文摘Recent evidence shows that certain microRNAs （miRNAs） play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases, miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios （HR） and 95% confidence intervals （95% CI） for recurrence free survival. A significantly （P=0.014） higher proportion of recurrent cases （78,6%） than non-recurrent cases （48.6%） had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese （HR=6.15, 95% CI= 1.04-36.48, P=-0.045）, but not in non-obese （HR= 1.28, 95% C1=0.30-5.49, P=0.74） cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.
文摘Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.
文摘Aim： To investigate the possible role of manganese in the regulation of mitochondrial aconitase （mACON） activity human prostate carcinoma cell line PC-3 cells. Methods： The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays. Results： In vitro study revealed that manganese chloride （MnCI2） treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC- 3 cells. Although results from transient gene expression assays showed that MnCI2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by cotreatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCh on the gene expression of mACON. Conclusion： These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.
基金supported by the National Natural Science Foundation of China No.81570180, 81072103 (to Dr. Wang)
文摘There are some current literatures describing the morphologic change of prostate carcinoma variants. Some subtypes do not respond to hormone deprivation therapy, for example adenosquamous and squamous cell carcinoma （SQCC）, basaloid and adenoid cystic carcinoma （ACC）, small cell carcinoma （SmCC）, sarcomatoid carcinoma, urothelial carcinoma; some are defined in special Gleason grade, some develop different prognosis. So, it is very important to identify these rare subtypes to avoid misdiagnosis. In this review, we aim to describe the typical clinicopathological features of the rare variants of prostate cancer, including prostate acinar adenocarcinoma morphologic variants.
文摘The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.
文摘The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer （PCa）. In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% （4/31）. Serum prostate-specific antigen （PSA） was 8.9 ± 1.2μg L^-1 after the neoadjuvant therapy and 0.4±0.3μg L^-1 one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group （n = 12） and the radical prostatectomy group （n = 19, P 〈 0.01）. The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.
文摘Intraductal carcinoma of the prostate(IDC-P)is an aggressive pathological pattern of prostate cancer(PCa).We investigated the association of IDC-P in prostate biopsy(PBx)with several pathological features after radical prostatectomy(RP)and its prognostic value in high-risk PCa.A total of 418 patients with high-risk PCa after RP were included in this study.IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification.Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features.Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P.IDC-P was identified in PBx in 36/418(8.6%)patients.Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP,including Gleason score 8-10(P<0.001),seminal vesicular invasion(P<0.001),and pathological T(pT)3a(P=0.043).Patients with IDC-P in PBx manifested poorer biochemical-free survival(BFS)than those without IDC-P(37.47 months vs not reached,P<0.001).The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools.We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa.In addition,IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.
基金The work at Johns Hopkins University School of Medicine was supported by National Institutes of Health Grants(R01 CA185297 and P30 CA006973)Department of Defense Prostate Cancer Research Program Grants(W81XWH-15-2-0050)+1 种基金Johns Hopkins Prostate SPORE Grant(P50 CA058236)the Prostate Cancer Foundation.
文摘Objective:Small cell prostate carcinoma(SCPC)is a rare and highly malignant subtype of prostate cancer.SCPC frequently lacks androgen receptor(AR)and prostate-specific antigen(PSA)expression,and often responds poorly to androgen deprivation therapy(ADT).AR splice variant-7(AR-V7)is a truncated AR protein implicated in resistance to AR-targeting therapies.AR-V7 expression in castration-resistant prostate cancers has been evaluated extensively,and blood-based detection of AR-V7 has been associated with lack of response to abiraterone and enzalutamide.However,whether AR-V7 is expressed in SCPC is not known.Methods:Using validated antibodies,we performed immunohistochemistry(IHC)assay for the full-length AR(AR-FL)and(AR-V7)on post-ADT surgical SCPC specimens.Results:Seventy-five percent(9/12)of the specimens showed positive staining for the AR-FL with various intensities.Thirty-three percent(4/12)of the specimens showed positive staining for AR-V7.Among the specimens with positive AR-V7 staining,two samples displayed very weak staining,one sample showed weak-to-moderate staining,and one sample showed strong staining.All positive specimens displayed a heterogeneous pattern of AR-FL/AR-V7 staining.All specimens positive for AR-V7 were also positive for AR-FL.Conclusion:The study findings support the existence of measurable AR-FL and AR-V7 proteins in SCPC specimens.The results also have implications in detection of AR-V7 in specimens obtained through systemic sampling approaches such as circulating tumor cells.A positive AR-V7 finding by blood-based tests is not impossible in patients with SCPC who often demonstrate low PSA values.
文摘Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.
文摘We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate （TRUSBX） and radical prostatectomy （RP）. Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative Study, We divided the patients into two groups using the Gleason score： an intermediate/high-grade group （≥7） and a low-grade group （〈6）. Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality （P〈 0.05）, and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation （P 〉 0.05）. Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer （PCa）. The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in Pca.
基金supported by grants from the Natural Science Foundation of China (NSFC 81272848, 81272820, 81302225, 81572540)
文摘The concept of intraductal carcinoma of prostate （IDC-P） has evolved over the years and its clinieopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraductal lesions that represent earlier stages of the malignant process in other anatomic sites such as the breast, IDC-P has now been generally recognized as a prognostically unfavorable manifestation of later stage spreading of its invasive counterpart. We here briefly review the evolution of the IDC-P concept, the histological diagnostic criteria and differential diagnosis, the clinical significance, as well as recent molecular data of IDC-P.
基金supported by grants from the National Natural Science Foundation of China(No.31800787 and No.81772739)the Natural Science Foundation of Liaoning Province(No.LQ2017025)+2 种基金the Doctoral Research Startup Foundation of Liaoning Province(No.20180540020)the Medical Scientific Research Project of Dalian City(No.1812038)the United Fund of the Second Hospital of Dalian Medical University and Dalian Institute of Chemical Physics,Chinese Academy of Sciences(UF-QN-202004).
文摘Primary signet ring cell carcinoma(SRCC)of the prostate is a rare neoplasm.However,its potential tumorigenic mechanism,clinicopathological features,and prognostic outcome have not been systematically described.To determine the pathogenic mechanism,we detected distributions of programmed cell death-ligand 1(PD-L1),programmed death 1(PD-1),and cellular components in the tumor microenvironment,including tumor-infiltrating lymphocytes(CD4 and CD8),tumor-associated macrophages(TAMs;CD163 and CD68),and tumor-associated fibroblasts(vimentin and alpha-smooth muscle actin[α-SMA]),in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma(PCa)by immunohistochemical staining.We found higher expression of PD-L1,CD163,and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores,indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate.For further analysis,we searched electronic journal databases and Surveillance,Epidemiology,and End Results(SEER)to identify 200 eligible patients including our four cases.According to Kaplan–Meier survival curve analysis,patients<68 years old,with radical prostatectomy(RP),Gleason score of 7–8,and lower clinical stage had longer overall survival(OS).Moreover,Cox multivariate analysis indicated that race(hazard ratio[HR]=1.422),surgical approach(HR=1.654),and Gleason score(HR=2.162)were independent prognostic factors for OS.Therefore,primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs,which warrants further clinical investigation.
基金the National Natural Science Foundation of China(No.81702518)the National Natural Science Foundation of China(No.81500636)the Innovation foundation of Huazhong University of Science and Technology(No.2019kfyXKJC06).
文摘We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate(IDC-P)for prognosis and the associations between IDC-P and clinicopathological parameters.Studies were identified in PubMed,Cochrane Library,EMBASE,Web of Science,and SCOPUS up to December 1,2019.Hazard ratios(HRs)for survival data and odds ratios for clinicopathological data with 95%confidence intervals(CIs)were extracted.Heterogeneity was evaluated by the I2 value,and quality was assessed by the Newcastle-Ottawa Scale criteria.A total of 4179 patients from 13 studies were included.The results showed that IDC-P presence was significantly associated with poor progression-free survival(PFS;HR=2.31;95%Cl:1.96-2.73),cancer-specific survival(HR=1.89;95%Cl:1.28-2.77),and overall survival(HR=2.14;95%Cl:1.53-3.01).In the subgroup analysis,IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy(HR=2.48;95%Cl:2.05-3.00)and treated by radiotherapy(HR=2.83;95%Cl:1.65-4.85).Regarding clinicopathological characteristics,patients with IDC-P presence had significantly higher tumor clinical stages,Gleason scores,probabilities of lymph node invasion,positive surgical margins,and positive extraprostatic extension.Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics.Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination.These conclusions need further validation,and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.
文摘To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79%and 60% , respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P<0.01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.
基金supported by grants from the National Natural Sciences Foundation of China(No.81001132)Special Scientific Research Foundation for the Doctoral Program of Higher Education from Ministry of Education(No.200804871105)Hubei Natural Science Foundation of China(No.2010CDB07601)
文摘The effect of Smac gene on the TRAIL-induced apoptosis of the prostate cancer cell line PC-3 and the molecular mechanism were investigated. The Smac gene was transfected into PC-3 cells under the induction of liposome. The intrinsic Smac gene expression was detected by Western blotting. After treatment with TRAIL as an apoptosis inducer, in vitro cell growth activity was assayed by MTT colorimetry. The apoptosis rate of PC-3 cells was determined by annexin Ⅴ-FITC and propidium iodide staining flow cytometry. The expression of cellular XIAP and caspase-3 genes was examined by Western blotting. Smac-transfected cells (PC-3/Smac group) had significantly increased Smac protein level as compared with PC-3 controls (P<0.01). After induction with 100–200 ng/mL TRAIL for 12–36 h, cellular proliferation rate in PC-3/Smac group was significantly lower than in PC-3 controls (P<0.05). After induction with 100 ng/mL TRAIL for 24 h, the apoptosis rate in PC-3/Smac group was significantly enhanced as compared with that of PC-3 controls (P<0.05). Accordingly, the XIAP expression level was down-regulated significantly (P<0.05) and caspase-3 subunit P20 was up-regulated significantly (P<0.05). It is suggested that the over-expression of cellular Smac can inhibit inhibitor of apoptosis proteins (IAPs), enhance caspases activity and the apoptosis rate of PC-3 cells induced by TRAIL, which may provide a useful experimental basis for prostate cancer therapy.
