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Circadian rhythm in prostate cancer: time to take notice of the clock

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Asian Journal of Andrology 2023年第2期25卷 184-191页

作者： Wei-Zhen Zhu Qi-Ying He De-Chao Feng Qiang Wei Lu Yang Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external *** of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers,including prostate cancer(PCa).Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with *** review begins with patterns of the circadian clock,highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels,and discusses possible new approaches to PCa therapy that target the circadian clock.

关键词： chronotherapy circadian clock circadian rhythm prostate cancer

Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression

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Asian Journal of Andrology 2013年第5期15卷 672-678页

作者： You-Yi Lu Bo Jian Fu-Jun Zhao Di Cui Qi Jiang Jun-Jie Yu En-Hui Li Xiao-Hai Wang Bang-Min Han Shu-Jie Xia Department of Urology The Affiliated First People's Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200080 China Department of Urology The Qingdao Municipal Hospital Qingdao 266071 China

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.

关键词： age factors androgen receptor human metastasis prostate cancer

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Asian Journal of Andrology 2023年第2期25卷 208-216页

作者： Wei-Zhen Zhu De-Chao Feng Qiao Xiong Xu Shi Fa-Cai Zhang Qiang Wei Lu Yang Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China

Given the dual role of autophagy presenting in tumorigenesis and inhibition,we established an autophagy-related gene prognostic index(ARGPI)with validation to well predict the biochemical recurrence(BCR),metastasis,as well as chemoresistance for patients with prostate cancer(PCa)who underwent radical radiotherapy or ***,Lasso and COX regression was used to develop the *** performed the whole analyses through R packages(version 3.6.3).Secreted phosphoprotein 1(SPP1),single-minded 2(SIM2),serine protease inhibitor b5(SERPINB5),aldehyde dehydrogenase 2(ALDH2),and acyl-CoA synthetase long-chain 3(ACSL3)were eventually used to establish the ARGPI *** were divided into two different-risk groups based on the median ARGPI score,high-risk patients with a higher risk of BCR than low-risk patients(hazard ratio[HR]:5.46,95%confidence interval[CI]:3.23–9.24).The risk of metastasis of high-risk patients was higher than low-risk patients(HR:11.31,95%CI:4.89–26.12).In The cancer Genome Atlas(TCGA)dataset,we observed similar prognostic value of ARGPI in terms of BCR-free survival(HR:1.79,95%CI:1.07–2.99)and metastasis-free survival(HR:1.80,95%CI:1.16–2.78).ARGPI score showed a diagnostic accuracy of 0.703 for drug *** of gene set enrichment analysis(GSEA)indicated that patients in the high-risk group were significantly positively related to interleukin(IL)-18 signaling ***,ARGPI score was significantly related to cancer-related fibroblasts(CAFs;r=0.36),macrophages(r=0.28),stromal score(r=0.38),immune score(r=0.35),estimate score(r=0.39),as well as tumor purity(r=−0.39;all Pprostatectomy.

关键词： autophagy biochemical recurrence immune checkpoint metastasis-free survival prostate cancer tumor immune microenvironment

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism： a meta-analysis

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Asian Journal of Andrology 2012年第5期14卷 726-731页

作者： Jie Yang Wen Gao Ning-Hong Song Wei Wang Jie-Xiu Zhang Pei Lu Li-Xin Hua Min Gu Department of Urology First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China cancer Biotherapy Centre First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

To determine the risk, malignant degree and clinical progression of prostate cancer （PCa） associated with mouse double-minute 2 protein （MDM2） T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk （0R=0.85, 95% CI： 0.74-0.97）; this was also the case for the homozygous comparison （0R--0.72, 95% Ch 0.55-0.95） and the dominant genetic model （0R=0.79, 95% Ch 0.65-0.96）. The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy （0R=0.85, 95% Ch 0.75-0.96） in the overall analysis, as well as in the heterozygous comparison （0R=0.79, 95% Ch 0.65-0.96）, homozygous comparison （0R=0.76, 95% Ch 0.58-0.98） and dominant genetic model （0R=0.81, 95% CI： 0.68-0.96）. Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk （0R=0.77, 95% Ch 0.61-0.96）; this was also the case in the homozygous comparison （0R=0.51, 95% Ch 0.31-0.86）. The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

关键词： clinical progression malignant degree MDM2 meta-analysis polymorphism prostate cancer risk

Inhibition of Proliferation of prostate cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge

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Chinese Journal of Integrative Medicine 2020年第7期26卷 533-538页

作者： Woong Jin Bae Jin Bong Choi Kang Sup Kim U Syn Ha Sung Hoo Hong Ji Youl Lee Tae-Kon Hwang Sung Yeoun Hwang WANG Zhi-ping Sae Woong Kim Department of Urology The Catholic University of KoreaCollege of MedicineSeoul(06591)Republic of Korea Catholic Integrative Medicine Research Institute College of MedicineThe Catholic University of KoreaSeoul(06591)Republic of Korea Korea Bio-Medical Science Institute Seoul(06106)Republic of Korea Department of Urology Second Hospital of Lanzhou UniversityLanzhou(730030)China

Objective:To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge.(SM)on the castration-resistant prostate cancer(CRPC)cell line DU-145 in vitro and in ***:prostate cancer cell line(DU-145)and normal prostate cell line(RWPE-1)were treated with SM at different concentrations(3.125,12.5,25 and 50μg/mL)to investigate the antiproliferative *** laddering analysis was performed to investigate the apoptosis of DU-145 *** mechanism was investigated by Western blot analysis of p53,Bcl-2,prostate specific antigen(PSA),and androgen receptor(AR).Six-week-old male BALB/c nude mice were randomly divided into normal control group(n=101)and treated group(n=101)which administered 500 mg/kg SM for 2 *** volumes were ***:Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with *** laddering analysis indicated the apoptosis of DU-145 *** with SM increased the expression of p53 and reduced the expression of Bcl-2 *** levels of PSA were considerably reduced in SM-treated group compared to the controls,and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in *** the tumour xenograft study,SM given once a day for 2 weeks significantly inhibited tumour ***:SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

关键词： apoptosis prostate cancer Salvia miltiorrhiza Bunge Chinese medicine

The prostate cancer bone marrow niche： more than just ＇fertile soil＇

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Asian Journal of Andrology 2012年第3期14卷 423-427,I0007页

作者： Elisabeth A Pedersen Yusuke Shiozawa Kenneth J Pienta Russell S Taichman Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor M148109-1078 USA Departments of Urology and Internal Medicine University of Michigan Medical School Ann Arbor MI 48109-1078 USA

The hematopoietic stem cell （HSC） niche in the bone marrow has been studied extensively over the past few decades, yet the bone marrow microenvironment that supports the growth of metastatic prostate cancer （PCa） has only been recently considered to be a specialized ＇niche＇ as well. New evidence supports the fact that disseminated tumor cells （DTCs） of PCa actually target the HSC niche, displace the occupant HSCs and take up residence in the pre-existing niche space. This review describes some of the evidence and mechanisms by which DTCs act as molecular parasites of the HSC niche. Furthermore, the interactions between DTCs, HSCs and the niche may provide new targets for niche-directed therapy, as well as insight into the perplexing clinical manifestations of metastatic PCa disease.

关键词： dormancy hematopoietic stem cell metastasis niche osteoblasts prostate cancer

Effect of statins type on incident prostate cancer risk： a meta-analysis and systematic review

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Asian Journal of Andrology 2017年第6期19卷 666-671页

作者： Ping Tan Chen Zhang Shi-You Wei Zhuang Tang Liang Gao Lu Yang Qiang Wei Department of Urology West China Hospital Sichuan University Chengdu China Institute of Urology West China Hospital Sichuan University Chengdu China Department of Cardiology West China Hospital Sichuan University Chengdu China Department of Cardiovascular and Thoracic Surgery West China Hospital Sichuan University Chengdu China

The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed （1984.1-2015.3）, MEDLINE （1984.1-2015.3）, and EMBASE （1990.1-2015.3）. Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk （RR） with 95% confidence intervals （CI）. Statistic heterogeneity scores were assessed with the standard Cochran＇s Q-test and F statistic, Publication bias was detected using the Begg＇s and Egger＇s tests. All statistical analyses were conducted by STATA version 10. Finally, fourteen studies were included in the meta-analysis. Both hydrophilic and hydrophobic statins showed no association with incidence of prostate cancer （RR = 1.00, 95% Ch 0.82-1.17; RR = 0.90, 95% CI： 0.73-1.08, respectively）. Meanwhile, the risk of prostate cancer was not reduced in simvastatin （RR = 0.89, 95% CI- 0.72-1.05）, pravastatin （RR = 1.02, 95% Ch 0.94-1.11）, atorvastatin （RR = 0.89, 95% CI： 0.76-1.02）, fluvastatin （RR = 0.99, 95% Ch 0.97-1.01）, or Iovastatin users （RR = 0.94, 95% CI： 0.79-1.08）. The funnel plot showed that there was no publication bias. The results showed that statins had a neutral effect on prostate cancer risk; hydrophilic and hydrophobic statins as well as any subtype of statins did not affect the risk of prostate cancer.

关键词： meta-analysis prostate cancer statins type systematic review

Genome-wide association analysis reveals regulation of at-risk loci by DNA methylation in prostate cancer

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Asian Journal of Andrology 2021年第5期23卷 472-478页

作者： Qiang Liu Gang Liu Darryl T Martin Yu-Tong Xing Robert M Weiss Jun Qi Jian Kang Department of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Urology Yale University School of MedicineNew HavenCT 06510USA Key Lab of Systems Biology Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Institute of Estuarine and Coastal Research East China Normal UniversityShanghai 20CXD62China

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic *** cancer(PCa)is characterized by variable clinical manifestations and frequently unpredictable *** performed an expression quantitative trait loci(eQTL)analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical *** multi-level information published in The cancer Genome Atlas,we performed eQTL-based analyses on DNA methylation and gene *** better interpret these data,we correlated loci and clinical indexes to identify the important loci for both PCa development and *** data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa,these genes are enriched in important cancer-related *** addition,single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci,including the 19q13.2-q13.43 and 16q22.2-q23.1 ***,an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site *** DNA methylation-regulated genes across PCa samples are a small proportion,the associated genes play important roles in PCa carcinogenesis.

关键词： CpG sites DNA methylation expression quantitative trait loci genome-wide association study prostate cancer

Saposin C stimulates growth and invasion,activates p42/44 and SAPK/JNK signaling pathways of MAPK and upregulates uPA/uPAR expression in prostate cancer and stromal cells

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Asian Journal of Andrology 2005年第2期7卷 147-158,页

作者： Shahriar Koochekpour Oliver Sartor Masao Hiraiwa Tae-Jin Lee Walter Rayford Natascha Remmel Konrad Sandhoff ArdalanMinokadeh DavidY.Patten Department of Microbiology Immunology and Parasitology Stantey S.Scott Cancer Center Stanley S.Scott cancer Center Department of Medicine Department of Neurosciences University of CaliforniaSan DiegoCenter for Molecular GeneticsLa JollaCalifornia 92093USA Department of Microbiology Immunology and Parasitology Stanley S.Scott Cancer Center Department of Urology Louisiana State University Health Sciences CenterNew OrleansLouisiana 70112USA Kekul■-Institut fuer Organische Chemie Und Biochemie Universitaet BonnD-53121 BonnGermany Department of Microbiology Immunology and Parasitology Stanley S.Scott Cancer Center

Aim:To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation,migration and invasion,as well as its effect on the expression of urokinase plasmonogen activator (uPA),its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate *** addition,we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) ***:We employed West- ern blot analysis,phospho-specific antibodies,cell proliferation assay,reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer ***:Saposin C,in a cell type-specific manner,upregulates uPA/uPAR and immediate early gene c-Jun expression,stimulates cell proliferation,migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer *** prostate epithelial cells were not responsive to saposin C treatment in the above ***:Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal *** results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.

关键词： saposin C prostate cancer uPA/uPAR prosaposin invasion growth factor SAPK/JNK MAPK MMP c-Jun