紫杉醇联合希罗达治疗晚期胃癌的初步观察

目的 观察联合希岁达与紫杉醇治疗晚期胃癌的疗效与毒副反应。方法 对68例晚期胃癌患者进行回顾性统计分析。结果 CR6％，PR47％，NC22％，PD25％。症状缓解率81％。一年总生存率72％。平均缓解时间5．5月。化疗副反应包括恶心呕吐（86％），手足综合征（45％）；Ⅰ、Ⅱ度骨髓抑制（55％）及Ⅲ、Ⅳ度骨髓抑制（12％）；无化疗相关死亡。结论 希罗达加紫杉醇方案对晚期胃癌疗效较好，毒副作用较轻。     

抗癌药物紫杉醇的发现,化学及构效关系

自从利用生物试验从植物提取物筛选新的抗癌化合物以来，已经发现了许多新的活性成分．但仅极少数化合物如长春碱、长春新碱、秋水仙碱、紫杉醇（Taxol）等，被最终研究开发成新的抗癌药物，而其中最令人们瞩目的则是近年来开发的紫杉醇．迄今发表。。有关紫杉醇及其类似物（taxoids）的研究资料颇为丰富，且有更加增多的趋势，已成为当今天然药物化学研究的“热点”．研究内容十分广泛，车要有植物化学（提取分离、结构测定）、分析、生理活性、化学修饰、合成、构效关系、生物技术、细胞生物学和分子生物学以及临床等。发表了许多综述、…     

几种植物来源不同作用机制的抗癌药抗侵袭作用

用细胞培养法和癌细胞侵袭实验,观察几种植物来源不同作用机理的抗癌药如紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱^[1],对黑色素瘤高转移株B16-BL6细胞及人纤维肉瘤细胞HT-1080的细胞毒作用和抗侵袭作用。结果表明紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱对B16-BL6和HT-1080细胞增殖均有很强的抑制作用。紫杉醇、三尖杉酯碱及高三尖杉酯碱对B16-BL6细胞侵袭和运动也有明显的抑制作用,而喜树碱在同样浓度下对B16-BL6细胞侵袭和运动均无明显抑制。     

Cytoskeletal modulation of the response to mechanical stimulation in human vascular endothelial cells

Possible interactions of cytoskeletal elements with mechanically induced membrane currents and Ca²⁺ signals were studied in human endothelial cells by using a combined patch-clamp and Fura II technique. For mechanical stimulation, cells were exposed to hypotonic solution (HTS). The concomitant cell swelling activates a Cl^– current, releases Ca²⁺ from intracellular stores and activates Ca²⁺ influx. To interfere with the cytoskeleton, cells were loaded either with the F-actin-stabilizing agent phalloidin (10 mol/l), or the F-actin-depolymerizing substance cytochalasin B (50 mol/l). These were administered either in the bath or the pipette solutions. The tubulin structure of the endothelial cells was modulated by taxol (50 mol/l), which supports polymerization of tubulin, or by the depolymerizing agent colcemid (10 mol/l) both applied to the bath. Immunofluorescence experiments show that under the chosen experimental conditions the cytoskeletal modifiers employed disintegrate the F-actin and microtubuli cytoskeleton. Neither of these cytoskeletal modifiers influenced the HTS-induced Cl^– current. Ca²⁺ release was not affected by cytochalasin B, taxol or colcemid, but was suppressed if the cells were loaded with phalloidin. Depletion of intracellular Ca²⁺ stores by thapsigargin renders the intracellular [Ca²⁺] sensitive to the extracellular [Ca²⁺], which is indicative of a Ca²⁺ entry pathway activated by store depletion. Neither cytochalasin B nor phalloidin affected this Ca²⁺ entry. We conclude that F-actin turnover or depolymerization is necessary for Ca²⁺ release by mechanical activation. The tubulin network is not involved. The Ca²⁺ release-activated Ca²⁺ entry is not modulated by the F-actin cytoskeleton.     

紫杉醇诱发人乳癌细胞凋亡的机制研究

探讨紫杉醇诱发人乳腺癌细胞凋亡的发生机制。方法应用细胞形态观察、琼脂糖凝胶电泳、流式细胞仪、活细胞视频观察和蛋白印迹免疫法进行检测和观察。结果癌细胞在紫杉醇作用下,细胞分裂阻滞在分裂期的中期,并诱导细胞发生凋亡。凋亡细胞表现为细胞固缩,核染色质凝聚或者断裂。细胞ＤＮＡ裂解片段呈现典型的“阶梯状”排列的条带。凋亡抑制基因Ｂｃｌ－２在细胞凋亡过程中呈低表达并发生修饰反应,而凋亡诱导基因Ｂａｘ先呈高表达然后表达降低。结论紫杉醇诱发的人乳癌细胞的凋亡与细胞分裂期阻滞密切相关,Ｂｃｌ－２和Ｂａｘ在紫杉醇诱发的人乳癌细胞凋亡中可能起着重要的调控作用     

Isolation,purification, and biological activity of mono- and dihydroxylated paclitaxel metabolites from human feces

Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1–3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was >97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and 6,3-p-dihydroxypaclitaxel. The two 6-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmockinetics studies.     

Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snailLymnaea stagnalis

Summary Cerebral ganglia of the freshwater snailLymnaea stagnalis were incubatedin vitro in 10 M Taxol for 8 and 24 h. Cremophor EL (0.1%) was used as a diluant. The tissue was processed for electron microscopy. Various ultrastructural parameters were assessed quantitatively. Cremophor EL appeared to seriously affect the cell somata of the multipeptidergic caudodorsal cells. In the Cremophor-controls the mean area of Golgi zones, the percentage dense material (neuropeptides) in these zones, the number of large electron dense granules (these are involved in neuropeptide processing) and the mean nuclear heterochromatin clump size, were significantly smaller than in the Ringer-controls, whereas the number of lipid droplets was higher. All these parameters, except for the lipid droplets, were not different in the Cremophor-controls and the Taxol-treated specimens. After 24 h treatment, but not after 8 h, Cremophor EL furthermore induced an increase in the number of axonal microtubules. It is argued that the results might signify activation of the neurons by Cremophor EL. Taxol induced a significant increase in the number of microtubules in axons and cell somata. Furthermore an increase in the number of Golgi zones was observed, suggesting activated neuropeptide synthesis. In all groups immunostaining with antibodies to neuropeptides produced by the caudodorsal cells was normal. Release of neuropeptide (exocytosis) from axon endings was elevated after Taxol treatment, and exceptionally high in specimens cotreated with Taxol and Org 2766 (incubation time 22 h). The effect of Org 2766 and Taxol on the number of microtubules was cumulative. It is argued that transport of neuropeptide granules from the cell somata to the axon terminals was not affected by Taxol. It is concluded that Taxol neurotoxicity is probably not due to impeded microtubular axonal transport.     

泰素加卡铂与泰素加顺铂治疗晚期肺腺癌的比较

目的 观察比较泰素加卡铂与泰素加顺铂治疗晚期肺腺癌的近期疗效及不良反应。方法 35例晚期肺腺癌患者随机分为Taxol+CRP组(A组)及Taxol+DDP组(B组),治疗2个周期后进行疗效及不良反应的评估。结果 A组18例,有效率为44.4％;B组17例,有效率为41.2％。两组的主要不良反应均为骨髓抑制、恶心呕吐、肝功能损害、脱发等。结论 Taxol+CBP及Taxol+DDP在治疗晚期肺腺癌方面均有较好疗效,不良反应可耐受。两组的疗效和不良反应无明显差别。     

Extragenital malignant mixed Müllerian tumor

Reports of extragenital malignant mixed Müllerian tumor (MMMT) type though extremely rare have increased. This represents the 15th reported case of MMMT outside the female reproductive tract. A 68-year-old black woman presenting with abdominal pain, increasing abdominal girth, and a provisional diagnosis of ovarian carcinoma, underwent exploratory laparotomy, total abdominal hysterectomy, omentectomy and cytoreductive surgery. Surgery and histology revealed MMMT of heterologous type in the pelvic peritoneum, with no tumor in the genitalia and no foci of endometriosis. Despite surgical debulking leaving residual tumor of less than 1 cm followed by aggressive systemic chemotherapy, the patient died of disease within 2 months. Increasing exploratory surgery may account for the increase in reports of extragenital MMMT. Aggressive tumor debulking and multiagent systemic chemotherapy is of limited efficacy since extragenital MMMT, like uterine MMMT with pelvic spread, has short survival.     

泰素治疗八例晚期复发的卵巢癌

目的：验证泰素对晚期、复发的卵巢上皮癌的疗效。方法：回顾分析1994年7月至1995年3月国内最早试用美国百时美施贵宝公司提供的商用泰素治疗8例卵巢癌的结果。结果：8例可评价病人中，3例达到部分反应（PR），总反应率37.5％（3／8），主要副作用是脱发、腹痛、腹泻和感觉异常。结论：证明泰素对晚期、复发的卵巢上皮癌治疗的有效性，特别是有效者明显延长了生存期。