PubMed · 5028900
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S Froland. 1972-04-20. [Lymphokines].. https://pubmed.ncbi.nlm.nih.gov/5028900/
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Angiogenesis is a complex process involving coordinated steps of endothelial cell activation, proliferation, migration, tube formation and capillary sprouting with participation of intracellular signaling pathways. Regulation of angiogenesis carries tremendous potential for cancer therapy. Our earlier studies showed that vitamin D-binding protein-macrophage activating factor (DBP-maf) acts as a potent anti-angiogenic factor and inhibits tumor growth in vivo. The goal of this investigation was to understand the effect of DBP-maf on human endothelial cell (HEC) and the mechanism of angiogenesis inhibition. DBP-maf inhibited human endothelial cell (HEC) proliferation by inhibiting DNA synthesis (IC(50) = 7.8 +/- 0.15 microg/ml). DBP-maf significantly induced S- and G0/G1-phase arrest in HEC in 72 h. DBP-maf potently blocked VEGF-induced migration, tube-formation of HEC in a dose dependent manner. In addition, DBP-maf inhibited growth factor-induced microvessel sprouting in rat aortic ring assay. Moreover, DBP-maf inhibited VEGF signaling by decreasing VEGF-mediated phosphorylation of VEGFR-2 and ERK1/2, a downstream target of VEGF signaling cascade. However, Akt activation was not affected. These studies collectively demonstrate that DBP-maf inhibits angiogenesis by blocking critical steps such as HEC proliferation, migration, tube formation and microvessel sprouting. DBP-maf exerts its effect by inhibiting VEGR-2 and ERK1/2 signaling cascades. Understanding the cellular and molecular mechanisms of anti-endothelial activity of DBP-maf will allow us to develop it as an angiogenesis targeting novel drug for tumor therapy.
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OBJECTIVE: To evaluate leucocytic infiltration of fetomaternal interface in ectopic pregnancy and to evaluate the changes in cell immunity against trophoblast (AT-CMI) in women with extrauterine pregnancy (GEU) in their medical history. To assess the effect of these factors on possible fertility disorders in a woman. DESIGN: A retrospective study. SETTING: Mother and Child Care Institute, Prague. METHODS: In most of the patients, we addressed GEU through laparoscopy. The tube was extirpated in toto and immediately fixed in Baker's solution. Thereafter, it was prepared in a dissection microscope and then processed in a standard way. In order to identify the intensity of AT-CMI, we used the leucocyte migration inhibition test. The cytotrophoblastic cell line JAR was used as an antigen. The degree of inhibition of the migration was monitored by means of a computer image analyser. Inhibition of migration below 75% was rated as favourable. RESULTS: We monitored the presence of inflammatory infiltrate in the place of implantation and correlated the findings with the hCG levels and the presence of the foetal ovum or its part in the tube. In 28 patients (23.5%) of the total number of 119 patients in the group, we observed an inflammatory infiltrate in the place of implantation. In these patients, the hCG levels were lower and in 17 of them (60.7%) we did not prove the presence of a foetal ovum or its parts. In women with GEU in their medical history, the AT-CMI positivity was established in 61.1% of the women 1 year after surgery, in 56.8% of the women 1-3 years after surgery and in 41.2% of the women 3 years after surgery. CONCLUSION: Ectopic pregnancy involves a pathological fetomaternal interface. The leucocytic infiltrate in the area of implantation may be of secondary character and may cause gradual destruction of the ectopically positioned product of conception. The results of our study indicate a possible participation of the increased AT-CMI in the destruction of the ectopically located trophoblast. Persisting anti-trophoblast immunity may influence the occurrence and course of further gravidities.