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Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
Patterns of gene expression were used to define three sub-groups, then subsequently nine.243 Supratentorial tumors, for example, express NOTCH and EPHB-EPHRIN pathways, whereas spinal ependymomas express members of the Homeobox (HOX) family. Particular importance is attached to expression of fusion genes involving REL-A and YAP-1.
Secreted effectors of the innate mucosal barrier
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Michael A. McGuckin, Andre J. Ouellette, Gary D. Wu
The Wnt pathway regulates cellular differentiation of the intestinal epithelium in several ways. First, the β-catenin/TCF transcriptional complex activates genes expressing Ephrin-B ligands and their receptors EphB, which have a role in establishing migratory pathways as well as maintaining cellular boundaries. The gradient of EphB receptor expression within the crypt maintains the correct cellular architecture with CBCs and Paneth cells located at the base of the crypt compartment. Deletion of EphB3 results in aberrant Paneth cell localization. Second, signaling through the Wnt pathway is required for Paneth cell maturation and their expression of antimicrobial peptides. Furthermore, the Wnt-dependent SOX9 gene is critical for Paneth cell development, because mice with a conditional deletion of Sox9 lack Paneth cells completely. Finally, Wnt signaling may have an effect on cell fate determination by impeding terminal differentiation of secretory cell lineages. TCF4−/− mice have goblet cells and enterocytes but lack enteroendocrine cells, whereas transgenic overexpression of Dkk1, an inhibitor of Wnt signaling, ablates the secretory cell lineages while absorptive enterocytes remain normal.
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
Patterns of gene expression have been identified that separate supratentorial, posterior fossa and spinal ependymoma into clearly distinct entities. Using array comparative genome hybridization, three subgroups of posterior fossa ependymoma have been identified, which are otherwise not distinguishable by conventional means. Supratentorial tumours, for example, express NOTCH and EPHB-EPHRIN pathways, whereas spinal ependymomas express members of the Homeobox (HOX) family. A putative stem cell of ependymomas, the radial glial cell, has been identified on morphological grounds and on the basis of region-specific gene expression.408,437
The role of Eph receptors in cancer and how to target them: novel approaches in cancer treatment
Published in Expert Opinion on Investigational Drugs, 2020
Oscar J Buckens, Btissame El Hassouni, Elisa Giovannetti, Godefridus J Peters
Erythropoietin-producing human hepatocellular (Eph) receptors are among the largest family of receptor tyrosine kinases (RTKs). It is well known that they play a role in embryonic development and over the past decade their role in disease is becoming more and more clear [1]. There are two subfamilies of Eph receptors, EphA and EphB, which both have a wide variety of implications in disease and especially in cancer [2]. The ligands of the Eph receptors are divided in two subclasses: Ephrin A and Ephrin B ligands. Ephrin ligands are attached to a membrane, therefore binding to a receptor can induce both forward and reverse signaling, a process known as bidirectional signaling [3,4]. Moreover, different Eph interactions between the same cells can either signal in parallel or in anti-parallel. Through these diverse signaling patterns, Eph signaling can influence a number of cellular progresses, such as cell repulsion, cell-cell adhesion, cell proliferation, tissue boundary information, cell migration or axon guidance [3].
A recurrent splice-site mutation in EPHA2 causing congenital posterior nuclear cataract
Published in Ophthalmic Genetics, 2018
Vanita Berry, Nikolas Pontikos, Monica Albarca-Aguilera, Vincent Plagnol, Andreas Massouras, DeQuincy Prescott, Anthony T. Moore, Gavin Arno, Michael E. Cheetham, Michel Michaelides
Eph receptors represent the largest family of receptor tyrosine kinases and are divided into EphA receptors and EphB receptors (9 EPHAs and 5 EPHBs), preferentially binding to type A and type B ephrins respectively (5 EFNAs and 3 EFNBs). The Eph family is capable of bidirectional signaling upon interaction between receptor-ligand pair (17). Eph-ephrin ligands play a major role in morphogenesis and in numerous developmental processes along with lens homeostasis (21–23). It has been shown that ephrin-A5 acts as a regulator for EPHA2, as loss of ephrin-A5 function can lead to progressive cataract in mice, thus describing the significance of EPHA2 signalling in maintaining lens transparency and architecture. Further studies have shown that the intraction of ephrin-A5 with EPHA2 receptor regulates the adherens junction complex; this is caused by enhanced recruitment of β-catenin to N-cadherin (24).
Anticancer Potential of Hydroxychavicol Derived from Piper betle L: An in Silico and Cytotoxicity Study
Published in Nutrition and Cancer, 2022
S. Vinusri, R. Gnanam, R. Caroline, V. P. Santhanakrishnan, A. Kandavelmani
EphB3 is one of the ephrin receptor protein kinases having a major role in cancer cell development. It is also involved in the progression of nonsmall-cell lung cancer (NSCLC) in a kinase-dependent manner by stimulating cell survival, migration, and metastasis (2). Several investigations are being performed onEphB3downregulation and silencing to reduce the rate of cancer cell survival in colorectal cancer cells (19). The current docking study demonstrated that hydroxychavicol formed two hydrogen bonds with EphB3 protein at GLU 682 with the binding energy of–5.19 Kcal/mol.