Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay

An in vitro assay, which evaluates drug effect on ³H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.     

高渗盐水对顺铂毒性及药物动力学的影响

本文以血清尿素氮及体重做为毒性评价指标,高渗盐水减低了顺铂的毒性。小鼠静注15mg/kg顺铂后,血浆总铂的药物动力学呈三室模型。高渗盐水缩短了血浆总铂的α相半衰期,提高了给药后各时间点血浆超滤铂的浓度,降低了肾脏内给药后2h内的铂浓度,没有明显改变肿瘤内铂浓度的药时曲线下面积。实验表明,高渗盐水提高了顺铂的治疗指数。     

硝酸铋与丙磺舒合用对顺铂肾毒性的防护作用

毒性剂量的顺铂（ＣＰ３０μｍｏｌ·ｋｇ－１ｉｐ）可引起血尿素氮（ＢＵＮ）升高。硝酸铋（ＢＮ）５μｍｏｌ·ｋｇ－１于ＣＰ前４８和２４ｈｓｅ，丙磺舒（Ｐｒｏ）７００μｍｏｌ·ｋｇ－１于ＣＰ前１５，１ｈ及ＣＰ后５ｈｉｇ，或ＢＮ与Ｐｒｏ二者半量合用，按上述给药，均能抑制ＣＰ引起的ＢＵＮ升高，尤以ＢＮ＋Ｐｒｏ组抑制作用显著。肾脏光镜和电镜标本显示，ＣＰ使肾小管受损严重；ＢＮ组，Ｐｒｏ组和ＢＮ＋Ｐｒｏ组均使ＣＰ引起的肾小管受损减轻，尤以ＢＮ＋Ｐｒｏ组减轻明显。ＢＮ２．５－２０μｍｏｌ·ｋｇ－１剂量依赖性地诱导小鼠肾脏金属硫蛋白合成。Ｐｒｏ可使ＣＰ后２４ｂ肾铂含量明显降低；Ｐｒｏ或Ｐｒｏ＋ＢＮ使尿铂累积排出量增加，血浆铂浓度降低。提示ＰＦＯ防护ＣＰ肾毒性与其减少肾铂分布，增加尿铂排出有关。     

NP与GP方案治疗局部晚期非小细胞肺癌近期疗效观察

目的：观察长春瑞宾（NVB）与顺铂（DDP）组成的NP方案和吉西他滨（GEM）与顺铂（DDP）组成的GP方案对局部晚期非小细胞肺癌（NSCLC）的近期疗效和毒副作用。方法：将经病理组织学或细胞学证实的45例局部晚期NSCLC患者随机分为两组,A组（NP方案组）23例,B组（GP方案组）22例,分别给予NVB＋DDP及GEM＋DDP化疗,21天为一周期。结果：A组有效率为47.8%,B组有效率为54.5%,无统计学差异（P〉0.05）。两组毒性反应均以骨髓抑制最为常见,消化道反应和静脉炎亦常见。Ⅲ～Ⅳ度白细胞减少发生率A组为34.8%,B组为31.8%;Ⅲ～Ⅳ度血小板减少发生率A组为4.3%,B组为9.1%。差异均无显著性（P〉0.05）。静脉炎发生率A组为34.8%,B组为0,差异有显著性（P〈0.05）。结论：NP方案和GP方案治疗NSCLC疗效相近,毒性反应均可耐受。     

斯奇康联合丝裂霉素顺铂胸腔内注射治疗肺癌恶性胸水的疗效观察

目的　探讨斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水的有效性和安全性。方法　对我科1999年以来确诊为肺癌恶性胸水的 5 3例患者 ,随机分为斯奇康组 ( 2 7例 )和对照组 ( 2 6例 ) ,进行胸腔内注药 ,观察治疗的有效率、Karnofsky评分及不良反应。结果　斯奇康组与对照组治疗有效率分别为 88 8%和 5 3 9%,两组比较有显著性差异 (P <0 0 1) ;两组治疗后生存质量均有改善 ,但Karnofsky评分 70分以上治疗组为 66 7%,对照组为 3 0 8%,两组比较差异显著 (P <0 0 1) ;两组均出现不同程度的白细胞、血小板减少 ,但治疗组与对照组相比反应明显较轻 ,有显著性差异 (P <0 0 5 )。结论　斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水疗效较好 ,毒副反应较轻。     

Inhibition on Telomerase Activity and Cytotoxic Effects by Cisplatin in Cultured Human Choroidal Melanoma Cells

Purpose: To study the changes of telomerase activity and cytotoxic effects by Cisplatin; cis-dichlorodiamine platinum (CDDP) in cultured human choroidal melanoma. Material and Methods: The primary cultured human choroidal melanoma cells were cultured in the presence and absence of CDDP with different concentration and time respectively. The toxic effects were evaluated by MTT and the level of telormarse was detected by PCR-ELISA assay. And the relationship between telomerase activity and cytotoxic effects were analyzed by a correlation analysis.Results: Following the increase of the concentration and the time of CDDP, gradually repressed telomerase activity was detected in cultured cells. Meanwhile, the restrain rate of the cells increased. The telomerase activity at 24h and 1μg/ml was repressed significantly compared with the control cells. However, the appearance of cell death lagged behind the decreasing of telomerase.Conclusions: CDDP is an effective telomerase inhibitor in cultured choroidal melan     

丙氧锗二酸对顺铂毒性的保护作用及其对抗癌效果的影响

 本文研究了丙氧锗二酸（Ge－132）对顺铂毒性及抗癌效果的影响，并对其保护作用与金属硫蛋白（metallothionein，MT）的关系进行了探讨。结果表明Ge－132对顺铂引起的肾脏、血液和致死的毒性具有明显的保护作用。其效果优于次硝酸秘、亚硒醚钠以及氧化锗；Ge－132无诱导MT的作用，经体内抑瘤实验及体外细胞毒性实验表明，Ge－132对顺铂的抑瘤作用无统计学意义的影响。     

Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma

The histogenesis of malignant fibrous hlstlocytoma (MFH) was studled using clsplatln (CDDP)-resistant MT-R8 and MT-R9 cells derlved from cloned undlfferentiated MT-8 and flbrohlstlocytic MT-9 cells, resoecthfely, which had been established from transplantable rat MFH. CDDP concentrations requlred for 50% suppression of prollferation of MT-R8 and MT-R9 cells were 5.4– and 3.3-fold greater than those of parental MT-8 and MT-9, respectively. MT-R8 and MT-Rg showed the higher positive rates to histimytic lysosomal/ antigenic (ED1 and ED2) markers. The number of a-smoath muscle actin (SMA)-positive cells significantly Increased in MT-RB; SMA-positlve cells were also obsenred in MT-R9, but no difference was seen between MT-9 and MT-R9. MT-R8 and MT-R9 expressed both histiwytic and myofibroblastic phenotypes. However, the histology of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-R9 did not always reflect their in vitro nature. MT-R8 developed undiffer-entlated sarcomas similar to parental MT-8 tumors. In contrast, MT-R9 induced tumors with polytypic histologies such as the storiform growth pattern, neoplastlc growth of granular cells and myofibroblasts, osteosarcoma-like areas, collagen-rich areas containing well-developed fibroblasts and areas involvlng many lipoblasts. These In vivo observatfons suggest the multidlrectional differentiation of MT-R9 cells. Phenotypic modulation of rat MFH cells seemed to be easily induced by CDDP. A possible histogenesis of MFH was discussed based on the data collected.     

Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma.