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Biomedical subjects

David Heber

Publications and source records attributed to David Heber.

77 records · Page 5Linked to original sources

Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells.

Investigators have shown that green tea and its main catechin epigallocatechin-3 gallate (EGCG) may decrease the risk of cancer. Our previous study showed that green tea extract (GTE) as well as its individual catechin components inhibited MDA-MB231 breast cancer cell and human umbilical vein endothelial cell (HUVEC) proliferation. Further, GTE suppressed breast cancer xenograft size and decreased the tumor vessel density in vivo. In the current study, we investigated the effect of GTE on the major angiogenic factor vascular endothelial growth factor (VEGF) in an in vitro experiment. GTE or EGCG (40 mg/L) significantly decreased the levels of the VEGF peptide secreted into conditioned media. This occurred in both HUVEC and human breast cancer cells and the effect was dose dependent. Furthermore, GTE and EGCG decreased the RNA levels of VEGF in MDA-MB231 cells. This inhibition occurred at the transcriptional regulation level and was accompanied by a significant decrease in VEGF promoter activity. We also showed that GTE decreased c-fos and c-jun RNA transcripts, suggesting that activator protein (AP)-1-responsive regions present in the human VEGF promoter may be involved in the inhibitory effect of GTE. Furthermore, GTE suppressed the expression of protein kinase C, another VEGF transcription modulator, in breast cancer cells. Inhibition of VEGF transcription appeared to be one of the molecular mechanism(s) involved in the antiangiogenic effects of green tea, which may contribute to its potential use for breast cancer treatment and/or prevention.

Beverages↗

Male gender is a predictor of morbidity and age a predictor of mortality for patients undergoing gastric bypass surgery.

PURPOSE: To determine preoperative risk factors predictive of adverse outcomes after gastric bypass surgery. SUMMARY BACKGROUND DATA: Gastric bypass results in sustained weight loss for seriously obese patients, but perioperative complications can be formidable. Preoperative risk assessment is important to establish the risk-benefit ratio for patients undergoing these operations. METHODS: Data for 10 risk factors predictive of adverse outcomes were collected on 1,067 consecutive patients undergoing gastric bypass surgery at the UCLA Medical Center from December 1993 until June 2000. Univariate analyses were performed for individual risk factors to determine their potential significance as predictors for complications. All 10 risk factors were entered into a logistic regression model to determine their significance as predictors for complications. Sensitivity analysis was performed. RESULTS: Univariate analysis revealed that male gender and weight were predictive of severe life-threatening adverse outcomes. Multistep logistic regression yielded only male gender as a risk factor. Male patients were heavier than female patients on entry to the study, accounting for weight as a potential risk factor. Patients older than 55 years had a threefold higher mortality from surgery than younger patients, although the complication rate, 5.8%, was the same in both groups. Sensitivity analysis demonstrated that the risk for severe life-threatening adverse outcomes in women increased from 4% for a 200-lb female patient to 7.5% for a 600-lb patient. The risk increased from 7% for a 200-lb male patient to 13% for a 600-lb patient. CONCLUSIONS: Large male patients are at greater risk for severe life-threatening complications than smaller and/or female patients. Risk factors thought to be predictive of adverse outcomes, such as a history of smoking or diabetes, proved not to be significant in this analysis. Older patients had the same complication rate but a threefold higher mortality, suggesting that they lack the reserve to recover from complications when they occur.

Adult↗

Overview of mechanisms of action of lycopene.

Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in numerous studies. Serum and tissue lycopene levels have also been inversely related to the risk of lung and prostate cancers. Lycopene functions as a very potent antioxidant, and this is clearly a major important mechanism of lycopene action. In this regard, lycopene can trap singlet oxygen and reduce mutagenesis in the Ames test. However, evidence is accumulating for other mechanisms as well. Lycopene at physiological concentrations can inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression specifically in prostate cancer cells without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin 43, whose expression is upregulated by lycopene and which allows direct intercellular gap junctional communication (GJC). GJC is deficient in many human tumors and its restoration or upregulation is associated with decreased proliferation. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibits a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression in the HL-60 promyelocytic leukemia cell line, suggesting some interaction at a nuclear or subcellular level. The combination of lycopene and lutein synergistically interact as antioxidants, and this may relate to specific positioning of different carotenoids in membranes. This review will focus on the growing body of evidence that carotenoids have unexpected biologic effects in experimental systems, some of which may contribute to their cancer preventive properties in models of carcinogenesis. Consideration of solubility in vitro, comparison with doses achieved in humans by dietary means, interactions with other phytochemicals, and other potential mechanisms such as stimulation of xenobiotic metabolism, inhibition of cholesterogenesis, modulation of cyclooxygenase pathways, and inhibition of inflammation will be considered. This review will point out areas for future research where more evidence is needed on the effects of lycopene on the etiology of chronic disease.

Animals↗

Inhibition of fibroblast growth factors by green tea.

Investigators have shown that green tea may decrease the risk of cancer. It is widely accepted that the main active component of green tea is EGCG (epigallocatechin-3-gallate). In our previous study, we examined the effect of green tea on breast cancer growth and endothelial cells both in in vitro assays and in animal models. Our data show that both mixed green tea extract (GTE) as well as its individual catechin components are effective in inhibiting breast cancer and endothelial cell proliferation in vitro, and that GTE suppresses breast cancer xenograft size and decreases the tumor blood vessel density in vivo. In the present study, we further demonstrate that 40 microg/ml GTE or EGCG can decrease the levels of the angiogenic factor bFGF (basic fibroblast growth factor) levels in the cells. This phenomenon is observed in both human umbilical vein endothelial cells (HUVECs) and in human breast cancer cells MDA-MB231. This effect is dose dependent. Furthermore, GTE and EGCG decrease the transcript levels of bFGF and aFGF (acidic fibroblast growth factor) in HUVECs and MDA-MB231 cells. Our findings suggest that the inhibition of the angiogenic fibroblast growth factors could account for one of the mechanisms of green tea's actions. Since cancer is angiogenesis dependent, this may partially explain the antineoplastic effects associated with green tea consumption.

Angiogenesis Inhibitors↗

Vegetables, fruits and phytoestrogens in the prevention of diseases.

The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer, and diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of ageing. These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits. Many phytochemicals are colourful, and recommending a wide array of colourful fruits and vegetables is an easy way to communicate increased diversity of intake to the consumer. For example, red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease. Green foods, including broccoli, Brussels sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer. Garlic and other white-green foods in the onion family contain allyl sulphides which may inhibit cancer cell growth. Other bioactive substances in green tea and soybeans have health benefits as well. Consumers are advised to ingest one serving of each of the seven colour groups daily, putting this recommendation within the United States National Cancer Institute and American Institute for Cancer Research guidelines of five to nine servings per day. Grouping plant foods by colour provides simplification, but it is also important as a method to help consumers make wise food choices and promote health.

Cardiovascular Diseases↗