BIOLOGY OF THE MOUSE HEPATOCARCINOGENESIS

这项研究的目的是检验这样一种假设，即 肥胖阶段，无论其原因如何，都会刺激 提高显微镜下肝细胞肿瘤的生长速度 老鼠。其临床含义是，肥胖的患者在 肿瘤启动对肿瘤生长刺激的风险要大得多。 那些在肿瘤开始之前变得肥胖的人。体视学- 本实验室开发的基于计算机的方法将用于 准确测定大量微观生物的生长速度 单次注射二乙基亚硝胺诱发的小鼠肿瘤 15日龄小鼠。这项研究将采用3种不同的肥胖模型 诱导(卵巢切除、下丘脑腹内侧立体定向损伤、 以及摄食非常可口的食物)，这在宿主的效率上有所不同 能源使用的重要性。肿瘤生长的动力学将与 体重增加的速度和身体成分(脂肪和蛋白质)的变化 在肥胖发展的动态期和稳定期期间， 模特们。因为真正的生长并不发生在下丘脑损伤中 模型中，它的研究可以帮助区分屠体脂肪和 蛋白质沉积。卵巢激素下降的直接作用 刺激肿瘤生长的研究将通过将卵巢移植到 致癌物处理的卵巢小鼠的脾-这一过程保持了 门脉血激素水平升高，而全身水平降低。 Ovex更有可能的间接影响也将通过 限制排卵小鼠的摄食量和体重增加。 脂肪细胞数量、大小和脂蛋白脂酶变化的作用 含量、血清胰岛素和血糖以及胰岛素和表皮生长因子受体 也将被研究为刺激肥胖的可能效果 卵巢切除与下丘脑损伤的关系。

The objective of this study is to test the hypothesis that the dynamic phase of obesity, regardless of its cause, provides a stimulus to increase the growth rate of microscopic hepatocellular neoplasms in the mouse. The clinical implication is that patients who becomes obese after tumor initiation are at much greater risk for tumor growth stimulation that those who becomes obese prior to tumor initiation. Stereologic- computer based methods developed in this laboratory will be used to accurately determine the growth rates of large numbers of microscopic tumors that were initiated by single injections of diethylnitrosamine in 15 day old mice. The study will employ 3 different models of obesity induction (ovariectomy, ventromedial hypothalamic stereotactic injury, and feeding of highly palatable diet) which vary in the host's efficiency of energy use. The kinetics of tumor growth will be correlated with the rate of weight gain, and change in body composition (fat and protein) during the dynamic and stable phases of obesity development in the 3 models. Since true growth does not occur in the hypothalamic injury model, its study can help to distinguish the effects of carcass fat from protein deposition. A direct role of a decline in ovarian hormones in stimulating tumor growth will be studied by implanting ovaries into the spleens of carcinogen treated ovexed mice- a procedure which maintains a high level of portal blood hormones while reducing the systemic level. The more likely indirect effect of ovex will also be tested by constraining the food intake and weight gain of mice that are ovexed. The roles of changes in adipocyte number, size and lipoprotein lipase content, serum insulin and glucose, and receptors for insulin and EGF will also be studied as possible effects of the obesity stimulating effect of ovariectomy and hypothalamic injury.