Dolivet G, Ton Van J, Sarini J, Wattel E, Lagarde P, Chomy F, Lefebvre J L
Unité de Chirurgie Cervico-Faciale, Centre Alexis Vautrin, Vandoeuvre les Nancy, France.
Rev Laryngol Otol Rhinol (Bord). 1996;117(1):19-26.
The retinoids are a pharmacologic class based on the vitamin A or retinol. The most known related derivatives are the all-trans (ATRA), 13 and 9 Cis retinoic acids. The antitumor and differenciative activities have been demonstrated in: in vitro, in vivo and clinical studies. In head and neck cancers, the clinical phase III trials in chemoprevention of second primary tumors have shown discordant results related to the type of retinoic acid. Nuclear retinoic acid receptors are members of the steroid-thyroid and vitamin D3 superfamily of nuclear receptors which regulate differenciation proliferation and apoptosis in cooperation with mediated proteins of the apoptosis (especially p53 protein). A thorough knowledge on the earlier mechanisms involved in carcinogenesis of squamous cell carcinomas would lead to futur reversal therapy with the reversal of pathologic to normal tissues by the restauration of mechanisms of the physiologic control. This futur clinical trial research could provide cancer prevention and control by the induction of cellular differentiation rather than proliferation (retinoids) and/or the expression of tumor-suppressor genes (p53 protein transfection). Finally, the retinoids treatment should be performed in control studies because of the toxicity at high doses.
类视黄醇是一类基于维生素A或视黄醇的药物。最知名的相关衍生物是全反式(ATRA)、13-顺式和9-顺式视黄酸。其抗肿瘤和分化活性已在体外、体内及临床研究中得到证实。在头颈癌中,关于预防第二原发性肿瘤的化学预防的临床III期试验显示,与视黄酸类型相关的结果并不一致。核视黄酸受体是类固醇-甲状腺和维生素D3核受体超家族的成员,它们与凋亡介导蛋白(尤其是p53蛋白)协同调节分化、增殖和凋亡。深入了解鳞状细胞癌发生过程中早期涉及的机制,将有助于未来通过恢复生理控制机制,使病理组织逆转至正常组织的逆转治疗。这项未来的临床试验研究可以通过诱导细胞分化而非增殖(类视黄醇)和/或肿瘤抑制基因的表达(p53蛋白转染)来提供癌症预防和控制。最后,由于高剂量时的毒性,类视黄醇治疗应在对照研究中进行。