Volume 8, Issue 1
The winter issue of Nutrition Frontiers showcases gut permeability and calcium supplementation, potential chemopreventive effects of dietary DHM for lung tumorigenesis, and the role of the MCP-1 chemokine on adiposity and inflammation. Learn about our spotlight investigator, Dr. Gregory Lesinski, and his research on dietary interventions to inhibit carcinogenesis, upcoming announcements and more.
RESEARCH UPDATE: ON THE CLINICAL FRONT
Circulating Biomarkers of Gut Barrier Function: Correlates and Non-response to Calcium Supplementation
Gut barrier dysfunction may contribute to colorectal cancer. Previous studies suggest calcium may play a role in modulating gut barrier function by preventing oxidative damage and inflammation in the colon.
In a randomized, double-blinded, placebo-controlled trial, Yang and colleagues tested the effects of two doses of calcium (1.0 or 2.0 g/d) on levels of circulating biomarkers of gut permeability (anti-flagellin and anti-lipopolysaccharide [LPS] immunoglobulins [Igs]) in 193 participants with a history of colorectal adenoma, a putative precursor of colorectal cancer, over a 4-month period. Supplemental calcium did not modify circulating levels of anti-flagellin and anti-LPS Igs. However, higher baseline levels of anti-flagellin and anti LPS Igs were found in men compared to women and in participants with higher overall or abdominal adiposity, suggesting that men and those with higher adiposity are exposed to a higher level of bacterial products (flagellin and LPS) likely due to impaired gut barrier function. Further studies are required to understand factors that influence gut permeability to inform development of treatable biomarkers of risk for colorectal cancer and other health outcomes.
The next Stars in Nutrition and Cancer lecture, Aflatoxin: An Old Carcinogen Teaches Us New Tricks, will take place on March 21st and will be given by John D. Groopman, PhD, Johns Hopkins University. The lecture will take place on the NIH Main Campus in Bethesda and will be available for viewing afterwards at https://prevention.cancer.gov/research-groups/nutritional-science/about-nutritional-science/stars-nutrition-cancer
The NCI Cancer Prevention Fellowship Program is accepting applications for the Summer Curriculum in Cancer Prevention Courses until February 15, 2017 for domestic and international applicants. To learn more about the courses, eligibility requirements and application details, please visit cpfp.cancer.gov, or contact NCISummerCurriculum@nih.gov.
In collaboration with Cancer Research UK, the NCI will host a "Sandpit" workshop on April 24-26, in Potomac, Maryland, which will focus on integrating knowledge across five key cancer-related health behaviors: tobacco use, alcohol consumption, dietary behavior, physical activity, and UV exposure. Applications are due by February 15.
Upcoming EventsFebruary 13-14, 2017
Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum: A National Cancer Policy Forum Workshop
National Academies of Science
Engineering and Medicine
February 17, 2017
The Potential Role of Sleep in Obesity Prevention and Management: A Virtual Workshop (Webinar)
Health and Medicine Division
National Academies of Sciences
Engineering and Medicine
February 18-21, 2017
Clinical Nutrition Week
February 22-24, 2017
Feeding Your Genome
Research Frontiers in Nutritional Sciences Conference 2017
The University of Arizona
March 20-24, 2017
John Milner Nutrition and Cancer Prevention Research Practicum
National Cancer Institute
National Institutes of Health
Rockville, MD (closed)
April 1-5, 2017
American Association for Cancer Research
April 22-26, 2017
American Society for Nutrition’s Scientific Sessions at Experimental Biology
Dietary Dihydromethysticin’s Chemopreventive Efficacy Against Lung Tumorigenesis
Dietary dihydromethysticin (DHM), found in the kava plant, has been found to block NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone], a tobacco-specific N-nitrosamine with potent pulmonary carcinogenicity. DHM blocks the initiation of lung tumorigenesis by NNK in mice, and it preferentially reduces NNAL (major metabolite of NNK)-derived DNA adducts in the lung. In a follow-up study, Narayanapillai and colleagues quantified NNK, NNAL, and glucuronidated NNAL in serum and urine from mice exposed to dietary DHM in comparison with control mice or dihydrokavain -treated mice (also serving as control), and evaluated the effect of DHM on lung and liver microsomes. They found that lung and liver microsomes from DHM-treated mice showed enhanced activities for NNAL O-glucuronidation, supporting that DHM increases NNAL detoxification, which may account for its chemopreventive efficacy against NNK-induced lung tumorigenesis in mice. However, dietary DHM had no effect on the abundance of NNK and NNAL in serum or urine, demonstrating that DHM does not inhibit the reductive formation of NNAL from NNK. DHM had a minimal effect on cytochrome P450, which catalyzes NNK and NNAL bioactivation, suggesting it is unlikely that dietary DHM inhibits the bioactivation of NNAL.
Chronic inflammation is an important mechanism linking obesity to disease risk. In mouse models of diet-induced obesity, chemokines increase macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine that is increased in white adipose tissue and is known for macrophage recruitment. Cranford and colleagues examined the role of MCP-1 in adiposity, cellular infiltration, inflammation and metabolic dysfunction in wild-type and MCP-1 deficient mice on a friend virus B NIH (FVB/N) background. Mice were fed either a low-fat diet or high-fat diet (HFD) for 16 weeks. The HFD increased fat mass, metabolic dysfunction, immune cell infiltration and inflammatory processes; however, MCP-1 deficiency led to an increase in many of these HFD-pathologies. This suggests that MCP-1 may be a necessary component of adipose tissue remodeling and healthy expansion in the FVB/N strain in response to HFD feedings. Further research utilizing multiple mouse strains and timing of obesity development are needed to understand the impact of HFDs and the role of this chemokine in obesity-related pathologies.
Gregory Lesinski, PhD, MPH has conducted translational research focused on the interactions between the immune system and cancer, knowledge being leveraged to develop novel preventative or therapeutic approaches for patients with cancer, and improve upon existing interventions. The Lesinski Laboratory also serves as the site for correlative studies associated with oncology clinical trials of prevention and therapy. His laboratory is addressing the overall hypothesis that particular dietary interventions inhibit carcinogenesis via downstream immunomodulatory effects that limit chronic inflammation. Dr. Lesinski worked as part of a group investigating how dietary intervention with whole foods or bioactive phytochemicals and metabolites can modulate immune function. Dr. Lesinski received his Ph.D. from the Medical College of Ohio, and completed an MPH from The Ohio State University. Following several years at Ohio State studying immunotherapy, melanoma and pancreatic disease, Dr. Lesinski was recruited to Emory University, where he is an Associate Professor and the Co-Director of the Translational GI Malignancy Program at The Winship Cancer Institute. Dr. Lesinski is a co-author on over 70 publications and three active NIH awards. He was awarded an R01 for his project, Modulation of Antitumor Immunity by Dietary Soy and Its Isoflavone Constituents.
Read more about Greg Lesinski
Pomegranate: The Seeded Apple
Pomegranates or Punica Granatum means “apple with many seeds” and reflects its red ruby, crunchy seeds in the center, known as “arils,” filled with a sweet-tart juice particularly high in tannins, anthocyanins, and ellagic acid, along with vitamin C and potassium! Pomegranates have long been revered by ancient cultures for the red dye from its blossom and peel. For Egyptians, pomegranates symbolize life after death. Scholars speculate that the irresistible fruit Eve indulged in the Garden of Eden was the famed pomegranate, and not an apple!
When choosing pomegranates, make sure the peel is firm and taut with a fresh “leather-like appearance.” Store them away from sunlight for several days or in plastic bags refrigerated for up to 3 months. Arils can be kept for up to 3 days refrigerated or 6 months frozen. The heavier the fruit, the more juice! A medium pomegranate yields ½ cup of delicious juice and about ¾ cup of refreshing arils to sprinkle in salads, fruit desserts, cakes, puddings or use as garnish.
Three-Steps to Open a Pomegranate:
- Cut off the crown;
- Lightly cut the skin in quarters from the stem to the crown end; and
- Firmly but gently break apart the sections and bend back the skin to scoop out the arils.