中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2011年
47期
3367-3370
,共4页
辛刚%杜鹃%朱琳%于云海%李跃%刘培淑
辛剛%杜鵑%硃琳%于雲海%李躍%劉培淑
신강%두견%주림%우운해%리약%류배숙
血管正常化%重组人内皮抑素%顺铂
血管正常化%重組人內皮抑素%順鉑
혈관정상화%중조인내피억소%순박
Vasculature normalization%Recombinant human endostatin%Cisplatin
目的 寻找重组人内皮抑素(rhES)使卵巢癌荷瘤鼠瘤组织微血管正常化时间窗.方法 建立卵巢癌移植瘤模型,通过动态观察重组人内皮抑素用药后肿瘤微血管α-平滑肌肌动蛋白(α-SMA),Ⅳ型胶原(CollagenⅣ)及缺氧诱导因子-1 α(HIF-1α)表达变化,确定rhES使肿瘤微血管正常化时间窗.按rhES使肿瘤微血管正常化时间窗前、中、后3个时间段分别给予顺铂治疗并设对照,通过抑瘤率,微血管密度(MVD),肿瘤细胞增殖活性等方面评价疗效.结果 在rhES用药第4、6天肿瘤微血管趋于成熟,基底膜,周细胞增加,α-SMA阳性表达微血管数与对照组比较明显升高,分别为(15.3±5.2)比(4.3±2.1)个/mm2 (P <0.01);(16.4±4.6)比(6.6±2.4)个/mm2(P <0.01),Ⅳ型胶原阳性表达的微血管与对照组相比也明显升高,分别是(14.7±4.3)比(6.7±5.1)个/mm2(P<0.01);(18.4±5.5)比(7.1±1.7)个/mm2 (P <0.01).在rhES用药第4、6天肿瘤乏氧区HIF-1α表达降低.rhES+ DDP(d4 ~6)组与其他各组比较抑瘤率最高,微血管密度降低,增殖核抗原(PCNA)表达下降.结论 rhES使卵巢癌移植瘤微血管正常化时间窗为用药第4~6天,在该时间段与顺铂联合用药治疗效果最佳.
目的 尋找重組人內皮抑素(rhES)使卵巢癌荷瘤鼠瘤組織微血管正常化時間窗.方法 建立卵巢癌移植瘤模型,通過動態觀察重組人內皮抑素用藥後腫瘤微血管α-平滑肌肌動蛋白(α-SMA),Ⅳ型膠原(CollagenⅣ)及缺氧誘導因子-1 α(HIF-1α)錶達變化,確定rhES使腫瘤微血管正常化時間窗.按rhES使腫瘤微血管正常化時間窗前、中、後3箇時間段分彆給予順鉑治療併設對照,通過抑瘤率,微血管密度(MVD),腫瘤細胞增殖活性等方麵評價療效.結果 在rhES用藥第4、6天腫瘤微血管趨于成熟,基底膜,週細胞增加,α-SMA暘性錶達微血管數與對照組比較明顯升高,分彆為(15.3±5.2)比(4.3±2.1)箇/mm2 (P <0.01);(16.4±4.6)比(6.6±2.4)箇/mm2(P <0.01),Ⅳ型膠原暘性錶達的微血管與對照組相比也明顯升高,分彆是(14.7±4.3)比(6.7±5.1)箇/mm2(P<0.01);(18.4±5.5)比(7.1±1.7)箇/mm2 (P <0.01).在rhES用藥第4、6天腫瘤乏氧區HIF-1α錶達降低.rhES+ DDP(d4 ~6)組與其他各組比較抑瘤率最高,微血管密度降低,增殖覈抗原(PCNA)錶達下降.結論 rhES使卵巢癌移植瘤微血管正常化時間窗為用藥第4~6天,在該時間段與順鉑聯閤用藥治療效果最佳.
목적 심조중조인내피억소(rhES)사란소암하류서류조직미혈관정상화시간창.방법 건립란소암이식류모형,통과동태관찰중조인내피억소용약후종류미혈관α-평활기기동단백(α-SMA),Ⅳ형효원(CollagenⅣ)급결양유도인자-1 α(HIF-1α)표체변화,학정rhES사종류미혈관정상화시간창.안rhES사종류미혈관정상화시간창전、중、후3개시간단분별급여순박치료병설대조,통과억류솔,미혈관밀도(MVD),종류세포증식활성등방면평개료효.결과 재rhES용약제4、6천종류미혈관추우성숙,기저막,주세포증가,α-SMA양성표체미혈관수여대조조비교명현승고,분별위(15.3±5.2)비(4.3±2.1)개/mm2 (P <0.01);(16.4±4.6)비(6.6±2.4)개/mm2(P <0.01),Ⅳ형효원양성표체적미혈관여대조조상비야명현승고,분별시(14.7±4.3)비(6.7±5.1)개/mm2(P<0.01);(18.4±5.5)비(7.1±1.7)개/mm2 (P <0.01).재rhES용약제4、6천종류핍양구HIF-1α표체강저.rhES+ DDP(d4 ~6)조여기타각조비교억류솔최고,미혈관밀도강저,증식핵항원(PCNA)표체하강.결론 rhES사란소암이식류미혈관정상화시간창위용약제4~6천,재해시간단여순박연합용약치료효과최가.
Objective To find the time window of normalization of tumor vasculature by endostar in tumor-bearing mice with ovarian cancer.Methods The nude murine model of ovarian cancer was established.The vasculature markers α-SMA (alpha-smooth muscle actin) and collagen Ⅳ covered tumor vessels and hypoxic zone following the treatment of endostar were monitored.According to the changes of microvascular morphology and tumor hypoxia zone,the time window was identified.Furthermore the treatment protocols of scheduling dosing of cisplatin plus endostar at different time points were designed.After treatment tumor volume,the parameters of microvascular density (MVD) and PCNA (proliferating cell nuclear antigen) were monitored to evaluate the effects of different protocols.Results At Days 4 and 6 posttreatment,more α-SMA and collagen Ⅳ covered vessels could be observed.The amount of microvasculature expressed α-SMA on days 4 compared with control was ( 15.3 ±5.2) vs (4.3 ±2.1 )/mm2 (P <0.01 ) ; at Day 6,the result was ( 16.4 ± 4.6) vs (6.6 ± 2.4 )/mm2 ( P < 0.01 ).The expression of collagen Ⅳ had a similar change.And the numbers of microvasculature expressing collagen Ⅳ was ( 14.7 ± 4.3 ) vs (6.7 ±5.1 )/mm2 at Days 4 and 6 ( P < 0.01 ) ; ( 18.4 ± 5.5 ) vs (7.1 ± 1.7 )/mm2 ( P < 0.01 ).The expression of HIF-1α decreased in hypoxic area.In the rhES + DDP (d4 -6) group,the value of microvessel density (MVD) decreased and the expression of PCNA significantly decreased versus other groups. Conclusion Endostar may normalize the tumor vasculature.And the time window is found at Days 4 -6 post-treatment.During the time of vascular normalization,a combination therapy of endostar plus cisplatin has optimal efficacies.