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Circulating cell-free nucleic acids as prognostic and therapy predictive tools for metastatic castrate-resistant prostate cancer
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作者 Navid Sobhani Marianna Sirico +2 位作者 Daniele Generali Fabrizio Zanconati Bruna Scaggiante 《World Journal of Clinical Oncology》 CAS 2020年第7期450-463,共14页
Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on... Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients. 展开更多
关键词 Metastatic castrate-resistant prostate cancer Circulating free deoxyribonucleic acid Cell-free tumor deoxyribonucleic acid Circulating free ribonucleic acid Liquid biopsy prostate cancer
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PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance 被引量:20
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作者 Merritt P Edlind Andrew C Hsieh 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第3期378-386,共9页
Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to first line androg... Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy (ADT). Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor (AR) signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors. 展开更多
关键词 androgen receptor crpc kinase inhibitors MTOR prostate cancer PI3K resistance
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The role of mRNA splicing in prostate cancer 被引量:3
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作者 Anna V Lapuk Stanislav V Volik +1 位作者 Yuzhuo Wang Colin C Collins 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第4期515-521,共7页
Alternative splicing (AS) is a crucial step in gene expression. It is subject to intricate regulation, and its deregulation in cancer can lead to a wide array of neoplastic phenotypes. A large body of evidence impli... Alternative splicing (AS) is a crucial step in gene expression. It is subject to intricate regulation, and its deregulation in cancer can lead to a wide array of neoplastic phenotypes. A large body of evidence implicates splice isoforms in most if not all hallmarks of cancer, including growth, apoptosis, invasion and metastasis, angiogenesis, and metabolism. AS has important clinical implications since it can be manipulated therapeutically to treat cancer and represents a mechanism of resistance to therapy. In prostate cancer (PCa) AS also plays a prominent role and this review will summarize the current knowledge of alternatively spliced genes with important functional consequences. We will highlight accumulating evidence on AS of the components of the two critical pathways in PCa: androgen receptor (AR) and phosphoinositide 3-kinase (PI3K). These observations together with data on dysregulation of splice factors in PCa suggest that AR and PI3K pathways may be interconnected with previously unappreciated splicing regulatory networks. In addition, we will discuss several lines of evidence implicating splicing regulation in the development of the castration resistance. 展开更多
关键词 alternative splicing prostate cancer androgen receptor PI3K pathway crpc neuroendocrine transdifferentiation REST repressor complex
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Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer 被引量:1
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作者 Qiong Wang Zean Li +10 位作者 Jin Yang Shirong Peng Qianghua Zhou Kai Yao Wenli Cai Zhongqiu Xie Fujun Qin Hui Li Xu Chen Kaiwen Li Hai Huang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2022年第8期1193-1210,共18页
Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We em... Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3.Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines.Cell and animal models of radiotherapy were established by using a medical electron linear accelerator.Flow cytometry was used to detect apoptosis or cell cycle progression.Western blot and qPCR were used to detect changes in the protein and RNA levels.Results:TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines,and NEIL3 was correlated with a high Gleason score but a good prognosis.Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells.However,cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells,while loss of NEIL3 activated radiotherapy resistance.Mechanistically,we found that NEIL3 negatively regulated the expression of ATR,and higher NEIL3 expression repressed the ATR/CHK1 pathway,thus regulating the cell cycle.Conclusions:We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients. 展开更多
关键词 crpc NEIL3 NEPC prostate cancer radiotherapy resistance
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Non-invasive actionable biomarkers for metastatic prostate cancer 被引量:1
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作者 Jun Luo 《Asian Journal of Urology》 2016年第4期170-176,共7页
In the current clinical setting,many disease management options are available for men diagnosed with prostate cancer.For metastatic prostate cancer,first-line therapies almost always involve agents designed to inhibit... In the current clinical setting,many disease management options are available for men diagnosed with prostate cancer.For metastatic prostate cancer,first-line therapies almost always involve agents designed to inhibit androgen receptor(AR)signaling.Castration-resistant prostate cancers(CRPCs)that arise following first-line androgen deprivation therapies(ADT)may continue to respond to additional lines of AR-targeting therapies(abiraterone and enzalutamide),chemotherapies(docetaxel and cabazitaxel),bonetargeting Radium-223 therapy,and immunotherapy sipuleucel-T.The rapidly expanding therapies for CRPC is expected to transform this lethal disease into one that can be managed for prolonged period of time.In the past 3 years,a number of promising biomarkers that may help to guide treatment decisions have been proposed and evaluated,including androgen receptor splice variant-7(AR-V7),a truncated AR lacking the ligand-binding domain(LBD)and mediate constitutively-active AR signaling.Putative treatment selection markers such as ARV7 may further improve survival benefit of existing therapies and help to accelerate development of new agents for metastatic prostate cancer.In the metastatic setting,it is important to consider compatibility between the putative biomarker with non-invasive sampling.In this review,biomarkers relevant to the setting of metastatic prostate cancer are discussed with respect to a number of key attributes critical for clinical development of non-invasive,actionable markers.It is envisioned that biomarkers for metastatic prostate cancer will continue to be discovered,developed,and refined to meet the unmet needs in both standard-of-care and clinical trial settings. 展开更多
关键词 prostate cancer Androgen receptor AR-V7 BIOMARKER crpc
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Targeting of Androgen Receptor Expression by Andro-miRs as Novel Adjunctive Therapeutics in Prostate Cancer
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作者 Jey Sabith Ebron Crystal M. Weyman Girish C. Shukla 《Journal of Cancer Therapy》 2013年第4期47-58,共12页
Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant pros... Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3’ untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of “andro-miRs” and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro-miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC. 展开更多
关键词 Androgen Receptor microRNA 3’ Untranslated Region prostate cancer CASTRATION-RESISTANT prostate cancer (crpc) Andro-miR
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m6A甲基化修饰在前列腺癌发生发展中的调控机制
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作者 张乐 王振 张钰哲 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2023年第8期1047-1058,共12页
N6-腺苷甲基化(N6-adenosine methylation)是腺苷N6位点的甲基化形式,常出现在真核生物的mRNA中,是最常见的RNA内部修饰的方式之一。研究表明,m6A通过调节基因的表达来影响细胞的生物过程;同时m6A的调控因子也在各种癌症的发生、发展中... N6-腺苷甲基化(N6-adenosine methylation)是腺苷N6位点的甲基化形式,常出现在真核生物的mRNA中,是最常见的RNA内部修饰的方式之一。研究表明,m6A通过调节基因的表达来影响细胞的生物过程;同时m6A的调控因子也在各种癌症的发生、发展中发挥着关键作用。前列腺癌(prostate cancer,PCa)是一种常见的男性恶性肿瘤,超过60岁的男性的患病风险逐年攀升,并且随着人口老龄化的问题,可以预计PCa的患病数目会继续升高。近年来,关于m6A在肿瘤发生发展中的作用逐渐受到广泛关注,但是m6A甲基化修饰在PCa中的研究仍然有限,因此,进一步探讨二者之间的关系显得尤为重要。本文综述了近年来关于m6A甲基化修饰在PCa中的作用、机制及应用的研究进展,尤其详细综述了METTL3,FTO,YTHDF2三种经典的m6A相关调控蛋白质在PCa中的作用机制;并阐述了m6A在晚期PCa(例如:去势抵抗性前列腺癌,骨转移性前列腺癌)中的潜在应用。从甲基化修饰角度为PCa的早期诊断、治疗和预后挖掘一套有效治疗策略,为实现个体化治疗提供更多理论参考。 展开更多
关键词 N6-腺苷甲基化 前列腺癌 去势抵抗性前列腺癌 骨转移性前列腺癌 免疫治疗
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Identification of PTPRR and JAG1 as key genes in castrationresistant prostate cancer by integrated bioinformatics methods 被引量:1
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作者 Ji-li WANG Yan WANG Guo-ping REN 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2020年第3期246-257,共12页
To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were ... To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC. 展开更多
关键词 BIOINFORMATICS Protein tyrosine phosphatase receptor-type R(PTPRR) Jagged1(JAG1) Differentially expressed genes(DEGs) Castration-resistant prostate cancer(crpc) Functional enrichment
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去势抵抗性前列腺癌药物治疗研究进展 被引量:4
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作者 郝继东 廖国强 +6 位作者 刘辉 杨波 邓晓俊 刘峰 王伟峰 刘四明 邹源 《海南医学》 CAS 2017年第24期4049-4053,共5页
前列腺癌当前在我国的发病率逐年上升,尤其在经济发达地区发病率迅速升高。通过雄激素剥夺(ADT)的前列腺癌患者几乎最终都会转变成为去势抵抗性前列腺癌(CRPC),通过化疗药物、免疫疫苗、雄激素合成抑制剂、雄激素受体拮抗剂、分子靶向... 前列腺癌当前在我国的发病率逐年上升,尤其在经济发达地区发病率迅速升高。通过雄激素剥夺(ADT)的前列腺癌患者几乎最终都会转变成为去势抵抗性前列腺癌(CRPC),通过化疗药物、免疫疫苗、雄激素合成抑制剂、雄激素受体拮抗剂、分子靶向等等治疗,去势抵抗性前列腺癌的治疗取得了疗效证据。本文将对去势抵抗性前列腺癌药物治疗研究进展做一综述,为临床治疗去势抵抗性前列腺癌提供参考。 展开更多
关键词 去势抵抗性前列腺癌 药物治疗 进展
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CK18、CK19在前列腺癌中的表达及其临床意义 被引量:8
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作者 张超 殷波 《现代肿瘤医学》 CAS 2018年第5期737-740,共4页
目的:研究细胞角蛋白18、19(CK18、CK19)在前列腺癌(prostate cancer,PCa)组织中的表达及临床意义。方法:根据以Gleason评分为标准确定的临床危险度,将选择的65例前列腺癌标本分为高危组和低危组。应用免疫组化SP方法检测CK18、CK19在... 目的:研究细胞角蛋白18、19(CK18、CK19)在前列腺癌(prostate cancer,PCa)组织中的表达及临床意义。方法:根据以Gleason评分为标准确定的临床危险度,将选择的65例前列腺癌标本分为高危组和低危组。应用免疫组化SP方法检测CK18、CK19在前列腺癌组织中的表达,并采用统计学方法分析CK18、CK19的表达与前列腺癌临床危险度的关系。结果:CK18在高危组、低危组前列腺癌中的阳性表达率分别是31.4%(11/35)、60.0%(15/25)(P=0.028);CK19在高危组、低危组前列腺癌中的阳性表达率分别是33.3%(11/33)、65.5%(19/29)(P=0.011);CK18的表达水平与病情进展到去势抵抗型前列腺癌阶段(castration-resistant prostate cancer,CRPC)的时间存在一定关系:在阳性表达组和阴性表达组中,进展到CRPC阶段的时间均值分别为4.82个月和6.95个月(t=2.501,P=0.018),结果存在统计学差异。结论:在前列腺癌中,随着临床危险度的增高,CK18、CK19的表达水平呈现降低的趋势;且随着CK18表达水平的下调,进展到CRPC阶段的时间缩短,这对于前列腺癌的辅助诊断、指导治疗及预后判断有一定的指导意义。 展开更多
关键词 前列腺癌 细胞角蛋白 去势抵抗型前列腺癌
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补益肺肾、化瘀解毒法治疗去势抵抗性前列腺癌临床研究 被引量:16
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作者 卢子杰 雷博涵 +4 位作者 张扬 章茂森 朱清毅 王省博 徐福松 《新中医》 CAS 2018年第1期91-94,共4页
目的:观察补益肺肾、化瘀解毒方联合内分泌疗法治疗去势抵抗性前列腺癌的临床疗效。方法:将符合纳入标准的72例患者随机分为2组。对照组采用单纯西医治疗,最大限度雄激素阻断疗法(MAB);治疗组在对照组治疗方案的基础上加用补益肺肾、化... 目的:观察补益肺肾、化瘀解毒方联合内分泌疗法治疗去势抵抗性前列腺癌的临床疗效。方法:将符合纳入标准的72例患者随机分为2组。对照组采用单纯西医治疗,最大限度雄激素阻断疗法(MAB);治疗组在对照组治疗方案的基础上加用补益肺肾、化瘀解毒方治疗,疗程均为3月。观察2组治疗前后总生存期、血清前列腺特异性抗原(PSA)、体力状况、生活质量和中医症状评分的变化。结果:治疗后,对照组患者血清PSA有明显上升,Karnofsky评分降低,各方面生活质量评分均有所下降,中医症状评分升高,治疗前后比较,差异均有统计学意义(P<0.05)。而治疗组患者PSA与治疗前比较,上升不明显,差异无统计学意义(P>0.05),且与对照组比较,低于对照组,差异有统计学意义(P<0.05)。治疗组Karnofsky评分明显升高,各方面生活质量评分均有改善,中医症状评分降低,差异均有统计学意义(P<0.05);且以上各项包括Karnofsky评分、生活质量评分、中医症状评分等分别与对照组比较,差异均有统计学意义(P<0.05)。治疗组患者死亡13例,平均生存期24.1月;对照组患者死亡15例,平均生存期19.7月。结论:中药补益肺肾、化瘀解毒方治疗去势抵抗性前列腺癌可减少西医治疗的副作用,稳定PSA水平,改善患者生活质量,进而延长患者总生存期。 展开更多
关键词 去势抵抗性前列腺癌(crpc) 补益肺肾 化瘀解毒 生活质量 总生存期
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低磷血症对去势难治性前列腺癌患者预后的预测价值 被引量:1
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作者 陈海燕 蒋宁 +2 位作者 李刚 孟甲 姜埃利 《中国肿瘤临床》 CAS CSCD 北大核心 2018年第24期1263-1267,共5页
目的:探讨低磷血症对去势难治性前列腺癌(castration-resistant prostate cancer,CRPC)预后的预测价值。方法:回顾性分析2009年1月至2012年1月56例天津医科大学第二医院收治的CRPC患者的临床资料,分为低磷组(血磷水平<0.8 mmol/L)、... 目的:探讨低磷血症对去势难治性前列腺癌(castration-resistant prostate cancer,CRPC)预后的预测价值。方法:回顾性分析2009年1月至2012年1月56例天津医科大学第二医院收治的CRPC患者的临床资料,分为低磷组(血磷水平<0.8 mmol/L)、血磷正常组(血磷水平为0.8~1.5 mmol/L)和高磷组(血磷水平>1.5 mmol/L),比较三组患者的临床病理特征,分析血磷水平对患者预后的影响。结果:56例CRPC患者中低磷组13例(23.2%)、血磷正常组39例(69.6%)、高磷组4例(7.2%),三组中位生存时间分别为18、27和24个月,低磷组与血磷正常组以及高磷组比较,差异均具有统计学意义(P<0.05)。单因素分析显示,患者临床分期(χ~2=3.940,P=0.047)、远处转移(χ~2=5.369,P=0.020)及低磷血症(χ~2=6.695,P=0.010)影响患者的生存时间,差异具有统计学意义。Cox模型多因素分析显示,患者低磷血症、高钙血症及远处转移是影响患者预后的相关危险因素,其HR分别为5.448、5.868及3.708,95%CI分别为1.532~19.379、1.897~18.147及1.300~10.578。结论:诊断为CRPC时血磷水平低的患者预后差,低磷血症、高钙血症和远处转移是CRPC患者预后的相关危险因素,血磷水平可以在一定程度上预测患者的预后。 展开更多
关键词 去势难治性前列腺癌 低磷血症 预后 生存时间
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米托蒽醌联合沙利度胺挽救治疗经多西他赛治疗失败的晚期去势抵抗性前列腺癌的疗效观察 被引量:3
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作者 田美娟 宋相瑾 +3 位作者 王丽 陆诚 张佳 谢宏俊 《现代肿瘤医学》 CAS 2019年第20期3644-3647,共4页
目的:观察米托蒽醌联合沙利度胺挽救治疗经多西他赛治疗失败的晚期去势抵抗性前列腺癌的疗效及不良反应。方法:回顾性分析我院收治的80例经多西他赛化疗失败的晚期去势抵抗性前列腺癌患者,按治疗方法不同分为两组,观察组40例接受米托蒽... 目的:观察米托蒽醌联合沙利度胺挽救治疗经多西他赛治疗失败的晚期去势抵抗性前列腺癌的疗效及不良反应。方法:回顾性分析我院收治的80例经多西他赛化疗失败的晚期去势抵抗性前列腺癌患者,按治疗方法不同分为两组,观察组40例接受米托蒽醌、泼尼松联合沙利度胺方案化疗,对照组仅接受米托蒽醌、泼尼松方案化疗。每2个疗程评价疗效,计算PSA缓解率及中位进展时间、ORR及中位TTP、骨痛缓解率和不良反应。结果:80例患者均可评价疗效,观察组和对照组的PSA缓解率分别为55.0%、47.5%,中位进展时间分别为4.2个月、3.5个月,mTTP分别为4.9个月、4.1个月,骨痛缓解率分别为74.3%、51.5%,ORR均为5.0%,两组差异比较无统计学意义(P>0.05)。观察组患者的骨髓抑制、胃肠道反应发生率稍低于对照组,但差异无统计学意义(P>0.05);观察组患者的失眠、消瘦症状较对照组明显得到改善,差异有统计学意义(P<0.05)。结论:米托蒽醌、泼尼松方案挽救治疗经多西他赛治疗失败的晚期去势抵抗性前列腺癌有较好的疗效,不良反应发生率低,联合沙利度胺可进一步改善晚期患者的失眠、消瘦症状。 展开更多
关键词 米托蒽醌 沙利度胺 去势抵抗性前列腺癌 抗血管生成治疗
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雄激素受体调控基因组表达与去势抵抗性前列腺癌关系探索 被引量:1
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作者 邵志强 刘子丰 +2 位作者 张振 李扬 杨渝 《中国医学工程》 2021年第4期5-8,共4页
目的探索雄激素受体调控基因与前列腺癌发生去势抵抗的关系。方法选取80例经病理检查和临床资料证实并采用内分泌治疗的前列腺癌患者,随访获取发生去势抵抗时间,定量即时聚合酶链锁反应(qRT-PCR)检测确诊时穿刺标本的六个雄激素受体调... 目的探索雄激素受体调控基因与前列腺癌发生去势抵抗的关系。方法选取80例经病理检查和临床资料证实并采用内分泌治疗的前列腺癌患者,随访获取发生去势抵抗时间,定量即时聚合酶链锁反应(qRT-PCR)检测确诊时穿刺标本的六个雄激素受体调控基因KLK3(PSA),PMEPA1,NKX3.1,ODC1,AMD1和ERG表达并分析两者之间的关系。结果将六个雄激素受体调控基因相对表达量进行Z分数标准化处理,将所有病例按去势抵抗时间由短向长排列,分析六个基因Z分数及累积强度(CI),发现六个基因的表达情况与患者去势抵抗时间无明显相关性。结论初诊前列腺癌时患者雄激素受体功能与前列腺癌去势抵抗性无直接关系。 展开更多
关键词 雄激素受体 去势抵抗性前列腺癌 雄激素 前列腺癌
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转移性前列腺癌(mPCa)患者睾酮水平的控制与疾病进展的相关性研究 被引量:1
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作者 马麒 邱瑞莹 +3 位作者 李钊 阿不都克尤木·麦麦提依明 摆俊博 安恒庆 《新疆医学》 2021年第6期622-626,657,共6页
目的研究使用不同剂型戈舍瑞林缓释植入剂控制血清睾酮水平对于转移性前列腺癌(metastatic prostate cancer,mPCa)患者疾病的进展是否存在影响,探寻血清睾酮水平变化情况对疾病进展的影响及预测价值。方法回顾性分析2016年1月到2019年9... 目的研究使用不同剂型戈舍瑞林缓释植入剂控制血清睾酮水平对于转移性前列腺癌(metastatic prostate cancer,mPCa)患者疾病的进展是否存在影响,探寻血清睾酮水平变化情况对疾病进展的影响及预测价值。方法回顾性分析2016年1月到2019年9月期间的共96例在本院行经前列腺穿刺活检确诊为前列腺癌,并通过影像学证实已经出现转移的患者。研究使用戈舍瑞林联合比卡鲁胺方案治疗的患者的血清睾酮水平对疾病进展至去势抵抗性前列腺癌(castration resistant prostate cancer,CRPC)的时间的影响,并对比患者使用戈舍瑞林不同剂量剂型(10.8 mg和3.6 mg)是否对其进展至CRPC阶段的时间存在影响。使用统计软件进行Kaplan-Meier生存分析和COX回归分析。结果戈舍瑞林缓释植入剂一个月型(3.6mg)和三个月型(10.8 mg)对控制患者睾酮水平及控制疾病进展至CRPC时间的差异无统计学意义(P> 0.05)。睾酮最低浓度(nadir testosterone,NT)是影响患者进展至CRPC时间的危险因素。结论戈舍瑞林一个月型(3.6 mg)和三个月型(10.8 mg)对疾病进展至CRPC的时间没有明显差异。mPCa患者进行ADT治疗后,睾酮所达到的最低水平(nadir testosterone,NT)越低、到达最低睾酮浓度时间(time to nadir testosterone,TTNT)越长,患者进展至CRPC的时间越长。患者接受ADT治疗后的NT和TTNT对于预测mPCa患者的预后情况和疾病进展速度有重要价值。 展开更多
关键词 前列腺癌 内分泌治疗 睾酮 crpc 戈舍瑞林
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非雄激素竞争型雄激素受体拮抗剂设计策略
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作者 刘阳光 吴萌 +1 位作者 岑山 周金明 《药学研究》 CAS 2017年第5期249-254,258,共7页
雄激素受体(androgen receptor,AR)是前列腺癌治疗中最为重要的药物靶点,但抗雄激素药物在使用过程中产生的耐药性问题给前列腺癌患者的治疗带来了巨大挑战。本文回顾了雄激素受体的结构功能及传统治疗位点产生药物抗性的原因,并总结非... 雄激素受体(androgen receptor,AR)是前列腺癌治疗中最为重要的药物靶点,但抗雄激素药物在使用过程中产生的耐药性问题给前列腺癌患者的治疗带来了巨大挑战。本文回顾了雄激素受体的结构功能及传统治疗位点产生药物抗性的原因,并总结非雄激素竞争型的雄激素受体拮抗剂设计策略,为发展新型抗前列腺癌药物提供依据。 展开更多
关键词 雄激素受体 抗前列腺癌 雄激素受体拮抗剂 激活功能区2 结合功能区3 去势低抗性前列腺癌
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Polo样激酶1在去势抵抗性前列腺癌中的研究进展
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作者 王丽丽 王海涛 《中国肿瘤临床》 CAS CSCD 北大核心 2015年第14期720-723,共4页
Polo样激酶1(Polo-like kinase,PLK1)是一种高度保守的丝氨酸/苏氨酸蛋白激酶,在细胞的有丝分裂过程中起着非常重要的作用。PLK1在人类80%肿瘤类型中均过表达,且该激酶的高表达是多数肿瘤不良预后的标志之一。PLK1是近几年医学领域的研... Polo样激酶1(Polo-like kinase,PLK1)是一种高度保守的丝氨酸/苏氨酸蛋白激酶,在细胞的有丝分裂过程中起着非常重要的作用。PLK1在人类80%肿瘤类型中均过表达,且该激酶的高表达是多数肿瘤不良预后的标志之一。PLK1是近几年医学领域的研究热点,其在去势抵抗性前列腺癌(CRPC)细胞中高表达,有望成为治疗CRPC的新靶点。本文就PLK1的基本结构与功能、PLK1与CRPC发生和发展的关系,以及抑制PLK1治疗CRPC的研究进行综述,为PLK1在CRPC分子靶向治疗研究中提供一定的理论依据。 展开更多
关键词 POLO样激酶1 去势抵抗性前列腺癌 合成致死 联合抗癌
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甲羟孕酮治疗去势抵抗型前列腺癌的疗效观察 被引量:3
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作者 沈志勇 王玲 +4 位作者 程惠华 付志超 廖绍光 骆华春 雷勇 《现代肿瘤医学》 CAS 2017年第2期246-248,共3页
目的:观察甲羟孕酮对于去势抵抗型前列腺癌(CRPC)的疗效及毒副反应。方法:观察62例CRPC患者口服甲羟孕酮后,对比口服药物前后PSA、生活质量KPS评分、血红蛋白、营养状况的变化,评价药物毒副反应。结果:62例患者经过口服甲羟孕酮后,PSA... 目的:观察甲羟孕酮对于去势抵抗型前列腺癌(CRPC)的疗效及毒副反应。方法:观察62例CRPC患者口服甲羟孕酮后,对比口服药物前后PSA、生活质量KPS评分、血红蛋白、营养状况的变化,评价药物毒副反应。结果:62例患者经过口服甲羟孕酮后,PSA下降的有效率为11.3%、稳定率达24.2%。KPS评分、血红蛋白较前明显改善(P值均<0.05)。营养状况的改善率为64.5%、稳定率达30.6%。未发现III-IV级毒副反应,6例出现轻度低钠血症,5例出现轻度低钾血症,Ⅰ度下肢水肿较治疗前增加4例。结论:甲羟孕酮可延缓部分CRPC患者的PSA进展,改善晚期肿瘤患者的生活质量,毒副反应小。 展开更多
关键词 甲羟孕酮 去势抵抗型前列腺癌 生活质量 疗效
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阿比特龙联合泼尼松治疗去势抗拒前列腺癌的临床观察 被引量:4
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作者 许玉霞 张华锋 李长岭 《肿瘤防治研究》 CAS CSCD 北大核心 2015年第4期382-384,共3页
目的探讨新型雄激素合成抑制剂醋酸阿比特龙(Abriaterone acetate)治疗去势抗拒前列腺癌(castration-resistant prostate cancer,CRPC)的疗效及安全性。方法经病理证实并符合入选标准的58例去势抗拒前列腺癌患者,中位年龄68岁(61~81岁)... 目的探讨新型雄激素合成抑制剂醋酸阿比特龙(Abriaterone acetate)治疗去势抗拒前列腺癌(castration-resistant prostate cancer,CRPC)的疗效及安全性。方法经病理证实并符合入选标准的58例去势抗拒前列腺癌患者,中位年龄68岁(61~81岁),接受醋酸阿比特龙治疗,化疗至少2周期后。按实体瘤疗效评价标准(RECIST)美国NCI制定的毒性评价指标(CTC-AE3.0)评价疗效和毒性反应;采用Kaplan-meier法对患者总生存时间(OS)进行分析。结果 5例未完成总评估过程。可评价疗效的53例患者中,总有效率(ORR)18.87%(10例),疾病控制率(DCR)62.26%(33例);中位OS为(15.0±1.2)月;28例前列腺特异性抗原(prostate-specific antigen,PSA)下降﹥50%,治疗前后PSA中位数分别为78 ng/ml(18~1 776 ng/ml)和37 ng/ml(9~320 ng/ml),两者比较差异有统计学意义(P﹤0.05);化疗不良反应多为Ⅰ~Ⅱ级。结论阿比特龙联合泼尼松治疗去势抗拒前列腺癌疗效较好,不良反应轻。 展开更多
关键词 醋酸阿比特龙 泼尼松 去势抗拒前列腺癌 疗效 安全性
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microRNA在前列腺癌诊断和治疗方面的研究进展 被引量:4
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作者 丁昊 高振华 郑云 《中国临床药理学与治疗学》 CAS CSCD 2022年第6期696-708,共13页
前列腺癌(prostate cancer,PCa)是发生于前列腺组织的上皮性恶性肿瘤,它是仅次于肺癌的男性第二大常见癌症,影响着全球数百万男性。microRNA(miRNA)是一种长度为20~22nt的非编码小RNA,在转录后调控基因表达,miRNA参与了细胞周期进展、... 前列腺癌(prostate cancer,PCa)是发生于前列腺组织的上皮性恶性肿瘤,它是仅次于肺癌的男性第二大常见癌症,影响着全球数百万男性。microRNA(miRNA)是一种长度为20~22nt的非编码小RNA,在转录后调控基因表达,miRNA参与了细胞周期进展、细胞增殖、细胞凋亡、细胞迁移等几乎所有重要的生物生命过程的调控。最近越来越多的研究表明,miRNA参与了包括PCa在内的各种人类肿瘤的发生,本综述总结了现阶段与PCa相关的miRNA的研究进展,分析了PCa患者体内表达失调的miRNA在PCa发病机制、诊断和治疗中的作用,并且重点阐述了miRNA在去势抵抗性前列腺癌(castration-resistant prostate cancer,CRPC)诊断和治疗中的作用。 展开更多
关键词 前列腺癌 MIRNA 去势抵抗性前列腺癌 生物标志物 调控机制 治疗
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