Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.
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DOI:
10.1038/cgt.2015.26
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发表时间:
2015-07
影响因子:
6.4
通讯作者:
Hoffman RM
Hoffman RM
中科院分区:
医学3区
文献类型:
--
作者:
Yano S;Hiroshima Y;Maawy A;Kishimoto H;Suetsugu A;Miwa S;Toneri M;Yamamoto M;Katz MH;Fleming JB;Urata Y;Tazawa H;Kagawa S;Bouvet M;Fujiwara T;Hoffman RM

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精确的荧光引导手术(FGS)治疗胰腺癌有可能大大改善这种恶性疾病的预后。为了实现这一目标,我们使用遗传报告基因对患者来源的原位异种移植(PDOX)模型中的癌症和基质细胞进行颜色编码。使用含有端粒酶依赖性绿色荧光蛋白(GFP)的腺病毒OBP401来标记胰腺癌PDOX的癌细胞。PDOX先前在红色荧光蛋白(RFP)转基因小鼠中生长,该转基因小鼠稳定地将PDOX基质细胞标记为亮红色。颜色编码的PDOX模型使FGS能够完全切除包括间质的胰腺肿瘤。双色FGS可显著预防局部复发,而强光手术(BLS)或单色手术则不能。具有颜色编码的癌症和基质细胞的FGS对于改善复发性癌症的结果具有重要的潜力。
Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. In order to achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP) containing adenovirus OBP401 was used to label the cancer cells of the pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery (BLS) or single color could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant cancer.