亚硒酸钠对顺铂致人体淋巴细胞增殖抑制的拮抗作用

目的 检测亚硒酸钠是否能够削弱或解除顺铂对植物血球凝激素(PHA)刺激的人体外周血淋巴细胞的增殖抑制。方法 用顺铂和亚硒酸钠单独或联合处理PHA刺激的人体外周血淋巴细胞，顺铂(0．05，0．20，0．50mg／L)在细胞培养24h时加入，亚硒酸钠(0．05mg／L)在不同处理中分别在细胞培养开始时加入或与顺铂同时加入；培养72h后检测转化淋巴细胞的有丝分裂指数。结果0．05mg/L亚硒酸钠在培养开始时加入，PHA刺激转化的淋巴细胞有丝分裂指数较对照增长42．8％(P＜0．05)，与顺铂同时加入，有丝分裂指数增长13．7％(P＞0．05)。0．05与0．20mg/L顺铂处理细胞，有丝分裂指数未发生显性改变，当顺铂剂量为0．50mg/L时，细胞有丝分裂指数较对照降低54．5％(P＜0．001)。亚硒酸钠预处理细胞可以解除0．50mg/L顺铂所致的细胞增殖抑制，使有丝分裂指数恢复正常，但亚硒酸钠与顺铂同时加入时，被顺铂抑制的有丝分裂指数只能部分提高。结论0．05mg/L亚硒酸钠单独作用于淋巴细胞可直接促进细胞增殖，与顺铂联合处理细胞时，可降低顺铂毒性，拮抗顺铂的抗增殖作用。亚硒酸钠在细胞培养开始时加入培养体系效果更佳。     

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m²) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P<0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.This work was partially supported by Grant No. 02454315 from the Japanese Ministry of Education     

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.     

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     

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.     

顺铂和替加氟联合放疗治疗中晚期食管癌疗效观察

目的观察顺铂和替加氟联合放疗治疗食管癌的临床疗效及其毒副反应。方法2003年1月至2006年2月对60例食管癌患者采取顺铂20mg·m-2·d,替加氟750mg·m-2·d,连用5天,序贯放疗60~70Gy/6~7周。结果60例患者中,CR24例,PR18例,SD9例,PD9例,RR(CR+PR)为70·0%,主要毒副作用为骨髓抑制、恶心呕吐。肝肾功损害及口腔炎、静脉炎等较轻。结论顺铂和替加氟联合放疗治疗食管癌疗效好,耐受性好值得推广应用。     

顺铂引起卵巢癌细胞周期变化及凋亡的观察

目的 :了解顺铂 (DDP)引起卵巢癌细胞COC1、COC1/DDP细胞周期变化及凋亡规律。方法 :用光镜、电镜及流式细胞术等方法观察细胞凋亡规律及进行细胞周期分析。结果 :DDP引起COC1、COC1/DDP细胞周期变化主要表现为S期阻滞 ,P <0 .0 1;细胞死亡方式主要是凋亡 ,凋亡细胞发生在S期 ,P <0 .0 1;COC1、COC1/DDP细胞凋亡率不同 ,COC1凋亡率高 ,两组相比差异有显著性 (P <0 .0 1)。结论 :DDP引起COC1、COC1/DDP细胞S期阻滞、S期细胞凋亡 ,细胞凋亡与获得性耐药有关     

高聚金葡素联用顺铂治疗恶性胸水64例疗效观察

目的 :观察生物反应调节剂高聚金葡素 (HASL)加顺铂 (DDP)联用治疗恶性胸水的疗效。方法 :将 64例恶性胸水患者男 4 0例 ,女 2 4例 ,随机分为 2组 ,治疗组选用HASL +DDP ,对照组单用DDP进行比较。结果 :胸水减少 ,治疗组有效率 82 .3 % ,对照组有效率 60 %。结论 :HASL联用DDP能有效控制恶性胸水 ,提高患者生存质量 ,减轻化疗药物毒副作用 ,值得临床推广应用。