Stroke Caused by Small Vessel Occlusion in a Patient Taking Etoricoxib and Thalidomide

We report a 33-year-old man with seronegative arthritis who had an acute infarct at the left lentiform nucleus while taking etoricoxib and thalidomide regularly. Extensive investigations did not find any evidence of large artery atherosclerosis, vasculitis, cardioembolic source or anti-phospholipid antibodies. While it is possible that a short smoking history, hyperlipidemia, and the use of thalidomide could have contributed to the thrombosis of a small penetrator vessel, we postulated that the prolonged use of etoricoxib is another possible contributing factor.     

Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma.     

反应停、紫杉醇对Lewis肺癌小鼠的抑瘤作用

目的　研究反应停、小剂量紫杉醇对 L ewis肺癌小鼠皮下移植瘤和肺转移瘤的抑制作用 ,并探讨其与肿瘤细胞凋亡和细胞周期的关系。方法　 50只荷 L ewis肺癌小鼠随机分为四组 ,分别给予生理盐水、反应停、小剂量紫杉醇、反应停联合小剂量紫杉醇治疗 ,第 2 1天处死动物 ,称取鼠重、瘤重、肺重 ,计数肺转移结节数 ,免疫组化染色记数肿瘤组织微血管密度 ,流式细胞仪检测肿瘤细胞凋亡率及细胞周期。结果　反应停、小剂量紫杉醇单独及联合治疗组肿瘤重量与对照组间差异无显著性 (P>0 .0 5)。反应停、小剂量紫杉醇单独及联合治疗组肺重、肺转移结节数及肿瘤组织微血管密度均小于对照组 ,差异有显著性 (P<0 .0 5)。各治疗组肿瘤细胞凋亡率及 G1、S、G2 期肿瘤细胞百分数与对照组间差异无显著性 (P>0 .0 5)。结论　反应停、小剂量紫杉醇不能抑制 L ewis肺癌皮下移植瘤生长 ,但可抑制肿瘤肺转移 ,两药间无协同或拮抗作用。反应停、小剂量紫杉醇不诱导 L ewis肺癌细胞凋亡 ,不影响肿瘤细胞生长周期     

Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.     

卡瑞利珠单抗联合沙利度胺治疗晚期肝细胞癌的疗效及安全性

目的:评估卡瑞利珠单抗联合沙利度胺在晚期肝细胞癌患者中的疗效和安全性。方法:收集2019年7月至2020年7月既往全身治疗进展或不耐受的晚期肝细胞癌患者24例,给予卡瑞利珠单抗200 mg静脉滴注,每3周给药1次;沙利度胺100 mg起始,1周后增至200 mg,每晚1次口服。评价疗效及安全性。结果:共24例患者纳入研究,其中1例完全缓解,8例部分缓解,9例疾病稳定,4例疾病进展,客观缓解率为37.5%（9/24）,疾病控制率为75.0%（18/24）。2例患者在随访期间死亡,死亡原因为疾病进展导致的多器官衰竭,中位PFS为6.5个月（95%CI,5.15~7.85）。最常见的不良反应是反应性皮肤毛细血管增生症（41.7%）、血小板减少（33.4%）、γ-谷氨酰转肽酶升高（25.0%）、白细胞减少（20.8%）和转氨酶升高（29.2%）,1例3级血小板减少事件,2例3级转氨酶升高事件,未发现4级及以上的不良反应。结论:卡瑞利珠单抗联合沙利度胺在晚期肝细胞癌患者中显示出一定的疗效和可控的安全性。对于既往全身治疗进展或不耐受的晚期肝细胞癌患者来说,这可能代表了一种新的治疗选择。     

沙利度胺对大鼠子宫内膜异位症模型血管生成的影响

目的探讨沙利度胺（thalidom ide,THD）对大鼠子宫内膜异位移植物生长和血管生成的影响。方法采用自体移植法建立SD大鼠子宫内膜异位症模型,3周后行剖腹术测量移植物的大小,然后将大鼠随机分为模型对照组（每天腹腔注射生理盐水2mL）,孕三烯酮（YSXT）组（腹腔注射孕三烯酮0.5mg.kg-1.d-1）,沙利度胺3个剂量组（分别腹腔注射5、20、40mg.kg-1.d-1）,联合用药组（腹腔注射孕三烯酮0.5mg.kg-1.d-1,沙利度胺20mg.kg-1.d-1）。4周后再次剖腹评价子宫内膜异位病灶大小和形态学的变化,并通过Ⅷ因子标记异位子宫内膜血管,采用免疫组化法检测异位内膜组织中微血管密度（Microvessel density,MVD）。结果各治疗组异位内膜呈现不同程度萎缩,腺体明显减少,移植物体积均小于模型对照组（P〈0.05）;各治疗组MVD均低于模型对照组（P〈0.05）,其中以沙利度胺40mg.kg-1.d-1剂量组最为明显。结论沙利度胺对大鼠子宫内膜异位病灶有抑制作用,可能是通过抑制血管生成起作用。     

沙利度胺治疗恶性肿瘤的研究进展

沙利度胺早期作为一种非巴比妥类镇静剂用于早孕反应的治疗,但由于严重的致畸作用而被禁用。随后的研究发现,沙利度胺具有抑制肿瘤坏死因子-α（TNF-α）作用,1998年美国FDA批准其用于麻风病结节性红斑的治疗。近年来研究发现,沙利度胺具有抗血管生成及调节免疫等作用。目前,沙利度胺已经成为复发和难治性骨髓瘤标准治疗的一部分,和其他药物联合应用对其他实体肿瘤如神经胶质细胞瘤、前列腺癌、肾癌、恶性黑色素瘤和肺癌等的治疗显示一定效果,但其作用机制尚不完全明了。     

生物化疗联合沙利度胺治疗晚期肾癌的临床观察

目的 观察生物化疗加沙利度胺对晚期肾癌的治疗作用。方法 选取病理证实均为肾细胞癌的晚期肾癌后患者61例。分两组：①对照组23例行生物化疗;②实验组38例行生物化疗加沙利度胺治疗。所有病人均行病肾姑息切除术或肾动脉栓塞术,术后1—2周开始生物化疗。生物化疗方法：IL-2200万U／次,3次／周皮下注射;IFN-2a300万u／次,3次／周皮下注射;IL-2和IFN-2a均用42周。5-FU500mg加入5％葡萄糖液500ml缓慢静脉滴注（4—6h）,第1-5天。21d为1周期,共4-6周期。沙利度胺用法为400mg／d,分2次口服,服用1年或至病情进展。结果 近期疗效两组均无CR病例。对照组PR5例,有效率（CR＋PR）21．7％;实验组PR18例,有效率（CR＋PR）47．4％,两组差异有显著性（P〈0．05）。两组未见严重不良反应发生。疾病进展期对照组4．7个月,平均5．2个月,实验组6-9个月,平均7个月。随访12个月对照组成活11例,1年生存率为43．4％;实验组成活19例,1年生存率为50％。随访24个月,对照组5例生存。生存率17．4％;实验组7例生存,生存率18．4％,两组差异无显著性（P〉0．05）。结论 生物化疗加沙利度胺对晚期肾癌的治疗与生物化疗相比,能提高近期疗效和延长疾病进展时间,对1年和2年生存率无差别。