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Abstract  Nuclear factor (NF)-κB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFκB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p = 0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p = 0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p = 0.0109) and bcl-2 (p = 0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta–T1; p = 0.0010 and p = 0.0008) as well as in muscle-invasive carcinomas (T2–T4; p = 0.0004 and p = 0.0003). Our results demonstrate that NF-κB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-κB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators. [ABSTRACT FROM AUTHOR]

Abstract  Glioblastoma, (grade IV astrocytoma), is characterized by rapid growth and resistance to treatment. Identification of markers of aggressiveness in this tumor could represent new therapeutic targets. Interleukins (IL)-6 and IL-10 may be considered as possible candidates, regulating cell growth, resistance to chemotherapy and angiogenesis. ELISPOT method provides a useful tool for the determination of the exact cell number of peripheral lymphocytes secreting a specific cytokine. IL-6 and IL-10 secretion levels were determined using ELISPOT methodology in peripheral blood mononuclear cells of 18 patients with astrocytic neoplasms (3 grade II and 15 grade IV), in parallel with 18 healthy controls. Additionally, immunohistochemical expression of these two cytokines was performed in paraffin-embedded neoplastic tissue in 12 of these patients. The secretion of IL-6 from peripheral monocytes was significantly higher in glioma patients compared to controls (P = 0.0003). In addition, IL-10 secretion from peripheral mononuclear and tumor cells of glioma patients was also higher as compared to healthy controls (P = 0.0002). Based on immunohistochemical staining, IL-6 expression was localized in tumor cells and macrophages as well as in areas of large ischemic necrosis, while the major source of IL-10 expression in glioblastomas was the microglia/macrophage cells. It is suggested that IL-10 contributes to the progression of astrocytomas by suppressing the patient’s immune response, whereas IL-6 provides an additional growth advantage. This study demonstrates for the first time the usefulness of ELISPOT in estimating the secretion of IL-6 and IL-10 from peripheral blood and the correlation of their expression in neoplastic cells. [ABSTRACT FROM AUTHOR]

Abstract  Nuclear factor (NF)-κB is a transcription factor constitutively activated in various neoplasms, including gastric carcinoma. However, its clinical significance in the latter remains an unresolved issue, as published information is limited and controversial. Furthermore, no data is available about the interaction of NFκB with its inhibitory protein IκBa in gastric carcinoma cases. In this study, the expression of NFκB1/p50 and pIκBa protein was evaluated immunohistochemically in paraffin-embedded tissues from 93 patients. The effect of NFκB1/p50 and pIκBa on clinical outcome was assessed. Positive immunostaining was detected for nuclear NFκB1/p50, cytoplasmic NFκB1/p50 and pIκBa in 91, 68 and 85.7% of cases, respectively. A positive correlation emerged between nuclear NFκB1/p50 and pIκBa (p < 0.0001) and a negative one between cytoplasmic NFκB1/p50 and pIκBa (p = 0.0033). Nuclear NFκB1/p50 was associated with stage (p = 0.0388), the depth of invasion (p = 0.0382), World Health Organization (WHO; p = 0.0326) and Lauren’s histological classification (p = 0.0046). NFκB1/p50 nuclear expression adversely affected survival in both univariate and multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results suggest that NFκB1/p50 nuclear expression and therefore activation is regulated by its interaction with IκBa and that the former may serve as a useful independent molecular marker for stratifying patients with gastric carcinoma in terms of prognosis. [ABSTRACT FROM AUTHOR]

AbstractObjective??Cyclooxygenase-2 (COX-2) is the enzyme isoform involved in the synthesis of prostaglandins (PGs) and thromboxane from arachidonic acid. The role of the up-regulation of COX-2 in the formation and progression of gliomas has been dealt with in earlier reports, which describe increased levels of PGs within gliomas. In the present study, we examined the expression of COX-2 in diffuse gliomas of astrocytic origin in relation to microvascular parameters, angiogenic factors and survival.Materials and methods??A total of 83 cases of diffuse astrocytomas (grade II?IV) were analyzed by immunohistochemistry for the presence of COX-2.Results??COX-2 expression was detected in 79 cases (95%) with an increased expression in grade IV as compared to grades II/III (p?=?0.024). A positive correlation occurred between COX-2 and angiogenic factors such as vascular endothelial growth factor (VEGF) (p< 0.0001) and hypoxia inducible factor (HIF)-1? (p?=?0.005), as well as the tumours? proliferative activity (expressed as the percentage of Ki-67 positive cells) (p?=?0.032), and total vascular area (TVA) (p?=?0.040). In univariate analysis, COX-2 was associated with shortened survival (p?=?0.050). Multivariate survival analysis showed that the interaction model of COX-2 with grade along with age were the only significant prognostic indicators.Conclusion??These results implicate COX-2 in the angiogenesis and biological aggressiveness of diffuse astrocytomas, and suggest that it would be worthwhile to examine how the inhibition of COX-2 expression may influence astrocytoma patients? survival. [ABSTRACT FROM AUTHOR]

Creutzfeldt–Jakob disease (CJD) is a fatal transmissible neurodegenerative prion disease with a rapid progression comprising familial, sporadic, iatrogenic and variant forms. A polymorphism at codon 129 of PRNP gene has been implicated in the development of variant CJD. We examined Met/Val allele frequencies and the genotype distribution, with respect to the polymorphic codon 129 of PRNP gene in 348 healthy individuals from the region of Athens, Greece. The following genotype frequencies were observed in the Greek population: Met/Met 50%, Met/Val 39% and Val/Val 11%. The presence of the Methionine allele frequencies in various European populations, according to the published data, increases gradually from northwestern to southeastern countries, implying the presence of a cline. The distribution of genotypes of Met homozygotes displays random declination across the 10 compared populations. The observed higher frequency of Met homozygotes at codon 129 does not necessarily suggest that these populations are at increased risk of developing CJD. [ABSTRACT FROM AUTHOR]