In vitro and in vivo Effects of Cisplatin and Etoposide in Combination on Small Cell Lung Cancer Cell Lines

The effects of cisplatin (CDDP) and etoposide (ETP) in combination were evaluated in vitro and in vivo using small cell lung cancer cell lines. The combination effects in vitro were investigated using isohologram analysis. Used together, CDDF and ETP showed a synergistic effect against cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lul30, Lul34AH, Lul35T and H69) and an antagonistic effect on 1 (SBC-1). In the in vivo experiment, nude mice were inoculated with SBC-1, SBC-3 and SBC-5 cells. Two or 5 mgAg CDDP and 10 or 30 mgAg ETP were administered intraperitoneally alone and simultaneously in combination to nude mice. The in vivo effects of the combination were determined by comparing the observed growth ratio in mice treated with the combination with the expected value of this ratio calculated based on the assumption that the effects of the drugs were simply additive. According to this definition, synergistic effects were observed against all 3 tumors. Thus, the in vivo and in vitro effects differed. The toxicity of the combination therapy, which was analyzed by estimating the body weight change of mice, was no higher than that of CDDP or ETP alone. These results suggest that the excellent clinical effects of CDDP and ETP combination therapy may he attributable not to drug interaction at the cellular level hut to the feasibility of combined use of them at full doses without overlapping side effects.     

EXPERIMENTAL AND CLINICAL STUDY OF CONCOMITANT RADIATION THERAPY AND CHEMOTHERAPY FORCERVICAL CARCINOMA

ＥＸＰＥＲＩＭＥＮＴＡＬＡＮＤＣＬＩＮＩＣＡＬＳＴＵＤＹＯＦＣＯＮＣＯＭＩＴＡＮＴＲＡＤＩＡＴＩＯＮＴＨＥＲＡＰＹＡＮＤＣＨＥＭＯＴＨＥＲＡＰＹＦＯＲＣＥＲＶＩＣＡＬＣＡＲＣＩＮＯＭＡ￥ＷｅｉＫｅ；魏克；ＣａｉＳｈｕｍｏ；蔡树模；ＷａｎｇＸｉａｎｇ－...     

鼻咽癌裸鼠移植瘤及其相应体外细胞株的建立与特性研究

从新鲜鼻咽活检组织建立了一株鼻咽癌（ＮＰＣ）裸鼠移植瘤株（ＳＵＮＴ一１）及其相应的体外传代上皮细胞株（ＳＵＮＥ一１）。证实ＳＵＮＴ一１和ＳＵＮＥ一１为典型低分化鳞癌细胞，染色体分析二者均为人类肿瘤核型。以ＰＣＲ技术检测ＳＵＮＴ一１的Ｐ１～Ｐ１８和ＳＵＮＥ一１直到第６１代培养的细胞中的ＥＢＶ一ＤＮＡ均为阳性。用原位溶细胞电泳技术（Ｉｎｓｉｔｕｌｙｉｎｇｇｅｌ）ＥＢＶ探针Ｓｏｕｔｈｅｒｎｂｌｏｔ分析，亦显示相应的ＥＢＶＤＮＡ区带。ＥＢＶ基因组为线性特征，且在ＳＵＮＴ一１Ｐ１８和ＳＵＮＥ一１Ｐ５３细胞的电镜检查中均发现直径为９６一１００ｎｍ的ＥＢＶ样颗粒。用不对称ＰＣＲ一ＳＳＣＰ检测，显示有Ｐ５３第８外显子突变。带ＥＢＶ基因的ＮＰＣ瘤株及相应的上皮细胞株建立，为从分子水平、细胞水平上研究肿瘤的发生发展过程，以及治疗等方面提供了丰富的和更切合人体肿瘤的材料和模型。     

博安霉素诱导人食管癌Eca-109细胞凋亡及其对细胞周期的影响

背景与目的：有研究报道博安霉素（boanmycin,BAM)是通过抑制肿瘤细胞的蛋白质合成来发挥抗人食管癌作用,但目前尚不清楚博安霉素是否还通过其他机制来实现其抗人食管癌作用。本文研究博安霉素诱导人食管癌Eca-109细胞凋亡及其对Eca-109细胞周期的影响。方法：运用形态学观察,流式细胞仪和琼脂糖凝胶电泳多种方法检测Eca-109细胞凋亡以及细胞周期分布的改变。结果：在经博安霉素处理的裸鼠移植瘤组织中,用电镜观察到不同阶段的凋亡细胞形态学改变;在体外实验中,博安霉素（50-125μg/ml）作用Eca-109细胞30-36h,用电镜观察到不同阶段的凋亡细胞形态学改变;在体外实验中,博安霉素（50-125μg/ml）作用Eca-109细胞30-36h,可以诱导Eca-109细胞凋亡并出现DNA梯形条带。作用42h后将其细胞周期阻断于G2/M期。结论：博安霉素能诱导Eca-109细胞凋亡将其细胞周期阻断于G2/M期。     

灵芝精粉和孢子粉混合物抑制肿瘤细胞生长的实验研究

背景与目的：灵芝是一种具有滋补强身作用的传统中草药。研究表明灵芝对小鼠移植性肿瘤具有生长抑制作用,这种作用一般认为是通过机体免疫系统介导的。我们实验室近来发现灵芝主要成分灵芝精粉和孢子粉混合物（lucid garoderma and lucid garoderma spore,MLGLGS）能抑制拓扑异构酶ⅠⅡ活性,因此,本研究欲进一步观察MLGLGS在体内外对人肿瘤细胞生长的抑制作用。方法：运用MTT法、SRB法研究MLGLGS体外对小鼠白血病P388细胞和10种不同类型人肿瘤细胞株的生长抑制作用,并利用裸小鼠移植瘤模型研究MLGLGS体内对人肺腺癌LAX-83细胞和人胃腺癌SGC-7901细胞的生长抑制作用。结果：MLGLGS对P388、U-937和HL-60细胞的IC50值都小于2mg/ml,对2株人胃癌和2株人肺癌细胞的IC50都小于4mg/ml。体内试验结果显示：当MLGLGS为1g/kg时,对人肺腺癌移植瘤的生长抑制率为49.47％;当MLGLGS为2g/kg时,对人胃腺癌移植瘤的生长抑制率为43.09％。结论：高浓度、高剂量MLGLGS有抑制肿瘤细胞生长的作用。     

裸鼠造血微环境损伤实验动物模型的建立

目的建立适合移植实验使用的裸鼠造血微环境损伤动物模型。方法分别用3．5Gy、5Gy、6．5Gy、8Gy4个^60Coγ辐射剂量照射裸鼠，检测经过辐照后各组裸鼠1、3、5、7、14、21d血象变化，检测辐射后1、7、14、21d裸鼠骨髓基质CFU—F形成情况，用流式细胞仪检测辐射后1、7、14、21d骨髓基质细胞VCAM-1的表达。结果8．0Gy辐射剂量裸鼠死亡率100%；3．5Gy、5Gy、6．5Gy辐射剂量组裸鼠的造血损伤均能在辐射后21天之内自我恢复；6．5Gy组骨髓CFU—F于移植后7d（22±6）、14d（33±6）较3．5Gy、5Gy组均具有显著降低（P〈0．01），VCAM-1表达于7d（21．67±7．45）、14d（22．33±9．07）、21d（23．33±4．51）较对照组显著降低（P〈0．01）、较3．5Gy组差异有显著性（P〈0．05），21d（23．33±4．51）较5Gy组（34．00±4．36）差异有显著性（P〈0．05）。结论6．5Gy是裸鼠造血微环境损伤实验动物模型的适宜辐射剂量。     

影响人软组织肉瘤异种移植成功的某些相关因素

研究裸小鼠体内异种肉瘤移植成功的可能因素。方法对移植成功群（Ｓ群）与移植失败群（Ｆ群）的临床状况，组织病理学、免疫特性、ＤＮＡ含量、增殖因子和癌基因蛋白等进行了比较研究。结果与肉瘤异种移植成功有关的可能因素为：组织来源、恶性程度高低（核分裂象、异形性、细胞密度）、间质成份多寡、Ｓ期细胞百分数等。增殖因子Ｋｉ┐６７和ＰＣＮＡ在Ｓ群中表达明显高于Ｆ群。ｐ５３蛋白表达在两群间有明显差别。结论Ｋｉ┐６７和ＰＣＮＡ是判定肉瘤生长速率和进展的较理想的指标。ｐ５３在肿瘤进展中具有重要作用。     

Enhanced Antitumor Efficacy of a Combination of CPT-11, a New Derivative of Camptothecin, and Cisplatin against Human Lung Tumor Xenografts

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carhonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c ( nu/nu ) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.     

^131I标记凝集素PNA在荷人胃癌裸鼠体内的分布

采用Ｉｏｄｏｇｅｎ法将放射性１３１Ｉ与花生凝集素（ＰＮＡ）进行标记，经腹腔注射１３１Ｉ－ＰＮＡ标记物到荷人胃癌裸鼠体内，在不同时间测定组织放射分布和γ照相。给药后第３天，肿瘤组织放射性强度是血液的４．３０倍，是正常肝组织的３．７６倍，是肌肉组织的３．８９倍；给药后第７天，肿瘤组织浓集１３１Ｉ－ＰＮＡ是正常胃组织的４．２１倍，是小肠组织的６．０５倍，是大肠组织的５．１３倍。４８小时可见肿瘤显像，７２小时显像清晰。本实验结果表明，凝集素ＰＮＡ在胃癌定位诊断和导向治疗中有着潜在的应用价值，对于人体某些表达Ｔ抗原的腺癌都可能具有作为导向治疗载体的研究前景。