Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat

The development of painful peripheral neuropathy is a dose-limiting side effect of numerous cancer chemotherapeutic agents. The present study utilized a rodent model of vincristine-induced neuropathy to determine whether a glial modulating agent, propentofylline, could attenuate vincristine-induced mechanical allodynia. Intravenous vincristine administered on days 1 through 5 and days 8 through 11 produced mechanical allodynia using 2 and 12 g von Frey filaments. Lumbar spinal cord from animals on day 15 expressed mild bilateral microglial and astrocytic activation as compared to saline-treated animals. Daily intraperitoneal propentofylline at 10 mg/kg attenuated mechanical allodynia induced by vincristine administration. In addition, propentofylline was found to decrease spinal microglial and astrocytic activation on day 15. These data suggest that central glial cells may play an important role in the development of painful neuropathy following vincristine administration.     

长春新碱和甲氨蝶呤行口腔鳞癌术前新辅助化疗的临床研究

目的:观察长春新碱(vincristine)和甲氨蝶呤(methotrexate)新辅助化疗方案(VM方案)在口腔鳞状细胞癌治疗中的临床疗效.方法:对联合应用长春新碱和甲氨蝶呤行新辅助化疗的45例口腔鳞癌患者(辅助化疗组)和既往术前未作任何辅助治疗的50例口腔鳞癌患者(对照组)进行回顾性分析,辅助化疗组术前接受1个疗程的VM方案化疗后进行手术,术后两组接受同样治疗.统计辅助化疗组化疗疗效、术后肿瘤复发率、不良反应和生存质量评分,比较两组患者的术后肿瘤复发率和生存质量评分.结果:经1个疗程VM化疗方案治疗后,45例口腔鳞癌患者中临床部分缓解26例(57.8%),稳定19例(42.2%),化疗总有效率57.8%.VM方案不良反应小,不影响患者接受手术治疗.随访期间辅助化疗组出现肿瘤复发10例(22.2%)、肿瘤远处转移4例(8.9%),对照组出现复发21例(42.0%),转移14例(28.0%),组间比较差异有显著性.结论:术前应用长春新碱和甲氨蝶呤联合化疗在口腔鳞癌治疗中疗效显著,能提高患者生存质量.     

正交试验优化硫酸长春新碱脂质体的制备工艺

目的：制备性质稳定的硫酸长春新碱脂质体。方法采用单因素试验考察磷脂与胆固醇比例、药脂比、脂质浓度、载药温度、载药时间、外水相 pH 值对硫酸长春新碱脂质体包封率的影响。以包封率为指标,分别以氢化磷脂（SPC-3）和二硬脂酰磷脂酰胆碱（DSPC）为磷脂材料,通过正交试验考察载药温度、药脂比和载药时间对制备工艺的影响,优化出硫酸长春新碱脂质体的最佳制备工艺。结果硫酸长春新碱脂质体的最佳制备工艺为：将药物溶液（按照药物含量计）和空白脂质体溶液（按照脂质含量计）按照1∶20的比例混合,用Na2HPO4直接调节外水相pH值至7.2。SPC-3脂质体在65℃条件下载药,载药时间30 min。DSPC脂质体在60℃条件下载药,载药时间10 min。结论优选出的硫酸长春新碱脂质体的处方工艺稳定可行。     

11例成人肾母细胞瘤临床治疗分析

目的：研究成人肾母细胞瘤的临床特征及治疗情况。方法：将11例成人肾母细胞瘤的临床表现，特征，分期，治疗及预后进行了回顾性分析。结果：11例患者中Ⅰ期3例，Ⅱ期5例，Ⅲ期3例，所有患者均接受了肾脏切除。7例术后接受了辅助性化、放疗，2例Ⅰ期患者至今无瘤生存28年和17年。尽管使用了多种治疗手段，其余较晚期患者预后不佳。结论：用治疗儿童肾母细胞瘤的方案治疗成人肾母细胞瘤预后不尽满意；早期分化发的成人成肾母细胞瘤预后较令人满意，晚期成人肾母细胞应采用多种手段积极治疗；只要可能，化疗方案中应该含有更生霉素。     

甲基莲心碱对耐长春新碱人胃癌细胞多药耐药性逆转机制的初步研究

目的探讨新的钙阻断剂甲基莲心碱(Nef)对耐长春新碱人胃癌细胞多药耐药性(MDR)的逆转作用及其机制。方法采用MTT比色法,检测药物的细胞毒作用;应用免疫细胞化学SP法及流式细胞术,检测Nef对人胃癌细胞Bcl-2蛋白表达的影响。结果 10μmol/L Nef对SGC7901及SGC7901/VCR无显著细胞毒作用;2.5、5、10μmol/L Nef能使VCR对SGC7901/VCR细胞的IC50从2.32μg/ml依次下降至0.340、0.128、0.053μg/ml,逆转倍数分别为6.8、18.1、43.8。当Nef浓度为10μmol/L时,逆转SGC7901/VCR多药耐药活性较VRP高(P<0.01);SGC7901/VCR细胞中Bcl-2蛋白表达水平较SGC7901细胞高,经Nef处理后,SGC7901/VCR细胞中Bcl-2蛋白表达水平明显下降,表明Nef能下调SGC7901/VCR细胞中Bcl-2蛋白表达水平。结论甲基莲心碱在体外能逆转耐长春新碱人胃癌细胞(SGC7901/VCR)的多药耐药性,其机制可能与下调Bcl-2蛋白表达水平有关。     

蛋白激酶C的下调与KBV200细胞多药耐药性的关系

目的　探讨蛋白激酶C (PKC)在肿瘤多药耐药 (MDR)中的作用。方法　3 2 P掺入法测定PKC的活性 ;Westernblot法检测KBV2 0 0细胞株PKC亚型的表达和亚细胞分布 ;实验组用十字孢碱 (SP)预孵育KBV2 0 0细胞 ;MTT法检测耐药株KBV2 0 0细胞的耐药性。结果　SP可下调膜组分和浆组分的PKC活性及总活性 ;使PKCα膜组分和浆组分的表达均降低 ,PKCβ的膜组分消失 ,浆组分PKCβ的表达稍增强 ,PKCε的膜组分和浆组分表达无变化 ;SP可降低VCR、ADR对KBV2 0 0细胞的IC50 值 (P <0 0 1)。结论　SP使KBV2 0 0细胞耐药性降低 ,可能与下调PKC有关。     

CTVP与CTOP方案治疗280 例非霍奇金淋巴瘤临床疗效分析

目的：比较含长春地辛（VDS ）的CTVP方案与含长春新碱（VCR ）的CTOP方案治疗初治非霍奇金淋巴瘤（NHL ）的近期疗效、远期生存及不良反应。方法：采用两种方案治疗初治NHL 患者共280 例,CTVP组162 例,CTOP组118 例。结果：两组患者临床特征指标相似（P>0.05）。 可评价疗效272 例,两组有效率分别为73.13% 和72.32% ,临床获益率分别为91.88% 和90.18%（P>0.05）。 骨髓抑制、胃肠道反应、乏力、外周神经毒性和脱发为主要不良反应。CTVP组外周神经毒性的发生率低于CTOP组（14.81% ：31.36% ,P<0.05）。 中位随访时间32个月（2～71个月）,两组5 年生存率分别为43.2% 和22.3%（P<0.05）。 结论：采用含VDS 的CTVP方案治疗初治NHL 疗效较好,毒性较低,远期生存率较高,值得临床进一步研究。     

误行鞘内注射长春新碱事件病例报告的系统评价

目的评价误行鞘内注射长春新碱事件的发生原因、患者神经损害的特点、抢救措施和预后。方法使用电子文献数据库、中英文纸质文献数据库和网络引擎三种方法检索误行鞘内注射长春新碱的病例报告,使用SPSS 15.0进行统计分析。结果最终纳入32例病例报告,分析显示鞘内注射长春新碱后患者结局不良,多数患者（25/32）结局为死亡,存活病例伴随下肢瘫痪或四肢瘫痪后遗症。患者临床进展过程表现为上行性脑脊髓病。早期识别错误并及时实施脑脊液脑室-腰椎脑脊液灌注引流术可以提高患者的生存概率。不同外科治疗措施组间、是否使用叶酸治疗组间、是否使用谷氨酸治疗组间和是否使用维生素B6组间的生存曲线差异有统计学意义。结论及时进行脑室-腰椎脑脊液灌注引流术、使用叶酸、谷氨酸对抢救患者生命十分重要,但难获得满意的临床转归,因此关键在于实施有效的预防措施。     

Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells

Experimental painful peripheral neuropathies produced by the chemotherapeutic drugs, paclitaxel and vincristine, are produced by relatively low doses that do not cause axonal degeneration in peripheral nerve. Using quantitative immunolabeling with the PGP9.5 antibody, we have investigated whether these painful neuropathies might be associated with degeneration that is confined to the region of the sensory fiber's receptor terminals in the skin. Because complete and partial nerve transections are known to cause an increase in PGP9.5 in epidermal Langerhans cells (LCs), we also examined whether this effect occurs in chemotherapy-treated animals. At the time of peak pain severity, rats with paclitaxel- and vincristine-evoked painful peripheral neuropathies had a significant decrease (24% and 44%, respectively) in the number of intraepidermal nerve fibers (IENF) in the hind paw glabrous skin and an increase (217% and 121%, respectively) in the number of PGP9.5-positive LCs, relative to control. However, neither loss of IENF nor an increase in PGP9.5-positive LCs was found in rats with a painful peripheral neuropathy evoked by the anti-HIV agent, 2',3'-dideoxycytidine. We also confirmed that there is a decrease in IENF and an increase in PGP9.5-positive LCs in rats with neuropathic pain following a partial nerve injury (CCI model) and in rats with a complete sciatic nerve transection. Partial degeneration of the intraepidermal innervation suggests mechanisms that might produce chemotherapy-evoked neuropathic pain, and activation of cutaneous LCs suggests possible neuroimmune interactions that might also have a role.     

Endangering cutaneous infantile hemangioma treated with vincristine: a case report

Infantile hemangiomas are the most common tumors of childhood. They have a well-defined self-limiting natural history. In about 10% of patients, the hemangioma threatens or potentially threatens life or function during the proliferative phase. The most common treatments for such endangering hemangiomas are intralesional and/or oral steroids. Although steroids are well known to slow growth and promote involution in hemangiomas, there may be no effect on proliferation in up to 30% of patients. There are several reports of the use of intravenous vincristine being successfully used for steroid-resistant hemangiomas, although most of these have been described as hemangioendotheliomas. The degree of improvement in such cases is somewhat subjective. We describe a patient with a large steroid-resistant cervicofacial infantile hemangioma causing stridor. The use of intravenous vincristine rapidly improved the clinical state so much that immediate tracheostomy was avoided, and adrenaline nebulizers could be stopped within 1 day of starting vincristine. We believe that this is the first report of objective improvement in the symptom associated with an infantile hemangioma as a result of treatment with vincristine.