Biomedical subjects

I T Johnson

Publications and source records attributed to I T Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Systematic review: Cyclo-oxygenase-2 in human oesophageal adenocarcinogenesis.

BACKGROUND: Published in vitro and animal in vivo studies have demonstrated that cyclo-oxygenase-2 plays an important role during oesophageal adenocarcinogenesis. However, the extent to which these studies are directly relevant to events in the human lower oesophagus is questionable. AIM: To perform a systematic review of all available human studies that have evaluated levels of cyclo-oxygenase-2 expression during the progression from Barrett's metaplasia to oesophageal adenocarcinoma. METHODS: A literature search was performed to identify all studies which qualitatively or quantitatively assessed cyclo-oxygenase-2 protein or gene expression in either Barrett's, dysplastic or adenocarcinoma tissue in humans. RESULTS: A total of 27 studies met the inclusion criteria. There was general agreement that cyclo-oxygenase-2 was either absent or very weakly expressed in normal oesophageal squamous mucosa, but considerable disagreement regarding the presence of cyclo-oxygenase-2 in Barrett's and low-grade dysplasia. All studies agreed that high-grade dysplasia and adenocarcinoma expressed cyclo-oxygenase-2 to some extent although levels varied considerably between tissue samples. CONCLUSIONS: There is conflicting evidence in the literature for cyclo-oxygenase-2 playing an important role in early oesophageal adenocarcinogenesis. Other non-cyclo-oxygenase-2 targets may account for the epidemiological data supporting the use of non-steroidal anti-inflammatory drugs in the chemoprevention of oesophageal adenocarcinoma.

Adenocarcinoma↗

PubMed2005

Systematic review: the chemoprevention of oesophageal adenocarcinoma.

The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma. We discuss gastro-oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined. Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non-steroidal anti-inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side-effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.

Adenocarcinoma↗

PubMed2005

Methylation of the ESR1 CpG island in the colorectal mucosa is an 'all or nothing' process in healthy human colon, and is accelerated by dietary folate supplementation in the mouse.

ESR1 is frequently silenced by CGI (CpG island) methylation, both in human colorectal tumours and, in an age-dependent manner, in healthy mucosa. It is not clear, however, whether methylation of individual cytosines occurs randomly within the epithelial genome, or preferentially within individual cells as an 'all-or-nothing' phenomenon. CGI methylation can be quantified in human DNA residues recovered from faecal samples. We used bisulphite genomic sequencing of human DNA from this source and from a colorectal cancer cell line (SW48) to show that the ESR1 CGI is methylated in an allele-specific manner. This provides support for the 'all or none' mechanism for methylation of this gene, and shows how age-dependent methylation of the ESR1 CGI leads rapidly to silencing of the gene within the cells, and hence the colonic crypt within which it occurs. Preliminary studies with a rodent model suggest the rate of age-dependent methylation of ESR1 is modifiable by dietary folate.

Aging↗

PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 1. Developing and validating the methodology.

OBJECTIVE: The aim of the study was to test the feasibility of using smart card technology to track the eating behaviours of nearly a thousand children in a school cafeteria. METHODS: Within a large boys' school a smart card based system was developed that was capable of providing a full electronic audit of all the individual transactions that occurred within the cafeteria. This dataset was interfaced to an electronic version of the McCance and Widdowson composition of foods dataset. The accuracy of the smart card generated data and the influence of portion size and wastage were determined empirically during two 5-day trials. RESULTS: The smart card system created succeeded in generating precise data on the food choices made by hundreds of children over an indefinite time period. The data was expanded to include a full nutrient analysis of all the foods chosen. The accuracy of this information was only constrained by the limitations facing all food composition research, e.g. variations in recipes, portion sizes, cooking practices, etc. Although technically possible to introduce wastage correction factors into the software, thereby providing information upon foods consumed, this was not seen as universally practical. CONCLUSION: The study demonstrated the power of smart card technology for monitoring food/nutrient choice over limitless time in environments such as school cafeterias. The strengths, limitations and applications of such technology are discussed.

Child↗

PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 2. The nutrient contents of all meals chosen by a group of 8- to 11-year-old boys over 78 days.

OBJECTIVE: The aim of the study was to test the abilities of the newly created smart card system to track the nutrient contents of foods chosen over several months by individual diners in a school cafeteria. METHODS: From the food choice and composition of food data sets, an Access database was created encompassing 30 diners (aged 8-11 years), 78 days and eight nutrients. Data were available for a total of 1909 meals. RESULTS: Based upon population mean values the cohort were clearly choosing meals containing higher than the recommended maximum amounts for sugar and lower than the recommended minimum amounts of fibre, iron and vitamin A. Protein and vitamin C contents of meals chosen were well above minimum requirements. Over the 1909 meals, nutrient requirements were met 41% of the time. CONCLUSIONS: The system created was very effective at continually monitoring food choices of individual diners over limitless time. The data generated raised questions on the common practice of presenting nutrient intakes as population mean values calculated over a few days. The impact of heavily fortified foods on such studies in general is discussed.

Child↗

PubMed2005

Using smart card technology to monitor the eating habits of children in a school cafeteria: 3. The nutritional significance of beverage and dessert choices.

OBJECTIVE: The consumption patterns of beverages and desserts features highly in the current debate surrounding children's nutrition. The aim of this study was to continuously monitor the choice of beverages and desserts made by nearly 1000 children in a school cafeteria. METHODS: A newly developed smart card system was used to monitor the food choices of diners (7-16-year-old boys) in a school cafeteria over 89 days. A wide variety of beverages and desserts were on offer daily. RESULTS: Despite coming from an affluent, well-educated demographic group, the boys' choices of beverages and desserts mirrored those of children in general. Buns and cookies were over 10 times more popular than fresh fruits and yogurts. Sugary soft-drinks were over 20 times more popular than fresh fruit drinks and milk combined. Appropriate choices could, over a month, reduce intake of added sugar by over 800 g and fat by over 200 g. CONCLUSION: The smart card system was very effective at monitoring total product choices for nearly 1000 diners. In agreement with a recent national school meal survey, where choice is extensive, children show a preference for products high in fat and/or sugar. The consequences of these preferences are discussed.

Adolescent↗

PubMed2004

New approaches to the role of diet in the prevention of cancers of the alimentary tract.

Cancers of the alimentary tract are, collectively, amongst the major causes of morbidity and deaths from cancer across the world today. Of the 10 million new cases of cancer diagnosed in 2000, about 2.3 million were cancers of the pharynx, oesophagus, stomach or colorectum. Nevertheless, epidemiological studies indicate that cancers of the digestive organs are also amongst the most susceptible to modification by dietary factors. International variations in incidence suggest that round three quarters of all sporadic colorectal cancers are attributable to diet. Even within the relatively uniform environment of the European Union, there are variations in the incidence of colorectal and oesophageal cancers of about two- and six-fold, respectively. Carcinomas of the alimentary tract arise from epithelial cells via distinct sequences of neoplastic change, which require a large fraction of an individual's lifespan. The best characterised of these is the adenoma-carcinoma sequence of colorectal carcinogenesis, in which progressive loss of differentiation and normal morphology in a growing lesion is associated with the acquisition of somatic mutations, and of aberrant methylation of CpG-islands, leading to gene silencing. These molecular events are accompanied by functional changes, including increased mitosis and evasion of apoptosis. There is little evidence that diet exerts its effects primarily through food-borne carcinogens that can be identified and eliminated from the food-chain. It is far more probable that the adverse effects of diet are caused largely by over-consumption of energy, coupled with inadequate intakes of protective substances, including micronutrients, dietary fibre and a variety of phytochemicals. The latter are biologically active secondary plant metabolites, many of which modify cell proliferation and induce apoptosis in vitro. There is growing evidence that such effects also occur in vivo, and that they can suppress the progress of neoplasia. Carcinomas of the oesophagus, stomach and colon all appear to be partially preventable by diets rich in fruits and vegetables. Plant foods contain a variety of components including micronutrients, polyunsaturated fatty acids, and secondary metabolites such as glucosinolates and flavonoids, many of which can inhibit cell proliferation and induce apoptosis, and which may well act synergistically when combined in the human diet. The future challenge is to fully characterise and evaluate these effects at the cellular and molecular level, so at to exploit their full potential as protective mechanisms for the population as a whole.

Anticarcinogenic Agents↗

PubMed2004

Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest.

Epidemiological studies suggest that the use of NSAIDs and/or a high intake of fruit and vegetables reduce the risk of oesophageal adenocarcinoma. Since COX-2 is up-regulated in Barrett's oesophageal carcinogenesis, the protective effect of NSAIDs and natural food components might reflect COX-2 inhibition. We explored the effects of quercetin, a natural flavonoid with a potent COX-2 inhibitory activity, and two commercially available selective COX-2 inhibitors (NS-398 and nimesulide) on cell proliferation, apoptosis, PGE2 production and COX-2 mRNA expression in a human oesophageal adenocarcinoma cell line (OE33). Changes in the relative numbers of adherent and floating cells were quantified and apoptotic cells were identified using ethidium bromide and acridine orange staining under fluorescence microscopy. Flow cytometric analysis of adherent and floating cells was used to quantify apoptosis and to examine the effects of the agents on the cell cycle. After 48 h exposure at concentrations of > or =1 microM both COX-2 inhibitors and quercetin suppressed cell proliferation (P < 0.01) and increased the fraction of floating apoptotic cells. At higher concentrations (50 microM) and longer exposure (48 h) the effects of quercetin were significantly greater than those of the selective COX-2 inhibitors (P < 0.01). Cell cycle analyses showed that quercetin blocked cells in S phase, while the selective COX-2 inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2 production by approximately 70% after 24 h exposure (P < 0.001). We conclude that OE33 is a useful model for the study of COX-2 expression and associated phenomena in human adenocarcinoma cells. Synthetic COX-2 inhibitors and the food-borne flavonoid quercetin suppress proliferation, induce apoptosis and cell cycle block in human oesophageal adenocarcinoma cells in vitro, and future studies should assess their effects in vivo.

Adenocarcinoma↗

PubMed2004

Functional evidence of a role for two-pore domain potassium channels in rat mesenteric and pulmonary arteries.

1. Experiments were performed to elucidate the mechanism by which alterations of extracellular pH (pH(o)) change membrane potential (E(M)) in rat mesenteric and pulmonary arteries. 2. Changing pH(o) from 7.4 to 6.4 or 8.4 produced a depolarisation or hyperpolarisation, respectively, in mesenteric and pulmonary arteries. Anandamide (10 microm) or bupivacaine (100 microm) reversed the hyperpolarisation associated with alkaline pH(o), shifting the E(M) of both vessels to levels comparable to that at pH 6.4. In pulmonary arteries, clofilium (100 microm) caused a significant reversal of hyperpolarisation seen at pH 8.4 but was without effect at pH 7.4. 3. K(+) channel blockade by 4-aminopyridine (4-AP) (5 mm), tetraethylammonium (TEA) (10 mm), Ba(2+) (30 microm) and glibenclamide (10 microm) depolarised the pulmonary artery. However, shifts in E(M) with changes in pH(o) remained and were sensitive to anandamide (10 microm), bupivacaine (100 microm) or Zn(2+) (200 microm). 4. Anandamide (0.3-60 microm) or bupivacaine (0.3-300 microm) caused a concentration-dependent increase in basal tone in pulmonary arteries. 5. RT-PCR demonstrated the expression of TASK-1, TASK-2, THIK-1, TRAAK, TREK-1, TWIK-1 and TWIK-2 in mesenteric arteries and TASK-1, TASK-2, THIK-1, TREK-2 and TWIK-2 in pulmonary arteries. TASK-1, TASK-2, TREK-1 and TWIK-2 protein was demonstrated in both arteries by immunostaining. 6. These experiments provide evidence for the presence of two-pore domain K(+) channels in rat mesenteric and pulmonary arteries. Collectively, they strongly suggest that modulation of TASK-1 channels is most likely to have mediated the pH-induced changes in membrane potential observed in these vessels, and that blockade of these channels by anandamide or bupivacaine generates a small increase in pulmonary artery tone.

Animals↗

PubMed2004

Micronutrients and cancer.

Adverse dietary factors account for approximately 30% of all cancers. Overconsumption of energy is undoubtedly one of the major risk factors, but dietary composition is also very important. In particular, a low consumption of fruits and vegetables appears to double the risk of carcinomas of the lung and alimentary tract. Epidemiological studies suggest that high plasma levels of Se, carotenoids and ascorbic acid are protective against cancer. However, intervention studies with antioxidant nutrients have given mixed results, and it has not been established that the benefits of a high intake of fruits and vegetables are invariably related to the prevention of oxidative DNA damage. Folic acid supplementation appears to protect against colo-rectal neoplasia, probably by preventing mutations associated with the repair of uracil mis-incorporation. However, there are indications from animal studies that exposure to high levels of folic acid at certain stages of development may lead to epigenetic effects that are, as yet, poorly understood. There seems little doubt that micronutrients contribute to the protective effects of plant foods against cancers of the lung and alimentary tract, but it has not been established that these benefits can be achieved using supplements.

Antioxidants↗

PubMed2003

Cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study.

BACKGROUND: The incidence of Barrett's oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo-oxygenase-2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo-oxygenase-2 expression in the sequence of Barrett's metaplasia-dysplasia-adenocarcinoma within the same patients. METHODS: Paraffin-embedded oesophago-gastrectomy specimens from 20 patients, containing successive stages of Barrett's metaplasia, high-grade dysplasia and adenocarcinoma, were analysed for cyclo-oxygenase-2 expression by immunohistochemistry. RESULTS: Cyclo-oxygenase-2 was constitutively expressed in the basal layers of cells in the adjacent normal squamous oesophageal epithelium, but a higher cyclo-oxygenase-2 expression was observed in Barrett's metaplasia. A further increase in cyclo-oxygenase-2 expression was detected in high-grade dysplasia, but cyclo-oxygenase-2 was decreased in adenocarcinoma tissue, regardless of its stage or level of differentiation. CONCLUSIONS: Cyclo-oxygenase-2 expression is progressively increased when squamous oesophageal epithelium develops into Barrett's metaplastic epithelium and then into high-grade dysplasia, but appears to decrease when adenocarcinoma develops. These findings may be significant for an effective chemo-prevention strategy with selective cyclo-oxygenase-2 inhibitors.

Adenocarcinoma↗

PubMed2003

Hydrolysis by lactase phlorizin hydrolase is the first step in the uptake of daidzein glucosides by rat small intestine in vitro.

1. Isoflavones are naturally occurring oestrogenic compounds found in plants, where they exist in the glycosylated form. A proportion of ingested glycosides appears to be absorbed in the upper gastrointestinal tract, where enterocytes play an important role in their metabolism. 2. One hypothesis is that ingestion may involve hydrolysis by the luminally exposed enzyme lactase phlorizin hydrolase (LPH), an enzyme expressed specifically at the small intestinal brush border. 3. Using an everted sac preparation of rat jejunum and an inhibitor of LPH, we investigated the absorption of daidzein-O(7)-glucoside (daidzin) and the effect of LPH inhibition on this process. It was demonstrated that LPH plays a major role in the deglycosylation of daidzin. 4. The hydrolysis product, daidzein, is absorbed by epithelial cells and glucuronidated to daidzein-O(7)-glucuronide, which is subsequently exported primarily to the serosal (vascular) side of the tissue rather than to the luminal side. 5. A small but significant proportion of the intact glycoside is also transferred to the serosal compartment, and in the presence of an LPH inhibitor this was enhanced with a corresponding reduction in deglucosylation and glucuronidation. 6. The results indicate that that LPH plays an important role in the metabolism of glycosylated phytochemicals, and that the expression and activity of this enzyme in the small intestine can modify the profile of metabolites appearing in the circulation.

Animals↗

PubMed2002

Anticarcinogenic effects of diet-related apoptosis in the colorectal mucosa.

The crypt is the fundamental unit of epithelial proliferation in the intestinal mucosa. The progeny of the pluripotent stem cells located near the base of the crypt migrate towards the crypt orifice, divide once or twice more, and then undergo differentiation, senescence and exfoliation. Programmed cell death (apoptosis) also occurs deep in the proliferative zone. Various lines of evidence suggest that apoptosis provides a protective mechanism against neoplasia by removing genetically damaged stem cells from the epithelium before they can undergo clonal expansion. Several different classes of food constituents, including certain polyunsaturated fatty acids, the short-chain fatty acid butyrate, and some phytochemicals including flavonoids and glucosinolates breakdown products, can modulate both cellular proliferation and programmed death. Each of these food components has also been shown to suppress the emergence of aberrant crypt foci in animal models of carcinogenesis. Further mechanistic and clinical studies are required to establish whether such dietary effects can be exploited to achieve preventive or therapeutic effects in humans.

Animals↗

PubMed2002

Evidence for consistent patterns between flavonoid structures and cellular activities.

A wide variety of plant-derived compounds, including the polyphenolic flavonoids, is present in the human diet or is consumed for medicinal reasons. Epidemiological and animal studies tend to suggest a protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological activity are still largely unknown. Antioxidant properties of the flavonoids have been postulated as a mechanism for putative protective effect against cardiovascular disease. Nevertheless, these properties alone are not sufficient to explain the anti-carcinogenic potential of these polyphenols. The mechanisms by which the molecules interact with cells or are absorbed by them are very important for determining the intracellular concentration and distribution of the metabolites to internal organs. With the exception of the cells lining the gastrointestinal tract, all other cells in the body are only exposed to flavonoid metabolites and degradation products. No previous studies have addressed this aspect of cellular exposure, except for some methylated metabolites. Within the last decade, reports on flavonoid activities have been largely associated with enzyme inhibition and anti-proliferative activity. From our recent work on the human colon cancer cell line HT29 and comparison with published studies, structure-function relationships demonstrate that antioxidant, enzyme inhibitor or anti-proliferative activities are dependent on particular structure motifs. The present review also presents a summary of mechanistic data on a few elected compounds.

Animals↗

PubMed2001

New food components and gastrointestinal health.

Apart from its main functions of digestion, absorption and faecal processing, the human gastrointestinal tract has a complex pattern of muscular activity regulated by a largely autonomous nervous system, and its various organs contain large concentrations of immune and endocrine tissues. Any failure of these closely-integrated systems can lead to diseases ranging from the mildly irritating to the life threatening. Food contains a huge variety of chemical species, many of which are biologically active, and the distal regions of the gut are colonised by a rich and metabolically-active commensal flora that depend on nutrients derived ultimately from the host's dietary residues. The present paper explores the evidence for significant effects of food ingredients on functional bowel disorders, intestinal infections, and aspects of epithelial cell physiology involved in the development of colo-rectal neoplasia. Various strategies, including the manipulation of the colo-rectal microflora with pre- and probiotics, and the development of new products and plant varieties containing biologically-active constituents, have the potential to underpin the development of novel functional food products. However, these products will need to be based on proven biological principles, and fully tested for efficacy and safety. The rapidly-developing fields of functional genomics and cell biology will open up new experimental strategies to explore these possibilities, and emerging processing technologies seem likely to provide novel methods for their exploitation.

Bacteria↗

PubMed2001

Chronic exposure to high levels of dietary iron fortification increases lipid peroxidation in the mucosa of the rat large intestine.

There is increasing evidence that excess dietary iron may be a risk factor for colorectal cancer. However, the majority of animal studies looking at possible mechanism have used unrealistically high concentrations of iron. The current study was designed to test whether chronic exposure to high levels of iron fortification affects the free radical generating capacity of the lumenal contents, mucosal lipid peroxidation and crypt cell proliferation. Rats were fed diets containing either 29 mg/kg or 102 mg/kg of elemental iron for 6 mo. The free radical generating capacity of lumenal contents was assessed using an in vitro assay. Crypt cell proliferation rate was measured in tissues taken from the cecum and colon, with the remaining tissue being used for the assessment of lipid peroxidation. Chronic feeding of iron did not increase crypt cell proliferation rate in either the colon or cecum, but it was associated with an increase in free radical generating capacity in the colon and increased lipid peroxidation, particularly in the cecum. These results may be relevant to epidemiological evidence showing that dietary iron is associated with the risk of proximal colon cancer in humans.

Analysis of Variance↗

PubMed2001

Effects of cellular redox balance on induction of apoptosis by eicosapentaenoic acid in HT29 colorectal adenocarcinoma cells and rat colon in vivo.

BACKGROUND AND AIMS: Epidemiological evidence suggests n-3 polyunsaturated lipids may protect against colorectal neoplasia. Consumption of fish oil modulates crypt cytokinetics in humans, and crypt apoptosis in animal models. To explore these effects, we investigated involvement of caspase enzymes and cellular redox balance in the induction of apoptosis by eicosapentaenoic acid (EPA) in HT29 cells, and in rat colon in vivo. METHODS: Survival of HT29 cells grown with EPA in the presence of caspase inhibitors, antioxidants, or buthionine sulphoximine, an inhibitor of glutathione neosynthesis, was determined. The effects of EPA enriched fish oil and glutathione depletion on apoptosis in rat colon were assessed using microdissected crypts. RESULTS: Treatment of HT29 cells with EPA reduced viable cell number and activated caspase 3, prior to cell detachment. Antioxidants and caspase inhibitors blocked HT29 cell death whereas glutathione depletion increased it. Rats fed fish oil had higher crypt cell apoptosis than those fed corn oil, and glutathione depletion enhanced this effect. CONCLUSIONS: Incorporation of EPA into colonic epithelial cell lipids increases apoptosis. The results of this study, using both an animal and cell line model, support the hypothesis that this effect is mediated via cellular redox tone, and is sensitive to glutathione metabolism. The data suggest a mechanism whereby polyunsaturated fatty acids may influence the susceptibility of colorectal crypt cells to induction or progression of neoplasia.

Animals↗

PubMed2001

Polyphenolic compounds: interactions with the gut and implications for human health.

Polyphenolic compounds are abundant throughout the plant kingdom and are found in a wide variety of human foods. The flavonoids, which are the best defined group of polyphenols in the human diet, themselves comprise a large and complex group, all of which contain a three-ring structure with two aromatic centres and a central oxygenated heterocycle. Recent evidence suggests that significant quantities of quercetin and possibly myricetin and kaempferol are absorbed in the gut. A larger fraction probably remains in the lumen, and thus a substantial proportion of the gastrointestinal mucosa is exposed to biologically significant concentrations of these compounds. A substantial body of experimental work has established that flavonoids can suppress carcinogenesis in animal models and there is considerable interest in the biological effects of these compounds at the cellular level. Flavonoids interact with cellular signal pathways controlling the cell cycle, differentiation and apoptosis. Their potentially antineoplastic effects include antioxidant activity, induction of Phase II enzyme activity, inhibition of protein kinases and interactions with Type II estrogen binding sites. Naturally occurring polyphenolic compounds may play a role in the protective effects of fruits and vegetables against cancers in general, and they appear to have considerable potential for pharmaceutical uses as chemopreventive agents against neoplastic changes in the alimentary tract. Future research should therefore focus on the biological effects of flavonoids in the human body, using biomarkers to define their effects at each stage in the onset of neoplasia.

Animals↗