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1.
DC Chhieng AR Frost S Niwas H Weiss WE Grizzle S Beeken 《Biotechnic & histochemistry》2013,88(1):25-36
Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA. 相似文献
2.
Houssen ME Haron MM Metwally SS Ibrahim TM 《Journal of physiology and biochemistry》2011,67(1):115-120
Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immuno-inflammatory mechanisms are
involved. Inflammatory cytokines are implicated in the development and progression of atherosclerotic lesions. Immunomodulatory
therapies have been proposed for the treatment of atherosclerosis. Therefore, the aim of this study was to investigate the
systemic anti-inflammatory and immunomodulatory effects of atorvastatin, cyclosporine A (CsA), and tacrolimus (FK506) on plasma
inflammatory markers in atherosclerotic rabbits. Male New Zealand rabbits were randomized into five groups each of 12 animals.
Standard diet-fed group served as control, and the cholesterol-fed group received a diet supplemented with 1% cholesterol
alone, cholesterol + atorvastatin, cholesterol + FK506, and cholesterol + CsA. Serum levels of lipid profile parameters (triglycerides,
cholesterol, and high-density lipoprotein) were measured using colorimetric methods. Serum levels of C-reactive protein (CRP),
interleukin-6 (Il-6), and interferon-gamma (INF-γ) were measured in all studied groups using ELISA techniques. Our results
revealed a significant decrease (p < 0.001) in the serum levels of lipid profile parameters, CRP, Il-6, and INF-γ in atorvastatin-treated group compared with
the cholesterol-fed group. On the other hand, a non-significant difference was observed for the same parameters in either
FK506- or CsA-treated groups compared with the cholesterol-fed group. In conclusion, atorvastatin has a systemic anti-inflammatory
role that far surpassed the cholesterol reduction effect alone. FK506 or CsA failed to suppress elevated plasma inflammatory
markers. Thus, low doses of these two immunomodulating drugs could not have generalized systemic anti-inflammatory or immunosuppressive
effects. 相似文献
3.
Badria FA Dawidar AA Houssen WE Shier WT 《Zeitschrift für Naturforschung. C, Journal of biosciences》2005,60(1-2):139-142
There is a wealth of evidence that hepatic stellate cells (HSCs) orchestrate most of the important events in liver fibrogenesis. After liver injury, HSCs become activated to a profibrogenic myofibroblastic phenotype and can regulate net deposition of collagens and other matrix proteins in the liver. The proliferation of HSCs is mainly stimulated by the platelet-derived growth factor (PDGF). In this study, some compounds from natural resources have been tested for their activity to inhibit PDGF-driven proliferative activity of rat HSCs. Apigenin, quercetin, genistein, daidzin, and biochanin A exhibited > 75% inhibitory activity against HSC-T6. It was found that, gamma-linolenic (gamma-Ln), eicosapentanoic (EPA) and a- linolenic (alpha-Ln) acids showed a high inhibitory effect on proliferation of rat HSCs at 50 nmol/1. Cholest-4-ene-3,6-dione and stigmastone-4-en-3,6-dione are the most active steroids with inhibitory activities > 80% and this is most likely due to the presence of the 4-en-3,6-dione moiety in both compounds. These results revealed that the compounds which effectively blocked HSC proliferation may be beneficial in liver fibrosis. Structure-activity relationships (SAR) may provide a basis for rational structure modification. 相似文献
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M. E. Shaker M. E. Houssen E. M. Abo-Hashem T. M. Ibrahim 《Journal of physiology and biochemistry》2009,65(3):225-233
This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl4 and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride
(CCl4) (1 ml/kg/3days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day,
i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter,
changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH)
content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In
CCl4-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy
order was vitamin E ≥ melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective
than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl4 and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant
actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was
nearly the same in CCl4 and diabetes-induced liver damage. 相似文献
6.
Early evolution of metazoan serine/threonine and tyrosine kinases: identification of selected kinases in marine sponges 总被引:14,自引:1,他引:13
The phylum Porifera (sponges) was the first to diverge from the common
ancestor of the Metazoa. In this study, six cDNAs coding for protein-
serine/threonine kinases (PS/TKs) are presented; they have been isolated
from libraries obtained from the demosponges Geodia cydonium and Suberites
domuncula and from the calcareous sponge Sycon raphanus. Sequence
alignments of the catalytic domains revealed that two major families of
PS/TK, the "conventional" (Ca(2+)-dependent) protein kinase C (PKC), the
cPKC subfamily, as well as the "novel" (Ca(2+)- independent) PKC (nPKC),
form two separate clusters. In each cluster, the sequence from S. raphanus
diverges first. To approach the question about the origin of
protein-tyrosine kinases (PTK), which are found only in Metazoa, we
analyzed two additional PS/TKs which have been cloned from S. domuncula:
the stress-responsive protein kinase (KRSvSD) and the
protein-kinase-C-related kinase (PRKvSD). The construction of the
phylogenetic tree, comprising the eight PS/TKs and the PTK cloned
previously from G. cydonium, revealed that the PTK derived from the branch
including the KRSvSD kinase. These data facilitate the first molecular
approach to elucidate the origin of metazoan PTK within the PS/TK
superfamily.
相似文献
7.
A cultured rat ovarian cell line (31 A-F(2)) was used to study the effect of growth factors (epidermal growth factor [EGF] and fibroblast growth factor [FGF]), a survival factor (ovarian growth factor [OGF]), a hormone (insulin), and an iron-binding protein (transferring) on cell proliferation and steroid production under defined culture conditions. EGF and insulin were shown to be mitogenic (half-maximal response at 0.12 nM and 0.11 muM, respectively) for 31A-F(2) cells incubated in serum-free medium. EGF induced up to three doublings in the cell population, whereas insulin induced an average of one cell population doubling. FGF, OGF, and transferrin were found not to have any prominent effect on cell division when incubated individually with 31A-F(2) cells in serum-free medium. However, a combination of EGF, OGF, insulin, and transferrin stimulated cell division to the same approximate extent as cells incubated in the presence of 5 percent fetal calf serum. EGF or insulin did not significantly affect total cell cholesterol levels (relative to cells incubated in serum-free medium) when incubated individually with 31A-F(2) cells. However, cell cholesterol levels were increased by the addition of OGF (250 percent), FGF (370 percent), or a combination of insulin and EGF (320 percent). Progesterone secretion from 31A-F(2) cells was enhanced by EGF (25 percent), FGF (80 percent), and insulin (115 percent). However, the addition of a mitogenic mixture of EGF, OGF, insulin, and transferrin suppressed progesterone secretion 150 percent) below that of control cultures. These studies have permitted us to determine that EGF and insulin are mitogenic factors that are required for the growth of 31A-F(2) cells and that OGF and transferrin are positive cofactors that enhance growth. Also, additional data suggest that cholesterol and progesterone production in 31A-F(2) cells can be regulated by peptide growth factors and the hormone insulin. 相似文献
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We have identified a novel N -acetylgalactosaminyltransferase activity in
lactating bovine mammary gland membranes. Acceptor specificity studies and
analysis of products obtained in vitro by 400 MHz1H-NMR spectroscopy
revealed that the enzyme catalyses the transfer of N - acetylgalactosamine
(GalNAc) from UDP-GalNAc to acceptor substrates carrying a terminal,
beta-linked N -acetylglucosamine (GlcNAc) residue and establishes a
beta1-->4-linkage forming a GalNAcbeta1-->4GlcNAc ( N, N
'-diacetyllactosediamine, lacdiNAc) unit. Therefore, the enzyme can be
identified as a UDP-GalNAc:GlcNAcbeta-R beta1-->4-N-
acetylgalactosaminyltransferase (beta4-GalNAcT). This enzyme resembles
invertebrate beta4-GalNAcT as well as mammalian beta4-
galactosyltransferase (beta4-GalT) in acceptor specificity. It can,
however, be clearly distinguished from the pituitary hormone-specific
beta4-GalNAcT by its incapability of acting with an elevated activity on a
glycoprotein substrate carrying a hormone-specific peptide motif.
Furthermore, the GalNAcT activity appeared not to be due to a promiscuous
action of a beta4-GalT as could be demonstrated by comparing the
beta4-GalNAcT and beta4-GalT activities of the mammary gland, bovine
colostrum, and purified beta4-GalT, by competition studies with UDP-GalNAc
and UDP-Gal, and by use of an anti-beta4-GalT polyclonal inhibiting
antibody. Interestingly, under conditions where mammalian beta4-GalT forms
with alpha-lactalbumin (alpha-LA) the lactose synthase complex, the mammary
gland beta4-GalNAcT was similarly induced by alpha-LA to act on Glc with an
increased efficiency yielding the lactose analog GalNAcbeta1-->4Glc.
This enzyme thus forms the second example of a mammalian
glycosyltransferase the specificity of which can be modified by this milk
protein. It is proposed that the mammary gland beta4-GalNAcT functions in
the synthesis of lacdiNAc- based, complex-type glycans frequently occurring
on bovine milk glycoproteins. The action of this enzyme is to be considered
when aiming at the production of properly glycosylated protein
biopharmaceuticals in the milk of transgenic dairy animals.
相似文献