Nakajima Takahiro, Geddie William, Anayama Takashi, Ko Hyang Mi, da Cunha Santos Gilda, Boerner Scott, Wang Tao, Wang Yu-hui, Li Ming, Pham Nhu-An, Tsao Ming Sound, Yasufuku Kazuhiro
Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Lung Cancer. 2015 Aug;89(2):110-4. doi: 10.1016/j.lungcan.2015.05.018. Epub 2015 Jun 3.
There has been limited utility for laboratory tumor models to predict clinical performance of cancer drugs. Clinical drug trials usually recruit patients that have advanced disease, therefore preclinical tumor models that closely reflect this characteristic will be more reliable to test candidate drugs. We evaluated the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to sample metastatic lymph nodes in patients to establish patient-derived tumorxenograft (PDX) models of advanced lung cancer.
Cell suspensions from TBNA aspirates were implanted into the subcutaneous tissue of NSG (NOD scid) gamma) mice. The success rate of PDX establishment was associated with tumor histopathology and the cellularity and cytopathological diagnosis of the primary EBUS-TBNA samples.
From December 2011 to June 2012, 19 patients were enrolled in this study. Successful engraftment was achieved in 8/19 cases (42.1%). The duration between inoculation and tumor formation averaged 62.4 days (13-144 days). The engrafted tumors included 3 adenocarcinomas (3/12: 25%), 2 squamous cell carcinomas (2/3: 67%), 1 large cell carcinoma (1/1: 100%), and 2 small cell carcinomas (2/3: 67%).
EBUS-TBNA samples can be used for establishment of tumor xenograft model in immunodeficient mice.
实验室肿瘤模型在预测癌症药物临床疗效方面的作用有限。临床药物试验通常招募患有晚期疾病的患者,因此能密切反映这一特征的临床前肿瘤模型在测试候选药物时会更可靠。我们评估了使用支气管内超声引导下经支气管针吸活检(EBUS-TBNA)对患者转移性淋巴结进行采样,以建立晚期肺癌患者来源的肿瘤异种移植(PDX)模型。
将TBNA吸出物中的细胞悬液植入NSG(NOD scid gamma)小鼠的皮下组织。PDX模型建立的成功率与肿瘤组织病理学以及原发性EBUS-TBNA样本的细胞数量和细胞病理学诊断有关。
2011年12月至2012年6月,19例患者纳入本研究。19例中有8例(42.1%)成功植入。接种与肿瘤形成之间的平均持续时间为62.4天(13 - 144天)。植入的肿瘤包括3例腺癌(3/12:25%)、2例鳞状细胞癌(2/3:67%)、1例大细胞癌(1/1:100%)和2例小细胞癌(2/3:67%)。
EBUS-TBNA样本可用于在免疫缺陷小鼠中建立肿瘤异种移植模型。