ANTITUMOR AGENTS FROM BLUE-GREEN ALGAE
蓝绿藻的抗肿瘤剂
基本信息
- 批准号:2086076
- 负责人:
- 金额:$ 25.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1977
- 资助国家:美国
- 起止时间:1977-08-01 至 1998-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The longterm goal of this project is to discover new antitumor drugs from
blue-green algae (cyanobacteria). The research will be concerned primarily
with searching for and finding cytotoxins that are significantly active
against slow-growing solid tumors which account for approximately 85% of
all cancer deaths in the United States. Not only will it be important to
discover new agents that are effective against solid tumors, but ones
which are capable of overcoming two major problems that develop in cancer
patients undergoing chemotherapy, viz. multiple drug resistance (MDR) and
immunosuppression. Two types of anti-MDR drugs are needed: (1) ones that
are equally efficacious toward drug-sensitive and drug-resistant tumors
and (2) ones that are able to potentiate the cytotoxicity of standard
antitumor drugs like vinblastine and adriamycin toward drug-resistant
cells, i.e. reverse multiple drug resistance. Using disk diffusion assays
to screen a large number of extracts of cultured blue-green algae for
selective cytotoxicity, it has been found that 0.8% of the extracts are
more cytotoxic toward murine and/or human solid tumor cells than leukemia
cells, i.e. solid tumor selective, and an additional 0.8% of the extracts
are more cytotoxic toward tumor (leukemia) cells than normal cells such as
CFU-GM, the stem cell of murine hematopoietic tissue. The first task of
this project is to isolate, identify, and evaluate in vivo the solid tumor
selective cytotoxins in the following 11 blue-green algae: Aulosira
fertillisima DO-8-1, Calothrix gloeocola DT-21 -1, Hapalosiphon hibernicus
DU-56-1, Tolypothrix scytonematoides HZ-48-1, Scytonema hofmanni HZ-50-1,
T. byssoidea IA-5-1, Plectonema radiosum IA-82-2 and IC-70-1, P.
phormidioides ID-66-1, Scytonema fremyii IA-90-1 and Stigonema sp. II-1.
P. radiosum IC-70-1 has the highest priority since the hydrophilic, solid
tumor selective extract of this cyanophyte shows a taxol-like mode of
action (i.e. inhibition of microtubule depolymerization) equal
cytotoxicity towards drug-sensitive and drug-resistant tumors, and greater
cytotoxicity towards leukemia cells than normal cells, i.e. tumor
selectivity. The next tasks are to isolate, identify, and evaluate tumor
selective cytotoxins in 12 additional cyanophytes, non-selective taxol-
like cytotoxins in five other blue-green algae, and multiple-drug-
resistance-reversing agents in still another 18 cyanophytes. The last
task is to isolate, identify, and evaluate the potent cytotoxins in eight
more cyanophytes, four of which show vinblastine-like activity (inhibition
of tubulin polymerization into microtubules). Concurrently with the tasks
described above, new isolates of blue-green algae (about 125/yr) will be
obtained from freshwater, terrestrial, and marine environments and grown
in culture for antitumor evaluation and isolation and identification of
drugs from positive leads.
该项目的长期目标是发现新的抗肿瘤药物
蓝绿藻(蓝藻)。研究将主要关注
寻找并发现具有显着活性的细胞毒素
对抗生长缓慢的实体瘤,约占实体瘤的 85%
美国所有癌症死亡。这不仅很重要
发现有效对抗实体瘤的新药物,但
能够克服癌症中出现的两个主要问题
接受化疗的患者,即。多重耐药性(MDR)和
免疫抑制。需要两种类型的抗 MDR 药物:(1)
对药物敏感和耐药肿瘤同样有效
(2) 能够增强标准品的细胞毒性的
长春花碱和阿霉素等抗肿瘤药物导致耐药性
细胞,即逆转多重耐药性。 使用纸片扩散测定
筛选大量培养的蓝绿藻提取物
选择性细胞毒性,已发现0.8%的提取物具有选择性细胞毒性
对鼠和/或人实体瘤细胞的细胞毒性比白血病更强
细胞,即实体瘤选择性,以及额外的 0.8% 提取物
对肿瘤(白血病)细胞比正常细胞(如
CFU-GM,小鼠造血组织干细胞。第一个任务是
该项目旨在分离、鉴定和评估体内实体瘤
以下 11 种蓝绿藻中的选择性细胞毒素:Aulosira
fertillisima DO-8-1、Caothrix gloeocola DT-21 -1、Hapalosiphon hibernicus
DU-56-1、Tolypothrix scytonematoides HZ-48-1、Scytonema hofmanni HZ-50-1、
T. byssoidea IA-5-1,Plectonema radiosum IA-82-2 和 IC-70-1,P.
phormidioides ID-66-1、Scytonema fremyii IA-90-1 和 Stigonema sp。 II-1.
P. radiosum IC-70-1 具有最高优先级,因为亲水性、固体
这种蓝藻的肿瘤选择性提取物显示出紫杉醇样模式
作用(即抑制微管解聚)等于
对药物敏感和耐药肿瘤的细胞毒性,以及更大的
对白血病细胞的细胞毒性高于正常细胞,即肿瘤
选择性。 接下来的任务是分离、识别和评估肿瘤
12 种其他蓝藻中的选择性细胞毒素,非选择性紫杉醇-
像其他五种蓝绿藻中的细胞毒素,以及多种药物
另外 18 种蓝藻中存在抗性逆转剂。 最后一个
任务是分离、鉴定和评估八种中的强效细胞毒素
更多的蓝藻,其中四种表现出长春花碱样活性(抑制
微管蛋白聚合成微管)。 与任务同时进行
如上所述,新的蓝绿藻分离株(约 125 个/年)将被
从淡水、陆地和海洋环境中获得并生长
培养物中用于抗肿瘤评价以及分离和鉴定
来自阳性线索的药物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RICHARD E MOORE其他文献
RICHARD E MOORE的其他文献
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{{ truncateString('RICHARD E MOORE', 18)}}的其他基金
ANTICANCER AGENTS FROM CYANOPHYTES AND MARINE ORGANISMS
来自蓝藻和海洋生物的抗癌剂
- 批准号:
3163672 - 财政年份:1977
- 资助金额:
$ 25.46万 - 项目类别:
ANTICANCER AGENTS FROM CYANOPHYTES AND MARINE ORGANISMS
来自蓝藻和海洋生物的抗癌剂
- 批准号:
3163670 - 财政年份:1977
- 资助金额:
$ 25.46万 - 项目类别:
ANTICANCER AGENTS FROM CYANOPHYTES AND MARINE ORGANISMS
来自蓝藻和海洋生物的抗癌剂
- 批准号:
3163671 - 财政年份:1977
- 资助金额:
$ 25.46万 - 项目类别:
ANTICANCER AGENTS FROM CYANOPHYTES AND MARINE ORGANISMS
来自蓝藻和海洋生物的抗癌剂
- 批准号:
3163669 - 财政年份:1977
- 资助金额:
$ 25.46万 - 项目类别:
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