Chai, C.S. and Liam, C (2017) Resistance mechanisms causing first-line epidermal growth factor receptor-tyrosine kinase inhibitor treatment failure. Annals of Oncology, 28 (10). ISSN 1569-8041 ...

MOESM12 of STAT3 induces G9a to exacerbate HER3 expression for the survival of epidermal growth factor receptor-tyrosine kinase inhibitors in lung cancers

TY - GEN. T1 - The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) suppresses proliferation and invasion of human oral squamous carcinoma cells via p53 independent and MMP, uPAR dependent mechanism. AU - Eun, Ju Lee. AU - Jin, Ha Whang. AU - Nam, Kyeong Jeon. AU - Kim, Jin. PY - 2007/1. Y1 - 2007/1. N2 - Oral squamous cell carcinomas (OSCCs) are characterized by a marked propensity for local invasion and dissemination to cervical lymph nodes. Overexpression of the epidermal growth factor receptor (EGFR) and high levels of certain matrix metalloproteinases (MMPs) have been implicated in the development of squamous cell carcinoma of oral cancer. ZD1839 (Iressa) is a quinazoline derivative that selectively inhibits the EGFR tyrosine kinase activity and is clinically used for cancer patients. This article attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level, and to characterize the effects of ZD1839 with regard to human OSCC cell ...

TY - JOUR. T1 - Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with chemotherapy for advanced non-small-cell lung cancer. AU - Hightower, Mary. AU - Belani, Chandra P.. AU - Jain, Vinay K.. PY - 2003/5. Y1 - 2003/5. UR - http://www.scopus.com/inward/record.url?scp=0038080166&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0038080166&partnerID=8YFLogxK. U2 - 10.1016/S1525-7304(11)70302-3. DO - 10.1016/S1525-7304(11)70302-3. M3 - Article. C2 - 14599299. AN - SCOPUS:0038080166. VL - 4. SP - 336. EP - 338. JO - Clinical Lung Cancer. JF - Clinical Lung Cancer. SN - 1525-7304. IS - 6. ER - ...

Panitumumab is the first human combinatorial antibody for the treatment of metastatic colorectal carcinoma. Dermatologic toxicity of all grades occurs in more than 90% of patients. However, there are few reports of purpura induced by anti-epidermal growth factor receptor antibody. Renal failure is also uncommon as an adverse event of anti-epidermal growth factor receptor antibody. A 67-year-old Japanese man with advanced colon cancer received monotherapy with panitumumab. General malaise, bilateral edema of his legs, and bilateral purpura of his forearms developed 2 days after the second cycle of panitumumab. A skin biopsy was performed to evaluate the purpuric lesions on his left leg and leukocytoclastic vasculitis was diagnosed. Blood tests showed grade III acute renal failure with a blood urea nitrogen level of 33.8 mg/dL and a creatinine level of 3.10 mg/dL. This is the first reported case of leukocytoclastic vasculitis followed by purpura and acute renal failure associated with panitumumab.

TY - JOUR. T1 - Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer. T2 - Molecular analysis of the IDEAL/INTACT gefitinib trials. AU - Bell, Daphne W.. AU - Lynch, Thomas J.. AU - Haserlat, Sara M.. AU - Harris, Patricia L.. AU - Okimoto, Ross A.. AU - Brannigan, Brian W.. AU - Sgroi, Dennis C.. AU - Muir, Beth. AU - Riemenschneider, Markus J.. AU - Iacona, Renee Bailey. AU - Krebs, Annetta D.. AU - Johnson, David H.. AU - Giaccone, Giuseppe. AU - Herbst, Roy S.. AU - Manegold, Christian. AU - Fukuoka, Masahiro. AU - Kris, Mark G.. AU - Baselga, José. AU - Ochs, Judith S.. AU - Haber, Daniel A.. PY - 2005/12/1. Y1 - 2005/12/1. N2 - Purpose: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the ...

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs.We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and ...

Over-expression of truncated epidermal growth factor receptor (EGFR) occurs in a variety of malignancies including glioblastoma multiforme, breast and lung cancer. The truncation deletes an extracellular domain and results in constitutive activation of the receptor. NIH3T3 cells were transfected with full length or truncated human EGFR and differences in growth rates in vivo and in vitro analysed. A growth advantage was seen for cells expressing mutant receptor compared to full length EGFR in vivo only. Administration of an anti-mutant EGFR antibody to mice transiently reduced the growth rates of mutant tumours, confirming that the mutant receptor itself was important in this enhanced tumorigenicity. This showed that stimuli present in vivo and not in vitro may be contributing to growth. We therefore analysed the regulation of the angiogenic factor vascular endothelial growth factor (VEGF). Although levels of secreted VEGF did not differ significantly between wild-type and mutant EGFR cell lines when

To determine the expression of nucleostemin (NS), epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) mRNA in human esophageal squamous cell carcinoma (ESCC) tissues and their association in a human ESCC cell line. The expression of NS, EGF and EGFR mRNA was determined in paired normal esophageal and ESCC tissues of 62 patients using in situ hybridization. The association between NS and EGF or EGFR was examined using immunoblotting and real time polymerase chain reaction in a human ESCC cell line transfected with NS siRNA or treated with a selective EGFR inhibitor. In normal esophageal and ESCC tissues, the positive detection rates were 21.0% (13/62) and 69.4% (43/62) for NS mRNA staining, 40.3% (25/62) and 77.4% (48/62) for EGF mRNA staining, and 30.6% (19/62) and 75.8% (41/62) for EGFR mRNA staining, respectively. These results indicated that NS, EGF and EGFR mRNA expression was upregulated mostly in ESCC tissues. Moreover, the expression of NS, EGF and EGFR mRNA was ...

Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11.7 months. Cox analysis showed that PS 0-1, recurrent disease, EGFR mutations, or EGFR-TKI treatment were associated with improved OS. In patients with EGFR-activating mutations, Cox analysis showed that patients with adenocarcinoma, recurrent disease, or EGFR-TKI treatment had significantly longer survival. Patients with EGFR-activating mutations who received EGFR-TKI therapy had a median OS of 24.3 months, which was significantly longer than

The epidermal growth factor receptor (EGFR/ERBB1) is the prototypical and first discovered member of the ERBB family of receptor tyrosine kinases. As transmembrane receptors, their primary function is to translate extracellular signals into cellular response. Signaling is initiated through binding by members of the EGF ligand family, which induces receptor homodimerization or heterodimerization with other ERBB receptors (ERBB2, ERBB3 or ERBB4). Activation of downstream cytoplasmic signaling pathways occurs, leading to alterations in biological responses such as cellular proliferation, survival, motility, and adhesion. As EGFR is expressed in most developing and adult tissues, misregulation or dysfunction of EGFR activity severely impacts embryonic viability, tissue maintenance and multiple disease processes. Since EGFR was first proposed as a cancer drug target over twenty years ago, substantial research has defined a central role for aberrant ERBB signaling in cancer and led to the design of ...

TY - JOUR. T1 - Lapatinib plus capecitabine resolved human epidermal growth factor receptor 2-positive brain metastases. AU - Glück, Stefan. AU - Castrellon, Aurelio. PY - 2009/11/1. Y1 - 2009/11/1. N2 - Brain metastases affect 25%-30% of women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and are associated with a high burden of disease and poor prognosis. A 55-year-old woman presented with HER2-positive, hormone receptor-positive, locally advanced infiltrating ductal carcinoma. She received 4 cycles of neoadjuvant docetaxel (75 mg/m2) plus trastuzumab (6 mg/kg) on a 21-day cycle, resulting in complete pathologic response at the time of surgery. Trastuzumab (6 mg/kg every 21 days) plus anastrozole (1 mg/d) was continued for 1 year. Two years later, the patient progressed with pulmonary nodules and a large pleural effusion. Computed tomography and positron emission tomography revealed multiple lesions in the liver and thoracic spine but no evidence of ...

TY - JOUR. T1 - Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia. AU - Bichsel, Kyle J.. AU - Gogia, Navdeep. AU - Malouff, Timothy. AU - Pena, Zachary. AU - Forney, Eric. AU - Hammiller, Brianna. AU - Watson, Patrice. AU - Hansen, Laura A.. PY - 2013/7/19. Y1 - 2013/7/19. N2 - Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla ...

TY - JOUR. T1 - Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma. AU - Sheikh Ali, Mahmoud A L. AU - Gunduz, Mehmet. AU - Nagatsuka, Hitoshi. AU - Gunduz, Esra. AU - Cengiz, Beyhan. AU - Fukushima, Kunihiro. AU - Beder, Levent Bekir. AU - Demircan, Kadir. AU - Fujii, Masae. AU - Yamanaka, Noboru. AU - Shimizu, Kenji. AU - Grenman, Reidar. AU - Nagai, Noriyuki. PY - 2008. Y1 - 2008. N2 - The epidermal growth factor receptor (EGFR)-RAS-RAF-mitogen-activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR, ErbB2, and K-ras. Exons encoding the hot-spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18-23), as well as exons 1 and 2 of K-ras ...

TY - JOUR. T1 - The benefits of achieving stable disease in advanced lung cancer. AU - Kelly, Karen. PY - 2003/7. Y1 - 2003/7. N2 - The cytostatic, molecular-targeted therapies becoming available for lung cancer and other human solid tumors are more likely to result in stable disease than to produce tumor regression. In the setting of advanced lung cancer, stable disease provides significant benefit to the patient. However, in the context of clinical trials, stable disease is vaguely defined, difficult to measure, and may represent a heterogeneous patient population. The inclusion of alternative trial end points such as symptom improvement and biologic activity may help to identify patients who have achieved clinically relevant stable disease. The epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib (Iressa) has been shown to produce partial responses and stable disease in patients with advanced lung cancer who have previously received treatment with standard chemotherapies. In ...

TY - JOUR. T1 - Epidermal growth factor receptor, c-kit, and her2/neu immunostaining in advanced or recurrent thymic epithelial neoplasms staged according to the 2004 world health organization in patients treated with octreotide and prednisone. T2 - an eastern cooperative oncology group study. AU - Aisner, Seena C.. AU - Dahlberg, Suzanne. AU - Hameed, Meera R.. AU - Ettinger, David S.. AU - Schiller, Joan H.. AU - Johnson, David H.. AU - Aisner, Joseph. AU - Loehrer, Patrick J.. PY - 2010/6. Y1 - 2010/6. N2 - BACKGROUND:: Advanced or recurrent nonresectable thymic epithelial tumors show only a modest response to standard chemotherapy. A recent study using octreotide and prednisone in thymic tumors, Eastern Cooperative Oncology Group study E1C97, was conducted to verify the activity of octreotide for thymic tumors. The aim of this study was to determine whether epidermal growth factor receptor (EGFR) immunoreactivity correlated with outcomes and to identify new biologic markers for potential ...

TY - JOUR. T1 - Uncommon frame-shift exon 19 EGFR mutations are sensitive to EGFR tyrosine kinase inhibitors in non-small cell lung carcinoma. AU - Improta, Giuseppina. AU - Zupa, Angela. AU - Natalicchio, Maria Iole. AU - Sisinni, Lorenza. AU - Marinaccio, Anna. AU - Bozza, Giovanni. AU - Vita, Giulia. AU - Aieta, Michele. AU - Landriscina, Matteo. PY - 2018/1/31. Y1 - 2018/1/31. N2 - Exons 19-21 EGFR activating mutations are predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, uncommon exon 19 EGFR mutations, due to their low frequency, have an uncertain biological and clinical significance and very little is known about their TKI sensitivity. This study was designed to describe the TKI sensitivity of a small cohort of lung adenocarcinomas bearing uncommon exon 19 mutations and to evaluate in silico the correlation between frame-shift exon 19 mutations and EGFR sequence/structure modification. Among 1168 NSCLCs screened for ...

In the present study, we examined whether eosinophils induce MUC5AC mucin synthesis in airway epithelial cells. Our results showed that activated human eosinophils caused MUC5AC mucin synthesis in NCI-H292 cells. Similarly, the supernatant of activated eosinophils induced MUC5AC gene and protein synthesis in NCI-H292 cells, indicating that this effect of activated eosinophils was related to a secreted product.. Because EGFR activation is reported to cause mucin synthesis (13), we examined whether EGFR activation is required for activated eosinophil-induced mucin synthesis. Activated eosinophil supernatant induced EGFR phosphorylation in NCI-H292 cells, and selective inhibitors of EGFR tyrosine kinase blocked activated eosinophil-induced EGFR phosphorylation and MUC5AC synthesis completely; a selective PDGFR inhibitor (AG1295) and a negative control for tyrphostins (AG9) were without effect. These findings implicate EGFR tyrosine kinase phosphorylation in mucin synthesis induced by activated ...

TY - JOUR. T1 - Abnormal epithelial cell polarity and ectopic Epidermal Growth Factor Receptor (EGFR) expression induced in Emx2 KO Embryonic Gonads. AU - Kusaka, Masatomo. AU - Katoh-Fukui, Yuko. AU - Ogawa, Hidesato. AU - Miyabayashi, Kanako. AU - Baba, Takashi. AU - Shima, Yuichi. AU - Sugiyama, Noriyuki. AU - Sugimoto, Yukihiko. AU - Okuno, Yasushi. AU - Kodama, Ryuji. AU - Iizuka-Kogo, Akiko. AU - Senda, Takao. AU - Sasaoka, Toshikuni. AU - Kitamura, Kunio. AU - Aizawa, Shinichi. AU - Morohashi, Ken Ichirou. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2010/12. Y1 - 2010/12. N2 - The gonadal primordium first emerges as a thickening of the embryonic coelomic epithelium, which has been thought to migrate mediodorsally to form the primitive gonad. However, the early gonadal development remains poorly understood. Mice lacking the paired-like homeobox gene Emx2 display gonadal dysgenesis. Interestingly, the knockout (KO) embryonic gonads develop an unusual surface ...

Abstract. A phase III clinical trial showed gemcitabine chemotherapy combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib significantly improved overall survival in patients with advanced pancreatic cancer. Therefore, we studied whether addition of gemcitabine to erlotinib in cancer cells having intrinsic or acquired erlotinib resistance could restore chemosensitization in these cells. We studied the synergistic effect of erlotinib and gemcitabine in EGFR-overexpressing A-431 cells with acquired erlotinib resistance and in intrinsic erlotinib-resistant triple negative breast cancer (TNBC) BT-549, MDA-MB-231 and MDA-MB-468 cell lines. Erlotinib and gemcitabine were synergistic in both parental intrinsically erlotinib-sensitive A-431 cells (combination index = 0.69 at the effective dose [ED50]) and in two A-431 cell pools that had acquired erlotinib resistance (combination indices = 0.63 and 0.49 at ED50). The synergistic effect of erlotinib and gemcitabine on ...

2014 SCI Comparison of targeted next-generation sequencing with conventional sequencing for predicting the responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in never-smokers with lung adenocarcinoma: Lung cancer. 85(2):161~167 (3.737 ...

Phenotype data for mouse gene Eps15. Discover Eps15s significant phenotypes, expression, images, histopathology and more. Data for gene Eps15 is all freely available for download.

Signals from the epidermal growth factor receptor (EGFR) have typically been considered to provide catabolic activities in articular cartilage, and accordingly have been suggested to have a causal role in osteoarthritis progression. The aim of this study was to determine in vivo roles for endogenous EGFR signal activation in articular cartilage. Transgenic mice with conditional, limb-targeted deletion of the endogenous intracellular EGFR inhibitor Mig-6 were generated using CreLoxP (Mig-6-flox; Prx1Cre) recombination. Histology, histochemical staining and immunohistochemistry were used to confirm activation of EGFR signaling in the articular cartilage and joints, and to analyze phenotypic consequences of Mig-6 loss on articular cartilage morphology, proliferation, expression of progenitor cell markers, presence of chondrocyte hypertrophy and degradation of articular cartilage matrix. The articular cartilage of Mig-6-conditional knockout (Mig-6-cko) mice was dramatically and significantly thicker than

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were ...

Oncotarget | https://doi.org/10.18632/oncotarget.12962 Xuejing Lin, Zhangxiao Peng, Xiaohui Fu, Chunying Liu, Yang Xu, Weidan Ji, Jianhui Fan, Lei Chen, Lin Fang, Yao Huang, Changqing Su

Duration of disease control, tumor growth rate, changes in overall tumor volume, and subjective symptoms are important predictors of the length of continued EGFR-TKI beyond RECIST PD [3,5,17]. CT or MRI scans, standard methods of assessment of RECIST criteria, can only be applied for evaluation of skeletal regions with identifiable soft tissue components [20]. The majority of skeletal metastasis regions are considered non-target areas, and PD is defined by new regions or unequivocal progression of preexisting skeletal metastasis [11,20]. Adjustment of RECIST PD in skeletal metastasis to previous classifications of progression patterns in EGFR-mutated NSCLC is difficult. Compared to previous studies, our study showed no differences in the duration of continued EGFR-TKI according to the presence of symptoms and changes or overall response of other extraskeletal or target regions [5,19]. Our data showed pain symptoms in 10 out of 12 patients in the group with disease progression of preexisting ...

Human Epidermal growth factor Receptor type 2 (HER2) is over expressed in 20.0-30.0% of breast cancers and is currently evaluated histopathologically. Immunohistochemistry and fluorescence in situ hybridization require invasive enucleation of the tumor tissue and may be affected by heterogeneity. Serum marker tests are more objective because of the uniformity of the study material. Serum HER2 levels are important for breast cancer care. However, the clinical utility of serum HER2 testing is unclear. We evaluated serum HER2 as a marker of therapeutic response in breast cancer.

The modest response of patients with head and neck squamous cell carcinoma (HNSCC) and non-small cell lung carcinoma (NSCLC) to epithelial growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib indicates the need for the development of biomarkers to predict response. We determined gefitinib sensitivity in a panel of HNSCC cell lines by a 5-day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and confirmed these responses with analysis of downstream signaling by immunoblotting and cell cycle arrest. Basal gene expression profiles were then determined by microarray analysis and correlated with gefitinib response. These data were combined with previously reported NSCLC microarray results to generate a broader predictive index. Common markers of resistance between the two tumor types included genes associated with the epithelial to mesenchymal transition. We confirmed that increased protein expression of vimentin combined with the loss of E-cadherin, ...

Materials and constructs. Sequence targeting the human PLCγ1 mRNA was subcloned into pSuper and pSuperior vectors (ref. 17; Supplementary Fig. S1B). Control vectors (pSuper 3Mut and pSuperior 3Mut) contain a three-point mutated sequence unable to target the human PLCγ1 mRNA (Supplementary Fig. S1B). Palm-HA-PLCγ1 was kindly provided by Dr. E. Bonvini (MacroGenics, Inc.). Antibodies were as follows: phosphorylated PLCγ1 (Tyr783), PLCγ1, phosphorylated epidermal growth factor receptor (EGFR; Tyr992), EGFR, phosphorylated AKT (Ser473), AKT, phosphorylated extracellular signal-regulated kinases (ERK), and ERKs from Cell Signaling; phosphorylated focal adhesion kinase (FAK; Tyr397) from BioSource; Rac1, FAK, paxillin, and glyceraldehyde-3-phosphate dehydrogenase from Santa Cruz Biotechnology; phosphorylated Tyr (4G10) from UBI; and CD44 from Novocastra Laboratories Ltd.. Cell culture, transfection, and RNA interference. MDA-MB-231 and U87 cells were grown in DMEM; MDA-MB-435 and TSA were grown ...

Esophageal adenocarcinoma typically arises in Barretts esophagus, following replacement of the normal stratified epithelium by specialized intestinal epithelium, and progressive transformation from metaplasia to low-grade dysplasia, high-grade dysplasia, and finally adenocarcinoma (reviewed in ref. 47). To determine the timing of EGFR mutations within this malignant transformation, we analyzed 5 cases of high-grade dysplasia as well as 21 cases of Barretts esophagus. In 8 of 21 cases, paired specimens of Barretts esophagus and adenocarcinoma were available for analysis. Three of 21 cases (14%) of Barretts esophagus had an EGFR mutation (Table 1): two had the delE746-A750 sensitizing EGFR mutation, whereas the third had the T790M drug-resistance mutation. This mutation is of particular interest because it was first identified as a secondary EGFR mutation associated with acquired resistance to gefitinib by reducing drug binding within the ATP pocket (28-31). However, we have recently reported ...

The first-generation epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib have been incorporated into treatment paradigms for patients with advanced non-small cell lung cancer. These agents are particularly effective in a subset of patients whose tumors harbor activati …

Gefitinib, as the first epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC), has been proved to significantly improve the progression-free survival (PFS) in the first-line setting but suffers from resistance 7-10 months after treatment initiation. Apatinib (YN968D1), a potent vascular endothelial growth factor receptor (VEGFR) 2-TKI, specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect. Concurrent inhibition of VEGFR and EGFR pathways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC. This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting. This multicenter, randomized, double-blind, placebo-controlled phase III study (NCT02824458) has been designed to assess the efficacy and safety of apatinib or placebo

131214PRTartifical sequenceChemically synthesized 1Glu Leu Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Asn Ile Ala Cys Arg Ala Ser Gln Ser Ile Glu Thr Asn 20 25 30 Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Arg Leu Leu Ile 35 40 45 Lys Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Ile Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 100 105 110 Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 115 120 125 Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 145 150 155 160 Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr ...

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein

Methods Thirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescence in situ hybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18-21 of the EGFR gene. Direct sequencing of the purified PCR products was performed. ...

Methods Thirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescence in situ hybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18-21 of the EGFR gene. Direct sequencing of the purified PCR products was performed. ...

TY - JOUR. T1 - STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization. AU - Kitai, Yuichi. AU - Iwakami, Masashi. AU - Saitoh, Kodai. AU - Togi, Sumihito. AU - Isayama, Serina. AU - Sekine, Yuichi. AU - Muromoto, Ryuta. AU - Kashiwakura, Jun Ichi. AU - Yoshimura, Akihiko. AU - Oritani, Kenji. AU - Matsuda, Tadashi. N1 - Funding Information: This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The authors declare that they have no conflicts of interest with the contents of this article. Publisher Copyright: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.. PY - 2017/11/24. Y1 - 2017/11/24. N2 - Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of ...

Free Online Library: Potential Anticancer Mechanisms of a Novel EGFR/DNA-Targeting Combi-Molecule (JDF12) against DU145 Prostate Cancer Cells: An iTRAQ-Based Proteomic Analysis.(Research Article, epidermal growth factor receptor , Report) by BioMed Research International; Biotechnology industry High technology industry Apoptosis Care and treatment Cancer treatment Cellular signal transduction Epidermal growth factor receptors Gene expression Prostate cancer Drug therapy Genetic aspects Protein-protein interactions Proteins

Maini, Raj, Collison, David J., Maidment, Jill M., Davies, Peter D. and Wormstone, I. Michael (2002) Pterygial derived fibroblasts express functionally active histamine and epidermal growth factor receptors. Experimental Eye Research, 74 (2). pp. 237-244. ISSN 0014-4835 Full text not available from this repository. (Request a copy ...

Product Description Product Description Erlotinib hydrochloride For Treat Non-small Cell Lung Cancer 183319-69-9 Erlotinib hydrochloride---------Basic info Product Name Erlotinib hydrochloride CAS 183319-69-9 MF C22H24ClN3O4 MW 429.9 Chemical Properties Off-White Solid Usage Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic Erlotinib HCl is an HER1/EGFR inhibitor with IC50 of 2 nM. Erlotinib HCl (OSI-744) is an…

Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer Jenn-Yu Wu,1 Jin-Yuan Shih2 1Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan Background: Clinical features of epidermal growth factor receptor (EGFR) mutations: L858R, deletions in exon 19, T790M, insertions in exon 20, G719X, and L861X in non-small-cell lung cancer (NSCLC) are well-known. The clinical significance of other uncommon EGFR mutations, such as E709X, is not well understood. This study aimed to improve the understanding of E709X, and the clinical response to tyrosine kinase inhibitors (TKIs) of NSCLC patients with such an uncommon mutation.Methods: Specimens from 3,146 patients were tested for EGFR mutations. We surveyed the clinical data and the effectiveness of TKI

Lung cancer is the leading cause of cancer-related mortality for both men and women in United States and is estimated to remain the most fatal cancer-related malignancy (1). Little improvement in the efficacy of chemotherapy has been made in the last 20 years, usually attributed to the overexpression and overactivity of EGFR in NSCLC (4, 29-31). However, the use of selective EGFR tyrosine kinase inhibitors (gefitinib) and monoclonal antibodies against EGFR toward the treatment of lung cancer has continuously failed (32, 33). Therefore, additional alternative therapies with low toxicity and increased efficacy should be explored. Although recent studies suggest that nonpsychoactive synthetic cannabinoids possess antitumor effects against various tumors, including breast cancer, not much is known about the effects of synthetic CB1/CB2 agonists on NSCLC growth and metastasis. In the present study, we analyzed the antitumorigenic and antimetastasis effects of CB1/CB2 agonists Win55,212-2 and CB2 ...

Objectives and Background To reveal the details system of miR-484 in myocardial ischemia-reperfusion (MI/R) damage. appearance of caspase-3/9 had been elevated in IR-C group. Weighed against the I/R Slc2a4 and IR-C groupings, the apoptotic index of myocardial cells in the ischemic area was reduced, the membrane potential was elevated, as well as the expression of caspase-3/9 was decreased in the miR group significantly. SMAD7 was the mark gene of miR-484. Conclusions MiR-484 protected myocardial cells from We/R damage by suppressing caspase-9 and caspase-3 appearance during cardiomyocyte apoptosis. MiR-484 decreased the appearance of IL-6, TNF-, and IL-1 in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells. Keywords: Apoptosis, Mitochondrial membrane potential, Caspase-3, Caspase-9 Launch Ischemia-reperfusion (I/R) damage is the injury caused when blood supply returns to the tissue after a period of ischemia. It is a Pyrazinamide complex process ...

Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than

The Human Epidermal Growth Factor Receptor (EGFR/HER1) can be activated by several ligands including Transforming Growth Factor alpha (TGF-α) and Epidermal Growth Factor (EGF). Following ligand binding, EGFR heterodimerizes with other HER family members, such as HER2 (human epidermal growth factor receptor-2). Previously, we showed that the EGFR is upregulated in trastuzumab resistant HER2 positive (HER2+) breast cancer cells. This study is aimed to determine the downstream effects on transcription following EGFR upregulation in HER2+ breast cancer cells. RNA-sequence and ChIP-sequence for H3K18ac and H3K27ac (Histone H3 lysine K18 and K27 acetylation) were conducted following an Epidermal Growth Factor (EGF) treatment time course in HER2+ breast cancer cells, SKBR3. The levels of several proteins of interest were confirmed by western blot analysis. The cellular localization of proteins of interest was examined using biochemically fractionated lysates followed by western blot analysis. Over the course

The identification of epidermal growth factor receptor (EGFR)-activating mutations and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) for advanced EGFR-mutant non-small cell lung cancer (NSCLC) represents a drastic change in treatment paradigms. Several randomised clinical trials have demonstrated that EGFR-TKI administration results in a superior response rate and longer progression-free survival than platinum-based chemotherapy for advanced EGFR-mutant NSCLC.1-3 However, patients who initially respond to EGFR-TKIs eventually acquire resistance.. The mechanisms of acquired EGFR-TKI resistance have been widely studied and several mechanisms have been identified. The most common mechanism of resistance to TKIs, observed in over 50% of patients, is a threonine-to-methionine substitution within the gatekeeper residue at amino acid position 790 (T790M) of the EGFR gene.4-7 EGFR-independent mechanisms include the MET proto-oncogene, receptor tyrosine kinase (MET) amplification ...

EGFR a receptor tyrosine kinase. This is a receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30, and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentiation. It is a single-pass transmembrane tyrosine kinase. Ligand binding to this receptor results in receptor dimerization, autophosphorylation (in trans), activation of various downstream signaling molecules and lysosomal degradation. It can be phosphorylated and activated by Src. Activated EGFR binds the SH2 domain of phospholipase C-gamma (PLC-gamma), activating PLC-gamma-mediated downstream signaling. Phosphorylated EGFR binds Cbl, leading to its ubiquitination and degradation. Grb2 and SHC bind to phospho-EGFR and are involved in the activation of MAP kinase signaling pathways. Phosphorylation on Ser and Thr residues is thought to represent a mechanism for attenuation of EGFR kinase activity. ...

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are current treatments for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR gene mutations. Although studies show an increased progression free survival (PFS) with use of EGFR TKIs in the first-line setting, most patients will develop resistance to therapy after the first about 10 months. Undoubtedly it is critical to choose an optimal clinical strategy for patients with EGFR sensitive mutation undergoing EGFR-TKI resistance. The second biopsy should be applied under condition permission to verify specific resistance mechanism. Here we discussed the mechanism of drug resistance and the choice of therapeutic regimen, also compared the superior and inferior of each treatment plan, which proposed a novel perspective for NSCLC target therapy.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently recommended by international guidelines as first-line treatment in patients with advanced EGFR-mutant non-small-cell lung cancer. With the availability of drugs, more and more patients choose EGFR-TKI treatment. However, pharmaceutical drugs used in clinical practice have side effects, such as diarrhea, paronychia, and hepatotoxicity. Mental or conscious disturbance has never been reported before. In our clinical center, we found that several patients with advanced lung adenocarcinoma developed a mental disorder or conscious disturbance after EGFR-TKI treatment. This situation has not previously been reported. We conducted a retrospective study of patients with advanced lung adenocarcinoma treated with EGFR-TKI who showed a mental disorder or conscious disturbance. We reported five cases of lung adenocarcinoma who developed a mental disorder or conscious disturbance after treatment with EGFR-TKI. The main ...

PURPOSE OF REVIEW: The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, are effective as first-line treatment of advanced nonsmall cell lung cancer (NSCLC) harboring activating EGFR mutations (deletions in exon 19 and exon 21 L858R mutation). EGFR T790 M resistance mutation (EGFR T790 M) ultimately emerged in most of these patients. The second and third-generation EGFR-TKIs were designed to have more potent inhibition of EGFR and to overcome EGFR T790 M. This review describes the recent developments of these novel EGFR-TKIs.. RECENT FINDINGS: The second-generation EGFR-TKIs, afatinib and dacomitinib, irreversibly bind to the tyrosine kinase of EGFR and other ErbB-family members. Afatinib has been approved as first-line treatment of advanced NSCLC harboring activating EGFR mutations. Dacomitinib is under development. Third-generation EGFR-TKIs, AZD9291, CO-1686, and HM61713, inhibit both EGFR activating and resistance mutations, ...

Increasing evidence supports the hypothesis that tannic acid, a plant polyphenol, exerts anticarcinogenic activity in chemically induced cancers. In the present study, tannic acid was found to strongly inhibit tyrosine kinase activity of epidermal growth factor receptor (EGFr) in vitro (IC50 = 323 nM). In contrast, the inhibition by tannic acid of p60c-src tyrosine kinase (IC50 = 14 μM) and insulin receptor tyrosine kinase (IC50 = 5 μM) was much weaker. The inhibition of EGFr tyrosine kinase by tannic acid was competitive with respect to ATP and non-competitive with respect to peptide substrate. In cultured cells, growth factor-induced tyrosine phosphorylation of growth factor receptors, including EGFr, platelet-derived growth factor receptor, and basic fibroblast growth factor receptor, was inhibited by tannic acid. No inhibition of insulin-induced tyrosine phosphorylation of insulin receptor and insulin-receptor substrate-1 was observed. EGF-stimulated growth of HepG2 cells was inhibited in ...

Looking for online definition of fibroblast growth factor receptor gene in the Medical Dictionary? fibroblast growth factor receptor gene explanation free. What is fibroblast growth factor receptor gene? Meaning of fibroblast growth factor receptor gene medical term. What does fibroblast growth factor receptor gene mean?

TY - JOUR. T1 - Clinicopathological characteristics of human epidermal growth factor receptor 2-positive Barretts adenocarcinoma. AU - Tanaka, Takehiro. AU - Fujimura, Atsushi. AU - Ichimura, Koichi. AU - Yanai, Hiroyuki. AU - Sato, Yasuharu. AU - Takata, Katsuyohi. AU - Okada, Hiroyuki. AU - Kawano, Seiji. AU - Tanabe, Shunsuke. AU - Yoshino, Tadashi. N1 - Copyright: Copyright 2021 Elsevier B.V., All rights reserved.. PY - 2012. Y1 - 2012. N2 - AIM: To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barretts adenocarcinoma in Japan. METHODS: We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barretts adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients. RESULTS: HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression ...

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. Clinical trials have reported its effectiveness in the treatment of brain metastases from non-small cell lung cancer by overcoming the blood-brain barrier. Gefitinib is generally regarded as a relatively safe agent, and several reports have described its efficacy in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer and a poor performance status. We herein described two patients with brain metastasis from non-small cell lung cancer who achieved the total regression of metastasis with the administration of gefitinib. A 70-year-old Japanese woman was referred to our hospital with a severe cough. Brain magnetic resonance imaging revealed a metastatic lesion in the left temporal lobe. The tumor was positive for an epidermal growth factor receptor L858R mutation in exon 21 using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. She was treated with 250 mg

TY - JOUR. T1 - Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene. T2 - A case report. AU - Mody, Kabir. AU - Strauss, Edward. AU - Lincer, Robert. AU - Frank, Richard C.. PY - 2010/10/20. Y1 - 2010/10/20. N2 - Background: Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene.Case presentation: A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine ...

TY - JOUR. T1 - Gefitinib enhances cytotoxicities of antimicrotubule agents in non-small-cell lung cancer cells exhibiting no sensitizing epidermal growth factor receptor mutation. AU - Tsai, Chun Ming. AU - Chiu, Chao Hua. AU - Chang, Kao Ting. AU - Chen, Jen-Ting (Tina). AU - Lai, Chun Liang. AU - Chen, Yuh Min. AU - Hsiao, Shih Yin. PY - 2012/8. Y1 - 2012/8. N2 - INTRODUCTIONS:: Although randomized clinical trials showed no benefit from combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with standard chemotherapy for advanced non-small-cell lung cancer (NSCLC), better results might be obtained by combining EGFR-TKI with individual agents that are substrates for the adenosine triphosphate binding cassette transporters (ABCTs) because EGFR-TKIs can inhibit their efflux. The combination effects deserved to be further examined in vitro. METHODS:: The combination effects of gefitinib with three antimicrotubule agents (AMTAs), paclitaxel, docetaxel or vinorelbine, ...

TY - JOUR. T1 - Heterologous Regulation of the Epidermal Growth Factor Receptor by Palytoxin, a Non-12-O-Tetradecanoylphorbol-13-acetate-type Tumor Promoter. AU - Wattenberg, Elizabeth V.. AU - Fujiki, Hirota. AU - Rosner, Marsha Rich. N1 - Copyright: Copyright 2016 Elsevier B.V., All rights reserved.. PY - 1987. Y1 - 1987. N2 - Previous results have established that 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters can alter the properties of the epidermal growth factor (EGF) receptor through activation of protein kinase C. In order to determine whether other, non-TPA-type tumor promoters might similarly influence growth-mediating receptors, we investigated the effect of palytoxin on EGF binding in Swiss 3T3 fibroblasts and human epidermal carcinoma (A431) cells. In both cell types, pretreatment with a low dose of palytoxin (1-11 pm) at 37°C causes a decrease in EGF binding. In Swiss 3T3 cells the inhibitory effect is temperature dependent and does not occur at 4°C, indicating ...

Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p＜0.01); resistance to ...

Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review Fang Hu,* Xiaowei Mao,* Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan ZhangDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients.Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating

TY - JOUR. T1 - Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma. AU - Hatakeyama, Hiromitsu. AU - Cheng, Haixia. AU - Wirth, Pamela. AU - Counsell, Ashley. AU - Marcrom, Samuel R.. AU - Wood, Carey Burton. AU - Pohlmann, Paula R.. AU - Gilbert, Jill. AU - Murphy, Barbara. AU - Yarbrough, Wendell G.. AU - Wheeler, Deric L.. AU - Harari, Paul M.. AU - Guo, Yan. AU - Shyr, Yu. AU - Slebos, Robbert J.. AU - Chung, Christine H.. PY - 2010. Y1 - 2010. N2 - Background: We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). Methodology/Principal Findings: Genome-wide changes in gene and miR expression were determined in cetuximabsensitive cell line, SCC1, and ...

TY - JOUR. T1 - Epidermal Growth Factor Protects Squamous Cell Carcinoma against Cisplatin-Induced Cytotoxicity through Increased Interleukin-1β Expression. AU - Ko, Shian Chin. AU - Huang, Chi Ruei. AU - Shieh, Jiunn Min. AU - Yang, Jhen Hong. AU - Chang, Wen Chang. AU - Chen, Ben Kuen. PY - 2013/2/1. Y1 - 2013/2/1. N2 - The expression of cytokines, such as IL-1β, and the activation of the epidermal growth factor receptor (EGFR) are crucial regulators in the process of carcinogenesis. The correlation between growth factor and activated cytokine signals in the control of tumor development is a critical issue to be clarified. In our study, we found that the IL-1β gene and protein expression were induced by EGF in squamous cell carcinoma. To clarify the mechanism involved in EGF-regulated IL-1β expression, we examined the transcriptional activity and mRNA stability of IL-1β in EGF-treated cells. We found that EGF induced the expression of IL-1β and was mediated through transcriptional ...

Proliferation and migration of SMCs in the arterial wall play pivotal roles in atherosclerosis and restenosis.1,28 In the present study, we demonstrate for the first time that balloon injury in arteries and PDGF in cultured SMCs stimulate the tyrosine phosphorylation of c-Cbl. We also show that the c-Cbl mutant, which is deficient in the major tyrosine phosphorylation sites, attenuates the activation of the Akt/mTOR pathway and inhibits SMC migration and proliferation in response to PDGF, FGF, and serum. Finally, we demonstrate that in vivo gene transfer of the c-Cbl mutant inhibits SMC proliferation and migration in vivo and prevents neointimal hyperplasia after balloon injury.. c-Cbl undergoes tyrosine phosphorylation in response to a multitude of stimuli, including activated growth factor receptor protein tyrosine kinases (PTKs; such as epidermal growth factor receptor, FGFR, and PDGFR), cytokines, hormones, and mechanical stimuli (such as shear stress). We describe here that c-Cbl undergoes ...

Background:. - Research has shown that the Epidermal Growth Factor Receptor (EGFR) gene is an important target for personalized lung cancer treatment. Individuals who have mutations in the EGFR gene have better responses when treated with certain personalized or targeted therapies compared with conventional chemotherapy. These mutations are more frequent in females with lung cancer who have never smoked, and different ethnic groups have different levels of frequency of the mutations. Researchers are interested in collecting more information on EGFR genetic mutations in Hispanics/Latinos with lung cancer, comparing the frequency of these mutations in males and females and smokers and nonsmokers. This study may lead to better, more personalized care approaches for all individuals with lung cancer.. Objectives:. - To study the frequency of Epidermal Growth Factor Receptor mutations in Hispanic/Latino individuals who have been diagnosed with non-small cell lung cancer.. Eligibility:. - Hispanic or ...

It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max),7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO,50% (P=0.023) and diameter ,15.5mm (P=0.006) on CT, or a well-differentiated histopathology ...

Background: Emerging evidence indicates that chemotherapy for lung cancer may alter EGFR mutation status. However, whether chemotherapy as a firstline treatment may increase or reduce the frequency of EGFR mutations in NSCLC remains uncertain. Therefore, we conducted a meta-analysis to evaluate whether chemotherapy leads to altered EGFR mutation status. Methods: A systematic literature search was performed using the PubMed, OVID, Science Direct, Cochrane Library, and CNKI databases for studies on pre- and post-chemotherapy EGFR mutation status. Relevant studies documenting perichemotherapy EGFR mutation ratios were included. Analyses of pooled odds ratios (OR) were performed. Results: Six studies involving 656 patients were included in this meta-analysis. It was found that chemotherapy may alter EGFR status (OR = 1.93, 95% CI 1.05 - 3.56; p < 0.0001). No significant differences in EGFR mutation alterations were observed in terms of gender, smoking history, EGFR loci, or chemotherapy response in NSCLC

Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts

Epithelial-mesenchymal transition (EMT) is normally one particular mechanism of possessed resistance to inhibitors of the skin growth factor receptor-tyrosine kinases (EGFR-TKIs) in non-small cell lung cancer (NSCLC). micro-RNA-200c, which can regulate ZEB1 adversely, was decreased in HCC4006EUr cells significantly. Our outcomes recommend that elevated can get EMT-related obtained level of resistance to EGFR-TKIs in NSCLC. Tries should end up being produced to explore concentrating on to resensitize TKI-resistant tumors. Launch Despite the advantage of skin development aspect receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancers (NSCLC) sufferers with mutation [1], obtained level of resistance to these therapies is normally a vital scientific issue. Although the Testosterone levels790M supplementary mutation [2] and gene amplification [3] may jointly accounts for 70% of this level of resistance, systems for the staying 30% are unsure. The epithelial-mesenchymal ...

We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a

In the present study, we evaluated the proliferative behavior of oral SCC cell lines including cetuximab-sensitive HSC3 and HSC4 and cetuximab-resistant SAS. Notably, all cell lines expressed EGFR in the cell membrane and phosphorylated, regardless of cetuximab sensitivity status.. The monoclonal antibody cetuximab targets the extracellular domain of EGFR with high specificity and affinity (37). Cetuximab blocks ligand binding and thereby inhibits EGFR phosphorylation (9). Thus, cetuximab should inhibit EGFR-dependent cell proliferation. In the present study, proliferation of HSC3 and HSC4 cells was strongly associated with EGFR ligand-EGFR signaling, since proliferation was markedly reduced by the EGFR kinase inhibitor AG1478. Thus, cetuximab prevented EGFR phosphorylation, reducing proliferation of HSC3 and HSC4. These data are consistent with those of a previous report that EGFR biomarker analysis in non-small cell lung carcinoma patients showed that those with higher EGFR expression levels ...

Background: Epidermal growth factor receptor (EGFR) mutations are frequently found in non-small cell lung cancer (NSCLC) patients. Various EGFR mutations respond differently to EGFR tyrosine kinase inhibitors (TKIs), and several TKIs have been approved for use on common mutations but none have been approved for EGFR exon 20 insertions, indicating a need for targeted therapy for this subpopulation. A systematic literature review (SLR) and meta-analysis were conducted to synthesize epidemiological and outcome data for the uncommon EGFR exon 20 insertion mutation. Methods: An SLR was performed on August 7, 2018 following the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the Population, Intervention Comparators, Outcomes and Study Design (PICOS) criteria. Studies were identified based on a systematic search using key biomedical literature databases: EMBASE, MEDLINE, and Cochrane. Relevant congress abstracts published between 2015-2018 were also ...

TY - JOUR. T1 - Anterior gradient 2 is correlated with EGFR mutation in lung adenocarcinoma tissues. AU - Narumi, Sodai. AU - Miki, Yasuhiro. AU - Hata, Shuko. AU - Ebina, Masahito. AU - Saito, Mikiyoshi. AU - Mori, Kazushige. AU - Kobayashi, Makoto. AU - Suzuki, Takashi. AU - Iwabuchi, Erina. AU - Sato, Ikuro. AU - Maemondo, Makoto. AU - Endo, Chiaki. AU - Inoue, Akira. AU - Kondo, Takashi. AU - Yamada-Okabe, Hisafumi. AU - Ichinose, Masakazu. AU - Sasano, Hironobu. PY - 2015/4/1. Y1 - 2015/4/1. N2 - Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) has demonstrated a promising therapeutic response in lung adenocarcinoma patients with EGFR gene mutations. However, the predictive factors for this therapy have not been established, except for the EGFR gene mutation status of carcinoma cells. Methods: We first performed microarray analysis in EGFR-TKI-sensitive lung adenocarcinoma cell lines. The results indicated anterior gradient 2 (AGR2) as a potential ...

A number of different strategies have been explored to therapeutically modulate tumor oxygenation. The studies described here show that the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib improves oxygenation within A431 squamous cell carcinoma xenografts. Using in vivo PET imaging with the hypoxia marker FAZA, it was seen that treatment with gefitinib reduced hypoxia in A431 xenografts in comparison with untreated control tumors. Importantly, serial PET imaging studies were able to show that gefitinib reduced hypoxia compared with pretreatment levels. These findings were verified in a parallel experiment in which hypoxia was assessed using pimonidazole binding at time points corresponding with the PET studies.. In vivo imaging of hypoxia was conducted using the PET hypoxia imaging agent FAZA. This compound displays different physical properties to fluoromisonidazole, in particular, a lower octanol/water partition coefficient, indicating the potential for more rapid ...

The targeted agent Tarceva® (erlotinib) nearly doubles progression-free survival compared with chemotherapy when used as initial treatment for advanced non-small cell lung cancer that contains an EGFR gene mutation. These results were recently presented at the 14th World Conference on Lung Cancer.. As cancer research has evolved, its become apparent that the specific characteristics of a tumor can have a profound effect on the behavior of the cancer and its response to particular treatments. In the case of non-small cell lung cancer (NSCLC), for example, mutations in the EGFR (epidermal growth factor receptor) gene may influence whether the cancer responds to the EGFR-targeted drugs such as Tarceva. Among people with NSCLC, EGFR mutations are most common in people of Asian ethnicity, women, never-smokers, and those with a type of lung cancer known as adenocarcinoma.. Tarceva is currently approved for the treatment of advanced NSCLC after initial treatment has failed, or as maintenance therapy ...

We compared the role of tyrosine kinases in α1A-adrenergic receptor (AR) and growth factor receptor stimulation of mitogen-activated protein kinase pathways in PC12 cells. Norepinephrine (NE) (noradrenaline), epidermal growth factor (EGF) and nerve growth factor (NGF) caused different patterns of tyrosine phosphorylation in PC12 cells stably expressing α1A-ARs. NE increased tyrosine phosphorylation of focal adhesion-related kinase Pyk2 and a 70 kDa protein, probably paxillin, whereas EGF strongly stimulated tyrosine phosphorylation of the EGF receptor and cytokine-activated kinase Jak2. The EGF receptor inhibitor AG1478 inhibited activation of extracellular signal-regulated kinases (ERKs) by EGF but not by NE. EGF and NGF strongly activated tyrosine phosphorylation of Shc and caused association of Src-homology collagen (Shc) with growth-factor-receptor-bound protein 2 (Grb2); however, neither NE nor UTP caused substantial activation of the Shc/Grb2 pathway. NE, UTP, EGF and NGF all increased ...

Furthermore, the development of novel chemotherapeutic agents for lung cancer has resulted in improvements in survival. Targeted agents in particular, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), compared to other cytotoxic chemotherapy agents, show superior pharmacokinetics in penetrating through the bloodbrain barrier. Despite the fact that few prospective data are available on the efficacy of EGFR TKIs in this setting, several authors have recently reported a growing number of cases showing partial or complete responses in brains treated with these agents. Park et al. [28] treated NSCLC patients with brain metastases and EGFR exon 19 or 21 mutations using EGFR TKIs. Out of 28 patients, 23 patients showed a partial response with EGFR TKIs only. If these drugs can adequately affect tumor cells in the brain, it would reduce the incidence of other intracranial recurrences. Unfortunately, we have no date on some of our patients have regarding chemotherapy or ...

At the 6th European Lung Cancer Conference (ELCC), held in Geneva, Switzerland, from 13-16 April 2016, Martin Reck, MD, PhD, from LungenClinic Grosshansdorf, Grosshansdorf, Germany, discusses ASSESS, a trial of the utility of circulating-free tumor DNA in the plasma for the detection of epidermal growth factor receptor (EGFR) mutation status in patients with advanced non-small cell lung cancer.

Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated.. ...

The ErbB family of receptors is dysregulated in a number of cancers, and the signaling pathway of this receptor family is a critical target for several anti-cancer drugs. Therefore, a detailed understanding of the mechanisms of receptors activation is critical. However, despite a plethora of biochemical studies and single particle tracking experiments, the early molecular mechanisms involving epidermal growth factor (EGF) binding and EGF receptor (EGFR) dimerization are not as well understood. Due to the large disparity of time and length scales involved in receptor dimerization reactions, we adapt the coarse-grained Monte Carlo (CGMC) simulation framework to enable the simulation of in vivo receptor diffusion and dimerization. Using the CGMC method, spatial modeling of ligand-mediated membrane receptor dimerization reaction dynamics was performed. Furthermore, the simulations demonstrate the importance of spatial heterogeneity in membrane receptor localization. Mathematical models, especially ...

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are current standard of care for patients with EGFR mutation and metastatic non-small-cell lung carcinoma (NSCLC), but most patients using EGFR TKIs acquire resistance later. So, overcoming resistance of EGFR TKIs has become an important issue in the treatment of NSCLC. Previously, therapeutics targeting Brutons tyrosine kinase (BTK) have been successful in treating several hematologic malignancies. However, the role of BTK in NSCLC is still unknown. In this study, by examining surgical specimens from 80 NSCLC patients and their clinicopathologic parameters, we found significant correlation between high BTK expression and tumor differentiation, p-stage, lymph node metastatic status, maximum tumor size, and poor prognosis of patients. Using two NSCLC cell lines A540 and PC9, we demonstrated that BTKpos cells exhibited more stemness (OCT4, SOX2) and EMT (E-Cadherin, Slug) markers than BTKneg cells. Knockdown of BTK ...

The aim of this study was to detect the epidermal growth factor receptor (EGFR)-activating mutations and other oncogene alterations in patients with non-small-cell lung cancers (NSCLC) who experienced a treatment failure in response to EGFR-tyrosine kinase inhibitors (TKIs) with a next generation sequencer. Fifteen patients with advanced NSCLC previously treated with EGFR-TKIs were examined between August 2005 and October 2014. For each case, new biopsies were performed, followed by DNA sequencing on an Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel version 2. All 15 patients were diagnosed with NSCLC harboring EGFR-activating mutations (seven cases of exon 19 deletion, seven cases of L858R in exon 21, and one case of L861Q in exon 21). Of the 15 cases, acquired T790M resistance mutations were detected in 9 (60.0 %) patients. In addition, other mutations were identified outside of EGFR, including 13 cases (86.7 %) exhibiting TP53 P72R mutations, 5 cases (33

TY - JOUR. T1 - The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status, as a potent accompanist in combined therapeutic regimens. AU - Wu, Yi Ying. AU - Wu, Hung Chang. AU - Wu, Jia En. AU - Huang, Kuo Yen. AU - Yang, Shuenn Chen. AU - Chen, Si Xuan. AU - Tsao, Chao Jung. AU - Hsu, Keng Fu. AU - Chen, Yuh Ling. AU - Hong, Tse Ming. PY - 2019/7/1. Y1 - 2019/7/1. N2 - Background: Lung cancer is the most common cause of cancer-related mortality worldwide despite diagnostic improvements and the development of targeted therapies, notably including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling has been shown to contribute to tumorigenesis, tumor progression, and resistance to therapy in most human cancer types, including lung cancer. Here, we explored the therapeutic effects of co-inhibition of PI3K and mTOR in non-small-cell lung ...

Symphogen A/S, a private biopharmaceutical company with leadership in recombinant antibody mixtures for therapeutic use, today reported preliminary safety and exploratory efficacy data from a Phase 1 clinical study of Sym004, an investigational anti-EGFR monoclonal antibody mixture, administered biweekly, that will be presented in a poster at the upcoming American Society for Clinical Oncology (ASCO) Annual Meeting being held May 30 - June 3, 2014 in Chicago, IL. The poster, entitled, Phase 1 study of biweekly (Q2W) anti-EGFR monoclonal antibody (mAb) mixture Sym004 in patients (29 pts) with metastatic colorectal cancer (mCRC) resistant to previous anti-EGFR treatment (abstract #3551) will be on view in the poster session on Gastrointestinal (Colorectal) Cancer (31 May 2014, 8:00 - 11:45 AM, McCormick Place Convention Center in Chicago, IL). Sym004 is a drug mixture of two mAbs targeting non-overlapping epitopes of EGFR which have been shown in pre-clinical studies to demonstrate synergistic ...

Search and download thousands of Swedish university dissertations (essays). Full text. Free. Dissertation: Thyroid hormone mediates fibroblast growth factor receptor expression, which both alter cell surface mechanical properties of the mammalian cochlea.

Epidermal growth factor receptor (EGFR) and nonreceptor tyrosine kinase c-Src, whose combined overexpression occurs in some breast cancers, cooperate to promote transformed characteristics when overexpressed in fibroblasts. Their synergistic interaction, which depends on c-Src phosphorylation of EGFR tyrosine 845 (pY845), is independent of EGFR kinase activity and of its activation of the mitogen-associated protein kinase signaling pathway. Boerner et al. screened a phage display library with a peptide corresponding to the region of EGFR that contains pY845 and identified cytochrome c oxidase subunit II (CoxII) as a binding partner. In mouse fibroblasts overexpressing EGFR and c-Src and in a breast cancer cell line that overexpresses both EGFR and c-Src, CoxII coimmunoprecipitated with EGFR. Coimmunoprecipitation, which was enhanced by EGF treatment, did not occur with overexpression of a catalytically inactive c-Src mutant or when Y845 was replaced by phenylalanine (Y845F-EGFR). The authors ...

Over the last decade, improvements in the investigators understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and tumor progression. Lapatinib is an oral selective and reversible inhibitor of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER-2), which are both frequently altered in human malignant tumors. Sorafenib is an oral multi-kinase inhibitor with a dual-action that prevents tumor cell proliferation and angiogenesis. The investigators suggest that through a complete blockade of ErbB signaling network it may be possible to sensitize tumor cells to antiangiogenic therapy, by lowering the tumor cell survival threshold, while through inhibition of vascular endothelial growth factor (VEGF) pathway to circumvent the problem of acquired resistance to EGFR ...

Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All were positive for T790M prior to treatment, but at resistance three molecular subtypes emerged: 6 cases acquired the C797S mutation, 5 cases maintained the T790M mutation but did not acquire the C797S mutation, and 4 cases lost the T790M mutation despite detecting of the underlying EGFR activating mutation. Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies

J. Clin Oncol 2009, 27:2653-9.PubMedCrossRef 18. Yung TK, Chan KC, Mok TS, Tong J, To KF, Lo YM: Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res 2009,15(6):2076-84.PubMedCrossRef 19. Zhou Q, Zhang XC, Chen ZH, Yin XL, Yang JJ, Xu CR, Yan HH, Chen HJ, Su J, Zhong WZ, Yang XN, An SJ, Wang BC, Huang YS, Wang Z, Wu YL: Relative Abundance of EGFR Mutations Predicts Benefit From Gefitinib Treatment for Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2011,29(24):3316-3321.PubMedCrossRef 20. Ellison G, Donald E, McWalter G, Knight L, Fletcher L, Sherwood J, Cantarini M, Orr M, Speake G: A comparison of ARMS and DNA sequencing for mutation analysis Acalabrutinib solubility dmso in clinical biopsy samples. J Exp Clin Cancer Res 2010, 29:132.PubMedCrossRef 21. Fan X, Furnari FB, Cavenee WK, Castresana JS: Non-isotopic silver-stained SSCP is more sensitive than automated direct sequencing ...

In this study, we armed the oncolytic adenovirus ICO15K with an EGFR-targeting BiTE (cBiTE). cBiTEs secreted from infected cells retained key features of BiTEs including target cell-dependent T-cell activation and proliferation and redirected lysis of cancer cells (27, 28). The anti-EGFR scFV in the cBiTE was derived from the monoclonal antibody cetuximab, which is used in patients with colorectal and head-and-neck squamous cell cancer (29, 30). One of the major mechanisms of resistance to cetuximab in colorectal cancer is the mutation of downstream signaling genes such as BRAF, KRAS, PIK3CA, and PTEN (31). A cetuximab-derived BiTE overcomes this resistance by successfully redirecting T cells to kill BRAF- and KRAS-mutated colorectal cancer cells (32). Here, we also demonstrate that ICO15K-cBiTE induces a T-cell-mediated killing of KRAS-mutated HCT116 cells in vitro and in vivo.. The potential of BiTE-armed oncolytic viruses has been previously demonstrated using an oncolytic vaccinia virus with ...

This months Cell and Bioscience highlights review articles by Mien-Chie Hung on EGFR biology and Yingzi Yang on Wnt signaling. Dr. Hung was the 2011 Society of Chinese Bioscientists in America (SCBA) Presidential Award winner. Dr. Yang was the 2011 SCBA Outstanding Young Investigator Award winner.

Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor®)-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased

Shop Fibroblast growth factor receptor ELISA Kit, Recombinant Protein and Fibroblast growth factor receptor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.

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TY - JOUR. T1 - Clinical Significance of Detecting Somatic Gene Mutations in Surgically Resected Adenosquamous Cell Carcinoma of the Lung in Japanese Patients. AU - Morodomi, Yosuke. AU - Okamoto, Tatsuro. AU - Takenoyama, Mitsuhiro. AU - Takada, Kazuki. AU - Katsura, Masakazu. AU - Suzuki, Yuzo. AU - Fujishita, Takatoshi. AU - Kitahara, Hirokazu. AU - Shimamatsu, Shinichiro. AU - Kohno, Mikihiro. AU - Tagawa, Tetsuzo. AU - Okano, Shinji. AU - Taguchi, Kenichi. AU - Ichinose, Yukito. AU - Maehara, Yoshihiko. PY - 2015/8/1. Y1 - 2015/8/1. N2 - Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) inhibitors are effective and useful agents for treating patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement. Therefore, the importance of determining the presence of these somatic mutations when treating lung adenocarcinomas is widely accepted. However, genetic ...