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Contrast agents
Published in Peter R Hoskins, Kevin Martin, Abigail Thrush, Diagnostic Ultrasound, 2019
Targeting specific biological markers can be achieved using an antibody-antigen link on the surface of the microbubble along with a targeting ligand specific to a cell marker. For example the targeting ligand can be specific to a marker for inflammation. Targeted microbubbles flowing through the vascular system come into contact with the cell marker of interest, bind to the marker and provide site-specific imaging of regions of inflammation. Novel contrast agents targeted to specific biological molecular markers have been developed and several clinical applications are currently under investigation in first-in-human studies. One molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2 – VEGFR2) has been targeted in a first-in-human prostate study (Smeenge et al. 2017), while kinase insert domain receptor (KDR) targeted contrast microbubbles were used in the first-in-human study with patients with breast and ovarian lesions (Willmann et al. 2016). Both studies have demonstrated the potential of using microbubbles targeted to specific molecules.
Herbal Medicine Induces Circulation and Proliferation of Endothelial Progenitor Cell (Epc)
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
Endothelial Progenitor Cell (EPC) is a type of stem cell with more limited ability in proliferation and differentiation. This cell is unipotent, which can differentiate into the mature endothelial cell. EPC has an important role in the formation of blood vessels and the remod- elisation of endothelial cells on damaged blood vessels (Frisca, Sardjono & Sandra, 2008; Nababan et al., 2007). EPC is defined as a part of Mononuclear Cells that has molecule haematopoietic stem cell markers. The markers are: Cluster of Differentiation (CD)34, a glycoprotein mediating stem cell adhesion at bone marrow extracellular matrix; CD133, a molecule marker for more primitive stem cells; and Kinase Insert Domain Receptor (KDR), a protein that plays a crucial role in stimulating proliferation, formation of new blood vessels and angiogenesis (Frisca et al., 2008, 2010; Nababan et al., 2007; Sandra et al., 2010).
Maturation, Barrier Function, Aging, and Breakdown of the Blood–Brain Barrier
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Elizabeth de Lange, Ágnes Bajza, Péter Imre, Attila Csorba, László Dénes, Franciska Erdő
Vascular endothelial growth factor (VEGF) has a fundamental role in embryonic angiogenesis including VEGF receptor 2 (VEGFr-2); fetal liver kinase 1 (Flk-1); and kinase insert domain receptor (Kdr). Activation of the PI3K-AKT/PKB and similarly the p38/MAPK-HSP27 pathways supports EC survival and promotes EC migration (Olsson et al. 2006, Jiang and Nardelli 2016).
An updated patent review of rearranged during transfection (RET) kinase inhibitors (2016–present)
Published in Expert Opinion on Therapeutic Patents, 2022
GlaxoSmithKline filed a patent describing a series of substituted pyridone compounds for various indications, including cancer and IBS[19]. Compounds of general formula 1 (Figure 2) are claimed to inhibit RET and KDR (kinase insert domain receptor, VEGFR2). Compounds 1–1, 1–2, 1–3, and 1–4 inhibit RET activity at concentrations less than 5 nM as shown in Table 2. Pyridones (ring A) were explored as hinge binders to improve physicochemical properties. Exploring the pyridone ring, instead of the amino-pyridine scaffold, provided an advantage by reducing potential genotoxicity. Homology modeling studies showed a small pocket in the hinge/solvent region and the ethyl ether on ring A was introduced at this position. R4 substitutions were also explored while maintaining ortho substitution on the B ring[20].
In silico insights into the identification of potential novel angiogenic inhibitors against human VEGFR-2: a new SAR-based hierarchical clustering approach
Published in Journal of Receptors and Signal Transduction, 2018
Kranthi Kumar Konidala, Uma Devi Bommu, Neeraja Pabbaraju
Angiogenesis or new blood vessel formation is an essential physiological process. In addition, it is a principal hallmark of malignant cell proliferation, progression, and the metastasis. As indicated by previous enormous reports on the angiogenesis in cancer maturity, the tumor endothelial cells are secreted myriad of growth factors, and their receptor tyrosine kinases have significantly implied the vascular permeability in the metastasis [1,2]. The VEGFR-2 (vascular endothelial growth factor receptor-2 or kinase insert domain receptor (KDR)) is acting as an assertive player in the complex angiogenesis process. The VEGFR-2 stimulates various signaling pathways, including PI3K (phosphatidylinositol-3-kinases), PKC (protein kinase C) and MAPK (mitogen-activated protein kinase), which vigorously sustaining the vascular networks of tumors [1,3,4]. Additionally, over-expressions of VEGFR-2 accounted by mutations and persistent organic pollutants (POPs) including perfluorinated chemicals (PFCs) in lung, breast, ovarian and colon cancers have been reported [5]. Inhibition of VEGFR-2 moderates both angiogenesis and metastases have been reported through in vivo experiments by receptor-specific antibodies and small molecules such as sorafenib, vandetanib, sunitinib and telatinib [6]. Despite, VEGFR-2 can forcefully instigate the drug resistance against receptor specific inhibitors in anti-angiogenic therapy through interfering with their gene plethora [7]. Hence, VEGFR-2 is considered as a potential target receptor for the recognition of conspicuous anticancer and anti-angiogenic ligands.
Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay
Published in Upsala Journal of Medical Sciences, 2018
Karin E. Lindgren, Fatma Gülen Yaldir, Julius Hreinsson, Jan Holte, Karin Kårehed, Inger Sundström-Poromaa, Helena Kaihola, Helena Åkerud
Although not significant when comparing high- and low-quality blastocysts, expression levels of PlGF, cystatin B, EpCAM, HE-4, and IL-8 in culture media are of interest. Previous research has concerned attempts to establish the role of PlGF in embryogenesis and implantation, but PlGF has not been detected in culture medium from human embryos (11). Thus, our study is the first to show that PlGF, as a protein, is secreted from human embryos in culture, and we suggest that the reason for detection in our study is the sensitivity of the PEA method used. The finding is in line with the results of a recent study carried out to investigate the gene expression profile of trophectoderm cells from day-5 blastocysts, where PlGF expression was reported to be up-regulated (40). The receptor for PlGF, kinase insert domain receptor (KDR), was up-regulated in endometrial cells at the same time (40). These findings suggest that PlGF has an autocrine role in trophoblast function during early embryo development and also a paracrine role in the subsequent angiogenesis of implantation and placentation, since trophectoderm cells at this stage were found without expression of KDR (40, 41).