Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine.
Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine.
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DOI：
10.1038/bjc.2014.123
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发表时间：
2014-04-29
影响因子：
8.8
通讯作者：
Berger, R.
中科院分区：
文献类型：
--
作者：
Golan, T.;Atias, D.;Barshack, I.;Avivi, C.;Goldstein, R. S.;Berger, R.
关键词：
胰腺导管腺癌（PDAC）药物开发面临的挑战包括获得转移性癌组织用于研究和验证生物标志物预测个性化治疗决策。我们最近开发了一种新的PDAC治疗模型来解决这些挑战，该模型基于从腹水中分离出有活力的PDAC细胞。腹水取自接受姑息性穿刺的PDAC患者。腹水来源的PDAC原代细胞被分离、培养并在卵和体外鉴定。我们在2-7天内成功建立了92%（101例中的93例）的腹水液体样本（来自36例不同的患者）的腹水来源的原代细胞培养。均质上皮pdac富集细胞培养物被鉴定和表征。我们观察到在不同的病人来源的细胞培养中，倍增时间和迁移特性的范围很广。每个个体患者细胞培养的多样性进一步证明了治疗敏感性和耐药性的差异。利用鸡毛囊尿囊膜在体内移植证实了细胞的致瘤性和侵袭性。我们开发了一种独特的由腹水衍生的PDAC原代细胞培养模型。该模型有潜力研究PDAC进展中的信号通路，并为个体患者快速评估靶向治疗，从而支持个性化治疗决策。
Challenges in developing drugs for pancreatic ductal adenocarcinoma (PDAC) include obtaining metastatic cancer tissue for research and validating biomarkers predicative for personalised therapeutic decisions. We have recently developed a novel therapeutic model for PDAC to address these challenges based on the isolation of viable PDAC cells derived from ascites fluid. Ascites fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro. We successfully established ascites-derived primary cell cultures within 2–7 days from 92% (93 out of 101) of the ascites fluid samples obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell cultures were identified and characterised. We observed a wide range in doubling times and migration properties among the different patient-derived cell cultures. The diverse nature of each individual patient's cell cultures was further demonstrated by differences in therapeutic susceptibility and resistance. The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts. We have developed a unique ascites-derived PDAC primary cell culture model. This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
7.5
作者：
Chu, PGG;Weiss, LM
通讯作者：
Weiss, LM
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
影响因子：
24.5
作者：
Neesse, Albrecht;Michl, Patrick;Tuveson, David A.
通讯作者：
Tuveson, David A.
影响因子：
6.3
作者：
Feldmann G;Rauenzahn S;Maitra A
通讯作者：
Maitra A