Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.. ...
Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms.
Malignant peritoneal mesotheliomas (MPM) are rare tumors representing 20% of all malignant mesothelioma cases. The median survival for these tumors is less than a year, and like other peritoneal surface malignancies, this is due primarily to intra-abdominal recurrence and progression. Currently there is a paucity of information about the biology of these tumors and molecular perturbations that are involved in tumor formation. Elucidation of mutations and biological pathways active in these tumors may identify valuable prognostic markers, as well as facilitate the development of novel therapies. In this study, we investigate the predictive value of epidermal growth factor receptor (EGFR) mutations in achieving optimal resectability. Twenty-nine patients with MPM were evaluated at a single tertiary care center and their tumors were probed for point mutations in the catalytic TK domain of epidermal growth factor receptor (mut+). All specimens were examined for somatic mutations by polymerase chain ...
Glioblastoma is a highly aggressive primary brain tumor in which the majority of cancer cells are undifferentiated. One of the most common oncogenic drivers for this malignancy is the epidermal...
TY - JOUR. T1 - Role of proneuregulin 1 cleavage and human epidermal growth factor receptor activation in hypertonic aquaporin induction. AU - Herrlich, Andreas. AU - Leitch, Virginia. AU - King, Landon S.. PY - 2004/11/2. Y1 - 2004/11/2. N2 - Mammalian cells are confronted with changes in extracellular osmolality at various sites, including the aqueous layer above the lung epithelium. Hypertonic shock induces the activation of mitogen-activated protein kinases and the expression of a defined set of genes, including aquaporins. We investigated upstream components of the response to hypertonicity in lung epithelial cells and found that before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-β is cleaved and binds to human epidermal growth factor receptor 3 (HER3). The signaling is prevented by matrix metalloproteinase inhibition, inhibition of neuregulin 1-β binding to HER3, and inhibition of HER tyrosine kinase activity. ...
Monoclonal antibodies (MoAbs) were raised against epidermal growth factor (EGF) receptors on a human epidermoid carcinoma cell line, A431. Administration of anti-EGF receptor MoAbs inhibited tumor formation in athymic mice by A431 cells and by another epidermal carcinoma cell line, T222. When one of the same MoAbs was used in therapy against Li-7 (a human hepatoma) and HeLa cells (a cervical carcinoma), tumor growth was not affected. The number of EGF receptors on A431 cells was about 100-fold higher than on T222, Li-7, and HeLa cells, suggesting that the number of EGF receptors may not be an important determinant in suppressing tumor growth. Three anti-EGF receptor MoAbs were used in the present studies. MoAbs 528 (immunoglobulin G2a) and 225 (immunoglobulin G1) are capable of competing with EGF for receptor binding and inhibit proliferation of A431 cells in culture. The other MoAb, 455 (immunoglobulin G1), is incapable of blocking the binding of EGF to its receptors and has no effect on the ...
TY - JOUR. T1 - Disruption of ETV6 leads to TWIST1-dependent progression and resistance to epidermal growth factor receptor tyrosine kinase inhibitors in prostate cancer. AU - Tsai, Yuan Chin. AU - Zeng, Tao. AU - Abou-Kheir, Wassim. AU - Yeh, Hsiu Lien. AU - Yin, Juan Juan. AU - Lee, Yi Chao. AU - Chen, Wei Yu. AU - Liu, Yen Nien. PY - 2018/2/19. Y1 - 2018/2/19. N2 - Background: ETS variant gene 6 (ETV6) is a putative tumor suppressor and repressed by epidermal growth factor receptor (EGFR) signaling in prostate cancer. Since EGFR antagonists seem ineffective in castration-resistant prostate cancer (CRPC), we aim to study the role of ETV6 in the development of drug resistance. Methods: Etv6 target gene was validated by ChIP and promoter reporter assays. Correlation of ETV6 and TWIST1 was analyzed in human clinical datasets and tissue samples. Migration, invasion, and metastasis assays were used to measure the cellular responses after perturbation of ETV6 -TWIST1 axis. Proliferation and tumor ...
Title: Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and New Therapeutic Perspectives in Non Small Cell Lung Cancer. VOLUME: 12 ISSUE: 6. Author(s):Laura Bonanno, Antonio Jirillo and Adolfo Favaretto. Affiliation:Medical Oncology 2, Istituto Oncologico Veneto-IRCCS, Via Gattamelata, 64, 35128 Padova, Italy.. Keywords:EGFR, Tyrosine kinase inhibitors, resistance, mutations, amplifications, MET, VEGFR, NSCLC, Gefitinib, Erlotinib. Abstract: EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of ...
TY - JOUR. T1 - Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth factor receptor antibodies. T2 - Improved immunogene approach. AU - Chen, Jiabing. AU - Gamou, Shinobu. AU - Takayanagi, Atsushi. AU - Ohtake, Yuichiro. AU - Ohtsubo, Masafumi. AU - Shimizu, Nobuyoshi. PY - 1998. Y1 - 1998. N2 - We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with poly-L-lysine to form a gene delivery vehicle (designated Fab "immunoporter"). Within 12 hours, the β-galactosidase (β-gal) gene was transferred via the Fab immunoporter to virtually all of the nuclei of human squamous carcinoma A431 cells that overproduce the EGFR, and the β-gal enzyme activity was detected within 24 hours and retained for more than 3 days. ...
Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have
Epidermal growth factor (EGF) rapidly stimulates receptor autophosphorylation in A-431 cells. After 1 min the phosphorylated receptor can be identified at the plasma membrane using an anti-phosphotyrosine antibody. With further incubation at 37 degrees C, approximately 50% of the phosphorylated EGF receptor was internalized (t1/2 = 5 min) and associated with the tubulovesicular system and later with multivesicular bodies, but not the nucleus. During this period, there was no change in the extent or sites of phosphorylation. At all times the phosphotyrosine remained on the cytoplasmic side of the membrane, opposite to the EGF ligand identified by anti-EGF antibody. These data indicate that (a) the tyrosine-phosphorylated EGF receptor is internalized in its activated form providing a mechanism for translocation of the receptor kinase to substrates in the cell interior; (b) the internalized receptor remains intact for at least 60 min, does not associate with the nucleus, and does not generate any ...
After the intraportal injection of EGF, the EGF receptor (EGFR) is rapidly internalized into hepatic endosomes where it remains largely receptor bound (Lai et al., 1989. J. Cell Biol. 109:2751-2760). In the present study, we evaluated the phosphotyrosine content of EGFRs at the cell surface and in endosomes in order to assess the consequences of internalization. Quantitative estimates of specific radioactivity of the EGFR in these two compartments revealed that tyrosine phosphorylation of the EGFR was observed at the cell surface within 30 s of ligand administration. However, the EGFR was also highly phosphorylated in endosomes reaching levels of tyrosine phosphorylation significantly higher than those of the cell surface receptor at 5 and 15 min after EGF injection. A 55-kD tyrosine phosphorylated polypeptide (pyp55) was observed in association with the EGFR at the cell surface within 30 s of EGF injection. The protein was also found in association with the EGFR in endosomes as evidenced by ...
In the current study, we report on differences in outcome based on EGFR genotype after treatment with gefitinib or erlotinib in patients with NSCLC. A total of 36 eligible patients with EGFR mutations were identified. Of these, 32 (89%) patients had either an exon 19 deletion (n = 22) or the L858R point mutation (n = 10). This is the second study to compare patients with exon 19 deletions with those harboring an L858R point mutation and provides important independent validation to earlier observations (35). In a previously reported study, Riely et al. analyzed 34 NSCLC patients with either an exon 19 deletion (n = 23) or an L858R mutation (n = 11). Of these, 22 were treated with gefitinib and 12 were treated with erlotinib. The baseline characteristics of the patients in both studies are remarkably similar with respect to age, gender, smoking status, tumor histology, performance status, number of prior chemotherapy regimens, and EGFR-TKI administered.. Although the radiographic response rate in ...
This trial will investigate the efficacy and tolerability of epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, in combination with
This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type
TY - JOUR. T1 - Developmental regulation of epidermal growth factor receptor kinase in rat intestine. AU - Thompson, John F.. AU - Van Den Berg, Merlijn. AU - Stokkers, Pieter C.F.. PY - 1994/11. Y1 - 1994/11. N2 - Background/Aims: Intraluminal epidermal growth factor (EGF) may regulate intestinal growth and function. The ontogeny, localization, and phosphorylation of the EGF receptor in rat small intestine were studied. Methods: EGF-receptor phosphorylation was assayed by antiphosphotyrosine Western blot after EGF administration in vivo and EGF incubation to everted sacs in vitro. EGF-receptor abundance and localization were assayed by Western blot and immunofluorescence using anti-EGF-receptor antibodies. Results: In vivo, orogastric EGF enhanced EGF-receptor phosphorylation in newborn rat jejunum and liver. However, intraluminal EGF had no effect on EGF-receptor phosphorylation in adult intestine or liver. In vitro, mucosal EGF stimulated a fourfold increase in EGF-receptor phosphorylation in ...
Title: Targeting Epidermal Growth Factor Receptor in Solid Tumors: Critical Evaluation of the Biological Importance of Therapeutic Monoclonal Antibodies. VOLUME: 16 ISSUE: 29. Author(s):Ch. Gialeli, D. Kletsas, D. Mavroudis, H. P. Kalofonos, G. N. Tzanakakis and N. K. Karamanos. Affiliation:Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece.. Keywords:Epidermal growth factor receptor, solid tumors, colorectal cancer, anti-EGFR therapy, monoclonal antibodies, cetuximab, panitumumab. Abstract: Numerous cellular pathways have a significant impact in the growth and metastatic potential of tumors. Essential element of such pathways is the epidermal growth factor receptor (EGFR), a member of the HER family of receptor tyrosine kinases. One of the most important issues in cancer, which attracted the attention of clinical oncologists, is the potential use of targeted therapies. EGFR signaling pathway is implicated in the control of cell survival, ...
Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen,
Background Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. In patients with ccRCC several prognostic markers have been suggested, enclosing epidermal growth factor receptor (EGFR) expression and chromosome 7 polysomy (C7p). Cancer cells addicted to EGFR bear activated mutations in the EGFR gene, and these mutations are useful in predicting susceptibility of ccRCC to EGFR inhibitors. The aim of this study was to evaluate the prognostic value of EGFR overexpression and C7p.. Patients and methods Archival specimens, coupled with clinical and survival data of 34 patients (20 men, 14 women, median age 58, range 42-79 years) who had undergone radical nephrectomy for ccRCC were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) specimens were sections of formalin-fixed paraffin-embedded tissue. EGFR expression was detected as membranous and cytoplasmic staining of neoplastic cells > 1%, and a ratio between ...
TY - JOUR. T1 - IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. AU - Shim, Jae Jeong. AU - Dabbagh, Karim. AU - Ueki, Iris F.. AU - Dao-Pick, Trang. AU - Burgel, Pierre Regis. AU - Takeyama, Kiyoshi. AU - Tam, Dominic Cheng Wei. AU - Nadel, Jay A.. PY - 2001/1. Y1 - 2001/1. N2 - Mucus hypersecretion contributes to the morbidity and mortality in acute asthma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophils is implicated in interleukin (IL)-13-induced mucin expression in GC. Treatment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-induced GC metaplasia dose dependently and completely. Instillation of IL-13 also induced tumor necrosis factor-α protein expression, mainly in infiltrating neutrophils. Control airway epithelium contained few ...
INTRODUCTION. Glioblastoma (GBM) is the most common intracranial cancer in adults but despite recent advances in therapy the overall survival remains about 20 months. The epidermal growth factor receptor variant III (EGFRvIII) is a truncated, constitutively active, and highly oncogenic form of the EGFR expressed on approximately 30% of GBMs. Sym004 is a recombinant IgG1 antibody mixture consisting of two antibodies against domain III of the epidermal growth factor receptor (EGFR). Like anti-EGFR monoclonal antibodies, Sym004 inhibits cancer cell growth and survival by blocking ligand-binding and receptor signaling. However, unlike the monoclonal antibodies, Sym004 induces a rapid and efficient internalization and degradation of the EGFR. Here, we examine whether the more efficient removal of the EGFR and the constitutive active EGFRvIII by Sym004 would translate into increased tumor growth inhibition of EGFRvIII GBM xenografts.. METHODS. Both subcutaneous (sc) and intracranial (ic) adult brain ...
The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly
Supplementary Material for: Role of Epidermal Growth Factor Receptor Expression on Patient Survival in Pancreatic Cancer: A Meta-Analysis
Close, J. L., Liu, J., Gumuscu, B. and Reh, T. A. (2006), Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina. Glia, 54: 94-104. doi: 10.1002/glia.20361 ...
The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients and to apply logistic regression analysis to investigate the factors associated with EGFR gene mutation to provide data for the treatment of NSCLC. Paraffin tissue, bronchoscopy or pleural effusion specimens were collected from 176 NSCLC patients following pathological diagnosis. The EGFR gene exon 19 delL747-S75linss and delL747-S752ins deletion mutations, and the exon 20 T790M and exon 21 L858R mutations were identified using amplification refractory mutation system analysis. The clinical data and laboratory results of the patients were collected, and the total mutation rate of the EGFR gene in exons 19, 20 and 21 in the 176 NSCLC patients was found to be 48.3% (85/176). In addition, the EGFR gene mutation rate in adenocarcinoma was found to be significantly higher than that in squamous cell and large cell carcinoma (χ²=12.454; ...
The epidermal growth factor receptor (EGFR) is a widely expressed Ag that is successfully targeted in tumor patients by mAbs or tyrosine kinase inhibitors. A clinical study in non-small cell lung cancer patients demonstrated a positive correlation between EGFR expression levels and the therapeutic efficacy of the EGFR mAb cetuximab. However, the impact of EGFR expression on the different mechanisms of action (MoAs) triggered by the EGFR mAb has not been defined. In this study, BHK-21 cells were stably transfected to express different EGFR levels, which were quantified by immunofluorescence and immunohistochemistry and compared with EGFR levels of clinical non-small cell lung cancer samples. These cells were used to systematically investigate the impact of target Ag expression levels on Fab- or Fc-mediated MoAs of EGFR mAb. A negative correlation between EGFR levels and potency of Fab-mediated MoA was observed. Interestingly, Ab-dependent cell-mediated cytotoxicity (ADCC) by NK cells, monocytes, ...
TY - JOUR. T1 - Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. AU - Lipton, Allan. AU - Leitzel, Kim. AU - Ali, Suhail M.. AU - Carney, Walter. AU - Platek, Greg. AU - Steplewski, Klaudia. AU - Westlund, Ron. AU - Gagnon, Robert. AU - Martin, Anne Marie. AU - Maltzman, Julie. PY - 2011/11/1. Y1 - 2011/11/1. N2 - BACKGROUND: Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first-line lapatinib monotherapy. METHODS: The EGF20009 study ...
TY - JOUR. T1 - Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer. T2 - Results of the randomized phase II CHER-LOB study. AU - Guarneri, Valentina. AU - Frassoldati, Antonio. AU - Bottini, Alberto. AU - Cagossi, Katia. AU - Bisagni, Giancarlo. AU - Sarti, Samanta. AU - Ravaioli, Alberto. AU - Cavanna, Luigi. AU - Giardina, Giovanni. AU - Musolino, Antonino. AU - Untch, Michael. AU - Orlando, Laura. AU - Artioli, Fabrizio. AU - Boni, Corrado. AU - Generali, Daniele Giulio. AU - Serra, Patrizia. AU - Bagnalasta, Michela. AU - Marini, Luca. AU - Piacentini, Federico. AU - DAmico, Roberto. AU - Conte, PierFranco. PY - 2012/6/1. Y1 - 2012/6/1. N2 - Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II ...
Epidermal growth factor receptors (EGF-Rs) are expressed at increasing levels on mouse preimplantation embryos. Immunofluorescence assays were used to show that unfertilized eggs and 2-cell embryos have a very low level of reactivity to antimouse EGF-R antibodies, but by the 4-cell stage and later t …
TY - JOUR. T1 - Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. AU - Carey,Lisa A.. AU - Berry,Donald A.. AU - Cirrincione,Constance T.. AU - Barry,William T.. AU - Pitcher,Brandelyn N.. AU - Harris,Lyndsay N.. AU - Ollila,David W.. AU - Krop,Ian E.. AU - Henry,Norah Lynn. AU - Weckstein,Douglas J.. AU - Anders,Carey K.. AU - Singh,Baljit. AU - Hoadley,Katherine A.. AU - Iglesia,Michael. AU - Cheang,Maggie Chon U.. AU - Perou,Charles M.. AU - Winer,Eric P.. AU - Hudis,Clifford A.. PY - 2016/2/20. Y1 - 2016/2/20. N2 - Purpose Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (PCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, ...
Targeted molecular therapy offers an exciting, new approach to treat human malignancy (1) and represents a fundamental change in cancer therapeutics (2) . Current treatment relies on cytotoxic drugs that, for the most part, lack specificity for tumor cells. A better understanding of the molecular pathogenesis of cancer has identified targets for therapeutic intervention that are specific against tumor cells and hence may reduce toxicity commonly associated with adjuvant treatment. The success of the TKI STI-571 in early clinical trials for the treatment of chronic myeloid leukemia (3) and gastrointestinal stromal tumors (4) highlights the unique potential for novel therapy based on specific molecular abnormalities present in a human cancer.. The EGFR3 pathway provides an attractive target for molecular therapy of HNSCC. Most work has focused on the use of anti-EGFR antibody preparations. Tumor proliferation in cell culture and tumor xenografts in athymic mice have been inhibited by these ...
Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR) expression and activation, causing goblet-cell metaplasia from Clara cells by a process of cell differentiation. These cells are also believed to be the cells of origin of non-small-cell lung cancer, but this occurs via cell multiplication. The mechanisms that determine which pathway is chosen are critical but largely unknown. Although no effective therapy exists for hypersecretion at present, the EGFR cascade suggests methods for effective therapeutic intervention.
... with a gene situated in the brief arm of chromosome 7. inhibitors (p=0.032). The outcomes of the existing study could be found in decision-making relating to the treating individuals with traditional EGFR exon mutations. solid course="kwd-title" Keywords: lung adenocarcinoma, traditional EGFR mutations, micropapillary design, tyrosine kinase inhibitors Intro Lung cancer may be the most popular reason behind cancer-related death world-wide, with non-small cell lung malignancy (NSCLC) being the most frequent type [1, 2]. Improved knowledge of hereditary alteration in lung malignancy has resulted in the development of several onco-targeted medicines and significant accomplishments [3C5]. Activating mutations of epidermal development element receptor (EGFR) are recognized in about 20% of lung adenocarcinomas in Traditional western countries [6] and 40%C60% of lung adenocarcinomas in East Asia [7C9]. These ...
Aida, S., et al., Distribution of epidermal growth factor and epidermal growth factor receptor in human lung: immunohistochemical and immunoelectron-microscopic studies. Respiration, 1994. 61(3):161-166.. Allahverdian, S., et al., Sialyl Lewis X modification of the epidermal growth factor receptor regulates receptor function during airway epithelial wound repair. Clin Exp Allergy, 2010. 40(4):607-618.. Blanchet, S., et al., Fine particulate matter induces amphiregulin secretion by bronchial epithelial cells. Am J Resp Cell Mol Biol, 2004. 30(4):421-427.. Burgel, P.-R. and J.A. Nadel, Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Resp J, 2008. 32(4):1068-1081.. Ciardiello, F., and Tortora, G. (2008). EGFR antagonists in cancer treatment. N Engl J Med, 2008. 358(11):1160-1174.. Casalino-Matsuda, S.M., et al., Role of hyaluronan and reactive oxygen species in tissue kallikrein-mediated epidermal growth factor receptor activation in human ...
Specific, high affinity receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have been demonstrated in human breast cancer cells. In addition, 1,25-(OH)2D3 has been shown to inhibit replication in some human breast cancer cell lines, although the mechanism(s) of this anti-tumor activity remain undefined. There is currently considerable interest in the role of autocrine growth factors in the control of breast cancer cell proliferation and the effects of steroid hormones on their production, receptor binding, and action. Since the epidermal growth factor (EGF) receptor mediates the effects of both EGF and the autocrine growth factor, alpha-transforming growth factor, we investigated the effect of 1,25-(OH)2D3 on EGF receptor levels in several human breast cancer cell lines. Preincubation of T-47D cells with 1,25-(OH)2D3 for 24 h resulted in a significant concentration-dependent decline in the specific binding of [125I]EGF. The effect was observed when EGF binding was assayed at either 0 or 37 degrees C,
Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PI3 kinase dependent pathway
The vaccine rindopepimut appears to benefit patients with epidermal growth factor receptor variant III mutation (EGFRvIII) in glioblastoma with regard to progression-free survival (PFS) and overall survival (OS).
International Scholarly Research Notices is a peer-reviewed, Open Access journal covering a wide range of subjects in science, technology, and medicine. The journals Editorial Board as well as its Table of Contents are divided into 108 subject areas that are covered within the journals scope.
We read with great interest the article by Arevalo-Perez et al, describing the potential value of T1-weighted dynamic contrast-enhanced MR imaging (DCE-MR imaging) as a biomarker for epidermal growth factor receptor variant III (EGFRvIII) mutation in patients with glioblastoma (GBM).
TY - JOUR. T1 - Src family kinases negatively regulate platelet-derived growth factor α receptor-dependent signaling and disease progression. AU - Rosenkranz, Stephan. AU - Ikuno, Yasushi. AU - Leong, Fee Lai. AU - Klinghoffer, Richard A.. AU - Miyake, Sachiko. AU - Band, Hamid. AU - Kazlauskas, Andrius. PY - 2000/3/31. Y1 - 2000/3/31. N2 - We tested the hypothesis that Src family kinases (SFK) contribute to c- Cbl-mediated degradation of the platelet-derived growth factor (PDGF) α receptor (αPDGFR). Using either a receptor mutant that does not engage SFKs (F72174), or cells that that lack SFKs, we found that SFKs contributed to degradation of the αPDGFR. Overexpression of c-Cbl also reduced the receptor half-life, but only if the receptor was able to engage SFKs. In cultured cells, prolonging the half-life of the receptor correlated with enhanced signaling and more efficient S phase entry, whereas accelerating receptor degradation had the opposite effect. Consistent with these tissue ...
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Currently, there is no standard salvage regimen after the failure of cisplatin-based chemotherapy for advanced urothelial carcinoma. Many novel agents have been developed and have shown modest activity in urothelial carcinoma. With the advancement of molecular biology and a deeper understanding of the pathogenesis of urothelial carcinoma, new approaches for treating patients using molecularly targeted therapies have emerged. Previous studies have shown that the over-expression of epidermal growth factor receptor (EGFR) predicts poor survival and stage progression [4, 5]. EGFR is more strongly expressed in invasive tumors (pT2-T4) and high-grade tumors than in superficial or low-grade tumors [4]. However, mutations within the kinase domain and truncations of the EGFR are rarely seen in bladder cancer, and they have emerged as attractive therapeutic targets. Cetuximab (an EGFR inhibitor) is a chimeric human/mouse monoclonal antibody that prevents dimerization by binding to the extracellular domain ...
The EGFR TKI erlotinib was shown to result in increased survival in previous clinical trials when used as monotherapy in previously treated patients with advanced NSCLC [30]. Toxicity to erlotinib is markedly lower than many alternative pharmacologic treatments, and would clearly be a preferred therapeutic option if survival was shown to be equivalent or better than treatment with other second line agents. Since only a fraction of patients respond to such therapy, a priori identification of responders could have a vast effect on survival. Many clinical parameters which have been shown to correlate with response to EGFR TKIs, including smoking history, gender, ethnicity, and tumor histology. Additionally, EGFR expression levels, phosphorylation status of EGFR, and mutations within the kinase domain [22, 28, 31] also correlate with sensitivity to some degree. While each of these predictors of response result in some overlap, potential responders to EGFR targeted therapeutics may be overlooked. In ...
Epidermal growth factor receptor signalling regulates ommatidial rotation during Drosophila eye development [Elektronische Ressource] / presented by Konstantin Gängel : Dissertationsubmitted to theCombined Faculties of the Natural Sciences and for Mathematicsof the Ruperto-Carola University of Heidelberg, Germanyfor the degree ofDoctor of Natural Sciencepresented byDiplombiologen Konstantin Gängelborn in HeidelbergOral-examination: 25. Mai 2005Epidermal growth factor receptor signalling regulates ommatidialrotation during Drosophila eye developmentReferees: Prof
Classic activating mutations in the EGFR tyrosine kinase domain, such as L858R and deletions in exon 19, have been strongly associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). Other mutations, e.g. T790M, show drug resistance. Detection of EGFR mutations has become an important issue for therapeutic decision-making in NSCLC. The clinical significance of uncommon EGFR mutations, however, remains poorly understood. The present study describes clinical outcomes of 6 patients with uncommon EGFR mutations, receiving TKI.. ...
TY - JOUR. T1 - Mechanisms and overcome of acquired resistance to EGFR tyrosine kinase inhibitors. AU - Soh, Junichi. AU - Toyooka, Shinichi. AU - Ueno, Tsuyoshi. AU - Miyoshi, Shinichiro. PY - 2012/4. Y1 - 2012/4. N2 - Development of effective therapies for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, which account for approximately 40% of lung adenocarcinoma patients in Japan, is important to improve the clinical outcome of NSCLC. EGFR-mutant NSCLCs are sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and elucidating the binding affinity of adenosine triphosphate (ATP) and EGFR-TKI to wild type or mutant EGFR helps our understanding of the mechanisms of resistance to EGFR-TKI. The mechanisms of acquired resistance to EGFR-TKIs are broadly classified into two categories: 1) secondly acquired EGFR mutations including T790M and 2) "oncogene kinase switch" such as MET gene amplification. To overcome the acquired resistance, it is ...
Growth factors transmit biological signals for the stimulation of cell growth and their stimulation may be involved in turnourigenesis. It is therefore of great importance to understand growth factor receptor reactions in response to stimuli such as calcium depletion or ultraviolet radiation, which normal human cells are invariably exposed to during their growth cycle. We have studied human skin cells i.e. fibroblasts, lceratinocytes and melanocytes and their growth factor receptor expression on the surface of cells, reactions in the plane of the cell membrane, intracellular trafficlcing, and gene expression after exposure to their ligand, serum, UVB radiation and calcium depletion. We have used Fluorescence recovery after photo bleaching (FRAP) to assess receptor characteristics in cell membranes, confocal laser scanning microscopy to visualize receptor internalization, Ratio imaging for calcium studies, Northern blot for detection of the gene for the epidermal growth factor receptor (EGF-R) ...
Inhibition of epidermal growth factor receptor (EGFR) signaling sensitizes human malignant glioma cells to death ligand-induced apoptosis. However, tumor cells may compensate the loss of EGFR signaling by activation of the type 1 insulin-like growth factor receptor (IGF-1R). We here report that anta …
The phosphorylated epidermal growth factor receptor (EGFR) initiates intracellular signaling processes that regulate cell growth, survival, and migration, and disregulated EGFR-mediated signaling occurs in many cancers. While the processes that lead to EGFR activation and phosphorylation have been studied in detail, quantitative aspects of the spatiotemporal regulation of EGFR by protein tyrosines phosphatases (PTPs) are not well understood. To begin to address this, we developed a new compartmentalized mechanistic model of EGFR phosphorylation dynamics and used it to interpret quantitative biochemical measurements to show that EGFR is dephosphorylated at the plasma membrane and in the cell interior with a time scale that is small compared to the time scales for EGFR internalization. By expanding our computational model and experimental data set, we went on to demonstrate that EGFR dephosphorylation at the plasma membrane surprisingly does not affect phosphorylation-dependent EGFR internalization
Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population. We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C|T, 142285G|A, 162093G|A, 181946C|T and 187114T|C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls. Of the 5 polymorphisms, the 181946C|T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45-0.88, P = 0.007). When the analyses were stratified by smoking status, the