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John A Milner

Publications and source records attributed to John A Milner.

16 recordsLinked to original sources
PubMed2006

Preclinical perspectives on garlic and cancer.

Evidence continues to point to the anticancer properties of fresh garlic extracts, aged garlic, garlic oil, and a number of specific organosulfur compounds generated by processing garlic. These anticarcinogenic and antitumorigenic characteristics appear to arise through both dose- and temporal-related changes in a number of cellular events involved with the cancer process, including those involving drug metabolism, immunocompetence, cell cycle regulation, apoptosis, and angiogenesis. The ability of garlic and related allyl sulfur compounds to block tumors in the colon, lung, breast, and liver suggests general mechanisms that are not tissue specific. Whereas relatively few studies have compared the relative efficacy of water- and lipid-soluble allyl sulfur compounds, those that have when using chemically induced carcinogen models suggest little difference in response, whereas tumor proliferation/apoptosis is highly dependent on the species provided. A shift in sulfhydryl groups, alterations in glutathione:oxidized glutathione ratios, and resultant changes in cellular redox status may be involved in some of the phenotypic changes caused by allyl sulfur compounds. Such changes in thiols by allyl sulfurs may also account for the observed hyperphosphorylation of specific cell cycle proteins and the histone hyperacetylation that has been correlated with suppressed tumor cell proliferation. Whereas the anticarcinogenic and antitumorigenic data to date are impressive, additional studies are needed with more modest exposure to allyl sulfur compounds over prolonged periods. Likewise, additional studies are needed that incorporate transgenic and knockout models to assist in the identification of molecular targets for garlic and its associated allyl sulfur components.

Allyl Compounds↗
PubMed2006

Allyl sulfur compounds from garlic modulate aberrant crypt formation.

The health benefits of garlic, including inhibition of carcinogenesis, are supported by several epidemiologic and laboratory findings. Garlic's sulfur components have been reported to suppress experimentally induced tumor incidence in several organs, including the colon. Studies in humans also suggest that dietary garlic constituents reduce the risk of colorectal adenomatous polyps, which are considered precursors to colon cancer. Aberrant crypt foci (ACF) are proposed to be early preneoplastic lesions of adenoma-carcinoma in humans and chemically induced colon cancer in rodents. In preclinical studies, both water- and lipid-soluble allyl sulfur compounds arising from processed garlic inhibited ACF. The response to these allyl sulfur compounds appears to depend on several factors, including the speciation, quantity, and duration provided.

Adenoma↗
PubMed2005

Estrogen receptor alpha as a target for indole-3-carbinol.

A wealth of preclinical evidence supports the antitumorigenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables. However, the underlying molecular mechanism(s) accounting for these effects remain unresolved. In the present study, estrogen receptor alpha (ER-alpha) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 microM I3C reduced ER-alpha mRNA expression by approximately 60% compared to controls. This reduction in ER-alpha transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3'-diindolylmethane (DIM), was considerably more effective in depressing ER-alpha mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 microM DIM on ER-alpha mRNA was comparable to that caused by 100 microM I3C. DIM is known to accumulate in the nucleus and is a preferred ligand for aryl hydrocarbon receptor (AhR) to I3C. The addition of other AhR ligands, alpha-naphthoflavone (alpha-NF, 10 microM) and luteolin (10 microM), to the culture media resulted in a similar suppression in ER-alpha mRNA levels to that caused by 5 microM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-alpha transcript. The results from these experiments suggest that the antitumorigenic effects of I3C in MCF-7 human breast cancer cells may arise from its ability to reduce ER-alpha expression through the binding of its metabolite, DIM, to the nuclear AhR.

Anticarcinogenic Agents↗
PubMed2005

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗
PubMed2005

Challenges and opportunities for support of nutritional science conferences and scientific meetings at National Institutes of Health.

Opportunities exist throughout the institutes, centers, and offices of the NIH for obtaining support for conferences and scientific meetings. The number of conferences funded by NIH that thematically involve nutrition, health, and biomedical research is very small relative to the total number of conference grants awarded by NIH. Only 4% of conference grant (R13 and U13) applications awarded by all institutes and centers of the NIH over the last 5 y were determined to be focused on nutrition in some way. The National Cancer Institute has the largest proportion of these awards, and the numbers of such applications submitted each year appear to be increasing. Only approximately 18 nutrition research-related conference grant applications appear to have been funded, on average, per year over the last 5 y. Success rates are high; an average of 85% of nutrition-related applications submitted over the last 5 y were funded. The purpose of this article is to encourage applications from the nutrition community and to provide information for consideration when developing an application for a conference or workshop.

Congresses as Topic↗
PubMed2004

Dietary selenium supplementation prolongs pentobarbital induced hypnosis.

The present studies characterized the influence of dietary selenium (Na2SeO3) on the duration of pentobarbital (PB) induced hypnosis (sleep) in the rat. Rats were fed semipurified diets varying from 0.01 to 2.0 mg Se/kg for up to 4 weeks. Consumption of diets containing 1.0 and 2.0 mg Se/kg significantly prolonged PB induced hypnosis. Hepatic selenium, but not hepatic glutathione peroxidase activity, correlated with the length of PB induced hypnosis. The prolongation of hypnosis caused by diets containing 1.0 mg Se/kg was substantially reduced or eliminated by repeated exposure to PB. Although single exposure to increasing quantities of PB (60-100 mg/kg body weight) led to a progressive increase in sleep duration, the proportional increase caused by supplemental selenium (2.0 vs 0.1 microg Se/g) remained relatively constant (approximately 25%). Increasing maturity was inversely related to the duration of PB induced hypnosis, regardless of dietary selenium provided. Consumption of the 2.0 mg Se/kg diet prolonged PB induced hypnosis to a greater degree in immature than in mature rats (P < 0.05). Consumption of the selenium enriched diet (2 microg Se/g) resulted in an increase in cytochrome 2B, but had no effect on cytochrome 1A compared to controls (0.1 microg Se/g). Pretreatment of rats with P450 enzymes activators (i.e., PB, Aroclor 1254, or 3-methylcholanthrene) shortened the duration of PB induced sleep and masked the effects of dietary selenium. The current studies document that dietary selenium can influence the response to pentobarbital induced hypnosis and likely relates to changes in drug detoxification enzymes.

Age Factors↗
PubMed2003

The antioxidant conundrum in cancer.

The health-related effects of interactions between reactive oxygen species (ROS) and dietary antioxidants and the consequences of dietary antioxidant supplementation on human health are by no means clear. Although ROS, normal byproducts of aerobic metabolism, are essential for various defense mechanisms in most cells, they can also cause oxidative damage to DNA, proteins, and lipids, resulting in enhanced disease risk. Dietary antioxidants (e.g., vitamin E, vitamin C, beta-carotene, and selenium), as well as endogenous antioxidant mechanisms, can help maintain an appropriate balance between the desirable and undesirable cellular effects of ROS. However, any health-related effects of interactions between dietary antioxidants and ROS likely depend on the health status of an individual and may also be influenced by genetic susceptibilities. Clinical studies of antioxidant supplementation and changes in either oxidative status, disease risk, or disease outcome have been carried out in healthy individuals, populations at risk for certain diseases, and patients undergoing disease therapy. The use of antioxidants during cancer therapy is currently a topic of heated debate because of an overall lack of clear research findings. Some data suggest antioxidants can ameliorate toxic side effects of therapy without affecting treatment efficacy, whereas other data suggest antioxidants interfere with radiotherapy or chemotherapy. Overall, examination of the evidence related to potential interactions between ROS and dietary antioxidants and effects on human health indicates that consuming dietary antioxidant supplements has pros and cons for any population and raises numerous questions, issues, and challenges that make this topic a fertile field for future research. Overall, current knowledge makes it premature to generalize and make specific recommendations about antioxidant usage for those at high risk for cancer or undergoing treatment.

Antioxidants↗
PubMed2003

Incorporating basic nutrition science into health interventions for cancer prevention.

Increasing evidence points to numerous dietary components that modify cancer incidence as well as the biological behavior of tumors. These inhibitory or stimulatory effects depend not only on the dietary component examined, but on a number of factors including the cellular DNA profile (nutrigenetic and nutrigenomic effects), protein formation and regulation (proteomic effect), and the effective delivery of the active intermediate at specific target sites (metabolomic effect). Unfortunately, the diet and cancer research domain is strewn with studies that were inadequately designed to monitor biological endpoints, used invalid biomarkers, or monitored irrelevant intakes or exposures. The scientific frontiers in health risk prediction and disease prevention strategies will greatly expand with the building of reliable nutrition and cancer biomarker databases that use modeling techniques to integrate information about intakes, effect biomarkers, and susceptibility biomarkers. Fundamental to this database will be the elucidation of the specific molecular sites of action (targets) for the specific dietary component. Clustering techniques that build on either genes or ratios of genetic expressions or their products will be needed to assess the merit of a particular dietary intervention. Models are already surfacing about how dietary-induced fluctuations in genes and their expression products can modify pathways associated with carcinogen activation and detoxification, alter rates of cellular proliferation, influence apoptosis, and modify angiogenesis. Embracing new genomic technologies offers exciting opportunities for advancing nutrition, especially those related to cancer prevention. We must effectively communicate, within a responsible bioethical framework, the potential value of knowledge about genes and gene products.

DNA Methylation↗
PubMed2003

Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report.

Adenocarcinoma of the pancreas is one of most catastrophic and least understood of cancers. Evidence from clinical studies indicates that the development of pancreas cancer progresses over many years before symptoms appear. Most people with pancreatic cancer die within six months of diagnosis. The lack of early disease markers, the paucity of direct subject/patient interview data and limited availability of high quality biological samples have slowed progress toward identifying environmental and genetic disease risk factors. Much remains to be learned about the development of pancreatic cancer and about potential interventions for disease prevention. Epidemiological and mechanistic studies examining risk factors for pancreatic cancer supply little consistent or strong evidence to provide a cohesive prevention strategy for this cancer, but offer clues for future research concerning the prevention and early detection of this devastating disease. This Executive Summary provides background discussion on pancreatic cancer and summaries of each of the topics discussed at the workshop, including 1) Molecular aspects, 2) Dietary and other risk factors for pancreatic cancer, 3) The metabolic hypothesis for pancreatic cancer, 4) Preclinical studies on pancreatic cancer, 5) Methylation, 6) Oxidative stress and 7) Biomarker Profiling. This document also contains a compilation of recommendations for future research, concluding remarks, a list of speakers and participants attending the workshop, and a selection of key references to aid future research into nutritional links to mechanisms underlying pancreas cancer. The recommendations section suggests gaps in current knowledge and articulates future directions for this area of investigation.

DNA Methylation↗
PubMed2002

Micronutrients in cancer chemoprevention.

The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin. The response to micronutrients may vary not only in magnitude but also in direction. This variation and response likely depend on individual genetic polymorphisms and/or interactions among dietary components that influence absorption, metabolism, or site of action. Research priorities include investigation of possible molecular targets for micronutrients and whether genetic and epigenetic events dictate direction and magnitude of the response.

Animals↗