RESUMEN
OBJECTIVE: Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated. MATERIAL AND METHODS: We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment. RESULTS: To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent. CONCLUSIONS: Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.
Asunto(s)
Interferones , Metaloproteinasa 8 de la Matriz , Melanoma , Neoplasias Cutáneas , Factor A de Crecimiento Endotelial Vascular , Humanos , Inmunoterapia , Interferones/uso terapéutico , Metaloproteinasa 8 de la Matriz/sangre , Melanoma/sangre , Melanoma/fisiopatología , Melanoma/terapia , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
BACKGROUND: Parasympatolytics are recommended as the first choice remedy in patients with the chronic obstructive lung disease. Though their side effects are rare, some physicians are afraid of they can in high doses influence the cardiovascular system. The aim of the work was to ascertain whether the inhalation of 0.12 mg of ipratropium bromide might affect the systemic and pulmonary circulation. METHODS AND RESULTS: 15 patients (10 males, 5 females, average age 61.8 +/- 10.3 years) with chronic obstructive lung disease (13) and idiopathic pulmonary fibrosis (2) were examined during the period of disease stabilisation. Results of the right-side catheterization were not statistically changed (p < 0.91) 30 or 60 minutes after the inhaling of 0.12 of ipratropium. Also the value of the pick expiratory forced rate (PEFR) was not statistically increased (p < 0.25). CONCLUSIONS: Inhaling of 0.12 mg of ipratropium in patients with serious chronic pneumopathies did not affect systemic or pulmonary hemodynamics. Such dose appears to be safe even for patients with the chronic ischaemic hart disease.