Roife David, Kang Ya'an, Wang Li, Fang Bingliang, Swisher Stephen G, Gershenwald Jeffrey E, Pretzsch Shanna, Dinney Colin P, Katz Matthew H G, Fleming Jason B
Department of General Surgery, The University of Texas Health Science Center at Houston, Houston, TX.
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.
Surgery. 2017 May;161(5):1246-1254. doi: 10.1016/j.surg.2016.11.020. Epub 2017 Jan 9.
Patient-derived xenografts have recently become a powerful tool for cancer research and may be used to guide personalized therapy. Thus far, patient-derived xenografts have been grown from tumor tissue obtained after operative resection; however, many cancer patients never undergo operative intervention for a variety of reasons. We hypothesized that xenograft tumors could be grown from smaller volumes of patient tissue, such as those obtained during diagnostic biopsies.
Surgical specimens were obtained after resection of primary or metastatic lesions of the following cancers: pancreatic carcinoma, non-small cell lung cancer, bladder (urothelial) carcinoma, and melanoma. At least 10 cases of each cancer were included in this study. To mimic clinical biopsies, small fragments of the surgical specimens were biopsied with a 22-gauge needle, and the needle contents were injected subcutaneously in immunocompromised mice. The tumor fragment from which the biopsy was taken was also implanted subcutaneously in the contralateral side of the same mouse as a control.
Success rates of the traditional method of xenograft implantation ranged from 27.3%-70%. Success rates of the fine needle aspirate technique ranged from 0%-36.4%. An attempt to engraft a percutaneous core needle liver biopsy of a metastatic pancreatic adenocarcinoma also was successful.
We have found that it is possible to engraft fine needle aspirates and core biopsies of solid tumors in order to generate patient-derived xenografts. This may open up xenografting to a wider cancer patient population than previously possible.
患者来源的异种移植最近已成为癌症研究的有力工具,可用于指导个性化治疗。迄今为止,患者来源的异种移植是从手术切除后获得的肿瘤组织培养而来;然而,许多癌症患者由于各种原因从未接受手术干预。我们推测异种移植肿瘤可以从较小体积的患者组织中生长,例如在诊断性活检时获得的组织。
获取以下癌症的原发性或转移性病变切除后的手术标本:胰腺癌、非小细胞肺癌、膀胱(尿路上皮)癌和黑色素瘤。本研究纳入每种癌症至少10例病例。为模拟临床活检,用22号针从手术标本中取小碎片进行活检,将针内物质皮下注射到免疫缺陷小鼠体内。取活检的肿瘤碎片也作为对照皮下植入同一只小鼠的对侧。
传统异种移植植入方法的成功率为27.3%-70%。细针抽吸技术的成功率为0%-36.4%。对一例转移性胰腺腺癌经皮芯针肝活检进行移植的尝试也获得成功。
我们发现,为了生成患者来源的异种移植,对实体瘤进行细针抽吸和芯针活检后进行移植是可行的。这可能使异种移植适用于比以前更广泛的癌症患者群体。