China
Africa
Explore chapters and articles related to this topic
Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Neovascularization follows from a number of different mechanisms. These include [1106] (Figure 3.7): (i) recruitment of vascular-wall resident endothelial progenitor cells (EPCs) or bone marrow hematopoietic cells generated from precursor cells with or without coalescence (i.e., vasculogenesis), (ii) angiogenesis, which involves new blood vessel formation by ECs from prior vessels (i.e., sprouting angiogenesis), (iii) intussusceptive angiogenesis (IA) or microvascular growth, a dynamic intravascular process involving the splitting of vessels by the insertion of tissue pillars or intussusceptive pillars (cylindrical microstructures spanning the lumen of capillaries and small vessels), (iv) vasculogenic mimicry (VM) where malignant cells mimic ECs and form blood vessel-like three-dimensional channels, (v) vessel cooption, which involves the migration of malignant cells along the current vasculature, and (vi) CSC transdifferentiation (i.e., tumor vasculogenesis) where precancerous or tumor vasculogenic stem cells or tumor vasculogenic progenitor cells transdifferentiate to ECs due to an intrinsic stem-like property for blood vessel generation [1106, 1109–1114]. In addition, recent reports identify an ‘angiogenic switch' from conventional ‘sprouting angiogenesis' (SA) to IA under selective pressures like anti-cancer treatment [1115]. This ‘angiogenic switch' is accompanied by sprouting angiogenesis-associated gene down-regulation (e.g., Tie2, EphrinB2, EphrinB4, Notch1, Notch2, Hes5) and intussusceptive angiogenesis associated gene upregulation (e.g., FGF2, SDF-1, CXCR4) [1115]. This reveals the complexity of the pathways involved and hints of concerns with antiangiogenic therapy effectiveness in cancer treatment [1077].
A comprehensive overview on utilizing electromagnetic fields in bone regenerative medicine
Published in Electromagnetic Biology and Medicine, 2019
Esmaeel Azadian, Bahar Arjmand, Zohreh Khodaii, Abdolreza Ardeshirylajimi
To investigate the possible role of Notch signaling pathway in osteogenesis, Bagheri et al. (2018) ran an in vitro study on bone marrow hMSCs using PEMFs. As expected, PEMF increased the expression of osteocalcin and osteogenic transcription factors (Runx2, Dlx5, Osterix) and promoted ALP activity, ECM mineralization. Interestingly, PEMF treatment affects some of Notch signaling pathway components (receptors, ligands, and nuclear target genes); it enhanced the expression of Notch4 (a Notch receptor), Dll4 (ligand), and the nuclear target genes of Hey1, Hes1, and Hes5. In addition, it has been shown that the inhibition of this pathway led to a significant reduction in the expression of osteogenic markers (Runx2, Dlx5, Osterix) and nuclear target genes (Hes1 and Hes5).
Notch signaling as a therapeutic target for acute lymphoblastic leukemia
Published in Expert Opinion on Therapeutic Targets, 2018
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Besides genetic abnormalities, epigenetic regulation of Notch signaling seems to play a critical role in leukemia pathogenesis. Notch3 and Hes5 were found preferentially hypermethylated in B-lineage lymphoblastic cell lines and primary B-ALL, but poorly methylated or even unmethylated in T-ALL cell lines or in primary T-ALL samples [18]. Distinct methylation pattern of Notch signaling genes in T-ALL and B-ALL suggests a tumor specific and lineage-specific DNA methylation profile. Therefore, in B-cell leukemia uncontrolled proliferation and apoptosis-resistance can be reversed by demethylation and deacetylation agents, relieving the epigenetic suppression of Notch pathway.
Regulation of differentiation of MEG01 to megakaryocytes and platelet-like particles by Valproic acid through Notch3 mediated actin polymerization
Published in Platelets, 2019
Ankita Dhenge, Rutuja Kuhikar, Vaijayanti Kale, Lalita Limaye
Notch signaling plays a very important role during development as it maintains a balance between progenitor population and the differentiated progeny. However, its role in hematopoietic stem cell lineage specification is not clear. We first checked the expression of Notch receptors N1, N2, N3, and N4 and ligands jagged 1, 2 and DLL1 and 4 and target genes Hes1 and Hes5 at RNA level by real-time PCR (Figure 4a and b). We found downregulation of N1, whereas interestingly we found an upregulation of Notch3, DLL4, Hes5 and PDGFR-β, whereas there was no change in the expression level of N2 and N4 at RNA level.