Smit Jürgen V, de Jong Elke M G J, van Hooijdonk Candida A E M, Otero Marisol E, Boezeman Jan B M, van de Kerkhof Peter C M
Department of Dermatology, University Medical Center, Nijmegen, The Netherlands.
J Am Acad Dermatol. 2004 Aug;51(2):257-64. doi: 10.1016/j.jaad.2004.03.002.
Bexarotene, a novel synthetic retinoid X receptor (RXR)-selective retinoid, has been reported to have antiproliferative and apoptotic stimulating effects in cutaneous T-cell lymphoma. In benign, hyperproliferative, and retinoid sensitive disorders, such as psoriasis, bexarotene has not been evaluated so far and no information on these parameters is available.
In the present study, immunohistochemical parameters for proliferation, differentiation, inflammation, and apoptosis were investigated in a group of bexarotene-treated psoriatic patients.
Twenty-nine patients with plaque-type psoriasis were treated for 12 weeks with oral bexarotene in four dose-defined treatment panels. Treatment was initiated in the following consecutive order: 1.0 mg/kg/day, 2.0 mg/kg/day, 0.5 mg/kg/day, and 3.0 mg/kg/day. Biopsies for immunohistochemical analysis were taken at the baseline and after 12 weeks of treatment.
Significant reductions in Ki-67, keratin 16, transglutaminase, dermal CD4, epidermal CD8, and inflammation scores were seen after bexarotene treatment in combination with a significant increase in keratin 10. No induction of keratin 13 and 19 and no alterations in apoptosis associated p53 expression were observed. Apart from a weak significant dose-response effect for Ki-67, no other significant dose-response effects were seen.
We have demonstrated efficacy of oral bexarotene in psoriasis in doses up to 3.0 mg/kg/day during 12 weeks of treatment for proliferation, differentiation, and inflammation parameters. Studies investigating higher doses of bexarotene in a larger number of patients are necessary to reveal potentially dose-related immunohistochemical effects of this new rexinoid and to elucidate the role of RXR-signaling in retinoid-associated keratin expression.
贝沙罗汀是一种新型合成视黄酸X受体（RXR）选择性类视黄醇，据报道在皮肤T细胞淋巴瘤中具有抗增殖和促凋亡作用。在良性、增殖性和对视黄醇敏感的疾病（如银屑病）中，贝沙罗汀迄今尚未得到评估，也没有关于这些参数的信息。
在本研究中，对一组接受贝沙罗汀治疗的银屑病患者的增殖、分化、炎症和凋亡的免疫组化参数进行了研究。
29例斑块型银屑病患者在四个剂量确定的治疗组中接受口服贝沙罗汀治疗12周。治疗按以下连续顺序开始：1.0mg/kg/天、2.0mg/kg/天、0.5mg/kg/天和3.0mg/kg/天。在基线和治疗12周后进行免疫组化分析活检。
贝沙罗汀治疗后，Ki-67、角蛋白16、转谷氨酰胺酶、真皮CD4、表皮CD8和炎症评分显著降低，同时角蛋白10显著增加。未观察到角蛋白13和19的诱导，凋亡相关p53表达也无改变。除了Ki-67有微弱的显著剂量反应效应外，未观察到其他显著的剂量反应效应。
我们已经证明，在12周的治疗期间，口服贝沙罗汀剂量高达3.0mg/kg/天对银屑病的增殖、分化和炎症参数有效。有必要开展更多患者、更高剂量贝沙罗汀的研究，以揭示这种新型视黄酸类药物潜在的剂量相关免疫组化效应，并阐明RXR信号在类视黄醇相关角蛋白表达中的作用。
