Human epididymal protein 4 (HE4) is a novel biomarker and a promising prognostic factor in ovarian cancer patients.

PURPOSE OF INVESTIGATION: The aim of this work was to compare serum concentrations of HE4 in patients with benign and malignant epithelial tumors and to determine the association of preoperative concentrations of HE4 with some clinicopathologic factors. METHODS: We enrolled 94 patients, including 39 females with freshly diagnosed ovarian cancer. HE4 concentrations were measured with ELISA HE4 EIA assay from Fujirebio Diagnostics. RESULTS: Serum concentrations of HE4 differed significantly in patients with ovarian cancer (324.1 pM) compared with benign epithelial tumors (26.1 pM; p < 000.1). There was also a significant difference between HE4 concentrations at diagnosis of ovarian cancer (324.1 pM) and in patients with complete clinical remission (23.3 pM; p < 0.0001). Patients with poorly differentiated tumors had significantly higher concentrations of HE4. Preoperative HE4 levels were higher in patients in whom relapse was noted and who died before the end of the two-year follow-up period. CONCLUSION: On the basis of these findings and reports in the literature it appears likely that HE4 can complement CA125 in the monitoring of therapy in ovarian cancer and may also serve for prognostication.

Serum YKL-40 levels in patients with ovarian cancer and women with BRCA1 gene mutation--comparison to CA 125 antigen.

PURPOSE OF INVESTIGATION: Our work was undertaken to determine the usefulness ofYKL-40 as a tumor marker in patients with ovarian cancer and women with BRCA 1 gene mutations. METHODS: Our study population consisted of 111 patients. They were divided into five study groups: I--newly diagnosed ovarian caner, II--recurrence of ovarian cancer, III--complete remission, IV--benign epithelial tumors and V--patients with BRCA 1 gene mutations. YKL-40 and CA 125 were determined in patient sera. RESULTS: YKL-40 in newly diagnosed ovarian cancer patients was significantly higher (181.17 n/ml) than in patients with BRCA 1 gene mutation (97.74 ng/ml, p < 0.01), women with benign epithelial cancer (57.19 ng/ml, p < 0.005) and patients with ovarian cancer at the time of complete remission (58.12 ng/ml, p < 0.005). Taking 124 ng/ml as a cut-off value for YKL-40 (95th percentile for healthly women) we observed higher levels in 50% of patients from group I and in 38% from group II. CONCLUSIONS: YKL-40 appears to demonstrate no advantage over CA 125 as a biomarker of ovarian cancer, particularly in women with early-stage tumors. More research is needed on carriers of the BRCA 1 gene muation in view of the elevated YKL-40 concentrations in this group.

Octapeptide but not nonapeptide from HIV-1 p24gag protein upregulates cell surface HLA-C expression.

OBJECTIVES: The HLA-Cw3 molecule has been reported to present peptides derived from HIV-1 p24gag protein to a cytotoxic T lymphocyte clone. We have shown previously that the synthetic octapeptide 145-152 derived from the p24gag sequence upregulated cell surface HLA-C expression on HLA-Cw*0303+ cells. Here, we examined the question of whether the nonapeptide 144-152 also exerts a similar effect. METHODS: The HLA-Cw*0303+ B-LCL PAJ and control HLA-Cw3-negative cells B-LCL HAJ and T-LCL 500/C9 were used. HLA expression on peptide-pulsed and non-pulsed cells was evaluated using specific antibodies and flow cytofluorimetry. Binding of dansylated peptides onto different cell lines was measured spectrofluorimetrically. RESULTS: The HIV-1 p24gag octapeptide upregulated cell surface HLA-C on PAJ (Cw*0303+) cells, whereas the nonapeptide did not. HLA-A2 expression was not affected by these peptides. Specificity of the effect of octapeptide was confirmed by the lack of HLA-C upregulation on HLA-Cw3- cells and by lower binding of dansylated peptide to the HLA-Cw3- cells HAJ and 500/C9. CONCLUSIONS: The above results indicate that HLA-Cw*0303 preferentially binds the octapeptide rather than the nonapeptide derived from HIV-1 p24gag protein.

[Influence of stimulation and inhibition of adrenergic receptors on ion transport in isolated rabbit trachea in electrophysiologic investigations]. / Oddzialywanie pobudzenia i blokowania receptorów adrenergicznych na transport jonów w izolowanej tchawicy królika w swietle badan elektrofizjologicznych.

Components of neural system in airways interact, and activation of one neural path can influence the releasing of mediators in other neural path. Electrophysiological investigations of mediators-influenced ion transport are one of many possibilities to study interactions between neural system in airway and airway's epithelium. Electrical transepithelial potential difference (PD) and transepithelial resistance (R) of isolated rabbit's tracheal wall were measured by using classical Ussing's method. Two types of stimulations applied on the tracheal mucosa were estimated; namely, the stimulation of adrenergic receptors by epinephrine (AD) and the mechanical stimulation (MS) by stream of fluid. The tissue reacted to both types of stimulations or was unresponsive in relation to both stimulations (Tab. 1). Changes of PD were reactions to AD or MS, whereas R remained without changes (Tab. 1 and 4). Ionic composition of the medium mimicked the composition of extracellular organism fluid. In such medium AD caused persistent depolarization of PD, whereas MS caused transient hyperpolarization of PD (Fig. 1). Regitin (RG) blocker of alpha-adrenergic receptors, beta-blocker propranolol (PR), and inhibition of prostaglandins synthesis by indomethacin diminished reaction of tracheal wall to AD (Tab. 2 and 3). Inhibition of chloride ions secretion by bumetanide diminished the reaction to AD, and lowered reaction to MS (Tab. 2). Inhibition of sodium ions absorption by amiloride had no influence on reaction after AD or after MS (Tab. 2). Indomethacin diminished reaction of the tissue to AD, while the reaction to MS remained without changes (Tab. 2). During the action of AD, RG, or PR reaction of tracheal wall to MS was upheld (Fig. 2, Tab. 4). Maintenance of reaction to MS despite previous influence on adrenergic receptors suggests that the epithelial cells, on the one hand, can be under adrenergic control and react in a manner being dependent on adrenergic system, and on the other hand they can independently respond to exogenous stimuli.

Studies on binding of HIV-1 p24gag peptide to HLA-Cw3+ cells.

Human major histocompatibility complex class I antigens, HLA-C, are expressed on the cell surface at approximately a tenfold lower level than HLA-A and -B. We hypothesized that the expression of HLA-C is limited by the quantity of high affinity peptides which bind to these molecules, thus allowing only a small fraction of HLA-C molecules to be transported and/or to remain stable on the cell surface. If this assumption is correct, then the addition of exogenous peptide should increase cell surface HLA-C expression. To verify the hypothesis, we pulsed lymphoblastoid cell line PAJ (HLA-Cw3+) with synthetic HIV-1 p24gag 145-152 peptide, known to be presented to T-lymphocytes by HLA-Cw3 molecule. PAJ (HLA-Cw3+) cells bound approximately two times more of the peptide than HAJ (HLA-Cw3-), and four times more than 500/C9 (HLA-Cw3-) cells. Accordingly, overnight pulsing of PAJ cells with the p24gag 145-152 peptide caused an increase in class I HLA expression detected on the cell surface by flow cytofluorimetric analysis with anti-HLA-B,C monoclonal antibodies but not by anti-HLA-A antibody. In contrast, HLA-Cw3- cells treated in the same manner did not show any increase of HLA class I expression. Our data suggest that low concentration of high affinity peptides within the cell may be one of the factors limiting cell surface expression of HLA-C molecules.

[Electrophysiologic studies of local ion transport changes in the tracheal wall in vitro]. / Elektrofizjologiczne badania miejscowych zmian transportu jonów w scianie tchawicy in vitro.

It is generally accepted that stimulation of sensory receptors of airways provokes cough reflex and liberates neuropeptides which influence the smooth muscle tonus, mucosal blood flow and secretion of mucus. The study tests the hypothesis that mechanical stimulation of airway wall changes also epithelial ion transport and in this way influences physiological performance of the organ. The global evaluation of ion transport was accomplished by measurements of transepithelial electrical potential difference and resistance of the front part of a wall of isolated rabbit trachea which was mounted in an Ussing apparatus (Fig. 1, Tab. 1). In response to a gentle rinsing of tracheal mucosal surface by isoosmotic bathing fluid it reacted with transient increases of both potential difference and current (Fig. 2, Tab. 2). Gentle touching of the mucosal surface also elicited changes and a stepwise return to the baseline value of potential difference. Application of the stimuli from the antilumenal side usually but not invariably failed to produce any changes in potential difference or current. Measurements of mechanosensitive changes of electrical potential difference in secretory or reabsorptive states of tracheal wall (modelled by inhibition of sodium or chloride transepithelial transport) revealed that according to functional status of epithelium sodium or chloride ions transport changes are responsible for the reactions (Fig. 4). We put forward the hypothesis that mechanosensitive changes of ion transport of airways in vivo could be responsible for adequate changes in the status of respiratory tract epithelial fluid lining during the cough reflex (Fig. 5).