p53 is one of the most frequently mutated genes in human tumors including head and neck tumors like oral squamous cell carcinoma. It might be responsible for more than 50% of all relapses in patients with surgically treated oral carcinoma and clean margins. The aim of the present study was to explore p53 protein expression in peritumoral tissue and correlate it with relapse of the disease. The study included 25 patients (17 males and 8 females) with oral squamous cell carcinoma in the period August 2006 till August 2008. For immunohistochemical assay, a monoclonal antibody against p53 protein was applied (clone DO-7, DAKO Glostrup, Denmark). Peritumoral expression of p53 was as follows: 10 out of 25 cases (40%) were negative, 2 cases (8%) showed weak, 5 cases (20%) moderate and 8 cases (32%) strong p53 positivity. No significant correlation between peritumoral expression of p53 protein and patient's relapse was found. In contrast, we found a trend toward association between intratumoral p53 expression and patient's relapse (p = 0.07). There was also trend toward higher peritumoral p53 expression in females comparing with p53 expression in males (52.9% of males did not have p53 expression while 87.5% females had mild, moderate or high p53 expression, p = 0.088). Peritumoral expression of p53 protein is frequently seen in oral squamous cell carcinoma and merits further research.
Summary Mycotoxins are today considered one of the main contaminants of food and feed. Widespread zearalenone and its metabolites have potent estrogenic and anabolic activity, proven in numerous studies worldwide. Th e aim is to investigate infl uence of zearalenone on the uterine weight of rats depending on the applied dose and duration of the observation period. In a controlled experimental study, 63 adult female Wistar rats were divided into three groups, depending on the oral test dose of zearalenone applied: 0.1, 0.3 and 0.5 mg / kg of body weight. At the end of each of the four observation periods of seven days, animals were sacrifi ced under general anesthesia with ether, and aft er an autopsy the mass of the uterus was determined. Zearalenone in the dose of 0.1 mg / kg of body weight has caused a signifi cant increase in uterine weight between the fi rst and fourth observation interval. Doses of 0.3 and 0.5 mg zearalenone / kg caused a decrease in uterine weight, which was at a dose of 0.5 mg / kg highly signifi cant between all observational intervals. Aft er 7 days of applying of the toxin, uterine weights did not diff er signifi cantly with respect to applied dose. Aft er 14, 21 and 28 days, diff erences in uterine weight were highly signifi cant, depending on the dose of zearalenone. Th e results show that prolonged application of large doses of zearalenone produced a signifi cant decrease in uterine weights in experimental animals.
Pacijenti s kroničnom bubrežnom bolešću (HBB) imaju smanjeni odgovor na vakcinaciju zbog općeg slabljenja imunološkog sustava povezanog s uremijom. U odnosu na vakcinaciju u pacijenata bez HBB-a, na primjer, dijalizni pacijenti imaju niži titar antitijela i nemogućnost održavanja adekvatnog titra antitijela tijeNovi protokol vakciNacije pacijeNata Na hemodijalizi protiv hepatitisa B iskustvo jedNog ceNtra
Epithelial–mesenchymal transition (EMT) is a developmental program, which can be adopted by cancer cells to increase their migration and ability to form metastases. Transforming growth factor β (TGFβ) is a well-studied inducer of EMT. We demonstrate that TGFβ potently stimulates hyaluronan synthesis via upregulation of hyaluronan synthase 2 (HAS2) in NMuMG mammary epithelial cells. This stimulatory effect requires the kinase active type I TGFβ receptor and is dependent on Smad signaling and activation of the p38 mitogen-activated protein kinase. Knockdown of HAS2 inhibited the TGFβ-induced EMT by about 50%, as determined by the phase contrast microscopy and immunostaining using the EMT marker ZO-1. Furthermore, real-time PCR analysis of the EMT markers fibronectin, Snail1 and Zeb1 revealed decreased expressions upon HAS2 suppression, using specific small interfering RNA (siRNA) for HAS2. Removal of the extracellular hyaluronan by Streptomyces hyaluronidase or inhibiting the binding to its cell surface receptor CD44 by blocking antibodies, did not inhibit TGFβ-induced EMT. Interestingly, HAS2 suppression completely abolished the TGFβ-induced cell migration, whereas CD44 knockdown did not. These observations suggest that TGFβ-dependent HAS2 expression, but not extracellular hyaluronan, has an important regulatory role in TGFβ-induced EMT.
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