甲基泼尼松龙联合长春新碱治疗系统性红斑狼疮伴血小板减少的效果分析

目的：分析甲基泼尼松龙联合长春新碱治疗系统性红斑狼疮伴血小板减少的效果。方法选择本院2010年1月~2014年3月收治的32例系统性红斑狼疮伴血小板减少患者,将其随机分为两组,观察组患者给予甲基泼尼松龙联合长春新碱治疗,对照组患者给予甲基泼尼松龙冲击治疗,疗程均为5周。比较两组患者的疗效以及不良反应。结果治疗后观察组患者的总有效率和不良反应率明显优于对照组。两组患者的血小板计数、尿蛋白含量、抗dsDNA、C3和C4差异有统计学意义（P〈0.05）。结论甲基泼尼松龙联合长春新碱治疗系统性红斑狼疮伴血小板减少的效果更好,并发症少,值得临床推广应用。     

39例长春新碱注射剂不良反应文献分析

目的:探讨长春新碱注射剂致不良反应的一般规律及特点,指导临床合理用药。方法:通过检索1994～2006年国内公开发行的医学期刊报道应用长春新碱注射剂致不良反应案例,并进行统计分析。结果:不良反应多发生于<20a和>60a年龄组,女性多于男性,其出现时间可发生于用药后的各个时间段。不良反应临床表现复杂多样,涉及机体多个器官、系统损伤,尤其是对胃肠的损伤。结论:临床医师、药师应了解长春新碱注射剂所致不良反应的规律和特点,加强其应用的监测,以减少不良反应的发生。     

Vincristine and oral etoposide in refractory multiple myeloma

A total of 15 patients with refractory multiple myeloma (MM; 4 primary unresponsive and 11 relapsed and resistant to re-induction/salvage therapy) received i.v. vincristine on day 1 and oral etoposide daily for 4 days, the treatment being repeated at 3-weekly intervals. The patients were re-assessed after three cycles of chemotherapy, and non-responders received no further therapy. There was no complete or partial response. A minimal response was seen in two patients, and two others showed stable disease. None of the responses was sustained, and all patients eventually had progressive disease. It is concluded that combination chemotherapy with vincristine and oral etoposide given by this schedule is unlikely to be of any value in refractory myeloma.     

研究药物对肿瘤细胞代谢的新方法──灌注细胞31P核磁共振谱

为连续观察药物对细胞代谢的影响,用含紫杉醇的灌注液对人口腔上皮癌KB细胞和人结肠癌HCT-8细胞在灌注条件下进行了细胞³¹P谱测定,从两种细胞在未给药、给药以及停药后的灌注条件下获得的代谢图谱中发现,紫杉醇使KB细胞和HCT-8细胞的ATP代谢水平均有升高,但KB细胞的ATP升高更为明显;同样剂量的长春新碱使KB细胞代谢中的ATP峰的改变不明显,推测可能与它们的作用机制不同有关。研究结果表明,灌注细胞³¹P谱测试法对观察药物对细胞代谢的作用是独特的。     

Vincristine-induced neuropathy in rat: electrophysiological and histological study

Peripheral sensory-motor neuropathy is one of the most frequent side effects of vincristine (VCR) administration, which often limits its usefulness in the treatment of a wide range of neoplastic diseases. The purpose of this work is to study VCR neurotoxicity in experimental animals from clinical, electrophysiological, and histological points of view. Sixty-five rats were used as a control group and 31 rats were divided into two groups and given VCR in two different regimens: the fixed-dose group (0.2 mg/kg) and the increasing-dose group (0.1 mg/kg, by an increment of 0.05 mg/kg/week). VCR was given intraperitoneally once weekly for five consecutive weeks. Electrophysiological examinations of the control and both treated groups were performed and included measurements of nerve conduction velocity and action potential (AP) amplitude of sciatic and tail nerves weekly during the period of treatment and 14 weeks after discontinuation of treatment. Histological sections of sciatic nerves were examined after the appearance of early electrophysiological changes, at the end of the 5th, and 19th weeks of the study (14 weeks after discontinuation of treatment). With the progress of the treatment, an increasing number of rats showing signs of neurological deficits were observed. During the first 5 weeks of this study, electrophysiological testing showed a nonsignificant difference in the conduction velocities of sciatic and tail nerves between the control and the treated groups, whereas a significant decrease in the amplitude of the sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) of the tested nerves was recorded. The reduction in the AP amplitude was associated with histological changes characterized by axonal degeneration with relative demyelination. Fourteen weeks after discontinuation of treatment, a significant increment in the SNAP and CMAP amplitudes of both sciatic and tail nerves was noticed. While the CMAP amplitude of the distal segment of the tail showed nonsignificant increment, lesser number of fibers with axonal and/or myelin lesions were found. The clinical, electrophysiological, and histological results suggest that VCR induces peripheral sensorimotor neuropathy of axonal type more prominent in the fixed- than the increasing-dose group. The discontinuation of VCR permitted the improvement of the electrophysiological and histological changes. The rat can be used as an animal model for studying VCR neurotoxicity. However, further studies on larger number of animals are required to evaluate the type of nerve fiber involvement and the site of damage.     

Low-risk gestational trophoblastic neoplasia outcome after treatment with VMP regimen from 2005 to 2017

ObjectiveTo evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital.Materials and methodsBetween 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis.ResultsThe first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4.ConclusionFor patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission.     

Expression of p53-family members and associated target molecules in breast cancer cell lines in response to vincristine treatment

As the antimitotic agent vincristine (VCR) has been reported to induce a weak p53 response in some studies, we hypothesised that p73 and p63, the recently described p53 homologues, may replace p53 in triggering apoptosis or cell cycle arrest effectors in VCR-treated cell lines. To address this issue, we measured p53, p73 and p63 mRNA and protein levels in two VCR-treated breast cancer cell lines, one p53-proficient (MCF7) and the other p53-deficient (MDA-MB157). We found an increase of p53 mRNA and protein levels in VCR-treated MCF7 cells, while, as expected, no p53 protein was detected in VCR-treated MDA-MB157 cells. Surprisingly, the p73 mRNA and protein expression levels decreased in both cell lines during VCR treatment, whereas p63 protein levels remained unchanged. In both cell lines, up-regulations of the canonical p53-target genes, such as p21 and GADD45, were consistently observed. We conclude that, in response to VCR treatment: (1) p53 is markedly induced in MCF7 cells, with the same extent than after DNA damaging drugs treatments; and (2) p63 is not involved, while p73 expression is down-regulated regardless of the p53 status of the cell lines. Our results therefore suggest the involvement of a fourth member of the p53 gene family, or the use of another pathway able to trigger canonical p53-target genes in response to VCR in p53-deficient cells.     

Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia

A boy with acute lymphoblastic leukemia (ALL) experienced life-threatening vincristine neurotoxicity while simultaneously exposed to itraconazole. Five pediatric and six adult cases of itraconazole-enhanced vincristine toxicity have been reported, all with ALL. Upon cessation of the itraconazole, the patient's symptoms resolved, which is similar to the outcome of the previously reported cases: 10 of 11 patients had complete resolution of symptoms.     

Inhibition of motor nerve regeneration in a rabbit facial nerve model

OBJECTIVES/HYPOTHESIS: We hypothesized that intramuscular injection of vincristine into the upper lip selectively prevents reinnervation of the target muscle (quadratus labii superioris) after facial nerve transection. STUDY DESIGN: Prospective controlled experiment. METHODS: Transection injuries with primary neurorrhaphy were performed just proximal to the buccal and zygomatic branches of both facial nerves in 20 rabbits. The left (experimental) quadratus labii superioris muscle was injected with 200 microg vincristine 72 hours after injury; the right (control) side was injected with saline. Functional, electrophysiological and histological studies were performed 6 weeks after surgery. RESULTS: After 6 weeks, the control side had a mean axon count (distal buccal branch) of 1160, conduction velocity of 50.4 m/s, reduction of compound action potential amplitude of 44%, and functional index of 1.67 units. The experimental side had a mean axon count of 265, conduction velocity of 16.5 m/s, reduction of compound action potential amplitude of 88%, and a functional index of 0.176 units. All parameters were significantly reduced by vincristine blockade (P <.05). The zygomatic division (not exposed to vincristine) displayed a trend toward increased axon counts, but this was not statistically significant (P =.131). CONCLUSIONS: These results demonstrate that reinnervation of a selected muscle can be prevented by injection of vincristine. Enhanced reinnervation of adjacent muscle groups may also occur. Thus, nerve blockade by vincristine may be useful for the prevention of synkinesis.