• Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. (spandidos-publications.com)
  • The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. (spandidos-publications.com)
  • The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. (spandidos-publications.com)
  • EGFR mutations were more frequent in females and patients that had never smoked. (spandidos-publications.com)
  • The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. (spandidos-publications.com)
  • The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). (medsci.org)
  • The EGFR mutation status and ERCC1 and TS expression were evaluated through direct DNA sequencing and immunohistochemical analyses, respectively. (medsci.org)
  • The EGFR mutation status and ERCC1 and TS expression were the significant predictors of clinical outcomes. (medsci.org)
  • The EGFR mutation status was the main outcome predictor for overall survival (OS) benefits in the overall population. (medsci.org)
  • In conclusion, the present results indicate that the EGFR mutation status and TS and ERCC1 expression can be used as the predictors of OS after subsequent second-line treatments for AC-NSCLC. (medsci.org)
  • The standard therapies for lung adenocarcinoma include epidermal growth factor receptor (EGFR) mutation targeted therapy and conventional chemotherapy, such as platinum- and pemetrexed-based chemotherapies. (medsci.org)
  • Several biomarkers have been used to predict treatment responses, such as the EGFR mutation status for targeted therapy or the excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression for conventional chemotherapy [ 3 - 8 ]. (medsci.org)
  • Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. (aacrjournals.org)
  • However, 25% to 30% of patients with EGFR -activating mutations show intrinsic resistance, and the responders invariably acquire resistance to gefitinib. (aacrjournals.org)
  • Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR -activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. (aacrjournals.org)
  • We develop a personalized and efficient model based on 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) to predict epidermal growth factor receptor (EGFR) mutations to help identify which non-small cell cancer (NSCLC) patients are candidates for EGFR-tyrosine kinase inhibitors (TKIs) therapy. (minervamedica.it)
  • RESULTS: The AUC, sensitivity and specificity of our radiomics model by LLR algorithm were 0.792, 0.967, and 0.600 for the training group and 0.643, 1.00, and 0.378 for the validation group, respectively, in predicting EGFR mutations. (minervamedica.it)
  • In patients whose lung adenocarcinomas harbor epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations, acquired resistance to the tyrosine kinase inhibitors (TKI) gefitinib (Iressa) and erlotinib (Tarceva) has been associated with a second-site EGFR mutation, which leads to substitution of methionine for threonine at position 790 (T790M). (aacrjournals.org)
  • We aimed to elucidate the frequency and nature of secondary EGFR mutations in patients with acquired resistance to TKI monotherapy. (aacrjournals.org)
  • Tumor cells from patients with acquired resistance were examined for secondary EGFR kinase domain mutations by molecular analyses. (aacrjournals.org)
  • Detection of epidermal growth factor receptor (EGFR) gene mutations is essential in deciding therapeutic strategy in non-small cell lung cancer (NSCLC) patients at initial diagnosis. (researcher-app.com)
  • Moreover, in EGFR mutation-positive ( EGFR m) NSCLC patients, re-biopsy at disease progression to clarify resistance mechanisms is also important. (researcher-app.com)
  • In some cases, only cytology samples can be collected, and studies have reported that cytology samples are appropriate for EGFR gene mutation testing. (researcher-app.com)
  • The cobas ® EGFR Mutation Test (Roche Molecular Systems Inc., Branchburg, New Jersey, USA) is approved as a companion diagnostic for osimertinib, a third-generation EGFR-tyrosine kinase inhibitor approved in Japan. (researcher-app.com)
  • However, it is not clear whether the EGFR T790M mutation can be detected in cytology samples using this test. (researcher-app.com)
  • The primary objective of this study was to assess concordance of EGFR T790M gene mutation detection between histology and matched cytology samples using the cobas ® EGFR Mutation Test. (researcher-app.com)
  • Overall, 41 EGFR m NSCLC patients who had both histology and cytology samples collected at the same time at re-biopsy and with the results of EGFR mutation test using histology samples were enrolled. (researcher-app.com)
  • The EGFR mutation status of both sample types was tested using the cobas ® EGFR Mutation Test and the concordance rates were calculated. (researcher-app.com)
  • The EGFR T790M mutation detection rate in histology and cytology samples was 42.5% and 37.5%, respectively. (researcher-app.com)
  • INTRODUCTION: Molecular testing for epidermal growth factor receptor (EGFR) and KRAS mutations is of increasing clinical importance in daily practice. (ru.nl)
  • In this study, we aimed to investigate the yield and applicability of molecular testing for KRAS and EGFR mutations in cytologic specimens obtained by EUS or endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA). (ru.nl)
  • All eligible samples were investigated for KRAS and EGFR mutations by polymerase chain reaction followed by direct sequencing. (ru.nl)
  • Mutation analysis showed KRAS and EGFR mutations in tumor samples from 10 (37%) and two (7%) patients, respectively. (ru.nl)
  • In one patient, two EGFR mutations (p.Thr790Met and p.Leu858Arg) were detected. (ru.nl)
  • CONCLUSIONS: Molecular analysis for KRAS and EGFR mutations can be performed routinely in cytologic specimens from EUS- and EBUS-guided FNA. (ru.nl)
  • Abstract OBJECTIVE: It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in nonsmall cell lung cancer (NSCLC) patients. (docksci.com)
  • The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood. (docksci.com)
  • METHODS: Plasma, serum and tumor tissue samples from 164 NSCLC patients were assessed for EGFR mutations using Amplification Refractory Mutation System (ARMS). (docksci.com)
  • RESULTS: Compared with matched tumor tissue, the concordance rate of EGFR mutation status in plasma and serum was 73.6% and 66.3%, respectively. (docksci.com)
  • In patients with mutant tumors, those without EGFR mutations in blood tended to have prolonged PFS than patients with mutations (19.7 months versus 11.0 months, P = 0.102). (docksci.com)
  • CONCLUSIONS: EGFR mutations detected in blood may be highly predictive of identical mutations in corresponding tumor, as well as showing correlations with tumor response and survival benefit from EGFR-TKIs. (docksci.com)
  • Therefore, blood for EGFR mutation detection may allow NSCLC patients with unavailable or insufficient tumor tissue the opportunity to benefit from personalized treatment. (docksci.com)
  • However, due to the high false negative rate in blood samples, analysis for EGFR mutations in tumor tissue remains the gold standard. (docksci.com)
  • EGFR mutations have been demonstrated to be the strongest predictive biomarkers for the efficacy of EGFR-TKIs [4-8]. (docksci.com)
  • Patients with EGFR activating mutations, mainly in-frame deletions in exon 19 (19Del) and L858R substitutions in exon 21, have dramatic tumor responses and favorable survival benefit from EGFR-TKIs [9,10]. (docksci.com)
  • Hence, it is of great clinical importance to analyze and track EGFR mutation status for predicting efficacy and monitoring resistance throughout EGFR-TKIs treatment in NSCLC patients. (docksci.com)
  • EGFR mutation analysis is recommended in National Comprehensive Cancer Network clinical guidelines for NSCLC. (docksci.com)
  • Partially because tumor tissue, the optimal DNA source for EGFR mutation analysis, is always difficult to obtain. (docksci.com)
  • Because the wa-2 mutation was mapped previously to the vicinity of the EGF/TGF-α receptor (EGFR) gene on mouse chromosome 11, we hypothesized that the wa-2 phenotype might result from a defect in either the expression or activity of EGFR, or both. (houstonmethodist.org)
  • To establish the nature of the wa-2 mutation, we determined the nucleotide sequence of the coding region of normal and wa-2 murine EGFR cDNAs. (houstonmethodist.org)
  • The importance of this mutation was confirmed by showing that its introduction into an otherwise normal EGFR markedly reduced the receptor's tyrosine kinase activity in transfected Chinese hamster ovary cells. (houstonmethodist.org)
  • As we previously localized TGF-α mRNA to the inner root sheath, this pattern of EGFR expression is consistent with the effect of the wa-2 mutation on hair structure, and together with our previous characterization of TGF-α- deficient mice, reveals a critical role for signaling by this ligand/receptor system in skin. (houstonmethodist.org)
  • Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? (cdc.gov)
  • A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype. (bmj.com)
  • The patient was homozygous for a point mutation in exon 2 of the insulin receptor gene which results in the substitution of methionine for isoleucine at codon 119. (bmj.com)
  • To gain insight into the signal transduction events mediating this response we compared the properties of the P2X 7 R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X 7 R to that of non-mutated receptors (Balb/C mice). (elsevierpure.com)
  • a Phe to Ser substitution at codon 174, a Cys to Tyr substitution at codon 197, and a point mutation at the splice acceptor site of intron 12, in patients with aganglionosis confined to the rectosigmoid colon, the transverse colon, and the total colon, respectively. (drugbank.com)
  • It is caused by a point mutation (G→T) at nucleotide position 559 of the gene, bovine solute carrier family 35 member 3 (SLC35A3). (researchgate.net)
  • Mutations in the genes encoding FGFRs, types 1-3, are responsible for various skeletal dysplasias and craniosynostosis syndromes. (nih.gov)
  • Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism. (tsh-receptor-mutation-database.org)
  • Mutation analysis of the RET, the endothelin-B receptor, and the endothelin-3 genes in sporadic cases of Hirschsprung's disease. (drugbank.com)
  • To date, three genes have been identified as susceptibility genes for Hirschsprung's disease (HSCR), the RET proto-oncogene, the endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3). (drugbank.com)
  • In this study, the authors performed mutation analysis of these three genes in 41 sporadic HSCR patients without any family history by using single-strand conformational polymorphism or denaturing gradient gel electrophoresis methods. (drugbank.com)
  • However, the low mutation rate of susceptibility genes in sporadically occurring HSCR suggests that other genes or environmental factors are involved in the development of the disease. (drugbank.com)
  • Response to "Mutations of the NOGGIN and of the activin A type I receptor genes in fibrodysplasia ossificans progressiva (FOP)" by Lucotte et al. (ox.ac.uk)
  • Hypertrophic cardiomyopathy (HCM) is triggered mainly by mutations in genes encoding sarcomeric proteins, but a significant proportion of patients lack a genetic diagnosis. (elsevierpure.com)
  • We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. (nature.com)
  • FH is a disorder of cholesterol metabolism associated with mutations in the low-density lipoprotein (LDL) receptor and a few other genes. (cdc.gov)
  • Peripheral blood for epidermal growth factor receptor mutation detection in non-small cell lung cancer patients. (docksci.com)
  • Using a customized panel, we comprehensively evaluated gene mutations and copy number variation (CNV) in paired primary and metastatic specimens. (unimi.it)
  • Deletion and Point mutations, structural gene mutations, and mutations inside the regulatory area are all regarded as involved with conferring the SLD phenotype [10-13]. (techblessing.com)
  • Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD's receptor binding motif. (biorxiv.org)
  • To monitor for similar antigenic evolution of SARS-CoV-2, it is important to determine which viral mutations impact human polyclonal antibody immunity. (biorxiv.org)
  • However, it remains unclear how mutations that escape specific monoclonal antibodies will affect the polyclonal antibody response elicited by infection or vaccination. (biorxiv.org)
  • Our complete maps of how mutations impact serum antibody binding identify three major epitopes in the RBD. (biorxiv.org)
  • Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. (pacb.com)
  • Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. (pacb.com)
  • The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. (pacb.com)
  • They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. (pacb.com)
  • Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution. (pacb.com)
  • A research group led by MedUni Vienna was able to demonstrate that distinct genetic variants of the CD16a antibody receptor are associated with the risk of severe COVID-19. (bionewscentral.com)
  • Working in collaboration with Alexander Zoufaly from the Favoriten hospital, a research group led by Hannes Vietzen and Elisabeth Puchhammer-Stöckl from the Center for Virology of the Medical University of Vienna has now shown that certain genetic variants of the CD16a antibody receptor are associated with the risk of severe COVID-19. (bionewscentral.com)
  • In subsequent cell culture experiments, the research team was able to show that this high-affinity variant of the antibody receptor results in a significantly elevated antibody-dependent activation of NK cells and in a particularly strong release of pro-inflammatory factors. (bionewscentral.com)
  • It is well established now that the receptor-binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) as its first step of entry. (biorxiv.org)
  • A human M 1 (HM 1 ) mutant receptor, HM 1 (S388Y, T389P), displayed significantly enhanced agonist potency, binding affinity, and G protein coupling. (aspetjournals.org)
  • These results demonstrate that the Ser388Tyr mutation is responsible for enhanced agonist potency and binding affinity, whereas the Thr389Pro mutation alters G protein interactions. (aspetjournals.org)
  • An activation switch in the rhodopsin family of G protein-coupled receptors: the thyrotropin receptor. (tsh-receptor-mutation-database.org)
  • Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. (louisville.edu)
  • Activation of guanyl nucleotide regulatory proteins (G proteins) by hormones and neurotransmitters appears to require the formation of high affinity agonist-receptor-G protein ternary complexes. (duke.edu)
  • In the case of the beta 2-adrenergic receptor, multiple regions of the molecule have been implicated in coupling to the stimulatory G protein Gs. (duke.edu)
  • This finding raises the possibility that discrete regions of the receptor mediate ternary complex formation, whereas different loci may be involved in other aspects of G protein activation. (duke.edu)
  • The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). (wikipedia.org)
  • In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. (wikipedia.org)
  • e.g. a truncation of the receptor protein at residue number 660 leads to domains 3,4 and 5 of the EGF precursor domain being missing. (wikipedia.org)
  • This precludes the movement of the receptor from the ER to the Golgi, and leads to degradation of the receptor protein. (wikipedia.org)
  • The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. (nih.gov)
  • Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis of skeletal muscle and fat tissue through the tyrosine kinase receptor pathway. (medscape.com)
  • Abstract In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to the backbone of therapy, estrogen deprivation by aromatase inhibition. (her2support.org)
  • Portions of this work have appeared in abstract and poster form and were presented at the 8th International Symposium on Subtypes of Muscarinic Receptors, Danvers, MA, August 1998, and at the 28th annual meeting of the Society for Neuroscience, Los Angeles, CA, November 1998. (aspetjournals.org)
  • abstract = "Background: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. (arizona.edu)
  • We then analyze the recent literature on how ESR1 mutations affect outcomes in estrogen receptor-targeting and combination therapies. (her2support.org)
  • For estrogen receptor-targeting therapies such as tamoxifen and fulvestrant, ESR1 mutations cause relative resistance in vitro but do not clearly lead to resist- ance in patients, making novel agents in this category promising. (her2support.org)
  • Regarding combination therapies, ESR1 mutations nullify any aromatase inhibitor component of the combination. (her2support.org)
  • Thus, combinations using endocrine alternatives to aromatase inhibition, or combinations where the non-endocrine component is efficacious as monotherapy, are still effective against ESR1 mutations. (her2support.org)
  • We also discuss future directions and open questions, such as studying the differ- ences among distinct ESR1 mutations, asking how to adjust clinical decisions based on molecular surveillance testing, and developing novel therapies that are effective against ESR1 mutation. (her2support.org)
  • Along with previously reported genomic alterations, including PIK3CA, TP53, CDH1, GATA3 and ESR1 mutations/deletions, we found that ESR1 gene amplification (confirmed by FISH) and MAP3K mutations were enriched in metastatic lesions as compared to matched primary tumors. (unimi.it)
  • Conclusions ESR1 amplification and activating MAP3K mutations are potential drivers of acquired resistance to adjuvant ETs employing estrogen deprivation in HR+ HER2- BC. (unimi.it)
  • In the version of this article initially published online, the estrogen receptor and RNA PolII binding data were aligned incorrectly in the top panel of Figure 3, which represents estrogen receptor binding at the ESR1 gene region. (nature.com)
  • Most of these mutations are inherited in an autosomal dominant fashion and are gain-of-function-type mutations. (nih.gov)
  • Here we report on DNA variants in MINAR2 , encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. (nih.gov)
  • It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants-i.e. intermediate-density lipoprotein (IDL), and LDL particles. (wikipedia.org)
  • Portions of the cytosolic sequence have been found in other lipoprotein receptors, as well as in more distant receptor relatives. (wikipedia.org)
  • Recently, several variants such as B.1.1.7, B.1.351, and P.1, with a key mutation N501Y on the RBD, appear to be more infectious to humans. (biorxiv.org)
  • Transmembrane domain VI of muscarinic acetylcholine receptors plays an important role in ligand binding and receptor function. (aspetjournals.org)
  • The mutations are located at the top of transmembrane domain VI and about two helical turns above Tyr381 and Asn382, which are important for ligand binding and receptor function. (aspetjournals.org)
  • In ligand binding experiments, mutation of Ser388Tyr resulted in significantly increased agonist binding affinity. (aspetjournals.org)
  • The N-terminal domain of the LDL receptor, which is responsible for ligand binding, is composed of seven sequence repeats (~50% identical). (wikipedia.org)
  • Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. (rcsb.org)
  • Genetic testing showed that the patient (proband), his mother , and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). (bvsalud.org)
  • Surprisingly, the sequence analysis of PCR product also revealed the presence of two previously unknown homozygous mutations (TG→CT) at nucleotide positions 554 and 555 in addition to the previously reported heterozygous mutation at position 559. (researchgate.net)
  • heterozygous mutation at position 559. (researchgate.net)
  • In spite of a homozygous abnormality of the insulin receptor gene and many of the clinical features of severe insulin resistance, the proband's clinical syndrome was noticeably different from previously described patients with leprechaunism who usually die within the first six months of life. (bmj.com)
  • Although all three family members have the same mutation , their clinical courses have been different. (bvsalud.org)
  • Clinical courses may differ even if the same genetic mutation is found in a family . (bvsalud.org)
  • Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. (lu.se)
  • We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis. (lu.se)
  • Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)
  • All 22 exons of the insulin receptor gene were screened for mutations using denaturing gradient gel electrophoresis. (bmj.com)
  • Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. (tsh-receptor-mutation-database.org)
  • Metz H, Busch SE, Hanke ML, Kargl J, Kim KH and Houghton M (2014) Insulin receptor substrate-1 regulates immune cell content in lung adenocarcinoma. (scielo.br)
  • The extracellular domain suppresses constitutive activity of the transmembrane domain of the human TSH receptor: implications for hormone-receptor interaction and antagonist design. (tsh-receptor-mutation-database.org)
  • Our results suggest that these novel mutations play a role in the phenotype of lung cancer. (scielo.br)
  • Met) in the insulin receptor gene in five sibs with familial insulin resistance. (bmj.com)
  • Mutations in the insulin receptor gene can cause genetic syndromes such as leprechaunism that are associated with extreme insulin resistance. (bmj.com)
  • Here, a novel p.L341V mutation as a cause of resistance to TRβ is described, suggesting an important role for L341 in TRβ function. (eur.nl)
  • Identification and functional analysis of novel inactivating thyrotropin receptor mutations in patients with thyrotropin resistance. (tsh-receptor-mutation-database.org)
  • A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation. (bvsalud.org)
  • Learning points Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance . (bvsalud.org)
  • The secondary T790M mutation in exon 20 accounts for approximately 50% of the mechanism of acquired resistance [11]. (docksci.com)
  • The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. (lu.se)
  • Background Previous studies have provided a comprehensive picture of genomic alterations in primary and metastatic Hormone Receptor (HR)-positive, Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer (HR+ HER2- BC). (unimi.it)
  • In contrast, mutation of Thr389Pro did not change agonist binding affinity but rendered multiple agonist binding sites, and the high-affinity binding was sensitive to GTP analogs. (aspetjournals.org)
  • Scholars@Duke publication: A mutation of the beta 2-adrenergic receptor impairs agonist activation of adenylyl cyclase without affecting high affinity agonist binding. (duke.edu)
  • Nevertheless, D267-273 exhibited high affinity agonist binding identical to that of the wild-type receptor. (duke.edu)
  • In addition, agonist-induced sequestration of the receptor, a property not mediated by Gs, was also normal. (duke.edu)
  • These findings indicate that the formation of high affinity agonist-receptor-Gs complexes is not sufficient to fully activate Gs. (duke.edu)
  • Our data thereby suggest that the molecular determinants of the beta 2-adrenergic receptor involved in formation of the ternary complex are not identical to those that transmit the agonist-induced stimulatory signal to Gs. (duke.edu)
  • [ 17 ] and a short course of a sedative-hypnotic or melatonin receptor agonist. (medscape.com)
  • C3H/HeJ (C3H) mice, with TLR-4 mutation and mice with combined genetic CBS enzyme deficiency and TLR-4 mutation (CBS+/-/C3H). (louisville.edu)
  • Mice harboring the waved-1 (wa-1) and waved-2 (wa-2) mutations exhibit skin and eye abnormalities that are strikingly similar to those of TGF-α- deficient mice, and wa-1 and TGF-α were recently shown to be allelic. (houstonmethodist.org)
  • We identified a potentially novel mutation in ryanodine receptor 2, RyR2-P1124L, in a patient from a genotype-negative HCM cohort. (elsevierpure.com)
  • The Nicotinic Receptor Polymorphism rs16969968 Is Associated with Airway Remodeling and Inflammatory Dysregulation in COPD Patients. (nih.gov)
  • To the our best of knowledge, this is the first study to report the existence of homozygous and heterozygous mutations at positions 554, 555 and 559 in exon 4 of SLC35A3 gene in Indian Holstein cattle. (researchgate.net)
  • However, it is surprising that no phenotypic effects were observed in the carrier bull, necessitating further studies to fully elucidate the effects of these novel homozygous mutations. (researchgate.net)
  • a nonsense mutation of Trp to stop at codon 275, and a T insertion at nucleotide 878, in patients with aganglionosis confined to the rectosigmoid colon, and the descending colon, respectively. (drugbank.com)
  • Figure 1: Summary of estrogen receptor and RNA PolII binding sites and correlation with nucleotide and gene number. (nature.com)
  • We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. (scielo.br)
  • Individuals with disruptive mutations (defined as nonsense, splice site, or indel frameshift) in LDLR have an average LDL-cholesterol of 279 mg/dL, compared with 135 mg/dL for individuals with neither disruptive nor deleterious mutations. (wikipedia.org)
  • Biomarkers of exposure (pyrethroids, organophosphates, carbamates, and thioethers in urine and butyrylcholinesterase activity in plasma), early effect (micronuclei in lymphocytes and reticulocytes, T-cell receptor mutation assay, chromosomal aberrations, comet assay and lymphocytes subpopulations) and susceptibility (genetic polymorphisms related to metabolism - EPHX1, GSTM1, GSTT1 and GSTP1 - and DNA repair-XRCC1 and XRCC2) were evaluated. (cdc.gov)
  • Mutations in the gene encoding the LDL receptor are known to cause familial hypercholesterolaemia. (wikipedia.org)
  • Taken together, we suggested that the reinforced interaction from N501Y mutation in RBD should play an essential role in the higher transmission of COVID-19 variants. (biorxiv.org)
  • Hallmark mutations of variants of concern are shown in color. (cdc.gov)
  • This interaction between antibodies and the NK cell surface receptor is influenced by certain genetic factors, resulting in either strongly (high-affinity) or weakly (low-affinity) binding genetic receptor variants. (bionewscentral.com)
  • P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation « Dott. (carinci.org)
  • Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction. (lu.se)
  • Fibroblast growth factors and fibroblast growth factor receptors (FGFRs) play important roles in human axial and craniofacial skeletal development. (nih.gov)
  • Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia, and disorders caused by type 2 mutations include Crouzon syndrome (CS), Apert syndrome (AS), and PS. (nih.gov)
  • Background A deletion mutation in the growth hormones receptor (in the skeletal muscle tissues of 14-day-old embryos aswell as 7-week-old deletion-type dwarf and normal-type hens. (techblessing.com)
  • The above research indicated that mutations in may lead to the blockage of normal individual and pet skeletal muscles development and unwanted fat deposition by leading to GH indication transduction blockage. (techblessing.com)
  • The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. (spandidos-publications.com)
  • In a separate analysis of 248 patients with sporadic acromegaly, a mutation in the GPR101 gene was found in about 4% of cases. (medscape.com)
  • Results: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO 4 , rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit. (arizona.edu)
  • Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRβ) function, but this has never been confirmed in functional studies. (eur.nl)
  • Persistent neonatal thyrotoxicosis in a neonate secondary to a rare thyroid-stimulating hormone receptor activating mutation: case report and literature review. (tsh-receptor-mutation-database.org)
  • Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population. (tsh-receptor-mutation-database.org)
  • Thyroid disease caused by receptor abnormality. (tsh-receptor-mutation-database.org)
  • It is metabolized so one iodine atom is removed to produce T3 - about 10 times as active as T4 in binding to a receptor that exerts the action as receptor to the thyroid hormone. (cdc.gov)
  • The IRS proteins function as adaptors and transmit signals from multiple receptors. (scielo.br)
  • The IRS proteins (IRS1-4) are the family of adaptors regulating metabolic and mitogenic signaling pathways ( Hanke and Mann , 2009 Hanke S and Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. (scielo.br)
  • Following insulin binding, the insulin receptor (IR) autophosphorylates itself and creates docking sites for IRS proteins. (scielo.br)
  • Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. (elsevierpure.com)
  • Distinct molecular determinants of the receptor are involved in physical coupling to and functional activation of Gs. (duke.edu)
  • These therapies include estrogen receptor-targeting agents, such as selective estrogen receptor modulators, covalent antagonists, and degraders (including tamoxifen, fulvestrant, and novel agents), and combination therapies, such as endocrine therapy plus CDK4/6, PI3K, or mTORC1 inhibition. (her2support.org)
  • Our previous studies have shown that the pore-forming P2X 7 R (P2X 7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. (elsevierpure.com)
  • Figure 2: Estrogen-mediated transcript changes and correlation with estrogen receptor binding. (nature.com)
  • Figure 3: Estrogen receptor and RNA PolII binding relative to specific gene targets. (nature.com)
  • Figure 4: Identification of enriched motifs within the estrogen receptor binding sites and validation of transcription factor binding. (nature.com)
  • Figure 5: Involvement of cooperating transcription factors at estrogen receptor binding sites. (nature.com)
  • Figure 7: Assessment of estrogen receptor binding properties in different cell systems. (nature.com)
  • Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. (nature.com)
  • In addition to binding to the insulin receptor, IRS1 also binds to and transmits signals from the receptors of prolactin, growth hormone (GH), leptin, vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), anaplastic lymphoma kinase (ALK), insulin like growth factor (IGF1), and integrins ( Vuori and Ruoslathi , 1994 Vuori K and Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. (scielo.br)
  • T3 binds to the nuclear receptor (TR) and combines with another receptor (RXR) then combines with a receptor element on DNA. (cdc.gov)
  • Thus, the mutant allele encodes a receptor that has a mutation in the putative insulin binding domain. (bmj.com)
  • Accordingly, the mutant receptor would be predicted not to transduce the insulin signal effectively. (bmj.com)
  • To date, however, mutagenesis studies with the beta 2-adrenergic receptor have not clarified this question since mutant receptors with impaired abilities to activate Gs have generally possessed a diminished capacity to form the ternary complex as assessed in binding assays. (duke.edu)
  • We have expressed in a mammalian cell line a mutant beta 2-adrenergic receptor comprising a seven-amino acid deletion in the carboxyl-terminal region of its third cytoplasmic loop (D267-273), a region proposed to be critically involved in coupling to Gs. (duke.edu)
  • When tested with beta-adrenergic agonists, the maximal adenylyl cyclase response mediated by this mutant receptor was less than one-half of that seen with the wild-type receptor. (duke.edu)
  • have used CRISPR/Cas9 technology in rice to selectively mutant subsets of the 13-member PYL family of ABA receptors. (plantae.org)
  • Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. (lu.se)
  • Thyrotropin-stimulating hormone receptor gene analysis in pediatric patients with non-autoimmune subclinical hypothyroidism. (tsh-receptor-mutation-database.org)
  • MAP3K mutations are associated with worse prognosis in patients with metastatic disease. (unimi.it)
  • Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor. (lu.se)
  • The discovery of the LDL receptor mutation in FH patients-for which Goldstein and Brown won the Nobel prize in 1985-led to the development of statins as a new class of drugs to combat high cholesterol, a major cause of heart disease in populations. (cdc.gov)
  • To understand its mechanism, we combined cell surface binding assay, kinetics study, single-molecule technique, and computational method to investigate the interaction between these RBD (mutations) and ACE2. (biorxiv.org)
  • Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain. (tsh-receptor-mutation-database.org)
  • Agarwal discovered that which the deletion mutation exhibited a 1.7-kb deletion between exon 10 as well as the 3′ untranslated region (3′ UTR) of lipogenesis in the liver organ [15]. (techblessing.com)