ROLE OF DIETARY RESTRICTION ON CELL TRANSFORMATION

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。

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.