Slide 1: Gastroenterologist
Research lab at Johns Hopkins
Study cancers of the GI tract
Early diagnosis in conditions that predispose to cancer formation
Primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD)
email@example.com Diet, Obesity ? Cancer : Diet, Obesity ? Cancer Florin M. Selaru, M.D.
Assistant Professor of Medicine, Gastroenterology and Hepatology
Johns Hopkins University
firstname.lastname@example.org What is cancer? : What is cancer? Inappropriate growth of cells
When is cell growth needed?
In adult, there is need to replace cells lost to normal/abnormal processes
Inside of GI tract is renewed every few weeks
The circulating cells in blood are renewed every few weeks
The growth of cells is tightly regulated
When control mechanisms become abnormal, cancer may arise Cancer causes : Cancer causes Historically, researchers concentrated on genetics and gene mutations
Genes = sentences
Gene mutation – the letters in the words that form the sentence are altered
Either the sentence is unintelligible or it means something else
Recently, diet and obesity came into focus Topics : Topics Caloric restriction
Does it prolong life?
Does it have anything to do with cancer?
Is there need (or room) for caloric restriction in the general population?
Can we modify cancer risk through diet? How do we study cancer? : How do we study cancer? Experimental models
Many conclusions drawn in these models hold true for humans Topics : Topics Does caloric restriction prolong life? Yeast : Yeast Species of fungus
Widely used for baking and for beer production
Caloric restriction in yeasts
Life span increased by up to 50% when yeasts were fed 60-80% of usual amount
In people, this is the equivalent
to approximately 40
additional years of life Mice : Mice Same moderate reduction in amount of food (20-40%)
Longevity increased by 50%
Same results in other experimental models, including monkeys McCay, C. M., Crowell, M. F. & Maynard, L. A. The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10, 63–79 (1935). Topics : Topics Does caloric restriction decrease the occurrence of cancer? Animal models : Animal models Mice on low fat diet (LFD), or on high-fat diet (HFD)
Looked at liver cells (hepatocytes)
Proliferation (growth of cells) is much increased in cells from HFD-fed animals
Apoptosis (cell suicide) – decreased in HFD End result : End result High fat diet
Yes, this means cancer is
more likely. EJ Park et al.
Cell, 2010 Topics : Topics Is there need (or room) for caloric restriction in the general population? Just adults? : Just adults? Prevalence of Overweight* Among U.S. Children and Adolescents (Aged 2 –19 Years)National Health and Nutrition Examination Surveys Forget mice. : Forget mice. Is there a real connection between overweight-obesity and cancer in HUMANS?
Cancer related mortality increases by 50% when BMI is more than 25 (overweight to obese area)
Liver cancer appears to be highly increased
Men with BMI 35-40 have a 4.5 FOLD increase in risk of liver cancer
In part related to the fact that obesity is associated with fat in the liver Bianchini et al., 2002; Calle and Kaaks, 2004; Calle et al., 2003. Why is obesity on the rise? : Why is obesity on the rise? Simple experimental design:
Mice followed for several generations
The obesity became worse from generation to generation
Maternal obesity before and during pregnancy
Affects the establishment of body weight regulatory mechanisms in her baby
Maternal obesity could promote obesity in the next generation Topics : Topics Can we modify cancer risk through diet? What gene is changed by caloric restriction? : What gene is changed by caloric restriction? Cohen HY, et al. Science 305:390-392, 2004. Can we increase SIRT1 without eating less? : Can we increase SIRT1 without eating less? Yes.
In yeast, reseveratrol increases life span
Later, the findings reproduced in other organisms
In mice the results are not very consistent Howitz KT, Bitterman KJ, Cohen HY, et al. (September 2003). "Small molecule activators of
sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6. Resveratrol : Resveratrol Skin of red grapes
The amount of resveratrol in red wine
does not appear to be enough to
actually prolong our lives… Mice getting more overweight from one generation to the next : Mice getting more overweight from one generation to the next Previous research
the addition of a methyl group to certain genes could prevent this phenomenon
These methyl groups are found in diet
folic acid, vitamin B12, betaine and choline
regular diet or
diet supplemented with these components Waterland RA et al. 2008 Obese mice : Obese mice Watch the diet! : Watch the diet! Exercise : Exercise What is on the horizon? : What is on the horizon? What is on the horizon? : What is on the horizon? More basic science studies to clearly identify the cause to effect relationship between various dietary components and cancer reduction
Rigorous clinical studies to assess the effects of various dietary components and cancer reduction Thank you! : Thank you! email@example.com