Nuclear maspin expression as a good prognostic factor in human epithelial ovarian carcinoma.

Maspin, a protein belonging to the serpin superfamily, seems to exert tumour-suppressive activity. Its significance in ovarian cancer prognosis is currently under investigation. In the present work, immunocytochemical maspin expression in 132 invasive epithelial ovarian carcinomas was assessed independently in the nucleus and cytoplasm, in correlation with histopathological and clinical data. Positive maspin expression was found in 117 cases: nuclear/cytoplasmatic in 71, exclusive nuclear in 29, and only cytoplasmatic in 17 cases. Cytoplasmatic maspin expression was positively correlated with tumour grade (p = 0.000), FIGO stage (p = 0.002), and distant metastases (p = 0.000) but exhibited no significant correlation with tumour type (p = 0.078). Nuclear maspin expression showed negative correlation with tumour grade (p = 0.025), FIGO stage (p = 0.05), distant metastases (p = 0.001), and cancer remission (p = 0.000) but showed no significant relationship with the patients' age (p = 0.948) or cancer subtype (p = 0.261). Kaplan-Meier survival analysis showed that strong cytoplasmatic maspin expression was correlated with shorter disease-free survival (p = 0.000) whereas strong nuclear expression was correlated with longer survival (p = 0.000). In Cox regression analysis, low nuclear maspin expression (score 2 and 3) remained a significant independent prognostic factor (p = 0.001) with a relative death risk of 5.337. The obtained results suggest that maspin expression may be a significant marker in epithelial ovarian carcinoma prognosis with its nuclear expression being a good prognostic factor.

Photooxidative action in cancer and normal cells induced by the use of photofrin in photodynamic therapy.

Photofrin-mediated PDT was applied to malignant (A549 and MCF-7) and normal (HUV-EC-C) cells. The cells were incubated for different lengths of time after PDT. The cell responses to the therapy were examined by changes in SOD activity, phototoxicity, and mode of the cell death. PDT induced dynamic changes in SOD activity. Initially, an increase in SOD activity was observed, and after 6 hours of culture it decreased to the control level. Results obtained from MTT and the comet assay indicate that PDT caused immediate cell death via apoptosis in the A549, MCF-7, and HUV-EC-C cell lines. Our studies confirm that SOD is involved in the response of both cancer and normal cells to PDT.

Activity of cysteine protease inhibitors in human brain tumors.

BACKGROUND: Cysteine proteases (mainly cathepsins B and L) are thought to play an important role in the progress of cancer, including brain tumors. Together with other proteases, they hydrolyze the extracellular matrix and basement membrane proteins, thus enabling the tumor to grow and spread. Therefore cysteine protease inhibitors are regarded as protective factors, able to prevent tumor growth and dissemination. MATERIAL AND METHODS: In this study, the activity of cysteine protease inhibitors (CPIs) was investigated in material derived from patients with brain tumors (astrocytoma and meningioma). The activity of CPIs was measured as antipapain activity in tissue homogenates, cerebrospinal fluid, and serum, with N-benzoyl-DL-arginine-2-naphthylamide hydrochloride (BANA) as a substrate, according to Barret's method. RESULTS: Tumorous tissues showed higher activity of cysteine protease inhibitors than control tissues, but this difference proved to be statistically insignificant. The activity of CPIs was lower in cerebrospinal fluid and serum from patients with brain tumors. CONCLUSIONS: The activity of CPIs measured in brain tumor tissue cannot be taken as a marker of any type of tumor, whereas CPI activity in cerebrospinal fluid and serum may be considered a marker of meningioma. In meningioma patients the level of CPIs may be too low to prevent the host tissues from the growing tumor.

Effect of angiotensin II on protein phosphorylation in PC12 cell line.

Two subtypes of angiotensin II receptors have been characterised so far: AT1 and AT2. In PC12W pheochromocytoma cells, only AT2 receptors have been found (acting probably through G1 proteins or via G protein-independent mechanism). Here, dynamic changes in phosphorylation pattern in PC12W cells upon induction of angiotensin II and under influence of redox agents were investigated. PC12W pheochromocytoma cell line was preincubated with angiotensin II, then incubated with redox agents. After lysis the cells were subjected to Western-Blotting technique with antiphosphotyrosine and anti-ERK2 antibodies, as well as phosphotyrosine phosphatases and kinases activity was measured. Angiotensin II through its AT2 receptor induced dephosphorylation of tyrosines of the proteins in the range of 60 to 150 kD in PC12W cells. The obtained phosphorylation pattern suggests that AT2 receptors may act comparably to leukocyte CD45 receptor pathway. Treatment of PC12W cells with H2O2 resulted in significant decrease in phosphotyrosine phosphatases activity. It could be assumed that signal transduction based on protein phosphorylation might be controlled by cellular redox mechanisms.

Fluorescence studies on glyceraldehyde-3-phosphate dehydrogenase from bovine heart muscle.

Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that catalyses conversion of glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate. ATP has been found to have an inhibitory effect on this enzyme. To establish the interaction between the enzyme and ATP, a fluorescence technique was used. Fluorescence quenching in the presence of ATP suggests cooperative binding of ATP to the enzyme (the Hill obtained coefficient equals 2.78). The interaction between glyceraldehyde-3-phosphate dehydrogenase and ATP may control not only glycolysis but other activities of this enzyme, such as binding to the cytoskeleton.

Decrease in vivo of cysteine endopeptidases in blood of patients with tumor of the larynx.

Since cysteine endopeptidase (cathepsins B and L) have been proposed to be implicated in tumor malignancy, we have attempted to decrease these in vivo. Large amounts of urine cysteine peptidase inhibitors (UCPI) are present in the urine of patients. Our results indicate protective effects of a UCIP preparation against human serum cysteine endopeptidases.