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NF-kB pathway is activated and COX-2 expression is upregulated in stromal myofibroblasts surrounding colon adenocarcinomas compared to normal colon. Induction of COX-2 expression is primarily induced by NF-kB. NSAIDs, selective COX-2 inhibitors and PPARgamma ligands may exert their chemoprophylactic properties through direct actions on these cells.

Identification of AR-positive gastric carcinomas in gastric biopsies may warrant a more aggressive therapeutic approach and anti-androgen or AR-targeted agents may represent a novel strategy in tackling this devastating malignancy.

Objectives:To investigate the expression of nuclear factor-kB (NF-kB) and estrogen receptor-b (ER-b) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Methods: Immunohistochemical methodology was carried out on formalin-fixed , paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-b and NF-kB, and tumor grade and T-stage were evaluated , along with demographic data, sex and age. Results: A significant decrease in ER-b expression in the nucleus of bladder cells during loss of cell differentiation (rs = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kB was shown. No correlation between NF-kB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-b and nuclear p65 immunoreactivity was observed (rs = -0.45, P-value < 0.001). There was no correlation with demographic data. Conclusions: Our immunohistochemical study suggests the possible inverse regulation of NF-kB and ER-b transcription factor during bladder carcinogenesis. Selective ER-b agonists and agents, inhibitors of NF-kB, might represent a possible new treatment strategy for bladder urothelial tumors.

Estrogen receptors alpha (ERα) and beta (ERβ) and their co-regulatory proteins are key components of complex signaling networks that specifically regulate the growth and development of various tissues and tumors. Still, their protein expression profiles and possible role in the pathogenesis of astrocytic tumors remain largely unknown. The purpose of the present study is to evaluate the differential protein expression of ΕRα, ERβ, and their co-activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health Organization (WHO) grade II-IV, using immunohistochemistry. Potential correlations with clinicopathological parameters and patient prognosis were also explored. ERα protein expression was undetectable while ERβ levels were significantly decreased with progression of tumor grade (P < 0.001). High expression of ERβ was an independent favorable prognostic factor on multivariate analysis (P = 0.003). Expression of AIB1, TIF2, and PELP1 was not correlated with ERβ expression and followed an opposite trend, with increasing levels in high-grade relative to low-grade tumors (P < 0.001). Univariate survival analysis revealed that high AIB1, TIF2, and PELP1 expression was associated with worse prognosis (P = 0.049, P = 0.033, and P = 0.020, respectively). ERβ and ER co-activators AIB1, TIF2, and PELP1 appear to play an important role in the pathogenesis and progression of astrocytic tumors and might have prognostic significance. The mechanisms underlying their involvement in astrocytic tumorigenesis, as well as their utility for prognostic and therapeutic purposes merit further investigation.