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Biomedical subjects

Y Pan

Publications and source records attributed to Y Pan.

240 records · Page 14Linked to original sources

Soy phytoestrogens improve radial arm maze performance in ovariectomized retired breeder rats and do not attenuate benefits of 17beta-estradiol treatment.

OBJECTIVE: Soy phytoestrogens (SPEs) seem to have beneficial effects on the cardiovascular system with no adverse effects on the breast and uterus. Our objective was to examine the effects of oral estradiol alone, soy protein with phytoestrogens alone, and combinations of estradiol and SPEs on working memory of ovariectomized retired breeder female rats using the radial arm maze test. DESIGN: Eighty-four bilaterally ovariectomized retired breeder female rats were randomized into 12 groups to examine the effects of chronic treatment (10 months) with oral micronized estradiol (0, 0.5, 1, and 2 mg/1,800 Cal), SPEs (0, 72, and 144 mg/1,800 Cal), and all combinations of these doses of estradiol and SPEs on working memory. RESULTS: Oral administration of estradiol or SPEs resulted in a dose-dependent improvement in the performance of the radial arm maze tests. In addition, at each of the three doses of oral micronized estradiol tested, the performance of the radial arm tests was not significantly different in the presence or absence of SPEs. CONCLUSIONS: Our data suggest that SPEs may function as estrogen agonists in improving working memory in the ovariectomized retired breeder female rats and that SPEs do not antagonize the beneficial effects of estradiol on the working memory of these rats. No additional benefits on the radial arm maze test performance were observed with the tested combinations of estradiol and SPEs.

Animals↗

A comparison of oral micronized estradiol with soy phytoestrogen effects on tail skin temperatures of ovariectomized rats.

OBJECTIVE: Whether phytoestrogen-containing soy supplements have beneficial effects on hot flashes of postmenopausal women and how those effects, if any, compare to estrogen replacement therapy has been uncertain. It is possible that the uncertainty is due to the low doses of soy isoflavones (30-60 mg per day) used in the studies. We used ovariectomized retired breeder rats and a higher dose of soy phytoestrogens to approach these uncertainties experimentally. DESIGN: The treatment groups were as follows: (1) Control group fed a casein/lactalbumin-based diet; (2) Soy(-) group fed alcohol-washed soy protein isolate with the phytoestrogens extracted; (3) Soy(+) group fed phytoestrogen-containing soy protein (equivalent to a woman's dose of 144 mg isoflavones per day)--a dose two to three times higher than that in most studies with women; and (4) E2 group fed oral micronized estradiol (E2) at a dose equivalent to a woman's dose of 1 mg per day. A temperature-transponder was taped to the surface of the tail to measure temperature. Tail skin temperature was significantly increased within a week after ovariectomy. The animals were pair-fed during the last 21 days of treatment for daily temperature measurement. RESULTS: Soy(-) had no effect on skin temperature. E2 had a large effect on skin temperature (about 1.4 degrees C reduction from Control). Soy(+) was intermediate between the E2 treatment and no treatment (about 0.8 degrees C reduction from Control). CONCLUSIONS: Soy phytoestrogens have a modest effect on average skin temperatures, being about half that of E2, even at high doses in the rat model.

Administration, Oral↗

Comparison of comparative genomic hybridization, fluorescence in situ hybridization and flow cytometry in urinary bladder cancer.

Comparative genomic hybridization (CGH) was applied to screen the genetic events in six invasive urinary bladder cancers. These cases were also studied by flow cytometry (FCM) and fluorescence in situ hybridization (FISH). Four samples showed partial gain on chromosome 8, with the common region involved was on 8q23-qter. Full or partial deletion on chromosome 2 and 17p in addition to gain on 20q was found in two cases. Interestingly one diploid tumor with low mitotic index, stage and grade showed more genetic aberrations (8 gains and 7 losses) by CGH than other aneuploid tumors with high mitotic index, stage and grade. The numerical chromosomal aberration detected by FISH for chromosomes 7, 8, 9, 10, 11 and 17 were 50% in T1 cases and 100% in T2-T4 cases. FISH was performed on chromosome 8q and 17p to compare and validate the sensitivity of CGH. The agreement was 100% for 8q24 locus and 50% for p53 locus. This indicates that different molecular genetic techniques showed relatively different aspect of genomic aberrations.

Chromosome Aberrations↗

IGF-I triple helix strategy in hepatoma treatment.

BACKGROUND/AIMS: To investigate the effect of gene therapy for hepatocellular carcinoma based on inhibition of cellular IGF-I expression, the technique of IGF-I triple helix was investigated in mice developing programmed hepatoma. METHODOLOGY: mhAT1F1 mouse hepatoma cell line was transfected in vitro with IGF-I triple helix expression vector (pMT-AG-TH) or with IGF-I antisense expression vector (pMT-Anti-IGF-I). 10 x 10(6) transfected cells of either triple helix or antisense type were inoculated intraperitonealy into transgenic ATIIITB6 mice developing genetically programmed hepatoma (mice die between the age of 6 and 7 months). In parallel, human cell cultures established from surgically removed hepatomas were investigated. RESULTS: mhAT1F1 and human primary cell cultures, transfected with pMT-AG-TH or pMT-Anti-IGF-I vectors resulted in total inhibition of IGF-I demonstrated by immunocytochemical and Northern blot techniques. Transfected cells changed their phenotype and recovered major histocompatibility complex I expression showed by fluorescence-activated cell sorting analysis and Western blot. Moreover, two phenomena were observed in IGF-I "antisense" or "triple helix" transfected cells: 1) the apoptosis, demonstrated by TUNEL technique; 2) the presence of IL-6 simultaneously with disappearance of tumor necrosis factor-alpha and IL-10, investigated by reverse transcriptase-polymerase chain reaction technique. In in vivo experiments, injection of murine transfected cells into mice in terminal-phase prolonged their survival 3-4 months in 100% of cases, as well in "antisense" group (8/8) as in "triple helix" group (10/10). CONCLUSIONS: Injection of hepatoma cells transfected with IGF-I triple helix expression vector, and showing immunogenic and apoptotic characteristics, can constitute an effective cellular therapy against hepatocellular carcinoma.

Animals↗

Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer are linked to stage and grade.

Chromosome 8 aberration and c-myc amplification have been suggested as playing important roles in the development of different human cancers. Using fluorescence in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can be detected in cells from bladder cancer. We investigated the correlation of chromosome 8 polysomy, c-myc gene alteration and p53 deletion with histopathological parameters. Twenty-four tumors obtained from patients with bladder cancer were analyzed by interphase cytogenetics using FISH with chromosome 8 and 17 centromere probes together with an YAC clone covering the c-myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8 polysomy was found in 12 tumors. The average copy number of chromosome 8 centromere signals were significantly higher in high grade and stage, cancers. Also the c-myc copy gain and p53 deletion were significantly correlated with grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy (p<0.001). On the contrary there was no significant correlation between c-myc protein over-expression and c-myc gene amplification. These results may indicate that alteration of chromosomal regions on 8q and 17p, including c-myc and p53 genes, may be linked to progression of bladder cancer.

Carcinoma, Transitional Cell↗

Milacemide metabolism in rat liver and brain slices by solids NMR.

The metabolism of 13C- and 15N-labeled milacemide, 2-(pentylamino)-acetamide, has been studied in rat liver and brain slices using solid-state NMR. This analysis is fast and efficient and can be used to monitor both major and minor metabolic pathways in mammalian tissue culture. The NMR work reported herein involves both conventional cross-polarization magic-angle spinning 13C and 15N NMR spectra and rotational-echo double resonance 13C-15N experiments. The latter measure quantitatively the breaking of isotopically labeled carbon-nitrogen chemical bonds. Our results, which are consistent with suggestions from previous metabolic studies, show that the first step in the breakdown of milacemide is the breaking of the pentylamine nitrogen bond to yield pentanoic acid and glycinamide. Total incorporation of 15N label from the resulting glycinamide fragment is comparable in rat liver and brain. In both tissues, considerably more of the 15N label from glycinamide is incorporated than the corresponding 13C label. Differences between the liver and brain tissue are also observed, with more synthesis incorporating the 13C labels taking place in the liver.

Acetamides↗