Role of SP-1 in SDS-Induced Adipose Differentiation Related Protein Synthesis in Human Keratinocytes

Skin irritation is a complex phenomenon, and keratinocytes play an important role in it. We have recently characterized the expression and protective role of adipose differentiation related protein (ADRP) in skin irritation. In particular, ADRP expression is induced to recover functional cell membrane following the cell damage caused by skin irritants

Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker

Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes

Delayed diagnosis of coeliac disease increases cancer risk

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Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial

Background Results from small randomised trials on tamoxifen in the treatment of hepatocellular carcinoma (HCC) are conflicting, We studied whether the addition of tamoxifen to best supportive care prolongs survival of patients with HCC. Methods Patients with any stage of HCC were eligible, irrespective of locoregional treatment. Randomisation was centralised, with a minimisation procedure accounting for centre, evidence of disease, and time from diagnosis. Patients were randomly allocated best supportive care alone or in addition to tamoxifen, Tamoxifen was given orally, 40 mg per day, from randomisation until death. Results 496 patients from 30 institutions were randomly allocated treatment from January, 1995, to January, 1997. Information was available for 477 patients. By Sept 15, 1997, 119 (50%) of 240 and 130 (55%) of 237 patients had died in the control and tamoxifen arms, respectively. Median survival was 16 months and 15 months (p=0.54), respectively, No differences were found within subgroups defined by prognostic variables. Relative hazard of death for patients receiving tamoxifen was 1.07 (95% CI 0.83-1.39). Interpretation Our findings show that tamoxifen is not effective in prolonging survival of patients with HCC

Effects of illicit dexamethasone and 17\u3b2-oestradiol on the expression of hepatic and testicular bovine responsive genes

Introduction. Since 1996, the use of growth promoters (GPs) in cattle fattening is banned at the European Union level. Despite this, the continuous illicit use of anabolic steroids (mainly androgens and estrogens), glucocorticoids (i.e. dexamethasone: DEX) or newly synthetic compounds has been demonstrated [1-2]. Besides analytical methods, a recent possible approach to detect illicit treatments consists in the identification of indirect molecular biomarkers (BMs) of effect in target tissues [3]. Therefore, a study was run in beef cattle administered illicitly either DEX or a combination of DEX plus oestradiol (OE). Pre-transcriptional effects of these GPs were investigated in liver and testis by using a set of candidate genes, including major drug metabolizing enzymes, their transcription factors and receptors as well as TAT gene, and a quantitative Real Time RT-PCR (QRT-PCR) approach. Materials and Methods. Eighteen French cross-bred beef cattle (about 500 kg bw, 13-18 months old) were used. They were divided into three groups: controls (n=6), DEX (n=6) and DEX+OE (n=6). DEX was given per os (0,75 mg/day for 42 days, layered on unifeed), while OE (20 mg) was injected sub cutis three times. Animals were slaughtered four days after the suspension of DEX administration. Liver and testis aliquots were collected in RNAlater\uae and stored at -80\ub0C. Total RNA was extracted by using Invisorb\uae Spin Tissue RNA Mini Kit. Primers sequences for Q RT-PCR were designed by using Primer Express Software. Data were expressed as \u2013fold change compared with controls group. The \u3b2-actin was considered as the reference gene. Results. In the liver CYP2B22 and CYP2E1 were significantly down-regulated in both treated groups. By contrast, CYP3A28, GSTA1-like, SULT1A1-like, RXR\u3b1-like and ER\u3b1-like were significantly up-regulated in DEX+OE group only. At the testis level, only CYP1A1 gene expression profile was significantly increased in DEX group; besides, CYP2E1 (in contrast to the liver) and ER\u3b1-like gene expression were significantly positively modulated only in DEX+OE group. Discussion and conclusion. In the present study, the effects of DEX, illicitly used alone or in combination with OE, were investigated at the pre-transcriptional level in cattle liver and testis. This latter was considered as a prototypical surrogate tissue. Most of genes known to be expressed in the liver were found to be constitutively expressed in the testis, too. As a whole, gene patterns of expression were similar in both tissues; however, some genes (i.e., ER\u3b1-like) were affected likewise (induction); some other, instead, were differentially modulated by GPs (i.e., CYP1A1 and CYP2E1). Molecular mechanisms by which GPs alter gene expression profiles in cattle target tissues are still unknown; therefore, further studies are required to increase knowledge on cattle responses to GPs, aiming to set up and validate BMs of exposure to assist official analytical methods in the screening of illicit GPs abuse in cattle fattening

Effects of illicit growth promoters upon steroidogenic enzyme gene expression profiles in cattle testis.

Recently, the effect of illicit growth promoters (GPs) upon cattle transcriptome have excited increasing interest within the scientific community. In the present study, pre-transcriptional effects of three illicit protocols upon most of cattle steroidogenic enzymes were investigated. Beef cattle were administered with: (A), dexamethasone, given either orally (DOS) or intramuscularly (DIM); (B), dexamethasone, alone (DOSS) or together with 17\u3b2-oestradiol (DOE); (C), dehydroepiandrosterone (DHEA) and 1,4-androstadiene-3,17-dione (ADD), orally administered either alone (DHEA, ADD) or in association (DHAD). The effect upon eight testicular steroidogenic enzymes and four nuclear receptors were measured by a quantitative Real Time RT-PCR approach. Significant (p<0.05, p<0.01), albeit not univocal, results were obtained. A GP-dependent effect was observed upon P450c17 and the mineralcorticoid-like receptor gene (experiment A, DIM group); P450c17, 3\uf062-HSD and 3\uf062-HSD, 17\uf062-HSD , estrogen receptor alpha (experiment B, DOSS and DOE, respectively); P450 aromatase, P450scc, 3\uf062-HSD and the androgen receptor gene (experiment C, DHEA and DHAD, respectively). Present results suggest that different GPs schedules are likely to affect most of genes involved in gonadal steroid synthesis. Consequently, testis might be hypothetically considered as a potential surrogate tissue, whose usefulness in the screening of GPs abuse has to be investigated more in depth

Constitutive expression of drug metabolizing enzymes and related transcription factors in cattle testis and their modulation by illicit steroids

In veterinary species, little information about extrahepatic drug metabolism is actually available. Therefore, the presence of foremost drug metabolizing enzymes (DMEs) and related transcription factors mRNAs was initially investigated in cattle testis; then, their possible modulation following the in vivo exposure to illicit growth promoters (GPs), which represent a major issue in cattle farming, was explored. All target genes were expressed in cattle testis, albeit to a lower extent compared to liver ones; furthermore, illicit protocols containing dexamethasone and 17\u3b2-oestradiol significantly up-regulated cytochrome P450 1A1, 2E1, oestrogen receptor-\u3b1 and peroxisome proliferator-activated receptor-\u3b1 mRNA levels. Overall, the constitutive expression of foremost DMEs and related transcription factors was demonstrated for the first time in cattle testis and illicit GPs were shown to affect pre-transcriptionally some of them, with possible consequences upon testicular xenobiotic drug metabolism

Steroidogenic enzyme gene expression profiles in the testis of cattle treated with illicit growth promoters

Recently, the effect of illicit growth promoters (GPs) upon the cattle transcriptome has drawn the increasing attention of the scientific community. In the present study, the pre-transcriptional effects of three different illicit protocols on a set of target genes, including steroidogenic enzymes and three related transcription factors, were estimated in cattle testis. Beef cattle were administered with dexamethasone (DEX) orally (group D(1)) or intramuscularly in experiment 1 (group DIM). In experiment 2, DEX was orally administered alone (group D(2)) or with 17\u3b2-estradiol (group DE), and in experiment 3, dehydroepiandrosterone and boldione were orally administered alone (group DHEA and group ADD) or in combination (group DHAD). The GP effects were measured by quantitative real time RT-PCR. The results of our study were significant but not univocal. A GP-dependent effect on target gene mRNA levels was noticed for 3\u3b2-hydroxysteroid dehydrogenase type 1 (HSD3\u3b21,p<0.05 and p<0.01 for the D(2), DE and DHAD groups, respectively), the cytochrome P450 side chain cleavage (DHAD, p<0.05), the cytochrome P450 17A1 (DIM and D(2), p<0.05), HSD17\u3b23 (DE, p<0.05), aromatase (DHEA, p<0.05), the androgen receptor (DHAD, p<0.05) and the mineralocorticoid receptor-like (DIM, p<0.05). Our present results suggest that different GP schedules are likely to affect genes involved in steroid synthesis and regulation in cattle testis. Thus, this tissue might be considered a potential surrogate tissue that warrants further study into its usefulness in the screening of GP abuse