ROLE OF DIETARY RESTRICTION ON CELL TRANSFORMATION
ROLE OF DIETARY RESTRICTION ON CELL TRANSFORMATION
批准号:
6106626
负责人:
JAMES C. BARRETT
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
超过三分之一的癌症死亡是由饮食造成的
在西方世界,饮食中影响癌症的因素
都没有得到澄清。卡路里摄入量的减少会显著减缓
啮齿类动物的癌症进展,这可能是一个主要因素
饮食对癌症的影响。在人类和大鼠身上,胰岛素样物质
生长因子-1(IGF-1)在饮食限制(DR)期间降低。
因为IGF-1调节细胞的增殖、凋亡和
肿瘤发生--DR保护作用背后的机制
可能取决于这种多方面的增长因素的减少。在……里面
我们的研究在DR期间恢复了IGF-1,以确定是否降低
IGF-1在延缓膀胱癌进展中的作用
在杂合子P53基因缺失的小鼠接受尿液
膀胱癌的致癌物,p-氯沙林,以诱导创业。之后
小鼠膀胱尿路上皮癌的确认
随机分为3组:1)随意组(AL),2)20%DR或
3)20%DR+IGF-1(IGF-1/DR)。血清IGF-1水平降低
24%由DR治疗,但在接受IGF-1/DR治疗的患者中完全恢复
应用重组IGF-1的小鼠渗透压给药
迷你泵。虽然DR减缓了肿瘤的进展,
恢复糖尿病视网膜病变小鼠血清IGF-1水平可增加糖尿病小鼠的病程
癌症。此外,IGF-1调控肿瘤进展
不受体重变化的影响。血管内皮细胞凋亡率
DR小鼠癌前病变的发生率是
IGF/DR和AL处理的小鼠。胰岛素样生长因子-1对糖尿病视网膜病变小鼠的作用
在增生灶中也能刺激细胞增殖5倍。在……里面
结论:DR降低了IGF-1,从而有利于细胞凋亡。
细胞增殖,最终减缓肿瘤进展。这是
第一个证明饮食变化的机械论研究
通过调节IGF-1水平影响癌症进展。
这将是这个项目的最后一年。
英文摘要
Diet contributes to over one third of cancer deaths
in the western world, yet the factors in the diet that influence cancer
are not elucidated. A reduction in caloric intake dramatically slows
cancer progression in rodents and this may be a major contributor
to dietary effects on cancer. In humans as well as in rats, insulin-like
growth factor-1 (IGF-1) is lowered during dietary restriction (DR).
Because IGF-1 modulates cell proliferation, apoptosis, and
tumorigenesis the mechanisms behind the protective effects of DR
may depend upon reduction of this multifaceted growth factor. In
our study, IGF-1 was restored during DR to ascertain if lowering of
IGF-1 was central to slowing urinary bladder cancer progression
during DR. Heterozygous p53 deficient mice received a urinary
bladder carcinogen, p-cresidine, to induce preneoplasia. After
confirmation of urinary bladder urothelial preneoplasia, the mice
were divided into three groups: 1) ad libitum (AL), 2) 20% DR or
3) 20% DR plus IGF-1 (IGF-1/DR). Serum IGF-1 was lowered
24% by DR but was completely restored in the IGF-1/DR treated
mice using recombinant IGF-1 administered via osmotic
minipumps. While tumor progression was decreased by DR,
restoration of IGF-1 serum levels in DR mice increased the stage of
the cancers. Furthermore IGF-1 modulated tumor progression
independent of changes in body weight. Rates of apoptosis in the
preneoplastic lesions were ten times higher in DR mice compared to
IGF/DR and AL treated mice. Administration of IGF-1 to DR mice
also stimulated cell proliferation five fold in hyperplastic foci. In
conclusion, DR lowered IGF-1, thereby favoring apoptosis over
cell proliferation and ultimately slowing tumor progression. This is
the first mechanistic study demonstrating that changes in diet
influence cancer progression due to the modulation of IGF-1 levels.
This will be the final year for this project.
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会议论文
A METASTASIS SUPPRESSOR GENE FOR PROSTATIC CANCER
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批准号:6106620
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
APOPTOSIS AND AIDS--ROLE OF TAT GENE
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批准号:6289925
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
SIGNALING OF APOPTOSIS DURING CELL TRANSFORMATION
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批准号:6162163
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Cell Senescence, Carcinogenesis, and Aging
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批准号:6559271
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY
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批准号:6162149
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:6162167
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
ETIOLOGY AND PROGRESSION OF BREAST CANCER
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批准号:6106625
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
ROLE OF MUTAGENESIS IN CARCINOGENESIS
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批准号:6289933
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
CELL SENESCENCE, CARCINOGENESIS, AND AGING
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批准号:6423757
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Metastasis Suppressor Genes For Prostate Cancer
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批准号:6763852
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Risk Factors for Cell Transformation and the Role of Apoptosis
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批准号:6106624
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
ETIOLOGY AND PROGRESSION OF BREAST CANCER
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批准号:6289931
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY
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批准号:6289922
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
RECEPTOR INTERACTION FOR TCDD & ITS STRUCTURAL ANALOGS-S
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批准号:6434999
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Risk Factors for Cell Transformation and the Role of Apoptosis
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批准号:6432272
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
ROLE OF DIETARY RESTRICTION ON CELL TRANSFORMATION
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批准号:6162165
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
APOPTOSIS AND AIDS--ROLE OF TAT GENE
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批准号:6162152
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Molecular Structure of Animal Viruses and Cells by Compu
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批准号:6762007
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
Molecular Genetic Basis for Gynecologic Neoplasias
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批准号:7055463
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY
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批准号:2574317
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JAMES C. BARRETT
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依托单位:
海外基金