Showing papers by "Jeffrey M. Peters published in 2011"
TL;DR: This special edition article reviews the history and current scope of xenobiotic metabolism and transport, with special emphasis on the discoveries and impact of selected "xenobiotic receptors."
316 citations
Medical College of Wisconsin1, Georgia Regents University2, University of California, San Diego3, Georgetown University4, George Washington University5, McMaster University6, University of Arizona7, Children's Mercy Hospital8, Pennsylvania State University9, University of Virginia10, Centers for Disease Control and Prevention11, University of Turku12, RTI International13
TL;DR: This updated evaluation of soy infant formula does not include an assessment on the potential reproductive toxicity of genistein following exposures during adulthood as was carried out in the 2006 evaluation, and focuses only on Soy infant formula and the potential developmental toxicity of its major isoflavone components.
Abstract: Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones (phytoestrogens) that occur naturally in some legumes, especially soybeans. Phytoestrogens are nonsteroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for National Toxicology Program (NTP) evaluation because of (1) the availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as few studies on human infants fed soy infant formula, (2) the availability of information on exposures in infants fed soy infant formula, and (3) public concern for effects on infant or child development. On October 2, 2008 (73 FR 57360), the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) announced its intention to conduct an updated review of soy infant formula to complete a previous evaluation that was initiated in 2005. Both the current and previous evaluations relied on expert panels to assist the NTP in developing its conclusions on the potential developmental effects associated with the use of soy infant formula, presented in the NTP Brief on Soy Infant Formula. The initial expert panel met on March 15 to 17, 2006, to reach conclusions on the potential developmental and reproductive toxicities of soy infant formula and its predominant isoflavone constituent genistein. The expert panel reports were released for public comment on May 5, 2006 (71 FR 28368). On November 8, 2006 (71 FR 65537), CERHR staff released draft NTP Briefs on Genistein and Soy Formula that provided the NTP's interpretation of the potential for genistein and soy infant formula to cause adverse reproductive and/or developmental effects in exposed humans. However, CERHR did not complete these evaluations, finalize the briefs, or issue NTP Monographs on these substances based on this initial evaluation. Between 2006 and 2009, a substantial number of new publications related to human exposure or reproductive and/or developmental toxicity were published for these substances. Thus, CERHR determined that updated evaluations of genistein and soy infant formula were needed. However, the current evaluation focuses only on soy infant formula and the potential developmental toxicity of its major isoflavone components, e.g. genistein, daidzein (and estrogenic metabolite, equol), and glycitein. This updated evaluation does not include an assessment on the potential reproductive toxicity of genistein following exposures during adulthood as was carried out in the 2006 evaluation. CERHR narrowed the scope of the evaluation because the assessment of reproductive effects of genistein following exposure to adults was not considered relevant to the consideration of soy infant formula use in infants during the 2006 evaluation. To obtain updated information about soy infant formula for the CERHR evaluation, the PubMed (Medline) database was searched from February 2006 to August 2009 with genistein/genistin, daidzein/daidzin, glycitein/glycitin, equol, soy, and other relevant keywords. References were also identified from the bibliographies of published literature. The updated expert panel report represents the efforts of a 14-member panel of government and nongovernment scientists, and was prepared with assistance from NTP staff. The finalized report, released on January 15, 2010 (75 FR 2545), reflects consideration of public comments received on a draft report that was released on October 19, 2009, for public comment and discussions that occurred at a public meeting of the expert panel held December 16 to 18, 2009 (74 FR 53509). The finalized report presents conclusions on (1) the strength of scientific evidence that soy infant formula or its isoflavone constituents are developmental toxicants based on data from in vitro, animal, or human studies; (2) the extent of exposures in infants fed soy infant formula; (3) the assessment of the scientific evidence that adverse developmental health effects may be associated with such exposures; and (4) knowledge gaps that will help establish research and testing priorities to reduce uncertainties and increase confidence in future evaluations. The Expert Panel expressed minimal concern for adverse developmental effects in infants fed soy infant formula. This level of concern represents a "2" on the five-level scale of concern used by the NTP that ranges from negligible concern ("1") to serious concern ("5"). The Expert Panel Report on Soy Infant Formula was considered extensively by NTP staff in preparing the 2010 NTP Brief on Soy Infant Formula, which represents the NTP's opinion on the potential for exposure to soy infant formula to cause adverse developmental effects in humans. The NTP concurred with the expert panel that there is minimal concern for adverse effects on development in infants who consume soy infant formula. This conclusion was based on information about soy infant formula provided in the expert panel report, public comments received during the course of the expert panel evaluation, additional scientific information made available since the expert panel meeting, and peer reviewer critiques of the draft NTP Brief by the NTP Board of Scientific Counselors (BSC) on May 10, 2010 (Meeting materials are available at http://ntp.niehs.nih.gov/go/9741.). The BSC voted in favor of the minimal concern conclusion with 7 yes votes, 3 no votes, and 0 abstentions. One member thought that the conclusion should be negligible concern and two members thought that the level of concern should be higher than minimal concern. The NTP's response to the May 10, 2010 review ("peer-review report") is available on the NTP website at http://ntp.niehs.nih.gov/go/9741. The monograph includes the NTP Brief on Soy Infant Formula as well as the entire final Expert Panel Report on Soy Infant Formula. Public comments received as part of the NTP's evaluation of soy infant formula and other background materials are available at http://cerhr.niehs.nih.gov/evals/index.html.
85 citations
TL;DR: The data show that PPARβ/δ activation potentiates GLP-1 production by the small intestine, which is a promising approach in the treatment of patients with type 2 diabetes mellitus, especially in combination with dipeptidyl peptidase IV inhibitors.
58 citations
TL;DR: The prevailing evidence would suggest that targeting PPARβ/δ is not only safe but could have anti-carcinogenic protective effects, and this review examines studies reporting the role of PPARδ in colon, breast, and lung cancers.
Abstract: Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a promising drug target since its agonists increase serum high-density lipoprotein; decrease low-density lipoprotein, triglycerides, and insulin associated with metabolic syndrome; improve insulin sensitivity; and decrease high fat diet-induced obesity. PPARβ/δ agonists also promote terminal differentiation and elicit anti-inflammatory activities in many cell types. However, it remains to be determined whether PPARβ/δ agonists can be developed as therapeutics because there are reports showing either pro- or anti-carcinogenic effects of PPARβ/δ in cancer models. This review examines studies reporting the role of PPARβ/δ in colon, breast, and lung cancers. The prevailing evidence would suggest that targeting PPARβ/δ is not only safe but could have anti-carcinogenic protective effects.
54 citations
TL;DR: Evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluorochemicals.
Abstract: The pervasive nature of perfluoroalkyl chemicals in the environment has generated considerable interest for developing new strategies for risk assessment. In experimental animal models, exposure to perfluoroalkyl chemicals can cause developmental toxicity and hepatotoxicity. Peroxisome proliferator-activated receptor-α (PPARα) is required to mediate some but not all of these effects. Since PPARα has a role in mediating some of these effects, and there is some overlap in the type of toxicities elicited by perfluoroalkyl chemicals, it has been suggested that a scaling system analogous to the toxic equivalency factor (TEF) system used for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) could be used for perfluoroalkyl chemicals. However, evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluoroalkyl chemicals. These differences and other data gaps preclude the development of a TEF approach for perfluoroalkyl chemicals.
44 citations
TL;DR: These studies are the most quantitative to date to demonstrate that expression of PPARβ/δ is lower in human and Apc+/Min‐FCCC mouse colon tumors than in corresponding normal tissue, consistent with the finding that increasing expression and activation in human colon cancer cell lines inhibits clonogenicity.
Abstract: This study critically examined the role of PPARb/d in colon cancer models. Expression of PPARb/d mRNA and protein was lower and expression of CYCLIN D1 protein higher in human colon adenocarcinomas compared to matched nontransformed tissue. Similar results were observed in colon tumors from Apc þ/Min-FCCC mice compared to control tissue. Dietary administration of sulindac to Apc þ/Min-FCCC mice had no influence on expression of PPARb/d in normal colon tissue or colon tumors. Cleaved poly (ADP-ribose) polymerase (PARP) was either increased or unchanged, while expression of 14-3-3e was not influenced in human colon cancer cell lines cultured with the PPARb/d ligand GW0742 under conditions known to increase apoptosis. While DLD1 cells exhibited fewer early apoptotic cells after ligand activation of PPARb/d following treatment with hydrogen peroxide, this change was associated with an increase in late apoptotic/necrotic cells, but not an increase in viable cells. Stable over-expression of PPARb/d in human colon cancer cell lines enhanced ligand activation of PPARb/d and inhibition of clonogenicity in HT29 cells. These studies are the most quantitative to date to demonstrate that expression of PPARb/d is lower in human and Apc þ/Min-FCCC mouse colon tumors than in corresponding normal tissue, consistent with the finding that increasing expression and activation of PPARb/d in human colon cancer cell lines inhibits clonogenicity. Because ligand-induced attenuation of early apoptosis can be associated with more late, apoptotic/necrotic cells, but not more viable cells, these studies illustrate why more comprehensive analysis of PPARb/d-dependent modulation of apoptosis is required in the future. 2011 Wiley-Liss, Inc.
36 citations
TL;DR: Stable over-expression of PPARβ/δ or PPARγ significantly increases the efficacy of ligand activation and represses UVB-induced expression of tumor necrosis factor α, interleukin 6 (IL6), or IL8 in HaCaT keratinocytes, thereby establishing an excellent model to study the functional role of these receptors in human keratinocyte cell lines.
33 citations
TL;DR: This review summarizes both the confirmed and conflicting mechanisms that have been described for PPARβ/δ and the potential for targeting this nuclear receptor for the prevention and treatment of colon cancer.
26 citations
01 Dec 2011
TL;DR: The focus of this chapter is to summarize PPAR-dependent regulation of cellular signaling in squamous epithelium, and how these changes influence cancer.
Abstract: Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that respond to endogenous and exogenous signaling molecules and modulate cellular functions. PPARs regulate many target genes that in turn influence cell growth, differentiation, and inflammatory signaling. These changes can occur through direct transcriptional up-regulation of target genes, through secondary changes subsequent to direct transcriptional up-regulation of target genes, and through protein-protein interactions. The focus of this chapter is to summarize PPAR-dependent regulation of cellular signaling in squamous epithelium, and how these changes influence cancer.
2 citations
TL;DR: Findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.
Abstract: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor β/δ (PPARβ/δ) and PPARγ. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.
2 citations