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Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway

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Asian Journal of Andrology 2024年第2期26卷 195-204页

作者： Zhao Yang Jia-Qi Chen Tian-Jie Liu Yu-Le Chen Zhen-Kun Ma Yi-Zeng Fan Zi-Xi Wang Shan Xu Ke Wang Xin-Yang Wang Lei Li Hong-Jun Xie Department of Urology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061China

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)*** is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment,even bone metastases,through ***,we found that exosomes isolated from PCa cells after knocking down androgen receptor(AR)or enzalutamide treatment can facilitate the migration of prostate cancer cells to *** addition,AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase(circ-DHPS)in PCa cells,which can be transported to osteoblasts by ***-DHPS acts as a competitive endogenous RNA(ceRNA)against endogenous miR-214-3p to promote C-C chemokine ligand 5(CCL5)levels in *** the level of CCL5 in osteoblasts could recruit more PCa cells into the bone ***,blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

关键词： androgen receptor circRNA exosome prostate cancer

Quantitative detection of citrate for early stage diagnosing of prostate cancer:Discriminating normal to cancer in prostate tissues

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Chinese Chemical Letters 2024年第2期35卷 501-506页

作者： Selvaraj Muthusamy Kanagaraj Rajalakshmi Palanisamy Kannan Yun-Sik Nam Dongwei Zhu Yeonggil Seo Jong-Won Song Dong Nyoung Heo Il Keun Kwon Yuanguo Xu School of Chemistry and Chemical Engineering Jiangsu UniversityZhenjiang 212013China College of Biological Chemical Sciences and EngineeringJiaxing UniversityJiaxing 314001China Advanced Analysis Center Korea Institute of Science & TechnologySeongbuk-guSeoul02792Republic of Korea School of Medicine Jiangsu UniversityZhenjiang 212013China Department of Chemistry Education Daegu UniversityGyeongsan-siGyeongsangbuk-do 38453Republic of Korea Department of Dental Materials School of DentistryKyung Hee UniversitySeoulRepublic of Korea

prostate cancer(PC)biomarker-citrate detection is clinically important to diagnose PC in early *** iodide(Q)conjugated indole-phenylboronic acid(IB)was designed as a red-emissive QIB probe for the detection of citrate through Lewis acid-base reaction and intramolecular charge transfer(ICT)sensing *** acid acts as Lewis acid as well as citrate(Lewis base)recognition *** probe reacted with citrate,showing enhanced red *** the probe has excellent water solubility and great biocompatibility,practical application in biological systems is *** was monitored precisely in the mitochondria organelle(in vitro)of living cells with a positive charge on ***,endogenous(in situ)citrate was detected quantitatively to discriminate non-cancerous and PC mice,observed strong and lower(negligible)emission intensity on non-cancerous and cancerous prostate tissues,***,the concentration of citrate is higher in healthy prostate compared with PC ***,the analysis of sliced prostate tissues can give PC-related information for clinical diagnosis to prevent and treat PC in the initial ***,we believe that the present probe is a promising biochemical reagent in diagnosing PC.

关键词： prostate cancer Biomarker-citrate Boronic acid Lewis acid/base-ICT Red-emissive Mitochondria targeting prostate tissue

^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer:A systematic review and meta-analysis

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Chinese Medical Journal 2024年第8期137卷 949-958页

作者： Zhengtong Lv Liuqi Song Miao Wang Huimin Hou Haodong Li Xuan Wang Jianye Wang Jianlong Wang Ming Liu Department of Urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730China Peking University Fifth School of Clinical Medicine Beijing 100730China Peking University China-Japan Friendship School of Clinical Medicine Beijing 100029China

Background:Lymph node staging of prostate cancer(PCa)is important for planning and monitoring of treatment.^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography(^(18)F-PSMA PET/CT)has several advantages over^(68)Ga-PSMA PET/CT,but its diagnostic value requires further *** meta-analysis focused on establishing the diagnostic utility of^(18)F-PSMA PET/CT for lymph node staging in medium/high-risk ***:We searched the EMBASE,PubMed,Cochrane library,and Web of Science databases from inception to October 1,*** cancer,^(18)F,lymph node,PSMA,and PET/CT were used as search terms and the language was limited to *** additionally performed a manual search using the reference lists of key *** and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included ***,specificity,the positive and negative likelihood ratio(PLR and NLR),diagnostic odds ratio(DOR),area under the curve(AUC),and 95%confidence interval(CI)were used to evaluate the diagnostic value of^(18)F-PSMA PET/*** 17 software was employed for calculation and statistical ***:A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this *** the patient level,the results of each consolidated summary were as follows:sensitivity of 0.57(95%CI 0.39-0.73),specificity of 0.95(95%CI 0.92-0.97),PLR of 11.2(95%CI 6.6-19.0),NLR of 0.46(95%CI 0.31-0.68),DOR of 25(95%CI 11-54),and AUC of 0.94(95%CI 0.92-0.96).At the lesion level,the results of each consolidated summary were as follows:sensitivity of 0.40(95%CI 0.21-0.62),specificity of 0.99(95%CI 0.95-1.00),PLR of 40.0(95%CI 9.1-176.3),NLR of 0.61(95%CI 0.42-0.87),DOR of 66(95%CI 14-311),and AUC of 0.86(95%CI 0.83-0.89).Conclusions:^(18)F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk *** diag

关键词： ^(18)F-PSMA PET/CT Diagnostic test Lymph node Meta-analysis prostate cancer

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data

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Asian Journal of Andrology 2024年第1期26卷 34-40页

作者： Chang-Ming Wang Lei Yuan Xue-Han Liu Shu-Qiu Chen Hai-Feng Wang Qi-Fei Dong Bin Zhang Ming-Shuo Huang Zhi-Yong Zhang Jun Xiao Tao Tao Department of Urology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Radiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Core Facility Center for Medical Sciences The First Affiliated Hospital of USTcDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Urology Affiliated Zhongda Hospital of Southeast UniversityNanjing 210009China Department of Urology Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Urology Shanghai Changhai HospitalSecond Military Medical UniversityShanghai 200000China Department of Urology Affiliated Anhui Provincial Hospital of Anhui Medical UniversityHefei 230001China

The overdiagnosis of prostate cancer(PCa)caused by nonspecific elevation serum prostate-specific antigen(PSA)and the overtreatment of indolent PCa have become a global problem that needs to be solved *** aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary *** this retrospective study,clinical data of 1807 patients from three Chinese hospitals were *** final model was built using stepwise logistic regression *** apparent performance of the model was assessed by receiver operating characteristic curves,calibration plots,and decision curve ***,a risk stratification system of clinically significant prostate cancer(csPCa)was created,and diagnosis-free survival analyses were *** multivariable screening and evaluation of the diagnostic performances,a final diagnostic model comprised of the PSA density and prostate Imaging-Reporting and Data System(PI-RADS)score was *** validation in the development cohort and two external cohorts showed excellent discrimination and ***,we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off *** follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7%and 99.4%,respectively,for patients with a risk threshold below O.05 after the initial negative prostate biopsy,which was significantly better than patients with higher *** diagnostic model and risk stratification system can achieve a personalized risk calculation of *** provides a standardized tool for Chinese patients and physicians when considering thenecessity of prostatebiopsy.

关键词： nomogram prostate biopsy prostate cancer prostate Imaging-Reporting and Data System prostate-specific antigen density

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy Yuen-Chun Teoh Samson Yun-Sang Chan Ho-Man Tam Chi-Kwok Chan Chi-Fai Ng Peter Ka-Fung Chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the prostate cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest prostateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

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BIOCELL 2024年第5期48卷 771-792页

作者： CHENG-GONG LUO JIAO ZHANG YUN-ZHAO AN XUAN LIU SHUAI-JIE LI WEI ZHANG KAI LI XU ZHAO DONG-BO YUAN LING-YUE AN WEI CHEN YE TIAN BIN XU Department of Urology Guizhou Provincial People’s HospitalGuiyangChina Department of Urology First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient ***:A risk model incorporating four ferroptosis-related genes was developed and *** risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological *** corroborate these results,we performed validation analyses utilizing datasets from both the cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in ***,we conducted further experiments involving ferroptosis-related analysis to validate its association with ***:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa ***-activated protein kinase 9(MAPK9)emerged as a crucial gene within the *** vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and ***:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

关键词： Ferroptosis Biochemical recurrence prostate cancer TCGA GEO MAPK9

Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 55-64页

作者： Xu-Yun Wang Wen-Jing Xu Bo-Nan Li Tian-Song Sun Wen Sheng Department of Andrology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha410021China School of Integrated Chinese and Western Medicine Hunan University of Chinese MedicineChangsha410208China Andrology Laboratory Hunan University of Chinese MedicineChangsha410208China School of Rehabilitation Medicine and Health Care Hunan University of MedicineHuaihua418000China School of Traditional Chinese Medicine Hunan University of MedicineHuaihua418000China

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying ***:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and *** expression was analyzed using monodansylcadaverine *** and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR *** damage was examined using the lactate dehydrogenase ***,cathepsin B and NLRP3 were detected by ***:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of *** levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus *** changes were reversed upon overexpression of ***,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol *** cathepsin B reversed the regulatory effects of icariin plus ***:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin *** findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

关键词： Icariin Curcumol Autophagy mTOR Cathepsin B Pyroptosis prostate cancer

CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis

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Oncology Research 2024年第3期32卷 529-544页

作者： JIANYUN XIE LINIE LU JIALI ZHANG QIRUI LI WEIDONG CHEN Depatment of Urology The Affliated People's Hospital of Fujian University of Traditional Chinese MedicineFuzhouChina Department of Internal Medicine Outpatient ainic The Afliated People's Hospital of Fujian University of Traditional Chinese MedicineFuzhouChina

Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of ***:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa *** addition,we performed a Western blot(WB)assay to detect high *** A2 protein(HMGA2)***,functional associations of two molecules were investigated through dual luciferase reporter *** Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell ***,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa ***:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa ***4 silencing within PCa cells markedly suppressed cell growth,migration,and colony ***4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft ***,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa ***,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR ***:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.

关键词： circTHSD4 Docetaxel resistance prostate cancer miR-203 HMGA2