Subject(s)
Antineoplastic Agents/pharmacology , Drug Carriers/metabolism , Nanoparticles/chemistry , Paclitaxel/pharmacology , Peptide Fragments/metabolism , Recombinant Proteins/chemistry , alpha-Fetoproteins/chemistry , Cell Line, Tumor , Drug Carriers/chemistry , Humans , Peptide Fragments/chemistry , Protein Structure, TertiaryABSTRACT
The objective of this study was to evaluate the vasculomotor function of endothelium in patients with type 2 diabetes mellitus and assess the role of its functional state in the development of ischemic episodes. A total of 93 patients (52 men and 41 women) of the mean age of 58.3+-4.8 years were involved in the study. Group 1 comprised 47 patients with coronary heart disease (CHD) and type 2 diabetes, group 2 included 46 patients with CHD in the absence of disturbances of carbohydrate metabolism. Patients of the two groups were matched for age, gender, and major risk factors. Their comprehensive examination included 24 hour ECG monitoring, veloergometry, echocardiography, and reactive hyperemia test (ultrasound evaluation of endothelium-dependent dilation of the brachial artery). The patients of group 2 showed longer total duration of episodes of myocardial ischemia, the elevated number of painless (PMI) episodes, and greater maximum depression of ST-segment compared with CHD patients having no disturbances of carbohydrate metabolism. Correlation analysis demonstrated significant negative relationship between endothelial dysfunction, the number and duration of PMI episodes, and delay of pain syndrome with respect to ischemic depression of ST-segment in patients of group 1.
ABSTRACT
Endogenous inhibitors of angiogenesis are proved to be a major factor preventing the emergence of clinically manifested stages of human cancer. The protein endostatin, a 20-kD proteolytic fragment of type XVIII collagen, is one of the most active natural inhibitors of angiogenesis. Endostatin specifically inhibits the in vitro and in vivo proliferation of endothelial cells, inducing their apoptosis through inhibition of cyclin D1. On the surface of endothelial cells, endostatin binds with the integrin alpha(5)beta(1) that activates the Src-kinase pathway. The binding of endostatin with integrins also down-regulates the activity of RhoA GTPase and inhibits signaling pathways mediated by small kinases of the Ras and Raf families. All these events promote disassembly of the actin cytoskeleton, disorders in cell-matrix interactions, and decrease in endotheliocyte mobility, i.e., promote the suppression of angiogenesis. Endostatin displays a high antitumor activity in vivo: it inhibits the progression of more than 60 types of tumors. This review summarizes results of numerous studies concerning the biological activity and action mechanism of endostatin.