query: oral intraepithelial neoplasia

positive: Differences in antioxidant levels of fresh, frozen and freeze-dried strawberries and strawberry jam. The present study was conducted to determine differences in antioxidant levels of fresh, frozen, and freeze-dried strawberries, and strawberry jam. Hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) were measured using the ABTS/H₂O₂/HRP decoloration method. HAA and LAA were then summed to calculate the total antioxidant activity (TAA). Mean differences in HAA and LAA were analyzed using one-way analysis of variance and Dunnett's T3 pairwise comparisons. The mean TAA for freeze-dried strawberries based on an 'as consumed' weight (95% confidence interval [CI]: 29.58, 30.58) was significantly higher than for fresh (95% CI: 3.18, 3.66), frozen (95% CI: 2.58, 2.79), and jam (95% CI: 1.10, 1.22). The mean TAA based on dry weight for fresh strawberries (95% CI: 40.48, 46.67) was significantly higher than for freeze-dried (95% CI: 29.58, 30.58), frozen (95% CI: 24.62, 26.59), and jam (95% CI: 1.48, 1.64). Results agree with previous studies reporting that strawberries are a valuable source of antioxidants for consumers.

positive: Is oral sex really a dangerous carcinogen? Let's take a closer look. INTRODUCTION: Questions have recently arisen in the popular press about the association between specific sexual behaviors, namely, fellatio and cunnilingus, with head and neck cancers. Although there has been an overall decline in the incidence of head and neck cancers over the past 25 years, there has been a shift in the distribution of these cancers toward a particular type known as oral squamous cell carcinomas (OSCCs), and a younger demographic. These particular cancers, OSCCs, have been shown to be associated with the human papillomavirus (HPV). Several researchers have suggested that this shift in the epidemiology of head and neck cancers might be attributable to changing sexual practices. While this speculation has caught on in the popular press, there are several interesting contradictions in the existing evidence that suggest this conclusion might be premature and overreached. AIM: The intent of this article is to help clarify the issues so that sexual medicine professionals can give accurate and up-to-date information to their patients. MAIN OUTCOME MEASURES: This is a review article; no outcome data are reported. This is a review article; no measures were collected. METHODS: Pubmed search on HPV, oral sex, oral cancers, and OSCCs. RESULTS: One hundred ninety-six articles on HPV were found; 63 articles on oral sex, 55 on oral cancer, and 5 articles on OSCCs were identified as relevant. CONCLUSIONS: HPV infections occur commonly and are usually cleared within 18 months, thus HPV infection should not be a cause for concern among monogamous couples with a rich and varied sex life as long as the sexual system remains closed and other immune compromising factors are not present. HPV becomes a concern in the context of immune system compromise and infection persistence. Factors contributing to immune system compromise, HPV persistence, and oncogenesis are reviewed. © 2012 International Society for Sexual Medicine.

positive: Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions Purpose The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene – associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties. Experimental Design Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes. Results Confirming earlier phase I data, none of the 27 participants developed FBR gel – associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene – associated loci. Conclusions These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.

positive: Oral sex, cancer and death: sexually transmitted cancers We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor.

positive: American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ... The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

positive: Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins Purpose The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)). Methods Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm. Results The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35–52 and 80–100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16–24 and 97–99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity. Conclusion PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.

positive: Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries. Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.

positive: Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.

negative: Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.

negative: Epithelial barrier biology: good fences make good neighbours The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.

negative: Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism. Avocados have a high content of phytochemicals with potential chemopreventive activity. Previously we reported that phytochemicals extracted from avocado meat into a chloroform partition (D003) selectively induced apoptosis in cancer but not normal, human oral epithelial cell lines. In the present study, we observed that treatment of human oral cancer cell lines containing high levels of reactive oxygen (ROS) with D003 increased ROS levels twofold to threefold and induced apoptosis. In contrast, ROS levels increased only 1.3-fold, and apoptosis was not induced in the normal cell lines containing much lower levels of basal ROS. When cellular ROS levels in the malignant cell lines were reduced by N-acetyl-l-cysteine (NAC), cells were resistant to D003 induced apoptosis. NAC also delayed the induction of apoptosis in dominant negative FADD-expressing malignant cell lines. D003 increased ROS levels via mitochondrial complex I in the electron transport chain to induce apoptosis. Normal human oral epithelial cell lines transformed with HPV16 E6 or E7 expressed higher basal levels of ROS and became sensitive to D003. These data suggest that perturbing the ROS levels in human oral cancer cell lines may be a key factor in selective apoptosis and molecular targeting for chemoprevention by phytochemicals.

negative: Intraepithelial Lymphocytes: To Serve and Protect The mucosal immune system is constantly exposed to a wide range of commensal and potentially pathogenic microbial species. Chronic exposure to foreign organisms makes generation of an appropriate immune response critical in maintaining a balance between elimination of harmful pathogens, peaceful coexistence with commensals, and prevention of autoimmunity. Intestinal intraepithelial lymphocytes provide a first line of defense at this extensive barrier with the outside world, and as such, understanding their role in immunity is critical.

negative: Fiber intake and the risk of oral, pharyngeal and esophageal cancer. The relation between various types of fiber and oral, pharyngeal and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in Italy. Cases were 271 hospital patients with incident, histologically confirmed oral cancer, 327 with pharyngeal cancer and 304 with esophageal cancer. Controls were 1,950 subjects admitted to the same network of hospitals as the cases for acute, nonneoplastic diseases. Cases and controls were interviewed during their hospital stay using a validated food frequency questionnaire. Odds ratios (OR) were computed after allowance for age, sex, and other potential confounding factors, including alcohol, tobacco consumption, and energy intake. The ORs for the highest vs. the lowest quintile of intake of oral, pharyngeal and esophageal cancer combined were 0.40 for total (Englyst) fiber, 0.37 for soluble fiber, 0.52 for cellulose, 0.48 for insoluble non cellulose polysaccharide, 0.33 for total insoluble fiber and 0.38 for lignin. The inverse relation were similar for vegetable fiber (OR = 0.51), fruit fiber (OR = 0.60) and grain fiber (OR = 0.56), and were somewhat stronger for oral and pharyngeal cancer than for esophageal cancer. The ORs were similar for the two sexes and strata of age, education, alcohol and tobacco consumption, and total non-alcohol energy intake. Our study indicates that fiber intake may have a protective role on oral, pharyngeal and esophageal cancer.

negative: The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomav... The definition of cervical neoplasia as a sexually determined disease caused by some types of human papillomavirus has been widely accepted. Recent epidemiologic studies, however, have failed to identify a correlation between sexual activity and human papillomavirus infection. Moreover, sexual activity has also been shown to be independent of human papillomavirus infection in increasing cervical cancer risk. These incoherences are analyzed with respect to etiologic models for cervical neoplasia and by considering the role of misclassification of human papillomavirus infection in interpreting the relations assumed under these models. Even small levels of misclassification can considerably distort (1) the presumed prevalence of viral infection, (2) the association between sexual activity and human papillomavirus infection, and (3) the ability to control the relation between sexual activity and cancer by human papillomavirus infection. In field surveys, the presumed rates of human papillomavirus infection based on a DNA assay such as the filter in situ hybridization may be a gross overestimation of the true viral prevalence. Use of moderately misclassified human papillomavirus infection test results for effect estimation and covariate adjustment in data analysis may seriously distort the underlying relations. Consequently, considering these conditions, the apparent incoherence of recent epidemiologic findings should not be construed as evidence against the role of human papillomavirus in the etiology of cervical cancer or the validity of the sexually transmitted disease model.

negative: IELs: enforcing law and order in the court of the intestinal epithelium. The intestinal intraepithelial lymphocytes (IELs) are mostly T cells dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. IELs are, therefore, strategically located at the interface between the antigen-rich outside world and the sterile core of the body. The intestine of higher vertebrates has further evolved to harbor numerous commensal bacteria that carry out important functions for the host, and while defensive immunity can effectively protect against the invasion of pathogens, similar immune reactions against food-derived antigens or harmless colonizing bacteria can result in unnecessary and sometimes damaging immune responses. Probably as a result of this unique dilemma imposed by the gut environment, multiple subsets of IEL have differentiated, which all display characteristics of 'activated yet resting' immune cells. Despite this common feature, IELs are heterogeneous with regard to their phenotype, ontogeny, and function. In this review, we discuss the different subtypes of IELs and highlight the distinct pathways they took that led to their unique differentiation into highly specialized effector memory T cells, which provide the most effective immune protection yet in a strictly regulated fashion to preserve the integrity and vital functions of the intestinal mucosal epithelium.

negative: The light and dark sides of intestinal intraepithelial lymphocytes The intraepithelial lymphocytes (IELs) that reside within the epithelium of the intestine form one of the main branches of the immune system. As IELs are located at this critical interface between the core of the body and the outside environment, they must balance protective immunity with an ability to safeguard the integrity of the epithelial barrier: failure to do so would compromise homeostasis of the organism. In this Review, we address how the unique development and functions of intestinal IELs allow them to achieve this balance.

negative: Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro. Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1-10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1-8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6-8 d of CGN exposure, the percentage of cells reentering G0-G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology.

negative: Do endodontic compounds induce genetic damage? A comprehensive review. Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.

negative: Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection. Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for cervical neoplasia, although infection alone is insufficient to produce disease. Cofactors such as nutritional factors may be necessary for viral progression to neoplasia. Results from previous studies have suggested that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical neoplasia. This study evaluated the role of vitamin A and carotenoids on HPV persistence comparing women with intermittent and persistent infections. As determined by the Hybrid Capture II system, oncogenic HPV infections were assessed at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the risk of persistent HPV infection associated with each tertile of dietary and circulating micronutrients. Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01). These data suggest that vegetable consumption and circulating cis-lycopene may be protective against HPV persistence.

negative: Acne, dairy and cancer A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.

negative: Pediatrician's role in screening and treatment: bullying, prediabetes, oral health. PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.

negative: Light alcohol drinking and cancer: a meta-analysis. BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

negative: Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer. Increasing evidence suggests that acetaldehyde, the first and genotoxic metabolite of ethanol, mediates the carcinogenicity of alcoholic beverages. Ethanol is also contained in a number of ready-to-use mouthwashes typically between 5 and 27% vol. An increased risk of oral cancer has been discussed for users of such mouthwashes; however, epidemiological evidence had remained inconclusive. This study is the first to investigate acetaldehyde levels in saliva after use of alcohol-containing mouthwashes. Ready-to-use mouthwashes and mouthrinses (n = 13) were rinsed in the mouth by healthy, nonsmoking volunteers (n = 4) as intended by the manufacturers (20 ml for 30 sec). Saliva was collected at 0.5, 2, 5 and 10 min after mouthwash use and analyzed using headspace gas chromatography. The acetaldehyde content in the saliva was 41 +/- 15 microM, range 9-85 microM (0.5 min), 52 +/- 14 microM, range 11-105 microM (2 min), 32 +/- 7 microM, range 9-67 microM (5 min) and 15 +/- 7 microM, range 0-37 microM (10 min). The contents were significantly above endogenous levels and corresponding to concentrations normally found after alcoholic beverage consumption. A twice-daily use of alcohol-containing mouthwashes leads to a systemic acetaldehyde exposure of 0.26 microg/kg bodyweight/day on average, which corresponds to a lifetime cancer risk of 3E-6. The margin of exposure was calculated to be 217,604, which would be seen as a low public health concern. However, the local acetaldehyde contents in the saliva are reaching concentrations associated with DNA adduct formation and sister chromatid exchange in vitro, so that concerns for local carcinogenic effects in the oral cavity remain.

negative: Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial. BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.

negative: A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity. The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.

negative: Update on the biological effects of ionizing radiation, relative dose factors and radiation hygiene. Diagnostic imaging is an indispensable part of contemporary medical and dental practice. Over the last few decades there has been a dramatic increase in the use of ionizing radiation for diagnostic imaging. The carcinogenic effects of high-dose exposure are well known. Does diagnostic radiation rarely cause cancer? We don't know but we should act as if it does. Accordingly, dentists should select patients wisely - only make radiographs when there is patient-specific reason to believe there is a reasonable expectation the radiograph will offer unique information influencing diagnosis or treatment. Low-dose examinations should be made: intraoral imaging - use fast film or digital sensors, thyroid collars, rectangular collimation; panoramic and lateral cephalometric imaging - use digital systems or rare-earth film screen combinations; and cone beam computed tomography - use low-dose machines, restrict field size to region of interest, reduce mA and length of exposure arc as appropriate. © 2012 Australian Dental Association.

negative: IP6: a novel anti-cancer agent. Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.

negative: The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis. PURPOSE OF REVIEW: The aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of environmental agents, modulates the activity of immune and nonimmune cells in the gut, and may represent an important link between the environment and the immune perturbations which underlie the pathogenesis of inflammatory bowel disease. This review will summarize the current knowledge of the role of AhR in regulation of intestinal immune homeostasis and inflammation. RECENT FINDINGS: Activation of AhR by dietary ligands is necessary for the maintenance or expansion of innate immune cells in the gut, such as intraepithelial lymphocytes (IELs) and interleukin (IL)-22-producing lymphoid cells (ILC22). AhR-deficient mice lack IELs, have reduced number of ILC22 cells, and are more susceptible to bacterial infections and experimental colitis. In animal models, AhR activators inhibit proinflammatory cytokine synthesis and attenuate colitis by a pathway that involves IL-22. Analysis of AhR in the human gut reveals that intestinal T cells and natural killer cells isolated from Crohn's disease patients express low levels of AhR and respond to AhR ligands by downregulating inflammatory cytokines and upregulating IL-22. SUMMARY: These novel findings may help explain how environmental factors may regulate mucosal immune responses.

negative: Dietary Restriction, Growth Factors and Aging: from yeast to humans Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.

negative: Starting at the beginning: new perspectives on the biology of mucosal T cells. The gastrointestinal tract is the central organ for uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment of the body and the outside world. In mammals, the intestine has further evolved to harbor a vast load of commensal bacteria that have important functions for the host. Discrimination by the host defense system of nonself from self can prevent invasion of pathogens, but equivalent responses to dietary or colonizing bacteria can lead to devastating consequences for the organism. This dilemma imposed by the gut environment has probably contributed significantly to the evolutionary drive that has led to sophisticated mechanisms and diversification of the immune system to allow for protection while maintaining the integrity of the mucosal barrier. The immense expansion and specialization of the immune system is particularly mirrored in the phylogeny, ontogeny, organization, and regulation of the adaptive intraepithelial lymphocytes, or IEL, which are key players in the unique intestinal defense mechanisms that have evolved in mammals.

negative: Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer. BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.

negative: Non-celiac gluten sensitivity: literature review. BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.

negative: Ductal carcinoma in situ: terminology, classification, and natural history. Ductal carcinoma in situ (DCIS) refers to breast epithelial cells that have become "cancerous" but still reside in their normal place in the ducts and lobules. In this setting, cancerous means that there is an abnormal increase in the growth of the epithelial cells, which accumulate within and greatly expand the ducts and lobules. DCIS is a nonlethal type of cancer because it stays in its normal place. However, DCIS is very important because it is the immediate precursor of invasive breast cancers, which are potentially lethal. This article provides a general overview of DCIS, including historical perspective, methods of classification, current perspective, and future goals.

negative: Oral cobalamin remains medicine's best kept secret. A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians, hematologists, and general practitioners, and to explore factors related to its use. The study population consisted of all geriatricians (n = 138) and hematologists (n = 317) listed in the Canadian Medical Directory plus a random sample of 307 general practitioners. The overall response rate was 40%. Intramuscular and oral cobalamin was prescribed by 76 and 32% of the respondents, respectively. Twenty seven percent reported using both oral and intramuscular cobalamin and 6% reported using only oral cobalamin. Only 25% of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey. After multivariate adjustment, only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use. Oral cobalamin has been shown to be an efficacious, cost efficient and safe method of treating cobalamin deficiency. Nonetheless, it is not used by the majority of physicians treating this condition. Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased.

negative: Chemoprevention in Barrett's oesophagus. Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus. Copyright © 2011 Elsevier Ltd. All rights reserved.

negative: Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India. In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered. Copyright 2003 Wiley-Liss, Inc.

negative: Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots. The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.

negative: Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal. Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.

negative: Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.

negative: Prostate cancer and inositol hexaphosphate: efficacy and mechanisms. There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.