Search

Cancer is one of the leading causes of mortality and morbidity among people worldwide. Cancer appears as solid tumors in many cases. Angiogenesis is the growth of blood vessels from the existing vasculature and is one of the imperative processes in tumor growth. Another vital phenomenon for formation and functionality of this vasculature network is lumen formation. The results of recent studies indicate the importance of blood pressure in this mechanism. Computational modeling can study these processes in different scales. Hence, wide varieties of these models have been proposed during recent years. In this research, a multi-scale model is developed for the angiogenesis process. In the extracellular scale, the growth factor concentration is calculated via the reaction diffusion equation. At the cellular scale, growth, migration, and the adhesion of endothelial cells are modeled by the Potts cellular model. At the intra-cellular scale by considering biochemical signals, a Boolean network model describes migration, division, or apoptosis of endothelial cells. A stochastic model developed for lumen formation via inverse membrane blebbing mechanism. A CFD simulation was also used to investigate the role of pulsated blood pressure in the inverse membrane blebbing mechanism. The lumen formation model shows stochastic behavior in blebs expansion and lumen expansion. Comparing the stochastic model's results with the CFD simulation also shows the vital role of pressure pulse and the topology of the blebs in bleb retraction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community's effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.

Posttranslational modifications of histone tails can alter chromatin structure and regulate gene transcription. While recent studies implicate the lysine/arginine protein methyltransferases in the regulation of genes for endothelial metabolism, the role of AMI-1 and AMI-5 compounds in angiogenesis remains unknown. Here, we show that global inhibition of arginine and lysine histone methyltransferases (HMTs) by AMI-5 induced an angiostatic profile in human microvascular endothelial cells and human umbilical vein endothelial cells. Based on FACS analysis, we found that inhibition of HMTs significantly affects proliferation of endothelial cells, by suppressing cell cycle progression in the G 0 /G 1 phase. Immunofluorescent studies of the endothelial cells replication pattern by 5-ethynyl-2'-deoxyuridine incorporation disclosed that AMI-5, and the arginine methyltransferase inhibitor AMI-1, induced heterochromatin formation and a number of nuclear abnormalities, such as formation of micronuclei (MNs) and nucleoplasmic bridges (NPBs), which are markers of chromosomal instability. In addition to the modification of the cell cycle machinery in response to AMIs treatment, also endothelial cells migration and capillary-like tube formation processes were significantly inhibited, implicating a stimulatory role of HMTs in angiogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)