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NON-SPECIFIC IMMUNOTHERAPY INHIBITS ANGIOGENESIS – RESULTS OF THE MONITORING 
OF SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND MATRIX METALLOPROTEINASE 8 IN PATIENTS WITH MALIGNANT 
MELANOMA RECEIVING ADJUVANT HIGH-DOSE INTERFERON THERAPY

Authors: Prošvicová J.1, Grim J.2, Kopecký J.2, Priester P.2, Slánská I.2, Trojanová P.2, Paulík A.2, Jílková V.2, Filip S.2, Lukešová Š.1,3, Prošvic P.1, Knížek J.4, Andrýs C.5

Authors - sphere of activity: 1Onkologické oddělení, Oblastní nemocnice Náchod, 2Klinika onkologie a radioterapie, Fakultní nemocnice Hradec Králové, 3Ústav klinické mikrobiologie, Lékařská fakulta v Hradci Králové, Univerzita Karlova, 4Ústav biofyziky a biostatistiky, Lékařská fakulta v Hradci Králové, Univerzita Karlova, 5Oddělení klinické imunologie, Fakultní nemocnice Hradec Králové

Article: Epidemiol. Mikrobiol. Imunol. 66, 2017, č. 1, s. 15-23
Category: Original Papers
Number of articles displayed: 42x

Specialization: Clinical microbiology Medical virology Hygiene and epidemiology

Summary

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.

KEYWORDS:
angiogenesis – immunomodulation – interferon alpha-2b – adjuvant therapy – malignant melanoma

 

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