Effects of thalidomide on DMBA-induced oral carcinogenesis in hamster with respect to angiogenesis

Background:  Thalidomide has been shown to have anti-angiogenic effects in pre-clinical models as well as a significant antitumor effect in hematologic tumors. However, the effects of thalidomide on oral pre-malignant lesions and oral carcinogenesis remain unexplored. The authors aimed to investigate the chemopreventive effect of thalidomide on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis.
Methods:  Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in group A and B, while animals in group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in group B and D received thalidomide daily (40 mg/kg body weight/day) by gavage, animals in group A and C received same volume of saline. Animals in group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for examinations.
Results:  Thalidomide significantly decreased the squamous cell carcinoma (SCC) incidence from 57.9 to 11.8%; angiogenesis was inhibited in dysplasia and SCC. The gene expression of vascular endothelium growth factor and tumor necrosis factor (TNF)-α was downregulated.
Conclusions:  Thalidomide has inhibitory effect against the malignant transformation of oral pre-cancerous lesion and angiogenesis during oral carcinogenesis. Such inhibition is related to its modulation of TNF-α.     

沙利度胺辅助化疗治疗晚期非小细胞肺癌

目的 观察沙利度胺辅助化疗对晚期非小细胞肺癌(NSCLC)的治疗作用. 方法 40例Kamofsky评分达到60分以上的NSCLC患者,随机分为治疗组(n=20)和对照组(n=20).治疗组接受化疗联合沙利度胺治疗,对照组则仅接受化疗,两组化疗方案均为长春瑞滨+卡铂.以近期有效率和中位缓解期评价各组疗效.结果 治疗组近期有效率和中位缓解期分别为61.1%和2.7月,对照组相应的为50.0%和2.4月,两组相比无显著差异(P>0.05).结论 沙利度胺辅助化疗用于晚期NSCLC耐受性良好,并具有一定的增效减毒作用.     

沙利度胺与地塞米松联合治疗多发性骨髓瘤的临床研究

目的 探讨沙利度胺与地塞米松联合治疗多发性骨髓瘤(MM)的临床疗效及不良反应.方法 39例初治MM患者,随机分为两组,VAD方案对照组:长春新碱加阿霉素加地塞米松;治疗组:沙利度胺加地塞米松,沙利度胺起始剂量为100～200 mg/d,以后每周加量50～100 mg/d,最大剂量400 mg/d,并加用地塞米松20 mg/(m2. d),第1～4天,第9～12天,第17～20天,30天后重复上述方案,至少治疗3个月.结果 治疗组部分缓解9例(45.0%),进步6例(30.0%),无效5例,总有效率75.0%(15/20),明显优于对照组(总有效率52.6%)(P＜0.05);能有效降低M蛋白,使骨髓瘤细胞下降,提高血红蛋白和改善生活自理状况(P＜0.05).副反应程度均可耐受.结论 沙利度胺联合地塞米松治疗多发性骨髓瘤(MM)具有副作用少、耐受性好、给药方便、费用低、疗效明显的优点,值得临床推广应用.     

沙利度胺对慢性充血性心力衰竭的影响

目的:探讨慢性充血性心力衰竭(CHF)病人应用沙度胺,治疗前后血浆心衰相关细胞因子水平及左室收缩功能变化。方法:将98例CHF病人(左室射血分数LVEF≤40％)随机分为2组,对照组常规应用治疗心衰药物,沙利度胺组在此基础上加用沙利度胺25～150mg·d-1,共用12wk,于治疗前后分别测定TNF-α,IL-6,超声心动图评价左室收缩功能。结果:CHF病人经沙利度胺治疗12wk后, TNF-α(p<0.01)、IL-6(P<0.05)水平均降低,且左室收缩功能显著改善(P<0.01)。结论:常规治疗慢性充血性心力衰竭基础上加用沙利度胺,安全易耐受,可显著改善CHF相关的临床症状和心功能。     

沙利度胺及其衍生物临床及作用机制研究进展

沙利度胺是一种合成的谷氨酸衍生物，原作为镇静剂治疗早孕反应，20世纪60年代出现严重的致胎儿缺陷而被禁止使用。但此后研究发现，沙利度胺具有免疫调节和抗血管生成作用，治疗多发性骨髓瘤等恶性肿瘤以及其他难治性疾病有效。通过对沙利度胺进行结构改造得到的一系列免疫调节药克服了原形药物的严重不良反应，这些药物的强大的抗癌作用意味着它们将走出沙利度胺的阴影，成为有效的抗肿瘤药物。现对沙利度胺及其衍生物的临床应用和作用机制的研究进展进行综述。     

反应停联合化疗治疗难治及复发性多发性骨髓瘤疗效观察及治疗前后VEGF变化

目的观察反应停联合VAD方案治疗难治及复发性多发性骨髓瘤的临床疗效并测定反应停治疗前后血清VEGF水平的变化。方法反应停剂量为400￣600mg/d,每5周联合VAD方案治疗难治及复发性多发性骨髓瘤28例。有效病例治疗前和治疗后12周测定血清中VEGF水平。结果总有效率89.3%,完全缓解率14.3%;其中25例有效患者治疗前血清VEGF水平为(326.00±33.67)ng/L,治疗后12周血清VEGF水平为(84.00±40.26)ng/L(P<0.01)。结论反应停联合VAD方案为治疗难治性复发性多发性骨髓瘤较好的选择,反应停可明显降低MM患者血清VEGF水平。     

The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma.

Thalidomide has shown efficacy in relapsed or refractory patients of multiple myeloma (MM). We present the adverse effect profile of thalidomide in 23 relapsed or refractory MM patients treated with this drug over a period of 15 months. Constipation (100% incidence) and sedation (87%) were the most common adverse effects. Neuropathy had low incidence and was late in onset (>12 months). Tolerance developed to sedation, constipation and skin lesions. All the adverse drug reactions were tolerable and did not warrant decrease or termination of therapy, except for peripheral neuropathy. Contrary to Western reports, peripheral neuropathy in Indian patients developed at a cumulative dose of 200 g or more after 10 months or more of therapy. Therapy was discontinued in one patient due to marked elevation of liver enzyme that was later attributed to acute hepatitis C infection. Only one patient dropped out of the trial for unknown reasons. Overall, thalidomide was found to be a relatively safe drug that can be used over a prolonged period of time.