2012-2013 Pilot Projects

“Effects of positive energy balance and moderate weight gain on in vivo colonocyte proliferation rate”

Project Leader
Faidon Magkos, PhD, Primary Investigator, Singapore Institute for Clinical Sciences

Project Summary
Obesity is associated with an increase in the risk of colon cancer, but the mechanisms responsible for this association are not clear. We will evaluate the effects of moderate weight gain induced by overfeeding on intestinal cell growth rate, which is an important risk factor for tumor development. We hypothesize that positive energy balance and moderate weight gain induced by overfeeding will increase intestinal cell growth. We will conduct a randomized controlled trial in obese patients who will be randomized to treatment with either a hypercaloric diet with 5% weight gain (Weight Gain group) or a weight maintaining diet (Control group), to determine the effects of weight gain induced by overfeeding on in vivo colonocyte proliferation and the putative factors involved in the pathogenesis of obesity-related colon cancer.

Project Aims

  1. Determine the effect of moderate (5%) weight gain on in vivo colonocyte proliferation rate and apoptosis.
  2. Determine the effect of moderate (5%) weight gain on putative factors involved in the pathogenesis of obesity-related colon cancer.

“The effects of obesity on breast cancer development and NK cell-mediated antitumor immune responses” 

Project Co-Leaders

Joan Riley, PhD, assistant professor, Department of Obstetrics and Gynecology, Washington University School of Medicine  
Ruby Chan, PhD, senior scientist, Janssen Pharmaceutical Companies of Johnson & Johnson

Project Summary
Studies indicate that over-nutrition increases the risk of breast cancer in postmenopausal women and that obese women have a higher rate of recurrence and death from breast cancer than nonobese women. The immune system recognizes and eliminates developing tumor cells by a process termed cancer immunosurveillance. Developing tumors can escape immune control resulting in overt cancer. Natural killer (NK) cells are a key component of the immune system that play a critical role in regulating tumor progression and metastases in animal models. Impaired NK cell maturation and killing ability have been reported in metastatic breast cancer, and human breast tumor progression is associated with NK cell dysfunction. We predict that diet-induced obesity shortens tumor onset, increases the metabolism and proliferation of the tumor cells, and ultimately accelerates the aggressiveness of the mammary tumors. In addition, we expect that understanding the metabolic pathways used to mediate NK cell antitumor responses may facilitate the development of pharmacological approaches that aim to promote the ability of NK cells to kill breast cancer cells, particularly in the context of obesity. 

Project Aims

  1. Determine the effects of diet-induced obesity on the development and progression of mouse mammary tumors.
  2. Identify the metabolic pathways utilized by activated mouse NK cells and determine if obesity adversely impacts NK cell metabolism and their ability to eliminate breast cancer cells.