Lippman S M, Meyskens F L
Department of Medicine, University of Arizona Medical Center, Tucson.
J Am Coll Nutr. 1988 Aug;7(4):269-84. doi: 10.1080/07315724.1988.10720244.
Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy.
维生素A对正常细胞的生长和分化至关重要。大量实验室数据已清楚证明维生素A及其合成类似物（类视黄醇）具有强大的抗增殖和诱导分化作用。最近的体外研究提出了一个令人兴奋的观点，即蛋白激酶-C可能在许多类视黄醇的抗癌作用中起核心作用，包括对鸟氨酸脱羧酶诱导、细胞内多胺水平和表皮生长因子受体数量的影响。几项干预试验清楚地表明，临床可耐受剂量的天然维生素A对人类肿瘤进程的活性有限。因此，临床工作集中在具有更高治疗指数的合成衍生物上。在人类癌症预防中，类视黄醇对皮肤病最为有效，包括光化性角化病、角化棘皮瘤、疣状表皮发育不良、发育异常痣综合征和基底细胞癌。然而，目前在类视黄醇试验中，几种非皮肤癌前病变受到了更多关注。在口腔白斑、喉乳头状瘤、浅表膀胱癌、宫颈发育异常、支气管化生和白血病前期已记录到明确的类视黄醇活性。在一些耐药性恶性肿瘤和其他几种难治性肿瘤中，这类药物也取得了重大治疗进展，包括晚期基底细胞癌、蕈样肉芽肿、黑色素瘤、急性早幼粒细胞白血病以及皮肤和头颈部的鳞状细胞癌。本报告全面介绍了将类视黄醇用作人类癌前疾病抗癌药物的临床数据，并概述了正在进行和计划进行的类视黄醇联合及辅助治疗研究。
