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Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Anthony J. Demetris, J.G. Lunz, Vladimir Subbotin, Tong Wu, Isao Nozaki, Sarah Contrucci, Xia Yin
All but one study in human cystic duct-derived BEC93 showed that EGF stimulates proliferation of primary cultures of mouse,94,95 rat,44,96 and human50 BEC. EGF family members include EGF, transforming growth factor-alpha (TGF-alpha), and amphiregulin, which bind specifically to ErbB1. Betacellulin, (8p)-i-epregulin and heparin-binding epidermal growth factor bind to ErbB1 and ErbB4.97,98 The neuregulins (NRG1 and NRG2) bind both ErbB3 and ErbB4, whereas NRG3 and NRG4 bind ErbB4, but not ErbB3.99 No direct ligand for ErbB2 has been discovered.
Epidermal Growth Factor Receptor Inhibition in Non–Small Cell Lung Cancer
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Antonio Jimeno, Manuel Hidalgo
The epidermal growth–factor receptor (EGFR, HER1) is a member of the HER family of membrane receptors (HER1–4). The other members are HER2 (also termed ErbB2 or HER2/neu), HER3 (also termed ErbB3), and HER4 (also termed ErbB4). These receptors share the same molecular structure with an extracellular, cysteine-rich, ligand-binding domain, a single α-helix transmembrane domain, and an intracellular domain with tyrosine–kinase (TK) activity in the carboxy-terminal tail (excepting the HER3) (1). The TK domains of HER2 and HER4 show an 80% homology to that of the EGFR (2). Epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and amphiregulin bind exclusively to the EGFR, whereas betacellulin and epiregulin bind both EGFR and HER4. Ligand binding induces EGFR homodimerization as well as heterodimerization with other types of HER proteins (3,4). HER2 does not bind to any known ligand, but it is the preferred heterodimerization partner for EGFR after ligand-induced activation (5). EGFR/EGFR homodimers are unstable, whereas EGFR/HER2 heterodimers are stable and recycle more rapidly to the cell surface (6).
Predictive Biomarkers for Epidermal Growth Factor Receptor Agents in Non-Small Cell Lung Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Penelope Bradbury, John Hilton, Janet E. Dancey
Ligands which target the epidermal growth factor receptor family consist of three main groups. The first group binds specifically to EGFR and consists of EGF, transforming growth factor-a (TGF-a) and amphiregulin. The second group has specificity for both EGFR and HER4 and includes betacellulin and heparin-binding EGF as members. The third group binds HER3 and HER4 and is composed of the neuregulins (Hynes, 2005). Relative to the evaluation of other EGFR biomarkers, there is a paucity of data on the prognostic and predictive implications of the EGFR ligands. Within the EGF ligand family, TGF-a and amphiregulin have been studied more extensively, either as circulating ligands within the blood or within the tumor. However, most work has been undertaken in single cohorts ofpatients with inconsistent results reported (Ishikawa, 2005; Fontanini, 1998; Tateishi, 1990). Currently, the only published study to evaluate the prognostic and predictive significance of circulating ligands within the context of a NSCLC clinical trial containing a placebo arm is a retrospective analysis of the BR21 clinical trial of erlotinib. Baseline plasma was collected from 565 patients of the randomized 731 patients which were analyzed for TGF-a and amphiregulin levels. In multivariate analysis, high amphiregulin levels (defined as >10 pg/mL) were prognostic for a poorer outcome compared to patients with low amphiregulin, but did not predict for benefit from erlotinib. Conversely, high TGF-a (defined as >12 pg/mL) was predictive of lack of benefit from erlotinib but was not prognostic (Addison, 2010). These results are exploratory and require validation. Furthermore, the prognostic and predictive significance of EGF ligands in patients defined by other EGFR biomarkers is unclear. For example, in a small series of patients with EGFR mutation-positive NSCLC, Masago and colleagues reported that 5 of the 6 patients who had primary resistance to gefitinib had TGF-a and amphiregulin-positive serum (Masago, 2008). In a study of 73 patients with EGFR mutation-positive NSCLC treated with first or second-generation EGFR TKIs, high plasma soluble heregulin levels were associated with reduced progression-free survival, compared with patients with low soluble heregulin for patients treated with first generation EGFR TKIs, but this was not the finding for patients treated with second-generation EGFR TKIs (Yonesaka, 2019).
Prediction, diagnosis, prevention and treatment: genetic-led care of patients with diabetes
Published in Expert Review of Precision Medicine and Drug Development, 2021
Watip Tangjittipokin, Nutsakol Borrisut, Patcharapong Rujirawan
A few proteins have been reported to play roles in the biological processes of islet cell formation, glucose metabolism, and anti-inflammation. For example, neurogenin-3 (NGN3) decides the endocrine fate of pancreas development [87]. Without NGN3, there would be no presence of endocrine cells in the pancreas [87]. Transfection of hepatic cells by adenoviral vectors containing NGN3 induced insulin production [88]. In one study, streptozotocin-diabetic mice were injected with NGN3 and betacellulin (BTC) via helper-dependent adenoviral vectors. Subsequent regeneration of islets was observed, and the neo-islets were similar to pancreatic islets in terms of their gene expression profile. Betacellulin is an epidermal growth factor (EGF). This protein can be found in the pancreas, and the expression of betacellulin can promote the proliferation of islet cells and insulin secretion [89].
Single-molecule measurements in microwells for clinical applications
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Connie Wu, Adam M. Maley, David R. Walt
Finally, researchers have developed a three-plex Simoa assay for measuring the epidermal growth factor receptor (EGFR) ligands, amphiregulin, betacellulin, and transforming growth factor α [81]. Misregulation of EGFR or its ligands is involved in the pathogenesis of many cancers, including breast, lung, ovarian, and colorectal cancers. Additionally, EGFR ligands are expressed differently in tumor cells compared to healthy cells. The researchers were able to measure the three EGFR ligands with high sensitivities using a three-plex assay in serum samples from breast cancer patients and healthy controls, with reported LODs of 0.16 µg/L for amphiregulin and 0.2 µg/L for both betacellulin and transforming growth factor α. Although no conclusions were drawn on the ability of the EGFR ligands to distinguish between the breast cancer patients and healthy controls, the developed Simoa assays provided a 40-fold increase in sensitivity compared to traditional ELISA.
Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Reyhaneh Nassiri Mansour, Ghasem Barati, Masoud Soleimani, Pegah Ghoraeian, Maryam Nouri Aleagha, Mousa Kehtari, Hossein Mahboudi, Fatemeh Hosseini, Hadi Hassannia, Mohammad Foad Abazari, Seyed Ehsan Enderami
Different growth factors including EGF, bFGF, betacellulin and activin A were used in this study to differentiate hiPSCs into insulin-secreting cells. Different studies showed that EGF and bFGF which play important roles in cell proliferation and survival have a key role in pancreatic lineage neogenesis. These growth factors were secreted from endocrine precursors during islet neogenesis and used as chemo-attractants in islet cell clustering [36–38]. Activin A is a member of the transforming growth factor-beta (TGF-β) superfamily. This protein increases proliferation of beta and ductal-cells during pancreas development, as well as enhancing insulin secretion in response to glucose stimuli [39]. It is observed that Activin A could induce high expression of endocrine genes including Pdx-1, insulin and glucagon in mouse embryonic stem cells [40]. Some studies showed that betacellulin as an EGF family could promote differentiation of the different types of stem cells into insulin-secreting cells [41,42]. One of the factors used in this study to IPC differentiation of hiPSCs was a B27 supplement. B27 is used as a neural supplement and preserve neural cells characteristics in culture [43]. Different studies proved that stem cells can differentiate into IPCs in neural pathways [44,45]. As a result, this supplement could support pancreatic differentiation used in different IPC differentiation studies.