Hemolytic uremic syndrome in a patient on cis-platinum,vinblastine and bleomycin

Summary A 23-year-old woman with metastatic Sertoli-Leydig cell tumor was treated with cisplatin, vinblastine, and bleomycin. Hemolytic uremic syndrome appeared, while no evidence of residual tumor was found. Infusion of fresh frozen plasma together with aspirin and dipyridamole resulted in recovery of microangiopathic hemolytic anemia and thrombocytopenia. Renal insufficiency, however, persisted.     

Effects of cytochalasin B and vinblastine on the release of acetylcholine from a sympathetic ganglion

The rate of release of acetylcholine from the in vitro superior cervical ganglion of the rat was measured during periods of electrical stimulation both before and after exposure to a drug. Cytochalasin B inhibited the release of acetylcholine in this preparation. Two stages of inhibition were observed. The first, which reduced the rate of release to 20% of control values, was produced by incubating the ganglion for 60 min in solutions containing cytochalasin B. Half-maximal inhibition was observed at concentrations of 3 × 10^?6 M. This stage was not reversed within several hr after cytochalasin B was removed. Uptake of calcium in the first stage was inhibited by cytochalasin B by a small but statistically insignificant amount (13%). The second stage, in which release was further reduced to zero, required both repeated changes of bathing solutions containing cytochalasin B and continual electrical stimulation during the 60 min period of exposure. The second stage was reversed 20–40 min after the drug was removed. It is suggested that the first stage inhibition involves a direct action of cytochalasin B upon the release of acetylcholine from the presynaptic terminal, while the second stage inhibition may be caused by a decrease in the supply of energy to the ganglion. Vinblastine at concentrations of 2.0 × 10^?6 and 1.2 × 10^-4M was also studied using the same experimental procedure. Vinblastine did not inhibit the electrically stimulated release of acetylcholine.     

Vinblastine and 5-fluorouracil sensitivity of xenografts of four pancreatic ductal adenocarcinomas: is there a correlation with histological and cytological tumour differentiation?

In a search for nuclear parameters which may predict chemosensitivity of ductal adenocarcinoma of the pancreas, the growth of four xenografted pancreatic carcinomas in response to chemotherapeutic agents was correlated with histological and cytological features of tumour differentiation. Histologically, the tumours were classified according to their ability to form glands into poorly (PaTu-2, PaTu-3), moderately (Panc-1) and well differentiated (PaTu-39) ductal adenocarcinomas. Cytologically, similar segregation of tumours was possible using the nuclear form factor, which was one of four nuclear parameters analysed by image cytometry on Feulgen stained tumour imprints. Histological and cytological differentiation correlated closely with tumour growth. One week after a single intraperitoneal injection of either vinblastine or 5-fluorouracil, both drugs inhibited the growth of PaTu-2 and PaTu-3 significantly. The growth of Panc-1 was only affected by vinblastine, while neither drug had an effect on PaTu-39. The results suggest that the response of pancreatic ductal adenocarcinoma to chemotherapeutic drugs may be, to some extent, predicted by histological and cytological differentiation features. However, within these lines, each tumour may show a specific response pattern.     

Investigating the Vinblastine Induced-Chromosomal Abnormality in the Already Gamma Irradiated L929 Cell Line Using Micronucleus Assay in Cytokinesis Blocked Binucleated Cells

Objectives: Vast number of studies show the relationship between aneuploidy and cancer. Ionizing radiation inaddition to induce all kinds of damages to the cells and structure of chromosomes, is also able to induce aneuploidythrough direct damages to chromosome division apparatus. Also irradiation of the cells induces mutations in severalgenes which might be involved in cell division fidelity and play a role in reversing the effect of aneugens. Therefore,irradiation of cells and tissues might produce sensitivity to agents with aneugenic capability in irradiated cells. Methods:To investigate the persistent genomic effect of ionizing irradiation on chromosomal instability, L929 cells were gammairradiated with the dose of 2 Gy. Cells were left to recover from the harmful effect of irradiation. They were treated withlow dose of vinblastine (0.5 ng.ml-1) 72h post-gamma irradiation. Finally, the induced chromosomal abnormalitieswere scored using micronucleus assay in cytokinesis-blocked binucleated cells (MnBi). Results: Irradiation-recoveredL929 cells treated with vinblastine showed a statistically higher frequency of MnBi compared to non-irradiated andvinblastine treated cells. Conclusion: The results indicate that gamma irradiation, in addition to direct induction ofchromosomal damages, is also able to create persisting genomic sensitivity in the cells to chromosomal instability,which is detectable when exposed to the second stimulus.     

Caspase-3 Activation Is Not Responsible for Vinblastine-induced Bcl-2 Phosphorylation and G2/M Arrest in Human Small Cell Lung Carcinoma Ms-1 Cells

Vinblastine arrests cells in the G2/M phase of the cell cycle and subsequently induces cell death by apoptosis. We found that treatment of cells with vinblastine induced phosphorylation of Bcl-2, resulting in the dissociation of Bcl-2 and Bax. Moreover, vinblastine-induced apoptosis was suppressed by an inhibitor of caspase-3, Ac-DEVD-CHO; and a 17-kDa active fragment of caspase-3 was detected following vinblastine treatment, suggesting that caspase-3 is involved in vinblastine-induced apoptosis. However, Ac-DEVD-CHO affected neither vinblastine-induced Bcl-2 phosphorylation nor vinblastine-induced G2/M arrest. Vinblastine caused G2/M arrest prior to apoptosis, whereas vinblastine-induced apoptosis was not dependent on the duration of the G2/M phase. Thus, vinblastine-induced apoptosis might be mediated by the phosphorylation of Bcl-2, resulting in Bcl-2 inactivation, and by subsequent activation of caspase-3.     

Accumulation of the antimalarial microtubule inhibitors trifluralin and vinblastine by Plasmodium falciparum

Malaria is a disease in desperate need of new chemotherapeutic approaches. Certain microtubule inhibitors, including vinblastine and taxol, have highly potent activity against malarial parasites and disrupt the normal microtubular structures of intra-erythrocytic parasites at relevant concentrations. While these inhibitors are useful tools, their potential as anti-malarial drugs is limited by their high toxicity to mammalian cells. In contrast, two classes of antimitotic herbicide, namely dinitroanilines (e.g. trifluralin and oryzalin) and phosphorothioamidates (e.g. amiprophosmethyl), exhibit moderate activity against the major human malarial parasite Plasmodium falciparum in culture but very low mammalian cytotoxicity. We examined the dynamics and kinetics of uptake and subcellular compartmentation of [14C]trifluralin in comparison with [3H]vinblastine. We wished to determine whether the relatively modest activity of trifluralin was the consequence of poor uptake into parasite cells. Trifluralin accumulated in parasite-infected erythrocytes to approximately 300 times the external concentration and vinblastine at up to approximately 110 times. Accumulation into uninfected erythrocytes was much lower. Uptake of trifluralin was rapid, non-saturable and readily reversed. It appears that the hydrophobic nature of trifluralin leads to accumulation largely in the membranes of the parasite, reducing the levels in the soluble fraction and limiting access to its microtubular target. By contrast, vinblastine accumulated predominantly in the soluble fraction and uptake was saturable and mostly irreversible, consistent with binding predominantly to tubulin. The results indicate that synthesis of more polar trifluralin derivatives may be a promising approach to designing microtubule inhibitors with more potent antimalarial activity.     

人肺腺癌耐药细胞模型的建立及生物学特性的初步鉴定

目的建立人肺腺癌耐药细胞模型Anitp973／NVB（去甲长春新碱）并鉴定其生物学特性。方法应用人肺腺癌细胞系Anip973,采用NVB逐步增加剂量法,诱导建立耐药细胞模型Anip973／NVB,观察其生长规律;用MTT法鉴定抗药性;观察细胞形态和超微结构;流式细胞技术检测其细胞周期分布;高效液相色谱法测定细胞内NVB的浓度变化。结果经MTT法鉴定Anip973／NVB细胞较Anip973细胞的NVB半数致死浓度（IC50）增大21．81倍。两细胞系的倍增时间无明显差异。光镜及电镜下观察到,两细胞系结构变化较大。经流式细胞仪测定Anip973／NVB细胞,S期细胞减少（P=0．035）而G0-G1期细胞增多（P=0．014）;高效液相色谱法检测发现Anip973细胞内药物浓度明显高于Anitp973／NVB。结论Anip973／NVB细胞是一个明确的多药耐药细胞模型,具有耐药细胞的基本生物学特性。     

微管功能变化对C6胶质瘤细胞葡萄糖摄取的影响

目的 观察微管功能变化对C6胶质瘤细胞葡萄糖摄取的影响。方法 用影响微管功能的药物长春花碱(抑制微管聚合)、紫杉醇(促进微管聚合)与C6胶质瘤细胞在37℃下孵育3h后，再用含125μmol／L未标记2—脱氧葡萄糖(2—deoxy—D-glucose，2—DOG)和37kBq[^3H]2-DOG的磷酸盐缓冲溶液(PBS)1ml室温下孵育5min。用液闪计数分析仪检测C6细胞葡萄糖摄取。GLUT1cDNA转染C6胶质瘤细胞后再与紫杉醇作用，观察转染后C6细胞的紫杉醇刺激葡萄糖摄取。结果 长春花碱抑制C6细胞葡萄糖摄取24％-36％。紫杉醇刺激葡萄糖摄取增加16％-23％；紫杉醇刺激GLUT1转染C6胶质瘤细胞的2—DOG摄取增加约35％。结论 微管功能变化与C6细胞葡萄糖摄取及葡萄糖转运体介导的葡萄糖转运过程密切相关。     

非小细胞肺癌3种化疗方案毒副作用比较

目的 :观察比较 3种化疗方案其药物的血液和非血液毒副作用。方法 :对 87例非小细胞肺癌 ( NSCL C)患者分别采用诺维本 ( NVB) +顺铂 ( DDP) 32例 ;泰素 ( TAX) +DDP2 8例 ;健择 ( GEM) + DDP2 7例静脉滴入化疗 ;化疗周期分别为 NVB5 2个 ,TAX45个 ,GEM34个。结果 :1 NVB、TAX、GEM联合顺铂化疗的毒副作用主要表现为骨髓抑制和消化道反应 ,大部分为 、 度 ;2 NVB组在影响白细胞方面较其他两组略强 ,而在其他方面无显著性差异。结论 :3种化疗方案其药物的血液毒性在骨髓中的蓄积作用不明显 ,非血液毒副作用有良好的耐受性 ,临床使用安全