CAJ | 학술논문

目的比较瘤内注射删除E1B基因的重组溶瘤腺病毒与无水乙醇消融两种方法联合吉西他滨化疗治疗裸鼠原位种植胰腺癌的有效性和安全性.方法构建裸鼠胰腺原位种植瘤模型并将造模成功的54只裸鼠随机数字表法分为6组,其中4组分别给予瘤内注射溶瘤腺病毒、无水乙醇、联合或不联合吉西他滨静脉化疗,另2组一组给予化疗并瘤内注射生理盐水,一组瘤内注射生理盐水对照,4周后处死裸鼠并观察各组瘤体生长、转移情况,间接免疫荧光观察肿瘤及正常组织中病毒分布情况,TUNEL法观察肿瘤细胞凋亡情况,电镜观察注射病毒后肿瘤细胞内结构的变化.结果注射无水乙醇组3只裸鼠于注射后48 h内死亡,死亡率16.7％,注射溶瘤病毒组均存活.注射病毒联合化疗组肿瘤体积增长明显小于对照组和单纯化疗组(P值分别为0.008和0.040),注射无水乙醇联合化疗组亦有同样变化(P值分别为0.000和0.006),同时单纯瘤内注射无水乙醇组肿瘤体积增长也明显小于对照和单纯化疗组(P值分别为0.012和0.041).间接免疫荧光表明注射后溶瘤病毒除肿瘤组织外在其余组织中无明显分布.TUNEL法检测表明各组间凋亡率存在显著差异(P=0.021),其中注射溶瘤病毒联合化疗组的凋亡率为(83.2±35.7)％远高于其余各组.电镜观察见病毒注射后肿瘤细胞内部出现趋向凋亡变化.结论溶瘤病毒瘤内注射对于加强吉西他滨的抗肿瘤作用是有益的,这种作用没有无水乙醇瘤内注射那么明显,但在安全性上是高于无水乙醇的.同时,该溶瘤病毒具有较明显的嗜肿瘤特性,瘤内注射对其它组织影响极小,是安全的.另外,溶瘤病毒抗肿瘤的效应可能还存在诱导凋亡等其它途径.
목적 비교류내주사산제E1B기인적중조용류선병독여무수을순소융량충방법연합길서타빈화료치료라서원위충식이선암적유효성화안전성.방법 구건라서이선원위충식류모형병장조모성공적54지라서수궤수자표법분위6조,기중4조분별급여류내주사용류선병독、무수을순、연합혹불연합길서타빈정맥화료,령2조일조급여화료병류내주사생리염수,일조류내주사생리염수대조,4주후처사라서병관찰각조류체생장、전이정황,간접면역형광관찰종류급정상조직중병독분포정황,TUNEL법관찰종류세포조망정황,전경관찰주사병독후종류세포내결구적변화.결과 주사무수을순조3지라서우주사후48 h내사망,사망솔16.7％,주사용류병독조균존활.주사병독연합화료조종류체적증장명현소우대조조화단순화료조(P치분별위0.008화0.040),주사무수을순연합화료조역유동양변화(P치분별위0.000화0.006),동시단순류내주사무수을순조종류체적증장야명현소우대조화단순화료조(P치분별위0.012화0.041).간접면역형광표명주사후용류병독제종류조직외재기여조직중무명현분포.TUNEL법검측표명각조간조망솔존재현저차이(P=0.021),기중주사용류병독연합화료조적조망솔위(83.2±35.7)％원고우기여각조.전경관찰견병독주사후종류세포내부출현추향조망변화.결론 용류병독류내주사대우가강길서타빈적항종류작용시유익적,저충작용몰유무수을순류내주사나요명현,단재안전성상시고우무수을순적.동시,해용류병독구유교명현적기종류특성,류내주사대기타조직영향겁소,시안전적.령외,용류병독항종류적효응가능환존재유도조망등기타도경.
Objective To compare the efficacy and safety of E1B gene-deleted adenovirus (H101)and ethanol in treating advanced pancreatic carcinomas by intratumoral injection combined with intravenous gemcitabine.Methods We constructed an orthotopic nude mouse model of pancreatic carcinoma through cancer cell injection into pancreas.A total of 54 nude mice were randomly allocated to 6 groups to accept H101,ethanol or saline (control) intratumoral injection,combined with or without intravenous gemcitabiein.The animals were sacrificed 4 weeks after the treatment and the pancreatic tumors were collected to determine the size,existence of metastasis,distribution of virus by indirect immunofluorescence and apoptosis in tumor by TUNEL and electron microscope.Results All mice completed the scheduled treatment,while 3 died in 48 hours after ethanol injection resulting in a mortality of 16.7％ (3/18).On the contrary,no mice died in the adenovirus injcction group.The average tumor size in group of H101 intratumoral injection combined with intravenous gemcitabie was significant smaller than that in group of saline injection with or without systemic gemcitabie (P =0.008,0.040,respectively).Similar differences were observed between ethanol intratumoral injection and control groups (P =0.012,0.041).Meanwhile,the H101 was absent in all the other organs except the pancreas,which meant that the selectivity of the H101 was tremcndous.The virus combine gemcitabie group had higher apoptosis rate in tumor (83.2 ± 35.7) ％,determined by TUNEL.Conclusion E1B gene-deleted adenovirus intratumral injection in combination with intravenous gemcitabine treating pancreatic carcinomas is efficient and safe,in spite of its lower effectiveness than ethanol.