ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。     

放线菌素23-21对裸小鼠人鼻咽癌细胞系移植瘤和人胃癌细胞系移植瘤的抑制作用

放线菌素23-21属放线菌素类抗癌抗生素,由浅黄色链霉菌产生,该菌从中国福州土壤样品中分离得到。采用裸小鼠人鼻咽癌细胞系(CNE-2Z)和人胃癌细胞系(MGc-803)两种移植模型观察了放线菌素23-21的作用。放线菌素23—21 50μg/kg,对CNE-27移植瘤和MGc803移植瘤的抑制率分别为58.4%(P<0.05)和68.7%(P<0.05)。肿瘤生长曲线显示,治疗组肿瘤生长缓慢。电镜检查,治疗组瘤细胞可见核仁分离和微球体形成。提示放线菌素23-21可能有抑制核仁rRNA合成的作用。在有效剂量下,未见重要脏器病理改变。     

Localizing and photosensitizing mechanism by tetra(3-hydroxyphenyl)porphin in vivo on human malignant melanoma xenografts in athymic nude mice

Observations on time-dependent localization of tetra(3-hydroxyphenyl)porphin (3-THPP) in human malignant melanoma transplanted to athymic nude mice from 1 to 120 h after intraperitoneal (i.p.) 10 mg kg^–1 b.w. administration were made by means of fluorescence microscopy. Fluorescence was found on the membrane of the melanoma cells and in the cytoplasm with a peak fluorescence intensity at 24 h post-injection of 3-THPP. The growth of the tumour cells was obviously inhibited at an early stage after PCT. Morphological changes of the tumour at various intervals after treatment by PCT with 3-THPP were also observed. Diffuse degeneration of the tumour cells with swelling of mitochondria and endoplasmic reticulum, heterochromatin aggregation and margination, etc., and subsequently diffuse necrosis with little or no the background of tumorous vascular response were found at an early stage after PCT. On the other hand, it was also observed that the necrosis of the melanoma areas was caused as a consequence of tumorous vascular injury at a later stage after PCT. Thus, two tumoricidal processes caused by PCT with 3-THPP were seen: a direct phototoxic action on tumour cells at an early stage after PCT and an indirect effect secondary to tumorous vascular injury at a later period after PCT.     

Influence of differences in tumor vascularity upon the effects of hyperthermia

Summary Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.     

Experimental studies of chemosensitivity testing of urothelial cancer grown in nude mice

Summary The present study provides information relevant to a number of variables which may influence response to treatment of nude mouse-grown human urothelial cancer. A number of xenotransplanted tumors were exposed to selected treatments at different transplant generations, and at various dose levels and treatment schedules. It was observed that nude mouse-grown tumors were characterized by consistency, reproducibility and biological stability not affected by the transplant generation at which they were examined. Treatment related dose response curves were steep, the sharpness of the curves depending on the degree of tumor sensitivity. Best therapeutic results were obtained at the maximum tolerated dose of cytotoxic agents under study and of importance, a 20% to 40% dose reduction with the same treatment schedule resulted in little or no activity. In addition, treatment schedule, timing and sequence of treatments and to a certain degree, tumor grade were important variables which could influence tumor response. The nude mouse-human tumor system provides important preclinical guidelines on dose, schedule, sequence and timing of treatments and can assist in designing more efficient clinical trials.     

天花粉蛋白对荷人肝癌裸小鼠的抑癌作用

目的 探讨天花粉蛋白(trichosanthin,TCS)对荷人肝癌裸小鼠的抑癌作用。方法 采用人肝癌原位移植模型。将24只裸小鼠分为TCSⅠ组、TCSⅡ组、TCSⅢ组和对照组，TCS剂量分别为0．2mg／kg、0．4mg／kg、0．6mg／kg，对照组用生理盐水0．2ml／只腹腔注射，共10次。第21天称瘤重和裸小鼠体重，计算抑癌率。应用免疫组织化学技术，检测瘤组织中Ki67的表达。结果 对照组、TCSⅠ组、TCSⅡ组和TCSⅢ组平均瘤重分别为0．99g、0．81g、0．22g和0．20g。用药组瘤重与对照组相比有显著性差异(P＜0．05)。TCSⅠ组、TCSⅡ组和TCSⅢ组抑癌率分别为18．18％、77．78％、79．80％。对照组、TCSⅠ组、TCSⅡ组和TCSⅢ组平均鼠重增加为2．22g、1．22g、0．28g、一2．37g。用药组与对照组鼠重变化有显著性差异(P＜0．05)。对照组、TCSⅠ组、TCSⅡ组和TCSⅢ组Ki67蛋白阳性表达百分率分别为31．33％、29．92％、10．25％和9．67％。TCSⅠ组Ki67百分率与对照组相比无显著性差异(P＞0．05)。TCSⅡ组和TCSⅢ组Ki67百分率与对照组相比有显著性差异(P＜0．05)。结论 TCS对荷人肝癌裸小鼠的移植瘤有明显的抑癌作用。TCS抑制肿瘤细胞增殖可能是其抑癌的机制之一。     

MDR1特异性核酶逆转肝癌多药耐药的实验研究

目的探讨MDR1核酶（N2A＋tRNAi^met-iMDRl-sRz，sRz）在裸鼠体内逆转人肝癌组织多药耐药（MDR）的可行性。方法将原发性MDR人肝癌组织裸鼠原位移植模型第2代随机分为A组（空白对照组：生理盐水40μl＋Lipofect AMINE^TM2000 10μ1）、B组（阴性对照组：N2A＋tRNAi^met 10μg／40μl＋Lipofect AMINE^TM2000 10μl）和C组（核酶组：sRz 10μg／40μl＋LipofectAMINE^TM2000 10μl），均开腹瘤内注射。瘤内注药1周后用表阿霉素15mg／kg腹腔注射，每周1次，连续4周。彩色B超测量肿瘤体积。化疗结束后1周处死裸鼠，RT-PCR、Western blot法检测肿瘤中MDR1 mRNA及其蛋白P-gp的表达。结果C组每次化疗后肿瘤体积均较前缩小（F=659．99，P〈0．05）。除第1次化疗外，其余各次化疗后C组的抑制率均高于A、B组（F=35．36，12．77，97．60，P〈0．05）。化疗结束后，C组与瘤源以及A、B组相比，肿瘤组织中MDR1 mRNA和P-gp的表达明显降低（F=45．36，3590．40，P〈0．05）。结论sRz可有效降低肝癌细胞表达MDR1 mRNA和P-gp，一定程度上逆转MDR，提高E-ADM的化疗效果。单纯E-ADM化疗可使肝癌组织MDR1 mRNA和P-gp表达升高，诱导MDR的产生。     

人喉癌裸鼠移植瘤模型的建立及部分生物学特性研究

用人喉癌手术切除标本建立了裸鼠移植瘤模型,已传至13代。原代移植成功率为66.7％,潜伏期30～70d;鼠间传代移植成功率为100％,潜伏期14～19d,生长稳定。经光学显微镜检查,各代移植瘤组织结构与原人喉癌组织基本一致。电镜检查证明,具有人喉癌特征,癌细胞间有大量桥粒,细胞浆中可见张力原纤维,有的张力原纤维与桥粒相连。细胞表面有较大的指状突,核膜较规则,胞浆中线粒体较多。     

125I粒子组织间种植对人胃癌裸鼠移植瘤的杀伤作用

目的 观察不同剂量^125I粒子对人胃癌裸鼠移植瘤的杀伤作用及组织损伤。方法 建立人胃癌BGC-823细胞裸鼠皮下移植瘤模型，随机分为对照组和实验组，将不同剂量（100、120、140Gy）地^125I粒子植于实验组。30、60d：比较移植瘤抑瘤率，病理组织学、局部皮肤反应、裸鼠体重及白细胞计数。结果30d，100、120、140Gy组抑瘤率分别为51．93％、79．18％、90．22％，病理组织学反应程度多为RCRG2（45．83％），各实验组组间除120Gy与140Gy（P〉O．05）组外，及分别与对照组比较，差异有统计学意义（P〈0．05）；局部皮肤反应各实验组与对照组比较，差异有统计学意义（P〈0．05），各实验组组间差异无统计学意义（P〉0．05）。60d，各组抑瘤率分别为97．97％、100％、96．69％，病理组织学反应程度以RCRG1居多（62．5％），与对照组比较，差异均有统计学意义（P〈0．05），各实验组组间差异无统计学意义（P〉0．05）；局部皮肤反应随剂量增高而加重，各实验组组间及其分别与对照组比较，差异有统计学意义（P〈0．05）。结论 不同剂量的^125I粒子在不同时间对人胃癌裸鼠皮下移植瘤有显著杀伤作用，但120Gy和140Gy组随剂量累积，损伤明显增加。提示100Gy可能是治疗人胃癌裸鼠皮下移植瘤的有效剂量。