Objective: To determine the relationships between the incidence rates of testicular and prostatic cancers and food consumptions in order to study the etiologic cause and the mechanism of the development of male genita...Objective: To determine the relationships between the incidence rates of testicular and prostatic cancers and food consumptions in order to study the etiologic cause and the mechanism of the development of male genital organ cancer. Methods: The incidence rates of testicular and prostatic cancers in 42 countries (region) were correlated with the dietary practices in these countries. These data came from the cancer rate database (1988–1992) and the food supply database (1961–1990) provided by the Department of Environmental Health, Medical University of Yamanashi, Japan. Results: The incidence rates of testicular and prostatic cancers varied greatly from country to country but in China the rates of the both malignancies were lower than that of USA and Japan. This may be due to the difference in lifestyle, especially in dietary practices. Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20–39, followed by animal fats and milk. The correlation coefficient (r) was the highest (r=0.804) when calculated for cheese consumed during the period of 1961–1965 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that cheese (1961–1965) made a significant contribution to the incidence of testicular cancer. Multiple coefficient (r) is 0.920. As far as prostatic cancer was concerned, milk was most closely correlated (r=0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk, meat, butter and coffee as significant factors contributing to the incidence of prostatic cancer (R=0.993). The results of our study suggest a role of milk and dairy practices in the development of testicular and prostatic cancers.展开更多
Objective： MR perfusion-weighted imaging（PWI） has been widely applied in the research of cerebral tumor, benign and malignant musculoskeletal neoplasms and so on. The aim of this study is to explore the application...Objective： MR perfusion-weighted imaging（PWI） has been widely applied in the research of cerebral tumor, benign and malignant musculoskeletal neoplasms and so on. The aim of this study is to explore the application of MR perfusion-weighted imaging in prostatic cancer （Pca）, and evaluate the correlation of PWI features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Twenty-eight consecutive patients who were diagnosed clinically as prostatic cancer and thirty healthy volunteers were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWI, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWI and that of immunohistochemistry. Results： （1） In the healthy volunteers, the steepest slope of signal intensity-time curve （SSmax） and ΔR2^＊peak of perfusion curve were： 0.430±0.011, 2.01±0.7 respectively; however, in the prostatic cancer, they were 57.8±5.0, 3.0±0.6 respectively; with significant difference （t=-4.11, 3.28, P〈0.01）. （2）The VEGF and MVD expression of twenty-eight Pca patients were significantly higher. Conclusion： On MR perfusion- weighted imaging, SSmax and ΔR2^＊peak can reflect MVD and VEGF expression levels in prostatic cancer, suggesting information on tumor angiogenesis. Thus they are beneficial to the diagnosis and treatment of prostatic cancer.展开更多
Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （V...Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWl, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊ peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWl and immunohistochemistry. Results： （1） In the benign prostate hyperplasia （BPH）, SSmax and ΔR2^＊ peak of perfusion curve were 34.2 ± 2.9 and 1.49 ± 0.11, respectively; however, in the prostatic cancer （Pca）, they were 58.6± 4.8 and 3.18 ±0.49 respectively; there were statistical differences （t = 2.16 and 2.31, P 〈 0.05）. （2） The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients （x2 = 28.64, P 〈 0.01; t = 21.2, P 〈 0.01）. MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions （P 〈 0.01）. On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak showed associations with MVD and VEGF expressions （P 〈 0.01）. Conclusion： On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.展开更多
Introduction: The burden of prostatic cancer is rising in Sudan. Usually, they present late in their disease with urinary tract obstruction, hematuria, bony pain, or cachexia because there is no screening program. Her...Introduction: The burden of prostatic cancer is rising in Sudan. Usually, they present late in their disease with urinary tract obstruction, hematuria, bony pain, or cachexia because there is no screening program. Here we present a patient with prostatic cancer who presented with left axillary mass as his main concern. Case Description: 82-year-old Sudanese male presented with a left axillary and left supraclavicular lymphadenopathy of a few months’ duration. He underwent a decisional biopsy which showed metastatic adenocarcinoma. Upper and lower GI endoscopy were performed but the latter was complicated by a sigmoid perforation with peritonitis. During laparatomy, multiple enlarged pelvic lymphnodes were encountered and a biopsy result suggested a metastatic prostatic neoplasm. Later, prostatic biopsy confirmed the diagnosis. The patient was treated with bilateral orchidectomy. Clinical discussion: Lymphatic metastasis to axillary lymph nodes is a very rare manifestation of prostate cancer and only a few cases have been reported in the literature. It can cause diagnostic difficulty since prostate cancer typically metastasis to the pelvic lymph node and very rarely involves he supradiaphragmatic lymph node. Conclusion: Metastatic prostatic carcinoma should be considered among the causes of supra-diaphragmatic lymph adenopathy. Careful physical and imaging examinations combined with PSA and pathological analysis are essential in the diagnosis of advanced prostate cancer with unusual presentation.展开更多
To assess the role of dynamic contrast-enhanced MRI (DCE-MRI) in thediagnosis and differentiation of prostatic cancer (PC). Methods: Five volunteers, 36 patients withbenign prostatic hyperplasia (BPH) and 13 patients ...To assess the role of dynamic contrast-enhanced MRI (DCE-MRI) in thediagnosis and differentiation of prostatic cancer (PC). Methods: Five volunteers, 36 patients withbenign prostatic hyperplasia (BPH) and 13 patients with biopsy-proven prostate cancer underwentconventional MRI, DCE-MRI and delayed enhancement MRI. The value of the signal intensity in DCE-MRIwas measured and calculated to draw the time-signal intensity curve of the normal peripheral zone(PZ), the prostate cancer and the benign prostatic hyperplasia. Results: In DCE-MRI, the normalperipheral zone was enhanced mildly and slowly and the peak value was located in late phase. Theenhancement of the lesions in 36 patients with the benign prostatic hyperplasia was obvious in earlyphase and strengthened gradually, and then turned to decrease in late phase after peak value. Thelesions in 9 of 13 cases with prostate cancer were enhanced obviously in early phase and washed outrapidly, and the peak value was located in early phase, but the peak value was in mediate and latephase in the other 4 cases with diffuse lesion in the prostate on T_2WI. Conclusion: In DCE-MRI, theenhancement patterns of the normal peripheral zone, the prostate cancer and the benign prostatichyperplasia were significantly different. DCE-MRI was very useful in the diagnosis anddifferentiation of prostate cancer.展开更多
OBJECTIVE To investigate the diagnostic value of modified prostate specific antigen(PSA)parameters in the diagnosis of prostate cancer(PCA) when the serum PSAis in a grey zone of 4~10 ng/ml. METHODS The results of ser...OBJECTIVE To investigate the diagnostic value of modified prostate specific antigen(PSA)parameters in the diagnosis of prostate cancer(PCA) when the serum PSAis in a grey zone of 4~10 ng/ml. METHODS The results of serum PSA determinations of the patients receiving a transrectal ultrasound-guided multiphase prostatic biopsy,were retrospectively analyzed.In the 88 patients with a serum PSA value of 4-10 ng/ml,the final diagnosis of PCA was made in 21,and that of benign prostate hyperplasia(BPH)in 67 patients.The percentage of the free-serum PSA([FPSA]/total-serum PSA[TPSA],F/T),PSA density(PSAD)and the sensitivity and specificity of the new PSA modified parameter(F/T)/PSAD in diagnosing PCA,within a set threshold value,was compared. RESULTS In the 88 patients with serum PSA in the grey zone of 4.0-10.0 ng/ml,there was no significant difference in comparing the TPSA between the 21 PCA patients and 67 BPH patients(P>0.05).However, there was a significant difference in the value of modified PSA parameters, such as F/T,PSAD and(F/T)/PSAD,between the PCA and the BPH groups (P<0.001).As the cut off point-value of the F/T,PSAD and(F/T)/PSAD was set at 0.16,0.15 and 0.8,the diagnostic sensitivity for PCA was 66.7%, 76.2%and 85.7%,and the specificity was 41.8%,43.3%and 68.7%,respectively.There was no significant difference in the sensitivity comparing the modified parameters for diagnosing PCA(P>0.05),whereas an overt predominance was present in the specificity of(F/T)/PSAD for PCAdiagnosis (P<0.05). CONCLUSION In the serum PSA grey zone of 4-10 ng/ml,a modified PSA parameter can improve the PCA diagnostic accuracy rate.With a considerably high sensitivity,application of the(F/T)/PSAD may effectively enhance the diagnostic specificity,which is superior to the F/T and PSAD, and can be expected to be one of the new indices derived from the PSA.展开更多
Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and ...Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and within specific regions.It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases.Methods:We obtained data on incidence,prevalence,mortality,and disability-adjusted life-years(DALYs)for the aforementioned urologic diseases by age,sex,location,and year from the Global Burden of Disease(GBD)2021.We analyzed the burden associated with urologic diseases based on socio-demographic index(SDI)and attributable risk factors.The trends in burden over time were assessed using estimated annual percentage changes(EAPC)along with a 95%confidence interval(CI).Results:In 2021,BPH and UTI were the leading causes of age-standardized incidence rate(ASIR)and age-standardized prevalence rate(ASPR),with rates of 5531.88 and 2782.59 per 100,000 persons,respectively.Prostate cancer was the leading cause of both age-standardized mortality rate(ASMR)and age-standardized DALYs rate(ASDR),with rates of 12.63 and 217.83 per 100,000 persons,respectively.From 1990 to 2021,there was an upward trend in ASIR,ASPR,ASMR,and ASDR for UTI,while urolithiasis showed a downward trend.The middle and low-middle SDI quintile levels exhibited higher incidence,prevalence,mortality,and DALYs related to UTI,urolithiasis,and BPH,while the high and high-middle SDI quintile levels showed higher rates for the three cancers.The burden of these 6 urologic diseases displayed diverse age and sex distribution patterns.In 2021,a high body mass index(BMI)contributed to 20.07%of kidney cancer deaths worldwide,while smoking accounted for 26.48%of bladder cancer deaths and 3.00%of prostate cancer deaths.Conclusions:The global burden of 6 urologic diseases presents a significant public health challenge.Urgent international collaboration is essential to advance the improvement of urologic disease management,encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.展开更多
Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype ...Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.展开更多
Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated...Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reduci...Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isol...Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.展开更多
To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China Methods The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinc...To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China Methods The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed Results The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16 1% (15?459/95?749) and 1 5% (1389/95?749), respectively The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7 6% and 0 6%, respectively, while it was 18 5% and 3 4% from 1991 to 1997 Conclusion The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China展开更多
Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calc...Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar＇s Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. Given the high incidence of susceptibility-weighted imaging （SWl） abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.展开更多
Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore...Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors （ARs） by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA （shRNA）, matrix metalloproteinase （MMP） expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.展开更多
To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 pr...To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 prostate cancer （Cap）,20 benign prostatic hyperplasia （BPH） and 10 normal prostate （NP） specimens. Omi/HtrA2 expression was positive in 30 （73.17%） prostate cancer specimens, and the positive rate of Omi/HtrA2 was lower in well differentiated than in poorly and moderately differentiated groups （P〈0.05）. By contrast, the cells in normal prostate and benign prostatic hyperplasia groups showed no or weak expression of Omi/HtrA2. Prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2 expression might be involved in prostate cancer development.展开更多
Objective To quantitatively evaluate the metabolic changes of benign prostatic hyperplasia(BPH) and prostate cancer in the transitional zone using magnetic resonance spectroscopic imaging(MRSI),and to analyze the char...Objective To quantitatively evaluate the metabolic changes of benign prostatic hyperplasia(BPH) and prostate cancer in the transitional zone using magnetic resonance spectroscopic imaging(MRSI),and to analyze the characteristics and differences of the spectra in this zonal area.Methods Eighteen patients with prostate cancer in the transitional zone underwent magnetic resonance imaging(MRI)/MRSI examinations.The(Choline+Creatine)/Citrate(CC/Ci) ratio and the Choline/Creatine(Cho/Cr) ratio were evaluated in each voxel with cancer or BPH confirmed by pathological results.Discriminant analysis was used to determine the power of the two ratios in differentiation between cancer and BPH.Results The CC/Ci ratio and Cho/Cr ratio for cancer voxels were significantly higher than those in the voxels with BPH in the transitional zone(CC/Ci:2.36±1.31 vs.0.85±0.29,P<0.01;Cho/Cr:4.14±1.79 vs.1.26±0.45,P<0.01).As for the discriminant function with the CC/Ci ratio and the Cho/Cr ratio,the specificity,sensitivity,and accuracy were 98.6%,85.7%,92.9% respectively for the differentiation between cancer and BPH.Conclusions The prostate cancer is characterized by higher CC/Ci ratio and Cho/Cr ratio compared to BPH in the transitional zone.Both CC/Ci ratio and Cho/Cr ratio have high specificity,sensitivity,and accuracy in their discriminative power between cancer and BPH in this zonal area.展开更多
文摘Objective: To determine the relationships between the incidence rates of testicular and prostatic cancers and food consumptions in order to study the etiologic cause and the mechanism of the development of male genital organ cancer. Methods: The incidence rates of testicular and prostatic cancers in 42 countries (region) were correlated with the dietary practices in these countries. These data came from the cancer rate database (1988–1992) and the food supply database (1961–1990) provided by the Department of Environmental Health, Medical University of Yamanashi, Japan. Results: The incidence rates of testicular and prostatic cancers varied greatly from country to country but in China the rates of the both malignancies were lower than that of USA and Japan. This may be due to the difference in lifestyle, especially in dietary practices. Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20–39, followed by animal fats and milk. The correlation coefficient (r) was the highest (r=0.804) when calculated for cheese consumed during the period of 1961–1965 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that cheese (1961–1965) made a significant contribution to the incidence of testicular cancer. Multiple coefficient (r) is 0.920. As far as prostatic cancer was concerned, milk was most closely correlated (r=0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk, meat, butter and coffee as significant factors contributing to the incidence of prostatic cancer (R=0.993). The results of our study suggest a role of milk and dairy practices in the development of testicular and prostatic cancers.
文摘Objective： MR perfusion-weighted imaging（PWI） has been widely applied in the research of cerebral tumor, benign and malignant musculoskeletal neoplasms and so on. The aim of this study is to explore the application of MR perfusion-weighted imaging in prostatic cancer （Pca）, and evaluate the correlation of PWI features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Twenty-eight consecutive patients who were diagnosed clinically as prostatic cancer and thirty healthy volunteers were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWI, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWI and that of immunohistochemistry. Results： （1） In the healthy volunteers, the steepest slope of signal intensity-time curve （SSmax） and ΔR2^＊peak of perfusion curve were： 0.430±0.011, 2.01±0.7 respectively; however, in the prostatic cancer, they were 57.8±5.0, 3.0±0.6 respectively; with significant difference （t=-4.11, 3.28, P〈0.01）. （2）The VEGF and MVD expression of twenty-eight Pca patients were significantly higher. Conclusion： On MR perfusion- weighted imaging, SSmax and ΔR2^＊peak can reflect MVD and VEGF expression levels in prostatic cancer, suggesting information on tumor angiogenesis. Thus they are beneficial to the diagnosis and treatment of prostatic cancer.
文摘Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWl, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊ peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWl and immunohistochemistry. Results： （1） In the benign prostate hyperplasia （BPH）, SSmax and ΔR2^＊ peak of perfusion curve were 34.2 ± 2.9 and 1.49 ± 0.11, respectively; however, in the prostatic cancer （Pca）, they were 58.6± 4.8 and 3.18 ±0.49 respectively; there were statistical differences （t = 2.16 and 2.31, P 〈 0.05）. （2） The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients （x2 = 28.64, P 〈 0.01; t = 21.2, P 〈 0.01）. MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions （P 〈 0.01）. On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak showed associations with MVD and VEGF expressions （P 〈 0.01）. Conclusion： On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.
文摘Introduction: The burden of prostatic cancer is rising in Sudan. Usually, they present late in their disease with urinary tract obstruction, hematuria, bony pain, or cachexia because there is no screening program. Here we present a patient with prostatic cancer who presented with left axillary mass as his main concern. Case Description: 82-year-old Sudanese male presented with a left axillary and left supraclavicular lymphadenopathy of a few months’ duration. He underwent a decisional biopsy which showed metastatic adenocarcinoma. Upper and lower GI endoscopy were performed but the latter was complicated by a sigmoid perforation with peritonitis. During laparatomy, multiple enlarged pelvic lymphnodes were encountered and a biopsy result suggested a metastatic prostatic neoplasm. Later, prostatic biopsy confirmed the diagnosis. The patient was treated with bilateral orchidectomy. Clinical discussion: Lymphatic metastasis to axillary lymph nodes is a very rare manifestation of prostate cancer and only a few cases have been reported in the literature. It can cause diagnostic difficulty since prostate cancer typically metastasis to the pelvic lymph node and very rarely involves he supradiaphragmatic lymph node. Conclusion: Metastatic prostatic carcinoma should be considered among the causes of supra-diaphragmatic lymph adenopathy. Careful physical and imaging examinations combined with PSA and pathological analysis are essential in the diagnosis of advanced prostate cancer with unusual presentation.
文摘To assess the role of dynamic contrast-enhanced MRI (DCE-MRI) in thediagnosis and differentiation of prostatic cancer (PC). Methods: Five volunteers, 36 patients withbenign prostatic hyperplasia (BPH) and 13 patients with biopsy-proven prostate cancer underwentconventional MRI, DCE-MRI and delayed enhancement MRI. The value of the signal intensity in DCE-MRIwas measured and calculated to draw the time-signal intensity curve of the normal peripheral zone(PZ), the prostate cancer and the benign prostatic hyperplasia. Results: In DCE-MRI, the normalperipheral zone was enhanced mildly and slowly and the peak value was located in late phase. Theenhancement of the lesions in 36 patients with the benign prostatic hyperplasia was obvious in earlyphase and strengthened gradually, and then turned to decrease in late phase after peak value. Thelesions in 9 of 13 cases with prostate cancer were enhanced obviously in early phase and washed outrapidly, and the peak value was located in early phase, but the peak value was in mediate and latephase in the other 4 cases with diffuse lesion in the prostate on T_2WI. Conclusion: In DCE-MRI, theenhancement patterns of the normal peripheral zone, the prostate cancer and the benign prostatichyperplasia were significantly different. DCE-MRI was very useful in the diagnosis anddifferentiation of prostate cancer.
文摘OBJECTIVE To investigate the diagnostic value of modified prostate specific antigen(PSA)parameters in the diagnosis of prostate cancer(PCA) when the serum PSAis in a grey zone of 4~10 ng/ml. METHODS The results of serum PSA determinations of the patients receiving a transrectal ultrasound-guided multiphase prostatic biopsy,were retrospectively analyzed.In the 88 patients with a serum PSA value of 4-10 ng/ml,the final diagnosis of PCA was made in 21,and that of benign prostate hyperplasia(BPH)in 67 patients.The percentage of the free-serum PSA([FPSA]/total-serum PSA[TPSA],F/T),PSA density(PSAD)and the sensitivity and specificity of the new PSA modified parameter(F/T)/PSAD in diagnosing PCA,within a set threshold value,was compared. RESULTS In the 88 patients with serum PSA in the grey zone of 4.0-10.0 ng/ml,there was no significant difference in comparing the TPSA between the 21 PCA patients and 67 BPH patients(P>0.05).However, there was a significant difference in the value of modified PSA parameters, such as F/T,PSAD and(F/T)/PSAD,between the PCA and the BPH groups (P<0.001).As the cut off point-value of the F/T,PSAD and(F/T)/PSAD was set at 0.16,0.15 and 0.8,the diagnostic sensitivity for PCA was 66.7%, 76.2%and 85.7%,and the specificity was 41.8%,43.3%and 68.7%,respectively.There was no significant difference in the sensitivity comparing the modified parameters for diagnosing PCA(P>0.05),whereas an overt predominance was present in the specificity of(F/T)/PSAD for PCAdiagnosis (P<0.05). CONCLUSION In the serum PSA grey zone of 4-10 ng/ml,a modified PSA parameter can improve the PCA diagnostic accuracy rate.With a considerably high sensitivity,application of the(F/T)/PSAD may effectively enhance the diagnostic specificity,which is superior to the F/T and PSAD, and can be expected to be one of the new indices derived from the PSA.
基金supported(in part)by the National Key Research and Development Program(2022YFC3600700)the Fundamental Research Funds for the Central Universities(2042024YXA008)the Young Top-Notch Talent Cultivation Program of Hubei Province(for Prof.Xian-Tao Zeng).
文摘Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and within specific regions.It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases.Methods:We obtained data on incidence,prevalence,mortality,and disability-adjusted life-years(DALYs)for the aforementioned urologic diseases by age,sex,location,and year from the Global Burden of Disease(GBD)2021.We analyzed the burden associated with urologic diseases based on socio-demographic index(SDI)and attributable risk factors.The trends in burden over time were assessed using estimated annual percentage changes(EAPC)along with a 95%confidence interval(CI).Results:In 2021,BPH and UTI were the leading causes of age-standardized incidence rate(ASIR)and age-standardized prevalence rate(ASPR),with rates of 5531.88 and 2782.59 per 100,000 persons,respectively.Prostate cancer was the leading cause of both age-standardized mortality rate(ASMR)and age-standardized DALYs rate(ASDR),with rates of 12.63 and 217.83 per 100,000 persons,respectively.From 1990 to 2021,there was an upward trend in ASIR,ASPR,ASMR,and ASDR for UTI,while urolithiasis showed a downward trend.The middle and low-middle SDI quintile levels exhibited higher incidence,prevalence,mortality,and DALYs related to UTI,urolithiasis,and BPH,while the high and high-middle SDI quintile levels showed higher rates for the three cancers.The burden of these 6 urologic diseases displayed diverse age and sex distribution patterns.In 2021,a high body mass index(BMI)contributed to 20.07%of kidney cancer deaths worldwide,while smoking accounted for 26.48%of bladder cancer deaths and 3.00%of prostate cancer deaths.Conclusions:The global burden of 6 urologic diseases presents a significant public health challenge.Urgent international collaboration is essential to advance the improvement of urologic disease management,encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.
基金supported by the National Natural Science Foundation[Grant Number:82102788]Anhui Province Key Project for Clinical Medical Research Translation and Advancement[202204295107020031,202204295107020007]Anhui Provincial University Excellent Scientific Research and Innovation Team Project[2022AH010071].
文摘Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.
文摘Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金supported by a grant from Kom op tegen Kanker(Stand Up to Cancer,Belgium).
文摘Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
文摘Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by the National Science and Technology Council(NSTC 113-2320-B-039-049-MY3 and NSTC 114-2314-B-039-051-MY3)China Medical University(CMU113-ASIA-05,CMU-114-ASIA-01).
文摘Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
文摘To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China Methods The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed Results The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16 1% (15?459/95?749) and 1 5% (1389/95?749), respectively The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7 6% and 0 6%, respectively, while it was 18 5% and 3 4% from 1991 to 1997 Conclusion The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China
文摘Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar＇s Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. Given the high incidence of susceptibility-weighted imaging （SWl） abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.
基金This work was supported by the Innovation Program of the Shanghai Municipal Education Commission （No. 102216） and by the National Natural Science Foundation of China （No. 81072096 and No. 81072114）.
文摘Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors （ARs） by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA （shRNA）, matrix metalloproteinase （MMP） expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.
文摘To study the expression and significance of the serine protease Omi/HtrA2 in prostate cancer and benign prostatic hyperplasia. The expression of Omi/HtrA2 was assayed by means of immunohistochemical technique in 41 prostate cancer （Cap）,20 benign prostatic hyperplasia （BPH） and 10 normal prostate （NP） specimens. Omi/HtrA2 expression was positive in 30 （73.17%） prostate cancer specimens, and the positive rate of Omi/HtrA2 was lower in well differentiated than in poorly and moderately differentiated groups （P〈0.05）. By contrast, the cells in normal prostate and benign prostatic hyperplasia groups showed no or weak expression of Omi/HtrA2. Prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2 expression might be involved in prostate cancer development.
文摘Objective To quantitatively evaluate the metabolic changes of benign prostatic hyperplasia(BPH) and prostate cancer in the transitional zone using magnetic resonance spectroscopic imaging(MRSI),and to analyze the characteristics and differences of the spectra in this zonal area.Methods Eighteen patients with prostate cancer in the transitional zone underwent magnetic resonance imaging(MRI)/MRSI examinations.The(Choline+Creatine)/Citrate(CC/Ci) ratio and the Choline/Creatine(Cho/Cr) ratio were evaluated in each voxel with cancer or BPH confirmed by pathological results.Discriminant analysis was used to determine the power of the two ratios in differentiation between cancer and BPH.Results The CC/Ci ratio and Cho/Cr ratio for cancer voxels were significantly higher than those in the voxels with BPH in the transitional zone(CC/Ci:2.36±1.31 vs.0.85±0.29,P<0.01;Cho/Cr:4.14±1.79 vs.1.26±0.45,P<0.01).As for the discriminant function with the CC/Ci ratio and the Cho/Cr ratio,the specificity,sensitivity,and accuracy were 98.6%,85.7%,92.9% respectively for the differentiation between cancer and BPH.Conclusions The prostate cancer is characterized by higher CC/Ci ratio and Cho/Cr ratio compared to BPH in the transitional zone.Both CC/Ci ratio and Cho/Cr ratio have high specificity,sensitivity,and accuracy in their discriminative power between cancer and BPH in this zonal area.
