Vincristine,an efficacious alternative for diffuse neonatal haemangiomatosis

Diffuse neonatal haemangiomatosis (DNH) is an uncommon condition characterized by multiple cutaneous and visceral haemangiomas frequently causing severe complications. Corticosteroids constitute the first therapeutic line; however, when they fail, other alternatives are available, provided possible side effects are closely monitored during and after treatment. We present a case of life‐threatening DNH, non‐responsive to corticosteroids, successfully treated with Vincristine with minor side effects. We conclude that Vincristine is a valid alternative in corticosteroid‐resistant DNH.     

小分子干扰RNA片段逆转KBv200细胞多药耐药的实验研究

目的：研究小分子干扰RNA片段（siRNA）对舌癌多药耐药（MDR）细胞系KBv200细胞的MDR1基因表达及其功能的影响，探讨siRNA作为未来化疗增敏剂的可能性。方法：运用针对MDR1基因序列的siRNA（MDR1-siRNA）在脂质体的介导下转染KBv200细胞；用RT—PCR分析MDR1 mRNA的表达水平；流式细胞术检测P-糖蛋白（P-gP）的表达；荧光分光光度法检测细胞内多柔比星（Dox）的积蓄；MTT法检测KBv200细胞对长春新碱（VCR）和Dox的敏感性变化。结果：MDR1-siRNA作用24和48h能抑制MDR1基因的表达（P〈0．05），其mRNA水平和P-gP水平均明显下降，同时使KBv200细胞对VCR和Dox的敏感性显著增加（P〈0．01），并显著增加细胞内Dox的蓄积（P〈0．01）。结论：MDR1-siRNA能显著抑制KBv200细胞内MDR1基因介导的MDR。     

3种用药方案治疗多发性骨髓瘤的成本-效果分析

目的:比较3种用药方案治疗多发性骨髓瘤的经济学效果。方法:108例多发性骨髓瘤住院患者按照不同药物治疗方案分为A、B、C组,A组给予VAD方案(长春新碱+阿霉素+地塞米松),B组给予VAD+T方案(长春新碱+阿霉素+地塞米松+沙利度胺),C组给予TD方案(沙利度胺+地塞米松)。治疗各1个疗程后观察疗效,并运用成本-效果法进行分析。结果:A、B、C组的显效率分别为91.43%、97.30%、94.44%,成本分别为8 796.39、9 183.67、8 937.94元,成本-效果比分别为9 620.90、9 438.51、9 464.15;B、C组相对于A组的增量成本-效果比分别为6 597.61、4 702.66。结论:从安全、有效、经济的角度分析,B组方案治疗多发性骨髓瘤较佳。     

Prokineticin 2 promotes and sustains neuroinflammation in vincristine treated mice: Focus on pain and emotional like behavior

Vincristine (VCR) treatment is often associated to painful neuropathy. Its development is independent from antitumoral mechanism and involves neuroinflammation. We investigated the role of the chemokine prokineticin (PK)2 in a mouse model of VCR induced neuropathy using a PK-receptors (PK-R) antagonist to counteract its development. We also evaluated emotional like deficits in VCR mice.VCR (0,1 mg/kg) was i.p. injected in C57BL/6J male mice once a day for 14 consecutive days. Pain, anxiety and depressive like behaviors were assessed in animals. PK2, PK-Rs, cytokines, neuroinflammatory markers (CD68, CD11b, GFAP, TLR4) and ATF3 were evaluated in DRG, spinal cord, prefrontal cortex and hippocampus. The PK-Rs antagonist PC1, was s.c. injected (150 μg/kg) twice a day from day 7 (hypersensitivity state) until day 14. Its effect on pain and neuroinflammation was evaluated.VCR mice developed neuropathic pain but not mood alterations. After 7 days of VCR treatment we observed a neuroinflammatory condition in DRG with high levels of PK-Rs, TLR4, CD68, ATF3 and IL-1β without relevant alterations in spinal cord. At day 14, an upregulation of PK system and a marked neuroinflammation was evident also in spinal cord. Moreover, at the same time, we observed initial alterations in supraspinal brain areas. PC1 treatment significantly counteracted neuropathic pain and blunted neuroinflammation.     

人喉癌长春新碱耐药细胞株的建立及其生物学特性

目的:建立人喉癌长春新碱多药耐药细胞系。方法:以药物浓度梯度递增法诱导筛选人喉癌Hep-2的多药耐药细胞株Hep-2/v,比较两组细胞的形态和倍增时间;MTT法确定细胞的IC50及其耐药指数;流式细胞仪检测两组细胞的细胞周期分布以及细胞内的罗丹明聚集情况;实时定量RT-PCR法检测MDR1基因的mRNA表达,Western blot法检测相应的蛋白表达情况。结果:建成的Hep-2/v耐药细胞株,其耐药性能稳定,耐药指数为45,并与顺铂及5-氟尿嘧啶有不同程度的交叉耐药性;Hep-2/v的体外群体细胞倍增时间较亲代细胞延长13.58小时;细胞周期分析结果显示其G0/G1期细胞升高,而S期细胞则明显降低(P0.05);罗丹明染色显示,Hep-2细胞内的罗丹明较Hep-2/v明显升高(P0.01);Hep-2/v细胞MDR1表达在基因及蛋白水平明显高于Hep-2细胞(P0.01)。结论:Hep-2/v细胞株具有明确及稳定的多药耐药性,是研究多药耐药机制及筛选逆转剂的良好模型。     

Role of vincristine in the inhibition of angiogenesis in glioblastoma

Objective: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α).

Methods: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O₂ (hypoxia).

Results: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G₂-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC₅₀), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels.

Conclusions: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.     

Advanced Breast Angiosarcoma Completely Responding to Gemcitabine-Containing Chemotherapy

Background

For patients with anthracycline-resistant metastatic angiosarcoma, there is currently no available standard for second-line therapy, and a need exists for novel effective regimens to improve response rates.

Case Report

We report here on a case of a primary angiosarcoma of both breasts in a 34-year-old woman presenting with lung metastases. Upon completion of 3 cycles of the MAID regimen (mesna, adriamycin, ifosfamide, dacarbazine), computed tomography showed disease progression. Subsequently, a second-line chemotherapy was started using the GVP regimen (gemcitabine, vincristine, cisplatin). Complete response of the lung metastases was achieved after 6 cycles of treatment.

Conclusion

In the absence of an effective therapy among patients with anthracycline-resistant metastatic breast angiosarcoma, a GVP chemotherapy regimen can be performed as a selective option.     

PAD和VAD方案治疗MM患者临床有效性及安全性比较

目的：探讨硼替佐米＋阿霉素＋地塞米松（PAD）化疗方案治疗多发性骨髓瘤（MM）的临床疗效和安全性．方法选取红河州第一人民医院收治的38例多发性骨髓瘤患者,随机将其分为观察组和对照组各19例．观察组采用硼替佐米＋阿霉素＋地塞米松（PAD）方案进行化疗,对照组采用VAD方案（长春新碱＋阿霉素＋地塞米松）进行化疗,对比2组患者的临床疗效和不良反应发生的情况．结果观察组的显效率为52.63%,显著高于对照组（P＜0.05）;观察组的总有效率为78.95%,高于对照组（P＜0.05;2组患者治疗过程中的不良反应事件的发生率对比,差异无统计学意义（P＞0.05）．结论硼替佐米＋阿霉素＋地塞米松（PAD）化疗方案可提高多发性骨髓瘤的临床疗效,且不良反应可以耐受,安全性良好,值得在临床上推广应用．     

鞘注甲氨蝶呤或阿糖胞苷污染微量长春新碱所致脊髓损伤不良事件患者半年随访观察

目的：初步观察鞘注甲氨蝶呤或阿糖胞苷污染微量长春新碱所致脊髓损伤患者半年预后情况。方法： 选取三个省份6家医院内发生的29例不良事件患者为随访对象。随访观察时间选择在出现神经损害症状后的6个月进行。由神经内科医生评价患者神经损害症状的转归、恢复情况,填写统一的设计问卷。结果：截止到随访时,该不良事件患者有2例死于原发恶性血液病,22例（81%）发生肌肉萎缩;6例（22%）完全性截瘫,21例（78%）为不完全性截瘫,7例二便障碍（26%）。采取多重治疗方式后,40%存活患者的肌力有改善,不完全截瘫患者肌力改善情况较好。结论：该不良事件病例,脊髓损伤半年后仍遗留不同程度的神经功能残障,预后不良;发生后应积极采取一些脊髓损伤的保护措施,有利于改善损伤病例的康复与预后。