Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models.

Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models.
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DOI:
10.1371/journal.pone.0099977
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Hoffman RM
Hoffman RM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hiroshima Y;Maawy A;Zhang Y;Sato S;Murakami T;Yamamoto M;Uehara F;Miwa S;Yano S;Momiyama M;Chishima T;Tanaka K;Bouvet M;Endo I;Hoffman RM

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本研究的目的是确定紫外线(UVC)照射联合荧光引导手术(FGS)是否可以根除原位裸鼠模型中的转移性人胰腺癌。裸鼠原位植入表达绿色荧光蛋白(GFP)的人MiaPaCa-2胰腺癌细胞2周后,对所有荷瘤小鼠(n = 24)进行强光手术(BLS)。BLS结束后,小鼠随机分为3个治疗组;BLS-only (n = 8)投篮(n = 8)或FGS-UVC (n = 8)。用荧光导航手持式便携式成像系统切除FGS和FGS- uvc治疗小鼠的残留肿瘤。FGS-UVC处理小鼠手术切除床以2700 J/m2 (254 nm) UVC照射。FGS术后平均肿瘤残余面积(n = 16)明显小于单纯BLS术后(n = 24)(分别为0.135±0.137 mm2和3.338±2.929 mm2, p = 0.007)。与FGS和FGS- uvc治疗小鼠相比,BLS治疗小鼠的无复发生存期(RFS)(分别p<0.001和p<0.001)和总生存期(OS)(分别p<0.001和p<0.001)均显著降低。与仅使用fgs处理的小鼠相比,fgs - uvc处理的小鼠RFS和OS增加(分别为p = 0.008和p = 0.025);RFS持续至少150天,表明动物已经治愈。本研究结果表明,UVC照射联合FGS具有提高生存率的临床潜力。
The aim of this study is to determine if ultraviolet light (UVC) irradiation in combination with fluorescence-guided surgery (FGS) can eradicate metastatic human pancreatic cancer in orthotopic nude–mouse models. Two weeks after orthotopic implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3 treatment groups; BLS-only (n = 8) or FGS (n = 8) or FGS-UVC (n = 8). The residual tumors were resected using a hand-held portable imaging system under fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical resection bed was irradiated with 2700 J/m2 UVC (254 nm) in the mice treated with FGS-UVC. The average residual tumor area after FGS (n = 16) was significantly smaller than after BLS only (n = 24) (0.135±0.137 mm2 and 3.338±2.929 mm2, respectively; p = 0.007). The BLS treated mice had significantly reduced survival compared to FGS- and FGS-UVC-treated mice for both relapse-free survival (RFS) (p<0.001 and p<0.001, respectively) and overall survival (OS) (p<0.001 and p<0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to FGS-only treated mice (p = 0.008 and p = 0.025, respectively); with RFS lasting at least 150 days indicating the animals were cured. The results of the present study suggest that UVC irradiation in combination with FGS has clinical potential to increase survival.
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