权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

STUDY NARCISSUS ALKALOID WITH ANTI-LEUKEMIC ACTIVITY

研究水仙生物碱的抗白血病活性

基本信息

批准号：
3163676
负责人：
EIICHI FURUSAWA
金额：
$ 5.25万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-12-01 至 1987-07-31
项目状态：
已结题

项目摘要

Narcissus alkaloids (pretazettine & pseudolycorine) possess superior therapeutic effect on advanced Rauscher leukemia (as a model of human myelogenous leukemia) in comparison with most of the standard anticancer drugs, interferon inducers (Poly I:C and tilorone), immunostimulator (levamisole) or reverse transcriptase inhibitors (rifamycin SV and ethidium Br.). Especially, pretazettine (PTZ) is also active against spontaneous AKR leukemia (as a model of human T-lymphocytic leukemia) and has definite or marginal anticancer activity against non-viral transplantable tumors B16 melanoma and P388 leukemia). PTZ has no adverse effects on natural defense mechanisms by the long-term administration of the antiviral dose which decreases the viremia in leukemia mice. PTZ is an inhibitor of protein synthesis and reverse transcriptase. The toxicity in cats is reversible and not cumulative. Recently, in the ip-implanted Lewis lung tumor system, PTZ demonstrated therapeutically synergistic or additive effects in combination with standard drugs such as adriamycin, BCNU, cyclophosphamide, actinomycin-D, 5-FU, 6-thioguanine, methotrexate, and cis-platinum. The proposed project is the further basic studies of the alkaloid necessary before the possible clinical application, and include: 1) Studies of therapeutic effect of PTZ on spontaneous leukemia in AKR mice as a model of human T-lymphocytic leukemia, especially focused on the remission-maintenance therapy with PTZ after the remission-induction by standard drugs. 2) Studies of therapeutic effect of PTZ on Lewis lung carcinoma in mice as a model of human metastatic solid tumor after removing the primary Lewis tumor by surgery or making the lung-metastasis by iv injection of tumor cells. The potential of PTZ as an adjuvant agent in combination chemotherapy with standard drugs will also be evaluated in the Lewis sc- or ip-lung tumor system.

水仙生物碱(雷公藤碱和假牡丹碱)具有较好的药用价值晚期Rauscher白血病(作为人白血病模型)的治疗效果髓系白血病)与大多数标准抗癌药物的比较药物、干扰素诱导剂(Poly I：C和替罗隆)、免疫刺激剂 (左旋咪唑)或逆转录酶抑制剂(利福霉素、SV和乙锭) Br.)。特别是，倍他西汀(PTZ)对自发性也有积极的作用 AKR白血病(作为人T淋巴细胞白血病的模型)，具有明确的或边缘抗癌活性对非病毒可移植肿瘤B16 黑色素瘤和P388白血病)。PTZ对自然防御无不良影响抗病毒药物长期给药的作用机制降低白血病小鼠的病毒血症。PTZ是一种蛋白质抑制剂合成和逆转录酶。猫的毒性是可逆的而不是累积的。最近，在植入IP的Lewis肺癌系统中， PTZ在治疗中显示出协同或相加作用与阿霉素、BCNU、环磷酰胺等标准药物联合使用，放线菌素-D、5-氟尿嘧啶、6-硫代鸟嘌呤、甲氨蝶呤和顺铂。建议的项目是对该生物碱的进一步基础研究所必需的。在可能的临床应用之前，包括：1)研究 PTZ对AKR小鼠自发性白血病的治疗作用人类T淋巴细胞白血病，尤其集中在 PTZ诱导缓解后的缓解维持治疗标准药物。2)甲氨蝶呤对Lewis肺的治疗作用小鼠肿瘤切除后作为人转移实体瘤模型的研究手术或静脉注射造成肺转移的原发Lewis瘤注射肿瘤细胞。四甲基偶氮唑盐作为佐剂的潜力与标准药物的联合化疗也将在 Lewis sc或ip-肺肿瘤系统。