High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma.

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells' proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients' survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma.

Elevated Farnesoid X Receptor (FXR) and Retinoid X Receptors (RXRs) expression is associated with less tumor aggressiveness and favourable prognosis in patients with pancreatic adenocarcinoma.

UNLABELLED: Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are considered to participate in crucial biochemical and cellular processes, being involved in the pathogenesis of several diseases, including cancer. The present study aimed to evaluate the clinical significance of FXR alone and in conjunction with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-α, -ß and -γ protein expression was assessed immunohistochemically on tumoral samples of 55 pancreatic adenocarcinoma cases and was statistically analyzed with clinicopathological characteristics, tumor proliferative capacity and patients' survival. Enhanced FXR expression was borderline associated with earlier histopathological stage (p=0.054). Concomitant elevated FXR/RXR-α expression was significantly associated with decreased tumor histological grade (p=0.017), while concomitant enhanced FXR/RXR-ß and FXR/RXR-γ expression with earlier histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-γ expression was additionally significantly associated with the absence of lymph node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR, FXR/RXR-ß or -γ expression showed significantly longer survival times compared to those with low expression (p=0.013, p=0.021 and p<0.001, respectively). In multivariate analysis, FXR and FXR/RXR-γ expression were identified as independent prognostic factors (p=0.044 and p=0.001, respectively). CONCLUSION: The present study suggested that FXR and RXRs were implicated in pancreatic malignant disease progression, reinforcing their utility as clinical markers for patients' management and prognosis, as well as targets for potential therapeutic interventions. KEYWORDS: FXR, RXR, pancreatic adenocarcinoma, immunohistochemistry, clinicopathological parameters, patients' survival.

Platelet-activating factor (PAF) receptor expression is associated with histopathological stage and grade and patients' survival in gastric adenocarcinoma.

Platelet activating factor (PAF) has been considered as potent inflammatory lipid mediator that exerts its actions by binding to PAF receptor (PAFR). PAF/PAFR system has been implicated in several pathophysiological states, including tumor progression, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of PAFR expression in gastric adenocarcinoma. PAFR protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation with clinicopathological parameters, tumor proliferative capacity and patients' survival. PAFR was abundantly expressed in all gastric adenocarcinoma cases examined. Increased PAFR expression was significantly more frequently observed in well/moderately compared to poorly differentiated gastric adenocarcinoma cases (p=0.011). PAFR expression was significantly increased in intestinal- compared to diffuse-type cases (p=0.020). Elevated PAFR expression was significantly associated with smaller tumor size, absence of lymph node and organ metastasis and low tumor histopathological stage (p=0.025, p<0.001, p=0.009 and p<0.001, respectively). Additionally, patients presenting elevated PAFR expression had significantly longer survival times compared to those with low PAFR expression (log-rank test, p<0.001). These results support an important potential role of PAFR signalling in gastric malignant disease progression and render further research in this field a necessity.

Clinical significance of Src expression and activity in human neoplasia.

Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient's survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1): a novel biomarker in the diagnosis and prognosis of human neoplasia.

The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumor-associated antigen that induces cell-cycle arrest and/or apoptosis in RCAS1 receptor-bearing human cells. Current evidence has revealed enhanced RCAS1 expression in the tumor malignant stage of several organs, which may play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. In the last few years, tissue RCAS1 protein expression and circulating levels in biofluids have further been the focus of extensive research as a diagnostic and prognostic marker in several human malignancies. The present article aimed to review the available data so far concerning the clinical significance of RCAS1 in human neoplasia. Reviewing of English literature revealed that tissue RCAS1 expression was associated with important clinicopathological parameters for patients' management and prognosis, being considered as an informative biomarker in several types of human malignancy. In addition, the current evidence supported a crucial role for RCAS1 in tumor immune escape, which renders this receptor a promising target for future (gene) therapeutic approaches. However, the clinical application of circulating RCAS1 concentrations in biofluids as a marker in the management and prognosis of tumor malignancies needs to be further explored, since the data so far are still extremely limited.

Application of the ion pair concept to the n-octanol-water partitioning of cefepime and cefpirome.

The ion pair concept was applied for the assessment of lipophilicity of cefepime and cefpirome. Octanol-water distribution coefficients were determined in presence of different concentrations [X-] of sodium octanesulphonate. The log Dx values within the linear part of the log Dx/[X-] relationships were extrapolated to log Do values corresponding to the partitioning in absence of the counter ion. Measurements were feasible at pH values close to the isoelectric points of the acidic and basic functions. In that pH range the conduction of the experiments in presence of the hydrophobic counter anion facilitated the partitioning of the two cephalosporins to octanol, circumventing the problems arising from their high hydrophilicity. This procedure could not be applied at lower pH, possibly due to a further drastic decrease in the 'intrinsic' lipophilicity or to reduced ion pairing potential of octanesulphonate, and at higher pH due to the disruption of the zwitterionic structure. Extrapolated log Do values were compared to actual log D measurements performed for a reference quinolinium compound and for cefpirome. Extrapolated retention factors log kw close to the isoelectric point were also determined by reversed phase HPLC and compared to the log Do values.