Vascular endothelial growth factor and survivin immunostaining in gastric adenocarcinoma.

UNLABELLED: Two molecules - vascular endothelial growth factor involved in new vessels formation and survivin - antiapoptotic protein, reported to be associated with worse prognosis in various malignancies have been chosen for the study. Both are potential target for novel therapies. THE AIM OF THE STUDY: Was to determine the immunostaining of VEGF and survivin in gastric carcinoma and to analyse their relationship to the selected clinicopathological features and survival. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded sections from 41 gastric adenocarcinomas were used for immunohistochemical reaction with monoclonal antibodies against vascular endothelial growth factor and survivin. The results were compared with selected clinicopathological features and survival. RESULTS: Positive immunohistochemical reaction for vascular endothelial growth factor and survivin was revealed in 24 (58,53%) and 30 (73,17%), gastric carcinomas respectively. Vascular endothelial growth factor-negative gastric carcinomas were significantly more common in cases without metastases to regional lymph nodes and distant organs and in less advanced cases. Similar, distant metastases were also statistically less common in survivin-negative carcinomas. The differences in immunohistochemical reactions for survivin between less and more advanced cases almost reach statistical significance. The only factors significantly influenced 1, 2 and 3-year survival were vascular endothelial growth factor and survivin status. Statistically significant higher percentage of survival was noted in patients with vascular endothelial growth factor- and survivin-negative tumors. CONCLUSIONS: It seems that vascular endothelial growth factor and survivin play role in local invasion and spread of gastric adenocarcinoma and negatively influences survival. However, further studies are required to assess their true usefulness in the clinical practice.

Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²âº balance protein levels.

Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX.

The redox imbalance and the reduction of contractile protein content in rat hearts administered with L-thyroxine and Doxorubicin.

Oxidative stress and disorders in calcium balance play a crucial role in the doxorubicin-induced cardiotoxicity. Moreover, many cardiotoxic targets of doxorubicin are regulated by iodothyronine hormones. The aim of the study was to evaluate effects of tetraiodothyronine (0.2, 2 mg/L) on oxidative stress in the cardiac muscle as well as contractility and cardiomyocyte damage markers in rats receiving doxorubicin (1.5 mg/kg) once a week for ten weeks. Doxorubicin was administered alone (DOX) or together with a lower (0.2T(4) + DOX) and higher dose of tetraiodothyronine (2T(4) + DOX). Two groups received only tetraiodothyronine (0.2T(4), 2T(4)). Coadministration of tetraiodothyronine and doxorubicin increased the level of lipid peroxidation products and reduced RyR2 level when compared to untreated control and group exposed exclusively to doxorubicin. Insignificant differences in SERCA2 and occasional histological changes were observed. In conclusion, an increase of tetraiodothyronine level may be an additional risk factor of redox imbalance and RyR2 reduction in anthracycline cardiotoxicity.