沙利度胺联合表阿霉素治疗小鼠H22肝癌移植瘤的实验研究

目的 探讨沙利度胺联合表阿霉素治疗小鼠 H22肝癌移植瘤的疗效。方法 培养 H22肿瘤细胞,制造皮下移植瘤小鼠模型60只。按照不同治疗方法将小鼠模型分成三组,每组20只,其中A组小鼠采用沙利度胺联合表阿霉素治疗;B组小鼠仅采用表阿霉素治疗;C组采用生理盐水对照,在治疗d7、d14、d21和d30测量各组小鼠肿瘤直径,统计治疗后12个月内三组小鼠死亡率。结果 A组小鼠d14肿瘤直径为（11．37 ± 1．03） mm ,显著短于同期B组（19．32 ± 1．12） mm和C组（28．39 ± 1．19） mm ;A组小鼠d30肿瘤直径为（9．23 ± 1．08）mm ,显著低于B组（12．23 ± 1．04 mm）和C组（29．29 ± 1．03 mm）。A组死亡率10％（2／20）显著低于B组45％（9／20）和C组80％（16／20）。结论 沙利度胺联合表阿霉素治疗小鼠 H22肝癌移植瘤疗效满意。     

沙利度胺治疗胃肠道血管畸形所致消化道出血的机制研究

【目的】探讨沙利度胺治疗胃肠道血管畸形所致消化道出血的作用机制。【方法】采用免疫组化法检测90例GIVM 所致消化道出血患者,及30例健康人肠黏膜中促血管生成素‐2（Ang‐2）、Notch‐1、DLL4的表达;采用RT‐PCR及Western blot检测50 mg／L、100 mg／L、200 mg／L沙利度胺对HUVEC细胞Ang‐2、Notch‐1、DLL4基因mRNA及蛋白表达的影响。【结果】与溶剂对照组比较,50 mg／L沙利度胺组中Notch‐1的mRNA表达量减少,100 mg／L沙利度胺组中Ang‐2,Notch‐1的mRNA表达量减少,差异具有统计学意义（ P ＜0．05）,200 mg／L沙利度胺组中Ang‐2,Notch‐1,DII4的mRNA表达量减少,差异均有统计学意义（ P ＜0．05）。与溶剂对照组比较,50 mg／L沙利度胺组中 Ang‐2、Notch‐1的蛋白表达量下降,100 mg／L ,200 mg／L沙利度胺组中的 Ang‐2, Notch‐1,DLL4的蛋白表达量均下降,差异都具有统计学意义（ P ＜0．05）。GIVM组织中血管扩张扭曲。Ang‐2的表达明显增高。DLL4和Notch‐1的表达在病变组织中亦明显增高。而胃肠道血管畸形（GIVM ）患者非病变组织及健康体检者正常肠黏膜组织中Ang‐2、Notch‐1、DLL4均呈弱阳性（＋）或阴性表达。【结果】GIVM 与Ang‐2、DLL4和Notch‐1的表达密切相关,且沙利度胺可抑制Ang‐2、DLL4和Notch‐1的mRNA及蛋白的表达。     

沙利度胺治疗克罗恩病的研究进展

克罗恩病（CD）是一种慢性非特异性肠道炎症性疾病,其发病机制尚未完全明确。近年来随着对肿瘤坏死因子（TNF）-α在CD发病机制中的认识,针对TNF—α的靶向治疗成为关注热点。沙利度胺因具有抑制TNF-α的特性,在CD尤其是难治性CD的治疗中起一定作用。本文就沙利度胺治疗CD的研究进展作一综述。     

Effects of the combined treatment with thalidomide, megestrol and interleukine-2 in cirrhotic patients with advanced hepatocellular carcinoma: A pilot study

BACKGROUND: Thalidomide, an anti-angiogenic agent, does not have a good therapeutic effect for advanced hepatocellular carcinoma when used alone. Megestrol and interleukin-2 have been proposed as a palliative treatment for hepatocellular carcinoma. AIMS.: We assessed the effectiveness/safety of a combined therapy with thalidomide+megestrol+interleukin-2 in cirrhotic patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Nine cirrhotic patients with advanced hepatocellular carcinoma received oral megestrol (160 mg/day) and thalidomide (from 50 mg/day to the maximal tolerated dose). Four patients also received subcutaneous interleukin-2 (1 million U/day for 21 days/month). RESULTS: The maximal tolerated dose of thalidomide was 150 mg/day. All patients complained of sedation and other neurological or digestive adverse effects. In all but one patient the adverse effects disappeared after thalidomide withdrawal or dose reduction. Interleukin-2 administration caused a flu-like syndrome and a reaction at the injection site. During treatment, alpha-fetoprotein increased in six patients, remained stable in two and decreased in one. Eight patients showed tumour progression and one had a stable disease. Eight patients died. The median survival was 9.9 (range 2.6-18.6) months. CONCLUSION: In cirrhotic patients, the combined treatment with thalidomide+megestrol (+/-interleukin-2) does not control hepatocellular carcinoma growth, possibly due to the low tolerance to thalidomide and interleukin-2 preventing the use of appropriate dosages.     

沙利度胺联合埃克替尼治疗进展期肺腺癌的临床研究

目的 探讨沙利度胺联合埃克替尼治疗肺腺癌的疗效和安全性。方法 收集2013年1月1日至2015年6月30日医院收治的确诊为进展期肺腺癌的患者作为研究对象。随机分为试验组33例和对照组30例,试验组给予埃克替尼联合沙利度胺治疗;对照组给予埃克替尼单药治疗。比较两组肺腺癌患者治疗反应率、疾病无进展生存期以及治疗1疗程后血清相关分子血管内皮生长因子、白细胞介素-8、肿瘤坏死因子-α、碱性成纤维细胞生长因子的水平,以及不良事件在两组患者中的发生情况。结果 两组患者皮疹、腹泻、肝功能损伤、肾功能损伤、血常规异常的发生率无明显差异,试验组大便隐血的发生率较对照组高。对照组30例肺腺癌患者,客观缓解率ORR为43.33%,而试验组达69.70%,差异有统计学意义(P＜0.05)。试验组疾病无进展生存期为（21.12±6.56）月,对照组疾病无进展生存期为（19.77±6.61）月(P=0.073)。对照组血清血管内皮生长因子水平为295.0 (122.67~572.54)pg/ml,试验组血清血管内皮生长因子水平为148.0 (56.33~337.42)pg/ml,显著低于对照组,差异有统计学意义(P<0.01)。白细胞介素-8、肿瘤坏死因子-α、碱性成纤维细胞生长因子水平两组间(P=0.0585)无统计学差异,但试验组白细胞介素-8、肿瘤坏死因子-α均低于对照组,碱性成纤维细胞水平试验组要高于对照组,提示两组实验数据存在差异的趋势。结论 相比仅接受埃克替尼治疗组,沙利度胺联合埃克替尼可提高进展期肺腺癌患者的近期疗效。试验组疾病无进展生存期相比对照组略有延长,但无统计学差异。试验组患者未见严重毒副反应,患者耐受性好,可以作为治疗进展期肺腺癌的新型治疗手段。     

单药地西他滨比较沙利度胺联合全反式维A酸治疗1型骨髓增生异常综合征

目的 :比较单药地西他滨(DAC)与沙利度胺联合全反式维A酸(TAT)治疗低危及中危-1型骨髓增生异常综合征(MDS)的临床疗效。方法:回顾性分析11例接受DAC治疗和25例接受沙利度胺联合TAT治疗的MDS患者临床资料,采用二代测序检测MDS患者常见突变基因,探讨2种治疗方案的临床疗效和影响因素。结果:DAC治疗组总有效率54.5%,其中3例(27.3%)获完全缓解(CR),2例(18.2%)获部分缓解(PR),1例(9.1%)获血液学改善(HI),持续有效5例(83.3%),中位无进展生存(PFS)时间为12个月。TAT治疗组总有效率36.0%,9例(36.0%)获HI,持续有效4例(44.4%),中位PFS时间为9个月。伴有基因突变患者采用DAC治疗较TAT治疗有较长的PFS时间,差异有统计学意义(P<0.05)。在TAT治疗组中,骨髓原始细胞≤2%是影响临床疗效HI的重要指标,HI与非HI组差异有统计学意义(P<0.05)。结论:DAC治疗低危及中危-1型MDS患者临床疗效优于TAT,尤其对于存在MDS基因突变的患者;TAT治疗方案可提高患者的HI。     

5′-Substituted Thalidomide Analogs as Modulators of TNF-α

The synthesis of 5′-substituted thalidomide analogs is described. The amino acids 2 necessary to synthesize the target compounds were prepared by Michael reaction. Condensation of 2 with phthalic anhydrides followed by reaction with urea yielded 4 as diastereomeric mixtures. Furthermore glutethimide ( 5 ) was brominated by an improved method and the resulting compound 6 was reacted in several steps with sodium azide, hydrogen, and phthalic anhydride to give 8 . In a similar manner, 6 was reacted with sodium azide and various phthalic anhydrides to give 9 , 10 , and 11 . All final compounds were tested in vitro for their inhibitory activity on the release of TNF-α, using stimulated peripheral mononuclear blood cells (PBMCs). Compounds with an additional aromatic substituent in position 5’ of the thalidomide molecule were more active than thalidomide. Compound 11 was able to reduce increased levels of IL-2 in vitro.     

利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤的疗效评价

目的评价利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)的有效性及安全性。方法回顾性分析甘肃省武威肿瘤医院血液科使用R-CHOP方案化疗后完全缓解的≥60岁的DLBCL患者86例,按其治疗方案分为2组。对照组患者在完全缓解后单用利妥昔单抗维持治疗(n=43);治疗组患者应用利妥昔单抗联合沙利度胺方案维持治疗(n=43例)。对两组患者的预后进行分析。结果治疗组4年、5年总生存期(OS)率高于对照组(P<0.01);3年、4年、5年无进展生存期(PFS)率高于对照组(P<0.01);治疗组总生存时间、无进展生存时间明显长于对照组(P<0.001)。结论利妥昔单抗联合沙利度胺维持治疗老年人DLBCL,可延长患者总生存时间及无进展生存时间,无严重不良反应发生。     

Effect of different doses of dexamethasone combined with bortezomib and thalidomide in treatment of elderly patients with multiple myeloma

Objective: To observe the efficacy and safety of different doses of dexamethasone combined with bortezomib and thalidomide in the treatment of elderly patients with multiple myeloma (MM). Methods: A total of 33 elderly MM patients treated in Shanghai Fifth People's Hospital between August 2014 and August 2019 were enrolled in the study. According to the dosage of dexamethasone, the patients were divided into the observation group (low dose dexamethasone, 20 mg/d on day 1-4, and 11-14) and the control group (high dose dexamethasone, 40 mg/d on day 1-4, 9-12, and 17-20). Twenty-eight days was a course of treatment. The clinical efficacy and safety of patients was assessed after 4 courses of treatment. The patients were followed up till June 30th, 2021. Kaplan-Meier and log-rank were used to analyze the survival. Results: The overall response rate (ORR) and median overall survival (OS) were not significantly different between the observation and control groups (82.4% vs 87.5%, P=0.973; 58 months vs 61 months, P=0.859). The incidence rates of lung infection and hyperglycemia in the observation group were both significantly lower than those in the control group (both P< 0.05). Conclusions: Different doses of dexamethasone combined with bortezomib and thalidomide have definite curative effects in the treatment of elderly MM patients. But low dose dexamethasone has fewer adverse reactions and better safety. © 2022, The Second Affiliated Hospital, College of Medicine, Zhejiang University.. All right reserved.