Clinical significance of serum epithelial cell adhesion molecule (EPCAM) levels in patients with lung cancer

Cellular adhesion molecules might be good markers in some types of malignant tumors, thus providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of epithelial cell adhesion molecule (EPCAM) in lung cancer patients. One hundred and thirty lung cancer patients were enrolled in this study. Serum EPCAM levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 34 healthy controls were included in the analysis. The median age was 58 years, ranging 35–80 years. The majority of the patients had NSCLC (83.8 %) and stage IV disease (60.8 %). There was no significant difference in the serum EPCAM levels between lung cancer patients and healthy controls (p = 0.16). Moreover, known clinical variables including age of patient, gender, histology, stage of disease, and response to chemotherapy were not found to be correlated with serum EPCAM concentrations (p > 0.05). Similarly, no prognostic role was found for outcome (1-year survival rate 62 vs. 65.1 %, p = 0.89). In conclusion, serum EPCAM concentrations have no diagnostic, predictive, and prognostic roles in lung cancer patients.     

Effect of penconazole and drought stress on the essential oil composition and gene expression of Mentha pulegium L. (Lamiaceae) at flowering stage

Effect of penconazole (PEN) on the expression level of two genes in the biosynthesis pathway of monoterpenes, isopiperitenone reductase (iPR) and pulegone reductase (PR), and essential oil (EO) compounds were studied at flowering stage of Mentha pulegium L. under drought stress. Plants were grown with different levels of field capacity (100 and 50 %) with or without PEN (15 mg l^?1). Results showed that drought stress decreased the growth and productivity parameters. PEN treatment to drought-stressed plants decreased the negative effects of drought stress on these parameters. The EO yield increased by about 1.6 times under drought stress, and the highest amount of EO was obtained in drought-stressed with PEN. Drought stress increased pulegone and decreased menthone percentage, and the highest pulegone percentage (78.2 % of total constituents) was obtained in drought-stressed with PEN treatment. Semi-quantitative RT-PCR showed drought stress increased the expression level of iPR and PR genes. PEN treatment promoted the impact of drought stress on iPR gene expression and repressed PR gene expression. Our results suggest that PEN may be a useful tool for the regulation of monoterpene metabolism in M. pulegium under stress condition.     

Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia

Background

ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL) and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients.

Materials and Methods

Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9) and healthy donors (n = 6). IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay.

Results

The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05).

Conclusion

ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.     

An assessment of the uses of homologous interactions

MOTIVATION: Protein-protein interactions have proved to be a valuable starting point for understanding the inner workings of the cell. Computational methodologies have been built which both predict interactions and use interaction datasets in order to predict other protein features. Such methods require gold standard positive (GSP) and negative (GSN) interaction sets. Here we examine and demonstrate the usefulness of homologous interactions in predicting good quality positive and negative interaction datasets. RESULTS: We generate GSP interaction sets as subsets from experimental data using only interaction and sequence information. We can therefore produce sets for several species (many of which at present have no identified GSPs). Comprehensive error rate testing demonstrates the power of the method. We also show how the use of our datasets significantly improves the predictive power of algorithms for interaction prediction and function prediction. Furthermore, we generate GSN interaction sets for yeast and examine the use of homology along with other protein properties such as localization, expression and function. Using a novel method to assess the accuracy of a negative interaction set, we find that the best single selector for negative interactions is a lack of co-function. However, an integrated method using all the characteristics shows significant improvement over any current method for identifying GSN interactions. The nature of homologous interactions is also examined and we demonstrate that interologs are found more commonly within species than across species. CONCLUSION: GSP sets built using our homologous verification method are demonstrably better than standard sets in terms of predictive ability. We can build such GSP sets for several species. When generating GSNs we show a combination of protein features and lack of homologous interactions gives the highest quality interaction sets. AVAILABILITY: GSP and GSN datasets for all the studied species can be downloaded from http://www.stats.ox.ac.uk/~deane/HPIV.     

The effects of the caffeic acid phenethyl ester (CAPE) on erythrocyte membrane damage after hind limb ischaemia-reperfusion

Reactive oxygen species have been implicated in pathogenesis injury after ischaemia-reperfusion (I/R). Caffeic Acid Phenethyl Ester (CAPE), an active component of honeybee propolis extract, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of CAPE on erythrocyte membrane damage after hind limb I/R. Rats were divided into two groups: I/R and I/R with CAPE pre-treatment. They were anaesthetized with intramuscular ketamine 100 mg kg(-1). A 4-h I/R period was performed on the right hind limb of all animals. In the CAPE-treated group, animals received CAPE 10 microm by intraperitoneal injection 1 h before the reperfusion. At the end of the reperfusion period, a midsternotomy was performed. A 5-ml blood sample was withdrawn from the ascending aorta for biochemical assays. Serum and erythrocyte membrane MDA levels were significantly lower in the CAPE-treated group when compared to the I/R group ( p = 0.001 and p<0.001, respectively). Erythrocyte membrane Na(+)-K(+) ATPases activity in the CAPE-treated group was significantly higher than the I/R group ( p<0.001). In conclusion, CAPE seems to be effective in protecting against oxidative stress. Therefore, we suggest that in order to decrease I/R injury, pre-administration of CAPE may be a promising agent for a variety of conditions associated with I/R.     

Human chorionic gonadotropin contributes to maternal immunotolerance and endometrial apoptosis by regulating Fas-Fas ligand system

The first known hormonal signal of the conceptus during implantation is human chorionic gonadotropin (hCG). Interestingly, increased apoptosis in human endometrium coincides with the implantation window. Factors from the fetal or placental origin as well as maternal hormonal factors are likely to have a potential role in the regulation of apoptotic signaling molecules. We hypothesized that hCG may be a placental link for the development of local maternal immunotolerance. Fas-Fas ligand (FasL) system is one of the apoptotic signaling pathways, shown to be important in the development of local immune tolerance during and after implantation. We report that hCG treatment decreases cell proliferation and increases apoptosis in endometrial cells. Moreover, hCG stimulates FasL mRNA and protein expression without affecting Fas mRNA in these cells. Interestingly, in coculture experiments, hCG-treated endometrial cells induce an increase in T cell apoptosis. Our in vivo results reveal that cells of early pregnancy decidua express strong FasL immunoreactivity, and decidual areas containing interstitial cytotrophoblasts have numerous TUNEL-positive cells. Compared with decidual areas devoid of interstitial cytotrophoblasts, we observed in decidual areas containing interstitial cytotrophoblasts clearly less amount of TUNEL-positive cells. These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance and may facilitate the trophoblast invasion by regulating proapoptotic molecules such as FasL in endometrial cells.