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High expression of GPR160 in prostate cancer is unrelated to CARTp-mediated signaling pathways

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1467-1471页

作者： Chenyu Ye Qingtong Zhou Shi Lin Wensheng Yang Xiaoqing Cai Yiting Mai Yanyan Chen Dehua Yang Ming-Wei Wang Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research center for Deepsea Bioresources Sanya 572025China Department of Pharmacy Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China State Key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China The National center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Department of Chemistry School of Sciencethe University of TokyoTokyo 113-0033Japan School of Pharmacy Hainan Medical UniversityHaikou 571199China

To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane *** playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and *** initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.

关键词： GPR160 CARTp prostate cancer Signaling pathway

Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 341-347页

作者： Philip J Saylor Division of Hematology-Oncology Massachusetts General Hospital Cancer Center Boston Massachusetts USA.

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-K-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

关键词： denosumab osteoporosis osteopenia osteoclast RANK (receptor activator of nuclear factor-kappa B) skeletal-relatedevents

Vascular endothelial growth factor A, secreted in response to transforming growth factor-β1 under hypoxic conditions, induces autocrine effects on migration of prostate cancer cells

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Asian Journal of Andrology 2012年第5期14卷 745-751页

作者： Eric Darrington Miao Zhong Bao-Han Vo Shafiq A Khan center for cancer Research and Therapeutic Development Clark Atlanta University Atlanta GA 30314 USA

Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA165 secretion from both normal cell lines （HPV7 and RWPE1） and prostate cancer cell lines （DU 145 and PC3）. Conversely, hypoxia-stimulated VEGFA165 secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β1 type I receptor （ALK5） kinase inhibitor partially blocked hypoxia-mediated VEGFA16s secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor （VEGFR） 1 （Fit-l） and 2 （FIk-I/KDR）. Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA165 treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERKI/2） in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA165 was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.

关键词： cell migration hypoxia prostate cancer transforming growth factor-β1 (TGF-β1) vascular endothelial growth factor A(VEGFA)

Heat shock and other apoptosis-related proteins as therapeutic targets in prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 359-363页

作者： Costantine Albany Noah M Hahn Indiana University Health Melvin and Bern Simon Cancer Center Indianapolis IN USA.

Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.

关键词： apatorsen apoptosis bcl-2 homologous antagonist-killer protein clusterin custirsen ganetespib heat-shock proteins prostatic neoplasms

PRSS3/mesotrypsin in prostate cancer progression： mplications for translational medicine

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Asian Journal of Andrology 2013年第4期15卷 439-440页

作者： Evette S Radisky Department of cancer Biology Mayo Clinic ComprehensiveCancer Center Jacksonville FL 32224 USA

prostate cancer morbidity and morta lity are caused by metastasis to othervital organs and tissues. Metastatic prostate cancer is a terminal disease in need of improved therapies. Hoclda et al. have iden tified prostate cancer cell upregulation of the digestive protease PRSS3/mesotrypsin in association with metastasis and recur rence. Gene silencing of PRSS3 led to pronounced reductions in invasion and metastasis in cell culture and in an orthoto pic mouse model of prostate cancer. Importantly, a recently developed inhibitor of mesotrypsin was equally effective in sup pressing invasion. These results identify mesotrypsin as a potential therapeutic tar get in metastatic prostate cancer. prostate cancer is a disease that can lie latent for decades or can progress rapidly to systemic metastasis and deathand the molecular pathways that distinguish between indolent and aggressive cancers are not well defined. Assessment of patient prognosis is therefore a critical challengewho is likely to benefit from further interventions, and who should be spared further treatment？ prostatespecific antigen assays provide a valuable surveillance tool, but prostatespe cific antigen is not a specific marker for aggressive prostate cancers, and only a frac tion of the many men who experience pro statespecific antigen relapse after initial treatment will ever develop overt meta stasis.1＇2 Thus, there is an unmet clinical need for additional and more specific biomarkers that define subsets of patients at greatest risk of metastatic progression. An additional unmet need is encountered by patients with advanced diseasecurrent therapies are inadequate, since metastatic prostate cancerinevitably develops resistance to androgen deprivation therapy, at which time sub sequent treatment of castrationresistant pro state cancer with standard chemotherapy agent docetaxel, and even with newer regi mens incorporating agents that block andro gen signaling via alternative mechanisms, can provide only mod

关键词： PRSS3/mesotrypsin progression implications

Combining active immunotherapy with immune checkpoint blockade for the treatment of advanced prostate cancer

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Asian Journal of Andrology 2012年第4期14卷 520-521页

作者： Emmanuel S Antonarakis Johns Hopkins Sidney Kimmel Comprehensive cancer center Baltimore MD 21231 USA

Combination immunotherapy is emerging as a promising approach for the treatment of advanced prostate cancer. This research highlight discusses the combination of a PSA-directed pox-viral vaccine and a monoclonal antibody blocking an important immune checkpoint molecule to treat men with metastatic castration- resistant prostate cancer. The results demonstrate feasibility and safety, as well as intriguing clinical responses to this combination therapy.

关键词： Dementia Nutrition Obesity Weight management

Construction of Antisense RNA Expression Plasmid for u-PAR and Its Transfection to Highly Invasive PC-3M Cell Subclones

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第4期23卷 369-372页

作者：廖国宁李清芬冯友梅邓耀祖李卓娅龚非力马丁 Department of Biochemistry and Molecular Biology Department of Immunology Molecular cancer center

To evaluate the specific inhibition of antisense u PAR on the u PAR expressions in highly invasive cell subclones and to determine its blocking function in the invasion by those cells, a cDNA fragment of u PAR obtained by RT PCR was inserted into a plasmid vector named pcDNA3 in antisense orientation. Then the antisense u PAR recombinant was transfected into highly invasive cell subclones. The u PAR expression in neo resistant cells was examined by RT PCR and immunohistochemical assay. Compared to the control cells, the content of mRNA and protein of u PAR in transfected cells decreased sharply, and the rate of inhibition was 53 % and 73 %, respectively, indicating that an antisense u PAR might have played a specific inhibitory role in its expression in the cells, which may provide a good cell model for making further investigation of the inhibitory effects of the antisense u PAR on invasion in highly invasive cell subclones of human prostate carcinoma.

关键词： tumor invasion prostate carcinoma antisense RNA u PAR

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy:using whole-mount histopathology as reference standard

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Asian Journal of Andrology 2023年第1期25卷 86-92页

作者： Zhang-Zhe Chen Wei-Jie Gu Bing-Ni Zhou Wei Liu Hua-Lei Gan Yong Zhang Liang-Ping Zhou Xiao-Hang Liu Department of Radiology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical College of Fudan UniversityShanghai 200032China Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Pathology Fudan University Shanghai Cancer CenterShanghai 200032China MR Research GE HealthcareShanghai 200032China

We aimed to study radiomics approach based on biparametric magnetic resonance imaging(MRI)for determining significant residual cancer after androgen deprivation therapy(ADT).Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy(62 with significant residual disease and 30 with complete response or minimum residual disease[CR/MRD]).Totally,100 significant residual,52 CR/MRD lesions,and 70 benign tissues were selected according to ***,381 radiomics features were extracted from T2-weighted imaging,diffusion-weighted imaging,and apparent diffusion coefficient(ADC)*** features were selected using a support vector machine with a recursive feature elimination algorithm(SVM-RFE).Then,ADC values of significant residual,CR/MRD lesions,and benign tissues were compared by one-way analysis of *** regression was used to construct models with SVM features to differentiate between each pair of ***,the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve(AUC).The ADC value(mean±standard deviation[s.d.])of significant residual lesions([1.10±0.02]×10^(-3)mm^(2)s^(−1))was significantly lower than that of CR/MRD([1.17±0.02]×10^(-3)mm^(2)s^(−1)),which was significantly lower than that of benign tissues([1.30±0.02]×10^(-3)mm^(2)s^(−1);both P0.05),but superior to ADC value in differentiating significant residual from CR/MRD(AUC:0.748 vs 0.558;P=0.041).Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

关键词： androgen deprivation therapy diffusion-weighted imaging prostate cancer radiomics

Genitourinary tumors and liver transplantation: A comprehensive review

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World Journal of Transplantation 2024年第3期14卷 52-58页

作者： Vibor Sesa Hrvoje Silovski Nikolina Basic-Jukic Iva Kosuta Maja Sremac Anna Mrzljak Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia Department of Hepatobiliary Surgery and Transplantation University Hospital Center ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia Department of Nephrology Arterial hypertensionDialysis and TransplantationUniversity Hospital Center ZagrebZagreb 10000Croatia Department of Intensive Care Medicine University Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease,but the persistent organ shortage emphasizes a need to explore unconventional donor sources,including individuals with a history of *** review investigates the viability of liver donation from individuals with current or past genitourinary malignancies,focusing on renal,prostate and urinary bladder *** rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor *** of transmission risks reveals low rates of donor-derived cancer transmission,partic-ularly for early-stage renal and prostate *** with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer ***,the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management *** for pre-transplant evaluation and post-transplant surveillance are discussed,highlighting the need for individualized approaches in this patient *** prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.

关键词： Liver transplantation Genitourinary malignancies Donor-transmitted cancer Malignancy recurrence Immunosuppression