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Biomedical subjects

David Heber

Publications and source records attributed to David Heber.

11 recordsLinked to original sources
PubMed2002

PC-SPES inhibits colon cancer growth in vitro and in vivo.

PC-SPES is a mixture of eight herbs with antiproliferative activity in prostate cancer cell lines and antitumor effects in animal models of prostate cancer. In addition, evidence of clinical efficacy in advanced prostate cancer has been reported. PC-SPES has also been shown to have antitumor activity against several other cancer cell lines including breast and neuroepithelial cancer, melanoma, and leukemia cell lines. Because of these findings, we investigated the effects of PC-SPES in vitro in colon cancer cell lines SW480, SW620, and DLD-1 and in vivo in the Apc(min) mouse, a murine model for intestinal carcinogenesis. For the in vitro studies, colon cancer cell lines were exposed to an ethanolic extract of PC-SPES compared with a diluent control [ethanol < or = 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 micro l/ml) caused a 95% inhibition of cell proliferation of the DLD-1 colon cancer cell line, and similar results were observed in the SW480 and SW620 colon cancer cell lines. Cell cycle analysis demonstrated a drastic (> or =60%) accumulation of cells in the G(2)-M phase with a concomitant decrease of cells in the G(0)-G(1) phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 micro l/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of beta-tubulin in the SW620 cell line exposed to PC-SPES. Terminal deoxynucleotidyl transferase-mediated nick end labeling analysis revealed an increase in apoptotic colon cancer cells incubated with PC-SPES. For the in vivo studies, female 4-5-week-old Apc(min) mice were randomized to two groups: a PC-SPES-treated group (n = 11) received 250 mg/kg/day (0.2 ml) PC-SPES via gastrointestinal gavage; and a control group (n = 10) received 0.2 ml of the vehicle solution (1.5% carboxymethylcellulose with 0.2% Tween 20) via gastrointestinal gavage. Both groups were treated five times a week for 10 weeks. After treatment, the gastrointestinal tract was dissected for polyp scoring by two observers blinded to treatment. The Apc(min) mice given PC-SPES had a 58% reduction in tumor number and a 56% decrease in tumor load. No effect on either food intake or body weight was observed in the treated versus sham groups. The present study is the first to report the potent activity of PC-SPES against colon cancer. Both cell cycle arrest and apoptosis occurred after treatment with PC-SPES. This suggests that the components of this herbal mixture, either independently or in combination, acted in colon cancer, resulting in a drastic effect on tumor initiation and tumor progression.

Animals↗
PubMed2002

Characterization and identification of alfalfa and red clover dietary supplements using a PCR-based method.

The use of herbal remedies is very popular in the United States, with >80 million people buying plant-derived preparations that are often highly degraded or potentially contaminated with nonefficacious plant material. A method utilizing DNA-based markers to identify highly fragmented or powdered plant material sold as botanicals in dietary supplements has been developed. By incorporating and streamlining a repair reaction that utilized fill-in and ligation reactions before the PCR steps, it was possible to amplify highly degraded or sheared DNA isolated from powdered plant material removed from over-the-counter capsules. The primers for the internal transcribed spacer (ITS) region of nuclear ribosomal DNA generate a PCR fragment compatible with the sizes of the repaired DNA. Moreover, a large data set in Genbank facilitated subsequent analysis. This method is a relatively rapid and simple system to facilitate the authentication, as well as the monitoring, of the purity of botanicals in dietary supplements, even those that are improperly dried or stored.

Base Sequence↗
PubMed2002

Curcumin exerts multiple suppressive effects on human breast carcinoma cells.

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells.

Antineoplastic Agents↗
PubMed2002

1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse.

Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1alpha,25-(OH)(2)-D(3) and a noncalcemic synthetic analogue of vitamin D(3) (VD(3)) in the Apc(min) mouse. Female Apc(min) mice 4-5 weeks old were randomized to four groups: a VD(3)-treated group (n = 11) were given injections of 0.01 microg of 1alpha,25-(OH)(2)-D(3) i.p. three times per week; an analogue-treated group (n = 10) received 5 microg of 1alpha,25-(OH)(2)-16-ene-19-nor-24-oxo-D(3) i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1alpha,25-(OH)(2)-D(3) or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD(3) groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P < or =0.001). In contrast, serum calcium in the VD(3) group was significantly elevated (P < or =0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD(3) group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apc(min) mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

Adenomatous Polyposis Coli↗
PubMed2002

PC-SPES: herbal formulation for prostate cancer.

PC-SPES is a potent eight-herb formulation sold directly to consumers; it has promising efficacy in the treatment of prostate cancer (CaP). The product induces a castrate status in most, if not all, men, resulting in a 50% or greater prostate-specific antigen reduction in the great majority of men with androgen-dependent CaP and in more than one half of the men with androgen-independent CaP. The duration of response is not yet clear. The efficacy of PC-SPES appears to exceed that of androgen ablation alone, but is not necessarily separate from an estrogenic effect. Common side effects include gynecomastia, nipple tenderness, loss of libido, and impotency; uncommon side effects include a 4% incidence of thromboembolic phenomena, but also two reports of bleeding diatheses. The mechanisms of action may involve downregulation of the androgen receptor, induction of apoptosis by way of inhibition of the bcl-2 gene, and increased expression of p53. Two marker compounds in PC-SPES are baicalin and oridonin, both of which exhibit antiproliferative effects in CaP cell lines. Thousands of men are currently obtaining this nonprescription medicine, and physicians should ask patients specifically about its use. PC-SPES is of great interest in men with androgen-independent CaP, an area in which future research should be primarily directed.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after biliopancreatic diversion for the treatment of morbid obesity.

BACKGROUND: Biliopancreatic diversion (BPD) has been advocated for the treatment of morbid obesity. This procedure has the theoretical advantage that patients retain normal eating capacity and lose weight irrespective of their eating habits. However, vitamin deficiencies may develop because BPD causes malabsorption. OBJECTIVE: This report describes a 40-y-old mother and her newborn infant, who developed vitamin A deficiency as a result of iatrogenic maternal malabsorption after BPD. Our primary objective is to show that BPD patients need close follow-up and lifelong micronutrient supplementation to prevent nutrient deficiencies in themselves and their offspring. DESIGN: The medical records of the mother and infant were reviewed, and their clinical course was followed until 10 mo postpartum. The mother was also interviewed on several occasions about her medical care, follow-up, and supplemental vitamin use. RESULTS: The mother developed night blindness with undetectable serum vitamin A concentrations in the third trimester of her pregnancy. Her vitamin A deficiency was untreated until she delivered her infant. At delivery, the infant also had vitamin A deficiency. He may have permanent retinal damage, but this is still unclear because the ophthalmologic examination performed at 2 mo of age was inconclusive. CONCLUSIONS: Complications of BPD may take many years to develop, and the signs and symptoms may be subtle. Because of the malabsorption that results from BPD, patients need lifelong follow-up and appropriate vitamin supplementation to prevent deficiencies. These nutrient deficiencies can also affect the offspring of female BPD patients.

Adult↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗