Karen Auborn, Ph.D., Head, Phytochemical Research, Associate Professor, Research Department, North Shore-Long Island Jewish Research Institute, "Indole-3-carbinol Is a Negative Regulator of Estrogen". From the abstract: "Studies increasingly indicate that dietary Indole-3-carbinol (I3C) prevents development of estrogen-enhanced cancers, including breast, endometrial, and cervical cancers. Epidemiology, laboratory, animal and translational studies support the efficacy of I3C. Whereas estrogen increases the risk for these cancers, I3C can abrogate or ameliorate effects of estrogen and thereby be more beneficial in exerting its anticancer activities. Our long-range goal is to best utilize I3C, together with other nutrients, to achieve maximum benefits for cancer prevention. This study examines opposing activities of I3C and estrogen, involvement of specific genes, and a synergistic effect of I3C and genistein. We used microarray profiling, real time RT-PCR, and Western analysis to evaluate expression of genes. Proliferation and apoptosis were evaluated by a mitochondrial function assay, FACS analysis, and DNA fragmentation. The luciferase reporter assay was used to specifically evaluate expression driven by ER-alpha. We show that I3C ameliorates effects of estrogen for 1) proliferation 2) prevention of apoptosis 3) ER-alpha driven gene expression We further show a synergistic effect of I3C and genistein in GADDs (growth arrest in response to DNA damage) genes and BRCA1, genes induced by I3C, as well as an array of estrogen-regulated genes whose induction is abrogated by I3C. Results support negative regulation of estrogen signaling and increased anticancer activities of I3C. Moreover, I3C and genistein have a synergistic effect such that reduced concentrations of these nutrients are beneficial. Dr. Auborn mentioned that DIM has only been available for study recently. It seems to be possible to use it both antagonist and agonistically. When I3C is given to mice with estradiol, cells become more normalized and apoptosis is induced as well. Emanuel F. Petricoin, Division of Therapeutic Products, Center for Biological Evaluation Research, Food and Drug Administration, gave a talk on "New Approaches to Protein Profiling of Cancer". This talk was all about the need for new technology to study each type of cell and aspect of a cell. He stated that his lab is looking at whether proteomics can have clinical value at this time. He believes that cancer is a proteomic disease at the functional level. The goal is to find proteomic patterns that correlate with the disease state toxicity or outcome. He said they are looking at ovarian cancer first as a test of their methods. His discussion of the 100% specificity and sensitivity of their work was somewhat scoffed at by others at the conference (spoken to me privately). He said they were also working with prostate too and hoped to take it to the clinic soon. He defined soon as 3-4 months. Dolph Hatfield, Ph.D., National Cancer Institute, NIH, "Role of Selenium-Containing Proteins in Health". From the abstract: The objectives for this project are to provide model systems for determining the role of selenium-containing proteins, designated selenoproteins, in health and, more specifically, their role as cancer chemopreventive agents". His discussion was all about the transgenic mice they are looking at. He mentioned the SELECT trial for prostate prevention which involves 32,000 men using either vitamin E and selenium, or vitamin E plus placebo or Selenium plus placebo or two placebos. He stated that selenium has been shown to have value in heart disease prevention (cardiovascular research) and is antiviral as well. It has been shown to delay the onset of AIDS in HIV positive patients. It has also been shown to delay aging and help with male reproduction. He suggested that two good sources of selenium in the diet were garlic and Brazil nuts. I asked him if he thought selenium and E would function better if given with vitamin C and he said it probably would. He told me to call him to discuss it. I will post the results of that talk on our website in the selenium section (see Relevant Studies-Vitamin section). Peter A. Jones, Ph.D, D.Sc, Director, Norris Comprehensive Cancer Center, University of Southern California, "Relationships Between Chromatin Organization and DNA Methylation". From the abstract (excerpts): "Epigenetic changes are acquired in a gradual process associated with cellular division, making them quite different from mutational changes that result in the rapid loss of gene function. The presence of these epigenetic changes in premalignant tissues makes them ideal targets for prevention strategies, because they can be potentially reversed". Conclusion: "Epigenetic changes that represent useful new markers and targets for therapeutic intervention in cancer prevention strategies." Jim Davie, Ph.D., Professor, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada, "Inhibition of Histone Deacetylase Activity by Butyrate". From the abstract: "Sodium butyrate in millimolar concentrations has a wide variety of effects on mammalian cells grown in tissue culture. Of the effects of butyrate on cultured cells, inhibition of DNA synthesis and hyperacetylation of the nucleosome core histones are generally observed. Histone acetylation is a dynamic process governed by histone acetyltransferases and histone deacetylases. In 1978, several groups reported that butyrate inhibits histone deacetylase (HDAC) activity, resulting in core histone hyperacetylation". Ann's NOTE: I am not at all sure what this means, but research started in 1978 which is a long time ago. Stephen Barnes, Ph.D., Professor, Department of Pharmacology and Toxicology, University of Alabama, Birmingham, "Genistein (GEN) Targeting: DINNG Proteins in Cancer and Osteoarthritis - Use of Intelligent Proteomics". From the abstract: "Because most noncancer cells are tolerant to high micromolar concentrations of GEN, inhibitory or stimulatory effects of GEN have been claimed for a wide variety of biochemical targets, leading to a plethora of potential mechanisms. However, because GEN is present in tissues in the nM range, most of these mechanisms are unlikely to be relevant in vivo (humans)". Dr. Barnes asked: "Are all estrogens the same?" Mammary tumors may develop in the presence of soy genistein but they grow much more slowly than with estrogen. He also suggested that DINGG may be composed of other polyphenols/phytochemicals than genistein. Dr. Barnes asked many questions of the other speakers throughout the meeting. The last feature of the conference was a panel discussion by other experts as to what we had heard. Jim Elliott, Ph.D., Research Leader, Human Nutrition Department, Roche Vitamins, Inc. suggested that cancer incidence was not a feasible endpoint for study so useful and accurate biomarkers were needed. He discussed some of the limitations if: steps are too far along the disease path, not in the pathway (i.e. PSA marker), have low predictive value with low specificity (PSA, polyps, CA 125), not sufficiently characterized or validated by routine use, few measure genotoxic. He mentioned a variety of nutrients that have all been shown to modify cancer risk: vitamins A, D, C, E, Folic Acid, Calcium, Selenium, Lycopene, Resveratrol, Tea Polyphenols, Curcumin, Genistein, Sulfurophane, etc. Genomic approaches will focus on disease state and identify the earliest genes, use them as targets to identify nutrients Databases are needed, archives of gene sequences expression. Mike Wargovich said we needed translation from population to individual level since individuals will always respond differently. We must fund research on interactions using both rodents and humans. A presymptomatic profile is needed too, perhaps then we can show dietary impact. Diet is a complex interaction. Vay Liang W. Go (Bill), M.D., Professor, Center for Human Nutrition, University of California, Los Angeles, suggested there is a long horizong for prevention and a short time for diagnostics before metastases. We are finding cancers earlier but still late in the actual process. And large numbers of cancers progress in people even now. We must use nutrients during years of slow progression. Healthy diet is useful for all, we are the totality of what we eat. Ann's NOTE: It is often pointed out that most people eat very few fruits and vegetable daily and very few varieties of them. This is shown again and again when I shop in healthfood stores. These stores carry many varieties of fruits and vegetables but the clerks often cannot identify them. Just today, (9/16) the woman asked me if my kiwi was an avocado? Since each type of fruit/vegetable contains many different phytochemicals, variety is good. Rabindra Roy, Ph.D., Research Scientist, Department of Carcinogenesis and Molecular Epidemiology, American Health Foundation, discussed the idea of good biomarkers to detect cancer initiation. We will need to understand pathways, not just biomarkers. Cancer susceptibility includes genome instability, inadequate monitoring and repair of mutagenic DNA damage, inadequate apoptosis, and mutation in DNA and cancer. When we seek to prevent cancer with nutrients, we will need to use a family of compounds to induce capacity to normal level. He mentioned tea, garlic, organo-selenium alpha, carotene and curcumin. Cheryl L. Rock, Ph.D., R.D., Professor, Department of Family and Preventive Medicine, University of California, San Diego, suggested we need dietary trials that make sure true changes occur in diet. Lab and cell cultures do not reflect the heterogeneity of human cancers. They do not mimic human beings, therefore we need to use all areas of research. Methodologies must be sufficiently robust to be usable even with stored samples. Tissue measurement must be feasible for inclusion, we need cells/animals for interpretation and translation. The timing may be very critical when using nutrition. Gary A. Miller, Ph.D., Vice President, Agriculture and Nutrition, Paradigm Genetics, Inc. said this was a strong opportunity for public health programs. We need to initiate studies in model systems but then go on to clinical trials, then the real world. He suggested, as many advocates have, that the clinical trial orientation is for pharmaceutical products looking for a big result in a short time. With mild acting compounds, there may be a long time line. Milieu matters also when looking at metabolism. Ann's NOTE: I went to this conference wanting the participants to understand the need for combining nutrients. This was mentioned by at least 4 speakers. During question periods, I suggested that researchers try to overcome the funding resistance to combination studies by including advocates on their panels. This conference was interesting and it is amazing that there are so many separate nutritional events that take place. In October the American Association for Cancer Research is holding a meeting 'Frontiers in Cancer Prevention Research'. Not many of these participants plan to attend. Ann Fonfa will be there, perhaps the only advocate. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. 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