长春新碱诱发外周神经病理性疼痛模型的建立

目的:建立长春新碱诱发外周神经病理性疼痛大鼠模型。方法:雄性SD大鼠,隔日尾静脉注射长春新碱,共注射五次,造成外周神经病理性疼痛模型。测定2g和12g力度机械刺激引起的缩爪反应观察机械性痛觉超敏,辐射热测痛仪测量热痛觉过敏,同时行组织切片光镜和电镜下观察坐骨神经结构的破坏情况。结果:100μg/kg和150μg/kg组大鼠在第二次注射长春新碱后,开始出现机械性痛觉超敏和痛觉过敏,150μg/kg组大鼠有热痛觉过敏表现;组织形态学研究显示坐骨神经退行性变,轴突变性。结论:从疼痛行为学、组织学研究的结果,表明长春新碱诱发外周神经痛大鼠模型建立成功。     

长春新碱对人成骨肉瘤MG63细胞的增殖抑制和凋亡促进作用及其机制

目的 观察长春新碱对人成骨肉瘤MG63细胞增殖的抑制及凋亡促进作用,探讨其作用的分子机制.方法 以0、5、10、20、50、100 μg·L-1不同浓度长春新碱处理的MG63细胞,分别经CCK-8及Hoechest 33342检测细胞增殖和细胞凋亡水平,用实时定量RT-PCR分析mRNA表达水平.结果 长春新碱可抑制MG63细胞增殖;长春新碱可以促进细胞凋亡;长春新碱可以下调c-myc及上调caspase9基因表达（P〈0.05）.结论 长春新碱从较低浓度起即有抑制细胞增殖及促进细胞凋亡作用,其作用机制是通过下调c-myc及上调caspase9的基因表达实现的.     

泼尼松联合长春新碱治疗慢性免疫性血小板减少症的疗效及对细胞免疫功能的影响

目的　研究泼尼松联合长春新碱治疗慢性免疫性血小板减少症的疗效及对细胞免疫功能的影响。方法　选取中山市人民医院2019年1月至2021年8月期间收治的136例慢性免疫性血小板减少症患儿为研究对象,进行前瞻性研究,按照随机数字表法等分为两组,分别予以不同的药物进行治疗。对照组中男33例,女35例,年龄（11.13±2.83）岁,采取泼尼松治疗;研究组中男34例,女34例,年龄（11.12±2.28）岁,在泼尼松治疗的基础上联合长春新碱治疗。持续治疗2个月后比较两组患者治疗前后的细胞免疫功能变化情况以及不同疗法的治疗效果和不良反应发生概率。使用SPSS 22.0统计软件分析数据,采用t、χ²检验。结果　治疗后,研究组的CD3⁺、CD4⁺、CD4⁺/CD8⁺分别为（54.87±4.59）%、（33.97±3.85）%、（1.85±0.36）,均高于对照组［分别为（52.35±5.24）%、（31.03±3.70）%、（1.72±0.21）］,研究组CD8⁺为（23.78±2.38）%,低于对照组的（25.32±2.43）%,两组比较差异均有统计学意义（t=2.983、4.720、2.572、3.733,均P<0.05）。研究组患者的治疗有效率为94.12%（64/68）,高于对照组的79.41%（54/68）,两组比较差异有统计学意义（χ²=6.403,P=0.011）。两组不良反应发生情况差异无统计学意义（χ²=0.119,P=0.730）。结论　泼尼松联合长春新碱治疗慢性免疫性血小板减少症患儿具有较好的效果,并且对患儿的细胞免疫功能具有积极影响,值得广泛推广。     

长春新碱联合低剂量环磷酰胺治疗系统性红斑狼疮的临床观察

目的评价长春新碱（VCR）联合低剂量环磷酰胺（CTX）治疗系统性红斑狼疮（SLE）的疗效和安全性。方法本研究为两个中心、随机、单盲、对照的临床试验。符合纳入和排除标准的50例SLE患者随机分为VCR＋CTX组（VCR1mg,12-24h内予CTX200-400mg,每3周1次）及单用CTX组（600-800mg/3周）,疗程24周,分别观察基线、12周、24周时各项指标及不良反应的发生情况,共41例患者完成试验。结果随访12周、24周与基线时相比及随访第24周与第12周相比,两组的SLEDAI、Cr显著下降（P〈0.05）,两组间变化均无差异（P〉0.5）;与基线值相比,随访第12周,VCR＋CTX组较CTX组BUN显著下降、PLT显著升高（P〈0.05）,随访第24周时,两组BUN均较基线、12周时显著下降（P〈0.05）,但PLT变化不明显（P〉0.5）。安全性方面,两组的不良反应发生率无差异（P〉0.05）。结论 VCR联合低剂量CTX可以有效改善SLE患者的症状,降低疾病活动度、改善肾功。两者联合安全性好,与CTX组相比,不良反应并未增加。     

Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel

A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy.     

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.     

硫酸长春新碱脂质体的质量评价研究

目的评价硫酸长春新碱脂质体的质量。方法采用p H梯度法制备硫酸长春新碱脂质体。透射电镜观察脂质体的外观形态,阳离子交换树脂柱法测定包封率,并考察其p H值、粒径、Zeta电位、稳定性及体外释放规律。结果形态学观察结果显示,脂质体均匀圆整度良好。硫酸长春新碱脂质体粒径为120 nm左右,Zeta电位约为10 m V,包封率均在90%以上。光照、4℃、18℃、25℃条件下,脂质体各项指标无显著变化。40℃条件下,包封率明显降低。结论本法准确,操作简便,可用于硫酸长春新碱脂质体的质量评价。     

Efficacy and Safety of First Line Vincristine with Doxorubicin,Bleomycin and Dacarbazine (ABOD) for Hodgkin’s Lymphoma: a Single Institute Experience

Background: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen inHodgkin’s lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. We aimed to evaluate the efficacyand safety of O as a part of ABOD in HL. Materials and Methods: Patients who had ABOD were enrolled. StageI-II HL were evaluated for unfavorable risk factors according to NCCN. National Cancer Institute CommonToxicity Criteria was used for toxicity. Results: Seventy-nine HL patients in our center between 2003 and 2007were evaluated retrospectively. Median follow-up was 54 months. Most of the patients were male in their thirddecade. Median ABOD cycles were 6 (2-8). Primary refractory disease rate was 17.7% whereas it was 5.1% forearly relapse and 5.1% for late relapse disease. Response rates were as 82.3% for complete response, 11.4%for partial response, 5.1% for stable disease and 1.3% for progressive disease. Half of relapsed patients hadautologous stem cell transplantation. Estimated 5-year failure-free survival was 71% and significantly longerin early stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05, p<0.0001, p=0.02;respectively). Estimated 5-year overall survival was 74% and significantly longer in those who had no RT(p=0.001). Dose modification rate was 5.1% and chemotherapy delay rate was 19%. There were no toxicityrelateddeaths. Conclusions: ABOD seems to be effective with managable toxicity in HL, even in those with poorprognostic factors.     

Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, VE-465, in myeloid leukemia cells

Aurora kinases play an essential role in the regulation of mitosis. The kinases are overexpressed in a variety of cancer cells and are involved in tumorgenesis. Although aurora kinase inhibitors are potential agents for treatment of leukemia, the establishment of efficacious combination therapies is an attractive approach for making good use of these agents. In this study, we examined the effects of a specific aurora kinase inhibitor, VE-465, in combination with various conventional anti-leukemia agents, including doxorubicin, daunorubicin, idarubicin, mitoxantron, cytosine arabinoside, vincristine and etoposide, on acute myeloid leukemia cell lines (HL60, U937, THP-1 and KY821), chronic myeloid leukemia cell lines (KCL22, K562 and KU812) and primary leukemia cells. We found that a combination of VE-465 and vincristine had a synergistic/additive inhibitory effect on the growth of leukemia cells. VE-465 initially increased G2/M-phase cells, followed by induction of sub-G1 cells. Vincristine enhanced this effect of VE-465. The combination of VE-465 and vincristine increased the levels of cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, cleaved PARP and Phospho-Chk2, suggesting that the combination caused Chk2-mediated activation of the G2/M checkpoint, resulting in sequential induction of apoptosis. Interestingly, the combination markedly decreased the level of Phospho-ERK1/2, suggesting that the combination alters a network of cellular signaling pathways. In contrast, combinations of VE-465 and other agents showed no synergistic inhibitory effect but rather had an antagonistic effect. In conclusion, our results indicate the utility of the combination of VE-465 and vincristine as a potential therapy for myeloid leukemia.