反应停的新生—抗肿瘤

抗肿瘤血管生成是现在肿瘤治疗研究的热点之一，研究发现曾因严重致畸作用而被禁用的反应停具有明显的抗血管生成作用，因此被用于抗肿瘤的研究。动物实验和临床试验都得到了一些令人鼓舞的结果，发现反应停对多种肿瘤具有明显的疗效，预示反应停将有可能在抗肿瘤领域获得新生。     

反应停治疗乳腺癌的研究进展

乳腺癌的生长、转移与复发是血管生成依赖的，故以肿瘤血管生成的各个环节及其发生过程中的生化改变为靶点，研制血管生成抑制剂，可有效地抑制肿瘤生长、侵袭、转移和复发。近年来随着动物及体外和体内实验发现反应停(酞咪哌啶酮，thalidomide)具有抑制血管生成及抗肿瘤的潜能等作用，特     

反应停的抗肿瘤机制

反应停(沙利度胺，酞胺哌啶酮，thalidomide Thd)于1954年在西德合成，1956年开始在西德及欧洲国家作为一种非巴比妥药物广泛使用。1961年因用于妊娠呕吐而致新生儿畸形及死产被禁用。在上世纪90年代，有文献报道其具有治疗艾滋病及抗肿瘤的作用^[1]，并于1998年获得美国FDA承认而     

反应停治疗肿瘤的机制和临床应用

反应停(thalidomide，沙利度胺)最早于1956年作为一种非巴比妥镇静剂上市，以后在欧洲被广泛用于早孕反应，1961年因其具有严重的致畸作用而被禁用。近年来的研究发现，反应停对恶性肿瘤有一定的治疗作用，由此引起了学者们的广泛关注。     

反应停治疗多发性骨髓瘤的研究进展

近年来有关反应停抗血管增生作用的研究不断深入，在治疗难治性多发性骨髓瘤(MM)方面取得了令人瞩目的效果。本文简要综述其药理学、临床试验研究及其作用机制。     

反应停抗肿瘤作用研究进展

肿瘤的生长有赖于血管生成，血管生成是肿瘤侵袭、转移的基础。抑制血管生成可使肿瘤萎缩坏死或使微转移灶长期处于“休眠”状态。反应停于上世纪中叶作为非巴比妥类镇静剂用于早孕反应，后曾因严重的致畸作用而被禁用。近年研究发现．反应停能明显抑制兔角膜血管生成，具有血管生成抑制作用，因而被应用于肿瘤研究。然而，实验研究中反应停对实体瘤的抗肿瘤效应并不一致，作用机制也未完全明了。我们对反应停药理作用、抗肿瘤效用、作用机制及临床应用等方面的研究进展予以综述。     

肿瘤血管生成抑制剂的临床研究新进展

血管生成 ( angiogenesis)是指在已形成的血管的基础上形成新血管的过程 ,它是肿瘤持续生长和发生转移的必要前提。在生长初期 ,肿瘤细胞可以通过扩散从细胞间隙获得氧气和营养 ,但当肿瘤增至1～ 2 mm3时 ,内部的细胞通过扩散已不能获得足够的氧气和营养满足其继续生长和分裂的需要 ,肿瘤内部形成缺氧状态 ,这时缺氧作为一种环境信号启动了瘤细胞中血管内皮生长因子 ( vascular endo-thelial growth factor,VEGF)、碱性成纤维细胞生长因子 ( basic fibroblast growth factor,b FGF)等血管生成正调控因子的表达 ,使肿瘤具有了促血管生成表…     

反应停治疗多发性骨髓瘤的研究进展

近年来有关反应停抗血管增生作用的研究不断深入，在治疗难治性多发性骨髓瘤（MM）方面取得了令人瞩目的效果。本文简要综述其药理学、临床试验研究及其作用机制。     

反应停抗肿瘤作用研究进展

肿瘤的生长有赖于血管生成,血管生成是肿瘤侵袭、转移的基础。抑制血管生成可使肿瘤萎缩坏死或使微转移灶长期处于“休眠”状态。反应停于上世纪中叶作为非巴比妥类镇静剂用于早孕反应,后曾因严重的致畸作用而被禁用。近年研究发现,反应停能明显抑制兔角膜血管生成,具有血管生成抑制作用,因而被应用于肿瘤研究。然而,实验研究中反应停对实体瘤的抗肿瘤效应并不一致,作用机制也未完全明了。我们对反应停药理作用、抗肿瘤效用、作用机制及临床应用等方面的研究进展予以综述。     

沙利度胺治疗实体瘤的研究新进展

血管生成在实体瘤的生长、侵袭及转移方面发挥重要作用,以肿瘤血管生成的各个环节及其发生过程中的生化改变为靶点,研究血管生成抑制剂可以有效的抑制肿瘤生长、侵袭及复发。沙利度胺作为一种血管生成抑制剂,已经在治疗难治性多发性骨髓瘤方面取得良好的效果。本文简要综述其在实体瘤中应用的研究进展。     

Antiangiogenic agent, thalidomide increases the antitumor effect of single high dose irradiation (gamma knife radiosurgery) in the rat orthotopic glioma model

Gliomas are primary brain tumors associated with a poor prognosis partly due to resistance to conventional therapies. To overcome this problem, we investigated the combined effects of gamma knife radiosurgery (GKS) and an antiangiogenic agent, thalidomide (THD), or a chemotherapeutic agent, temozolomide (TMZ), on a rat glioma model. GKS (20 Gy single dose) alone and/or drugs (for 3 days) were delivered 14 or 18 days after stereotactic implantation of C6/LacZ glioma cells into the brains of Sprague-Dawley rats. A group of animals treated with or without drugs for 3 days was irradiated on day 18 and sacrificed at 24 h after GKS to evaluate cell proliferation, apoptosis and microvessel density. The other group of animals was irradiated on day 14 and sacrificed at day 5 after GKS for the measurement of tumor volume. Apoptosis of endothelial cells in the tumor beds was only observed in the early period after GKS. Decreased cell proliferation and increased tumor cell apoptosis were observed in rat gliomas treated with GKS and THD or TMZ. The combination treatments with GKS and THD or GKS and TMZ also decreased microvessel density, i.e. angiogenesis, more effectively compared with GKS treatment alone. The combination of GKS and THD was the most effective regimen, resulting in a significant decrease of tumor volume. We suggest that the antitumor effect of GKS on glioma is enhanced by the addition of THD. Therefore, combined therapy with GKS and THD might be a favorable treatment for gliomas.     

沙利度胺治疗实体瘤的研究新进展

血管生成在实体瘤的生长、侵袭及转移方面发挥重要作用,以肿瘤血管生成的各个环节及其发生过程中的生化改变为靶点,研究血管生成抑制剂可以有效的抑制肿瘤生长、侵袭及复发.沙利度胺作为一种血管生成抑制剂,已经在治疗难治性多发性骨髓瘤方面取得良好的效果.本文简要综述其在实体瘤中应用的研究进展.     

Treatment of Waldenstrom's macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin,thalidomide and dexamethasone

To evaluate the activity of thalidomide in Waldenstrom's macroglobulinemia (WM), 20 patients were treated on a dose schedule that escalated from 200 mg/d to 600 mg/d. On an intention-to-treat basis, five (25%) patients achieved a partial response, which was noted within 3 months of treatment. Adverse effects were common and prevented dose escalation of thalidomide in 75% of patients and led to premature discontinuation of treatment in 35%. We subsequently evaluated the oral combination of clarithromycin (500 mg twice per day), low-dose thalidomide (200 mg once daily), and dexamethasone (40 mg once per week). Our preliminary analysis on 12 previously treated patients indicate activity of this regimen in WM: three patients achieved a partial response and two patients demonstrated monoclonal protein reduction of greater than 25%. This combination was associated with a variety of side effects due not only to thalidomide, but also to corticosteroids and to clarithromycin. Our preliminary data indicate that this combination may be a useful salvage regimen for some patients with heavily pretreated macroglobulinemia.     

Leukocytoclastic vasculitis due to thalidomide in multiple myeloma

Thalidomide is successfully used in the treatment of multiple myeloma, leprosy and various autoimmune diseases due to its anti-angiogenic, immunomodulatory and anti-inflammatory effects. Thalidomide's most common side effects are constipation, neuropathy, fatigue, sedation, rash, tremor and peripheral edema. We achieved complete response with a 400 mg/day dose thalidomide therapy in a 58-year-old male patient diagnosed with relapsing refractory multiple myeloma. While continuing thalidomide for sustainable response, the therapy was terminated at the ninth month due to development of leukocytoclastic vasculitis. We describe the case and discuss the place of thalidomide in the treatment of multiple myeloma and the rare occurrence of leukocytoclastic vasculitis during thalidomide therapy in multiple myeloma, since only one such case has been reported in the literature thus far.     

Unusual responses to thalidomide in refractory solid tumors

Despite the positive impact of newer chemotherapeutic agents on responses and survival in patients with solid tumors, challenges in recurrent and metastatic solid tumors include acquired drug resistance, poor responses and poor tolerance by the patient. Use of antiangiogenic agents appears to be a logical, rational and effective approach. Of these agents, thalidomide has shown to specifically inhibit endothelial cell growth in various experimental animals. The advantages of thalidomide include the convenience of the oral route of administration and low toxicity profile. Furthermore, thalidomide has been found to be effective in cancer cachexia syndrome, chronic nausea, insomnia, profuse sweating and pain, which are often part of advanced malignancies. In this case report of six patients, we present encouraging responses to thalidomide used in a dose of 200 mg in patients with refractory solid tumors.