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D Bagheri

Publications and source records attributed to D Bagheri.

8 recordsLinked to original sources
PubMed2000

Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays.

Black tea extracts (hot aqueous, polyphenols and theaflavins) and green tea extracts (hot aqueous, polyphenols, epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate) were tested in nine standardized cell culture assays for comparative cancer chemopreventive properties. Most black and green tea extracts strongly inhibited neoplastic transformation in mouse mammary organ cultures, rat tracheal epithelial cells and human lung tumor epithelial cells. Nearly all tea fractions strongly inhibited benzo[a]pyrene adduct formation with human DNA. Induction of phase II enzymes, glutathione-S-transferase and quinone reductase, were enhanced by nearly all tea fractions, while glutathione was induced by only a few fractions. Ornithine decarboxylase activity was inhibited by nearly all the green tea fractions, but none of the black tea fractions. 12-O-tetradecanoylphorbol-13-acetate-induced free radicals were inhibited by most tea fractions. These results provide strong evidence of both anti-mutagenic, anti-proliferative and anti-neoplastic activities for both black and green tea extracts. Such anticancer mechanisms may well be responsible for the cancer preventive efficacies seen in both experimental and human studies.

Animals↗
PubMed1996

Use of in vitro assays to predict the efficacy of chemopreventive agents in whole animals.

Five in vitro assays have been applied to screen the efficacy of potential chemopreventive agents. These assays measure a) inhibition of morphological transformation in rat tracheal epithelial (RTE) cells, b) inhibition of anchorage independence in human lung tumor (A427) cells, c) inhibition of hyperplastic alveolar nodule formation in mouse mammary organ cultures (MMOC), d) inhibition of anchorage independence in mouse JB6 epidermal cells, and e) the inhibition of calcium tolerance in human foreskin epithelial cells. The efficacy of many of these same agents in whole animal studies of lung, colon, mammary gland, skin, and urinary bladder carcinogenesis has also been measured. The aim herein is to estimate the positive and negative predictive values of these in vitro assays against whole animal chemopreventive efficacy data using the same chemicals. For three of these assays--using RTE, A427 cells and mouse mammary organ culture (MMOC)-enough data are available to allow the estimate to be made. Such extrapolations of in vitro data to the in vivo situation are difficult at best. There are many dissimilarities between the two assay systems. The in vitro assays use respiratory and mammary epithelial cells, while the in vivo assays use respiratory, mammary, colon, bladder and skin cells. The in vitro assays use the carcinogens benzo(a)pyrene (B(a)P) and 7,12-dimethylbenz(a)anthracene (DMBA), while the in vivo assays use B(a)P, DMBA, N-methyl-N-nitrosourea (MNU), N,N'-diethylnitrosamine (DEN), azoxymethane (AOM), and N-butyl-N-(4-hydroxybutyl)nitrosoamine (OH-BBN). There are vast differences in pharmacodynamics and pharmacokinetics in vitro and in vivo, yet it is possible to rapidly screen chemicals in vitro for efficacy at one-tenth the cost and complete tests in weeks instead of months. A positive in vitro assay was defined as a 20% inhibition (compared with control) for the RTE and A427 assays and a 60% inhibition for the MMOC assay at nontoxic concentrations. For in vivo assays, the criterion for a positive result was a statistically significant inhibition of incidence, multiplicity or a significant increase in latency (mean time to first tumor). For an agent to be considered negative in animals, it required negative results in at least two different organ systems and no positive results. Using the battery of three in vitro tests, the positive predictive value for having one, two, or three positive in vitro assays and at least one positive whole animal test was 76%, 80%, and 83% respectively. The negative predictive values for one, two or all three in vitro assays was 25%, 27%, and 50%. From these data it is observed that in vitro assays give valuable positive predictive values and less valuable negative predictive values. The mechanisms of chemoprevention are not well understood. Seven categories of agents were examined for their cancer preventing both in vitro and in vivo: antiinflammatories, antioxidants, arachadonic acid metabolism inhibitors, GSH inducers, GST inducers, ODC inhibitors, and PKC inhibitors. Three or even five in vitro assays cannot be all-inclusive of the many mechanisms of cancer prevention. However, three assays help to predict whole animal efficacy with reasonable positive predictive values. Much work and development remains to be done to rapidly identify new chemopreventive drugs.

Animals↗
PubMed1996

Strategy and planning for chemopreventive drug development: clinical development plans II.

This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs.

Animals↗
PubMed1994

Preclinical efficacy evaluation of potential chemopreventive agents in animal carcinogenesis models: methods and results from the NCI Chemoprevention Drug Development Program.

In the NCI, Chemoprevention Branch drug development program, potential chemopreventive agents are evaluated for efficacy against chemical carcinogen-induced tumors in animal models. This paper summarizes the results of 144 agents in 352 tests using various animal efficacy models. Of these results, 146 were positive, representing 85 different agents. The target organs selected for the animals model are representative of high-incidence human cancers. The assays include inhibition of tumors induced by MNU in hamster trachea, DEN in hamster lung, AOM in rat colon (including inhibition of AOM-induced aberrant crypts), MAM in mouse colon, DMBA and MNU in rat mammary glands, DMBA promoted by TPA in mouse skin, and OH-BBN in mouse bladder. The agents tested may be classified into various pharmacological and chemical structural categories that are relevant to their chemopreventive potential. These categories include antiestrogens, antiinflammatories (e.g., NSAIDs), antioxidants, arachidonic acid metabolism inhibitors, GST and GSH enhancers, ODC inhibitors, protein kinase C inhibitors, retinoids and carotenoids, organosulfur compounds, calcium compounds, vitamin D3 and analogs, and phenolic compounds (e.g., flavonoids). The various categories of compounds have different spectra of efficacy in animal models. In hamster lung, GSH-enhancing agents and antioxidants appear to have high potential for inhibiting carcinogenesis. In the colon, NSAIDs and other antiinflammatory agents appear particularly promising. Likewise, NSAIDs are very active in mouse bladder. In rat mammary glands, retinoids and antiestrogens (as would be expected) are efficacious. Several of the chemicals evaluated also appear to be promising chemopreventive agents based on their activity in several of the animal models. Particularly, the ODC inhibitor DFMO was active in the colon, mammary glands, and bladder models, while the dithiolthione, oltipraz, was efficacious in all the models listed above (i.e., lung, colon, mammary glands, skin, and bladder).

Animals↗
PubMed1993

Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation.

Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta 1 cDNA placed under the control of regulatory elements of the pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the development and function of the mammary gland.

Animals↗
PubMedDate not supplied

A quantitative structure-toxicity relationships model for the dermal sensitization guinea pig maximization assay.

We have developed quantitative structure-toxicity relationship (QSTR) models for assessing dermal sensitization using guinea pig maximization test (GPMT) results. The models are derived from 315 carefully evaluated chemicals. There are two models, one for aromatics (excluding one-benzene-ring compounds), and the other for aliphatics and one-benzene-ring compounds. For sensitizers, the models can resolve whether they are weak/moderate or severe sensitizers. The statistical methodology, based on linear discriminant analysis, incorporates an optimum prediction space (OPS) algorithm. This algorithm ensures that the QSTR model will be used only to make predictions on query structures which fall within its domain. Calculation of the similarities between a query structure and the database compounds from which the applicable model was developed are used to validate each skin sensitization assessment. The cross-validated specificity of the equations ranges between 81 and 91%, and the sensitivity between 85 and 95%. For an independent test set, specificity is 79%, and sensitivity 82%.

Administration, Topical↗