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患者帮助研究人员推进前列腺癌的治疗 精选

已有 3239 次阅读 2021-8-24 15:29 |个人分类:新观察|系统分类:海外观察

患者帮助研究人员推进前列腺癌的治疗

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Fig. 2 Pathological and clinical features of tumors used to establish PDXs. a Pie charts show the number of patients consented and the number of primary prostate tumor samples collected for xenografting compared to the number of samples that maintained tumor tissue in the first generation (G1) PDX and established as serially transplantable (ST) PDXs. Color denotes the site that each sample was taken from. b–d The percentage of Ki67-positive tumor cells in pre-grafted tissue (b; n = 14 ST, 38 non ST), time to first generation (c; n = 14 ST, 49 non ST), and tumor volume at surgery for radical prostatectomy (RP; orange) and transurethral resection of the prostate (TURP; purple) specimens (d; n = 13 ST, 28 non ST, P = 0.016) that established ST PDXs compared to those that did not. Unpaired two-sided T test for ST vs non ST; data shown as mean ± SEM. e The percent of primary tumors with a Gleason grade group of 1–5 that did (n = 13) or did not establish ST PDXs (n = 30; not significant, Mann Whitney test comparing the distribution of Gleason grade groups between ST vs non ST). f Kaplan–Meier curve comparing the survival of patients whose RP specimen did (orange; n = 13) or did not (blue; n = 37) establish ST PDXs. P = 0.0072; log rank test; HR = 10.93; 95% CI 1.51 to 79.08. g Pie charts show the number of patients consented and the number of metastatic tumor samples collected for xenografting compared to the number of samples that maintained tumor tissue in the G1 PDX and established as serially transplantable PDXs. Color denotes the site that each sample was taken from. h–i The percentage of Ki67-positive tumor cells in pre-grafted tissue (h; n = 25 ST, 94 non ST, P < 0.0001), and time to first generation (i; n = 28 ST, 117 non ST, P <  0.0001) for metastatic tumor samples obtained from surgery/biopsy (yellow) or autopsy (purple) that did or did not establish ST PDXs. Unpaired two-sided T test for ST vs non ST; data shown as mean ± SEM. j The percentage of androgen receptor (AR)-positive and AR-negative metastatic tumors that did (n = 25) or did not establish ST PDXs (n = 80), based on immunohistochemistry for AR in the original tumor tissue. Not significant; Fisher’s exact test. Source data are provided as a Source Data file. Credit: DOI: 10.1038/s41467-021-25175-5

据澳大利亚莫纳什大学(Monash University2021823日提供的消息,该校研究人员与澳大利亚彼得·麦卡伦癌症中心(Peter MacCallum Cancer Centre)、澳大利亚墨尔本大学(University of Melbourne)、墨尔本莫纳什医院(Monash Health)、莫纳什大学东部卫生临床学院(Eastern Health and Monash University Eastern Health Clinical School)、英国谢菲尔德教学医院国民保健服务基金会信托(Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England)、澳大利亚死亡后癌症组织收集(CASCADE)计划{ Cancer Tissue Collection After Death (CASCADE) Program }、新加坡杜克国立大学医学院(Duke-National University of Singapore Medical School)、墨尔本大学奥斯丁医院(Austin Hospital, The University of Melbourne)、墨尔本的爱普沃斯医疗保健(Epworth Healthcare)、东墨尔本的爱普沃斯健康中心(Epworth Health, East Melbourne)、澳大利亚泌尿外科协会(Australian Urology Associates)、澳大利亚伯威克的凯西医院(Casey Hospital, Berwick, Australia)、澳大利亚爱普沃斯医院(Epworth Hospital, Richmond, Australia)、澳大利亚芒特·韦弗利的TissuPathTissuPath, Mount Waverley, Australia)以及澳大利亚墨尔本卡布里尼健康的卡布里尼学院(Cabrini Institute, Cabrini Health, Melbourne, Australia)的研究人员合作研究发现:患者帮助研究人员推进前列腺癌的治疗(Patients helping researchers to advance treatments for prostate cancer)。

莫纳什大学(Monash University)的研究人员已经建立了世界上最大的前列腺癌患者活体肿瘤收集库之一,这加快了前列腺癌新疗法的测试,并使患者更快受益。

前列腺癌是最常见的癌症之一,也是最难在实验室中进行研究的癌症之一,经常使用的模型来源于40多年前。随着墨尔本泌尿学研究联盟(Melbourne Urological Research Alliance简称 MURAL)的建立,数百名维多利亚男性(Victorian men)慷慨地捐赠了他们的癌症组织样本,使研究小组能够研究更多种类的活体肿瘤,并测试更多种类的治疗方法的有效性,以阻止肿瘤生长。

患者来源的异种移植物(patient-derived xenografts简称PDX)集合(PDX collection)是由莫纳什生物医学发现研究所(Monash Biomedicine Discovery Institute简称BDI)的盖尔·里斯布里杰教授(Professor Gail Risbridger)和雷内亚·泰勒副教授(Associate Professor Renea Taylor)领导的多学科联盟开发的,现在包括59种肿瘤,这些样本是2012年到2020年从30名患者收集的,目前是世界上收集前列腺癌模型最多的国家之一。PDX集合的完整特征于2021819日已经在《自然通讯》(Nature Communications)杂志网站发表——Gail P. RisbridgerAshlee K. ClarkLaura H. PorterRoxanne ToivanenAndrew Bakshi, Natalie L. ListerDavid PookCarmel J. PezaroShahneen SandhuShivakumar Keerthikumar, Rosalia Quezada UrbanMelissa PapargirisJenna KraskaHeather B. MadsenHong Wang, Michelle G. RichardsBirunthi NiranjanSamantha O’DeaLinda TengWilliam Wheelahan, Zhuoer LiNicholas ChooJohn F. OuyangHeather ThorneLisa DevereuxRodney J. Hicks, Shomik SenguptaLaurence HarewoodMahesh IddawalaArun A. AzadJeremy GoadJeremy GrummetJohn KourambasEdmond M. KwanDaniel MoonDeclan G. MurphyJohn PedersenDavid CloustonSam NordenAndrew RyanLuc FuricDavid L. GoodeMark FrydenbergMitchell G. LawrenceRenea A. Taylor. The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology. Nature CommunicationsPublished: 19 August 2021, volume 12, Article number: 5049. DOI: 10.1038/s41467-021-25175-5. https://www.nature.com/articles/s41467-021-25175-5

墨尔本泌尿学研究联盟(MURAL)的PDXs是新的癌症模型的持久资源,可以与其他学术研究人员或制药公司共享。患者和他们的家人直接参与了这项风险投资,包括EJ惠腾基金会(EJ Whitten Foundation),该基金会在过去10年提供了超过100万美元($1M)的捐款,使这一资源得以开发,并使该项目成为国际领域的前沿。

盖尔·里斯布里杰教授说:“该个项目始终与像EJ惠腾(EJ Whitten)这样的病人联系在一起。我们提取病人的组织在实验室中进行测试,这些发现随后又推进了对病人的治疗。我们的前列腺癌新模型吸引了全世界科学家和制药行业的兴趣。

EJ惠腾基金会的执行董事(executive director)和创始人泰德·惠腾(Ted Whitten)祝贺莫纳什大学生物医学发现研究所(Monash University Biomedicine Discovery Institute)最近在前列腺癌研究方面的发现。“我们相信莫纳什大学是前列腺癌研究的领导者,我们很高兴能够在过去十年中资助他们的许多重要项目。”

上述研究的资深作者、来自莫纳什生物医学发现研究所(BDI)的米切尔·劳伦斯博士(Dr. Mitchell Lawrence)说:“这一资源提供了一个机会,将前列腺癌的分子变化与病理学联系起来,培养类器官(grow organoids)并测试治疗的功能反应,由于缺乏合适的模型,这些疗法很少应用于前列腺癌(prostate cancer)。”

上述介绍,仅供参考。欲了解更多信息敬请注意浏览原文或者相关报道

Experts band together to eradicate prostate cancer

Abstract

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012–2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 × 1 × 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.




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