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Epidermal growth factor receptor

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https://www.readbyqxmd.com/read/29040782/egfr-heterogeneity-and-implications-for-therapeutic-intervention-in-glioblastoma
#1
Eskil Eskilsson, Gro V Røsland, Gergely Solecki, Qianghu Wang, Patrick N Harter, Grazia Graziani, Roel G W Verhaak, Frank Winkler, Rolf Bjerkvig, Hrvoje Miletic
Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials...
October 10, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29036807/obtaining-and-characterization-of-monoclonal-antibodies-against-recombinant-extracellular-domain-of-human-epidermal-growth-factor-receptor-2
#2
Sarina Nurgul, Abeldenov Sailau, Turgimbayeva Aigerim, Zhylkibayev Assylbek, Ramankulov Erlan, Khassenov Bekbolat, Eskendirova Saule
Human epidermal growth factor receptor 2 (HER2) is an important biomarker for detection and treatment of different types of cancers such as breast, ovarian, stomach cancer. In this study, we developed a monoclonal antibody against the extracellular domain (ECD) of HER2 biomarker of breast cancer. For this purpose, the ECD-HER2 gene was amplified and cloned into an expression vector. Gene was generated in Escherichia coli BL21 (DE3) strain for expression of recombinant protein. The expressed protein was separated by SDS-PAGE and detected by anti-his monoclonal antibody in immunoblotting...
September 8, 2017: Human Antibodies
https://www.readbyqxmd.com/read/29036586/epigenetic-mechanisms-underlie-the-crosstalk-between-growth-factors-and-a-steroid-hormone
#3
Yehoshua Enuka, Morris E Feldman, Animesh Chowdhury, Swati Srivastava, Moshit Lindzen, Aldema Sas-Chen, Renaud Massart, David Cheishvili, Matthew J Suderman, Yoav Zaltsman, Chiara A Mazza, Kirti Shukla, Cindy Körner, Noa Furth, Mattia Lauriola, Moshe Oren, Stefan Wiemann, Moshe Szyf, Yosef Yarden
Crosstalk between growth factors (GFs) and steroid hormones recurs in embryogenesis and is co-opted in pathology, but underlying mechanisms remain elusive. Our data from mammary cells imply that the crosstalk between the epidermal GF and glucocorticoids (GCs) involves transcription factors like p53 and NF-κB, along with reduced pausing and traveling of RNA polymerase II (RNAPII) at both promoters and bodies of GF-inducible genes. Essentially, GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal inhibitory loops...
September 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036463/multiple-links-between-shade-avoidance-and-auxin-networks
#4
María José Iglesias, Romina Sellaro, Matias D Zurbriggen, Jorge José Casal
Auxin has emerged as a key player in the adjustment of plant morphology to the challenge imposed by variable environmental conditions. Shade-avoidance responses, including the promotion of stem and petiole growth, leaf hyponasty, and the inhibition of branching, involve an intimate connection between light and auxin signalling. Low activity of photo-sensory receptors caused by the presence of neighbouring vegetation enhances the activity of PHYTOCHROME INTERACTING FACTORs (PIFs), which directly promote the expression of genes involved in auxin biosynthesis, conjugation, transport, perception, and signalling...
September 27, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29036202/toxoplasma-gondii-induces-fak-src-stat3-signaling-during-infection-of-host-cells-that-prevents-parasite-targeting-by-autophagy
#5
Jose-Andres C Portillo, Luis Muniz-Feliciano, Yalitza Lopez Corcino, So Jung Lee, Jennifer Van Grol, Sarah J Parsons, William P Schiemman, Carlos S Subauste
Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling...
October 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29035465/enhanced-specificity-of-braf-v600e-genotyping-using-wild-type-blocker-coupled-with-internal-competitive-reference-in-a-single-tube
#6
Jia Peng, Kun Wei, Shu Yu, Xiang Yang, Xiang Zhao, Yu Liu, Xiao-Yan Zhu, Na Zhao, Qing Huang, Wei-Ling Fu
BACKGROUND: Mutations in the BRAF gene have been strongly associated with failure in cancer treatment using epidermal growth factor receptor (EGFR) antibodies. To better diagnose and assess the prognosis of cancer patients, mutation screening of the BRAFV600E gene should be performed prior to clinical anti-tumor drug therapy to avoid ineffective treatment. METHODS: In our previous study, we developed a real-time wild-type blocking PCR (WTB-PCR), which can amplify the mutant allele at high efficiency while simultaneously inhibiting the amplification of wild-type alleles...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29035388/a-novel-her2-gene-body-enhancer-contributes-to-her2-expression
#7
Q Liu, M V Kulak, N Borcherding, P K Maina, W Zhang, R J Weigel, H H Qi
The transcriptional regulation of the human epidermal growth factor receptor-2 (HER2) contributes to an enhanced HER2 expression in HER2-positive breast cancers with HER2 gene amplification and HER2-low or HER2-negative breast cancers following radiotherapy or endocrine therapy, and this drives tumorigenesis and the resistance to therapy. Epigenetic mechanisms are critical for transcription regulation, however, such mechanisms in the transcription regulation of HER2 are limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and acetylated histone 3 lysine 9 (H3K9ac) at the HER2 promoter region...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#8
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29034878/generation-of-an-induced-pluripotent-stem-cell-line-cscrmi001-a-from-a-patient-with-a-new-type-of-limb-girdle-muscular-dystrophy-lgmd-due-to-a-missense-mutation-in-poglut1-rumi
#9
Jianbo Wu, Samuel D Hunt, Nadine Matthias, Emilia Servián-Morilla, Jonathan Lo, Hamed Jafar-Nejad, Carmen Paradas, Radbod Darabi
Recently, a new type of limb-girdle muscular dystrophy (LGMD type 2Z) has been identified due to a missense mutation in POGLUT1 (protein O-glucosyltransferase-Rumi), an enzyme capable of adding glucose to a distinct serine residue of epidermal growth factor-like repeats containing a C-X-S-X-(P/A)-C consensus sequence such as Notch receptors. Affected patients demonstrate reduced Notch signaling, decreased muscle stem cell pool and hypoglycosylation of α-dystroglycan, leading to LGMD phenotype. Here we report the generation and characterization of an iPSC line (CSCRMi001-A) from a LGMD-2Z patient with missense mutation in POGLUT1 which can be used for in vitro disease modeling...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034207/targeting-novel-but-less-common-driver-mutations-and-chromosomal-translocations-in-advanced-non-small-cell-lung-cancer
#10
REVIEW
Alia Daoud, Quincy S Chu
Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. Such concerted efforts have been variably successful in both non-squamous and squamous cell carcinomas of the lung. Some of the targeted therapies for these oncogenic drivers have received regulatory approval for clinical use, while others have modest clinical benefit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29033568/in-vivo-evaluation-of-cetuximab-conjugated-poly-%C3%AE-glutamic-acid-docetaxel-nanomedicines-in-egfr-overexpressing-gastric-cancer-xenografts
#11
Maya Sreeranganathan, Saji Uthaman, Bruno Sarmento, Chethampadi Gopi Mohan, In-Kyu Park, Rangasamy Jayakumar
Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29032724/reintroducing-the-sodium-iodide-symporter-nis-to-anaplastic-thyroid-carcinoma
#12
Kathrin Alexandra Schmohl, Patrick Dolp, Christina Schug, Kerstin Knoop, Kathrin Klutz, Nathalie Schwenk, Peter Bartenstein, Peter Jon Nelson, Manfred Ogris, Ernst Wagner, Christine Spitzweg
Anaplastic thyroid carcinoma (ATC), the most aggressive form of thyroid cancer, is unresponsive to radioiodide therapy. In the current study, we aimed to extend the diagnostic and therapeutic application of radioiodide beyond the treatment of differentiated thyroid cancer by targeting the functional sodium iodide symporter (NIS) to ATC. We employed nanoparticle vectors (polyplexes) based on linear polyethylenimine (LPEI), shielded by polyethylene glycol (PEG) and coupled to the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand in order to target a <i>NIS</i>-expressing plasmid (LPEI-PEG-GE11/NIS) to EGFR overexpressing human thyroid carcinoma cell lines...
October 15, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29032173/the-reduced-osteogenic-potential-of-nf1-deficient-osteoprogenitors-is-egfr-independent
#13
S E Tahaei, G Couasnay, Y Ma, N Paria, J Gu, B F Lemoine, X Wang, J J Rios, F Elefteriou
Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 gene. Recalcitrant bone healing following fracture (i.e. pseudarthrosis) is one of the most problematic skeletal complications associated with NF1. The etiology of this condition is still unclear; thus, pharmacological options for clinical management are limited. Multiple studies have shown the reduced osteogenic potential of Nf1-deficient osteoprogenitors. A recent transcriptome profiling investigation revealed that EREG and EGFR, encoding epiregulin and its receptor Epidermal Growth Factor Receptor 1, respectively, were among the top over-expressed genes in cells of the NF1 pseudarthrosis site...
October 11, 2017: Bone
https://www.readbyqxmd.com/read/29031688/vitamin-d-deficiency-is-associated-with-poor-breast-cancer-prognostic-features-in-postmenopausal-women
#14
Benedito de Sousa Almeida-Filho, Heloisa De Luca Vespoli, Eduardo Carvalho Pessoa, Murilo Machado, Jorge Nahas-Neto, Eliana Aguiar Petri Nahas
This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45-75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. Clinical and anthropometric data were collected...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29031038/isocitrate-dehydrogenase-mutations-are-better-prognostic-marker-than-o6-methylguanine-dna-methyltransferase-promoter-methylation-in-glioblastomas-a-retrospective-single-centre-molecular-genetics-study-of-gliomas
#15
M Houdova Megova, J Drábek, Z Dwight, R Trojanec, V Koudeláková, J Vrbková, O Kalita, S Mlcochova, M Rabcanova, M Hajdúch
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29030480/intersectin-s-interaction-with-dennd2b-facilitates-recycling-of-epidermal-growth-factor-receptor
#16
Maria S Ioannou, Gopinath Kulasekaran, Maryam Fotouhi, Justin J Morein, Chanshuai Han, Sarah Tse, Nadya Nossova, Tony Han, Erin Mannard, Peter S McPherson
Epidermal growth factor (EGF) activates the EGF receptor (EGFR) and stimulates its internalization and trafficking to lysosomes for degradation. However, a percentage of EGFR undergoes ligand-independent endocytosis and is rapidly recycled back to the plasma membrane. Importantly, alterations in EGFR recycling are a common hallmark of cancer, and yet, our understanding of the machineries controlling the fate of endocytosed EGFR is incomplete. Intersectin-s is a multi-domain adaptor protein that is required for internalization of EGFR Here, we discover that intersectin-s binds DENND2B, a guanine nucleotide exchange factor for the exocytic GTPase Rab13, and this interaction promotes recycling of ligand-free EGFR to the cell surface...
October 13, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29030356/cell-cycle-and-dna-damage-response-pathway-is-involved-in-leptomeningeal-metastasis-of-non-small-cell-lung-cancer
#17
Yun Fan, Xuehua Zhu, Yan Xu, Xuesong Lu, Yanjun Xu, Mengzhao Wang, Haiyan Xu, Jingyan Ding, Xin Ye, Luo Fang, Zhiyu Huang, Lei Gong, Hongyang Lu, Weimin Mao, Min Hu
PURPOSE: Leptomeningeal metastases (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood. EXPERIMENTAL DESIGN: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF) and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM...
October 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29030307/egfr-targeted-multifunctional-polymersomal-doxorubicin-induces-selective-and-potent-suppression-of-orthotopic-human-liver-cancer-in-vivo
#18
Yuan Fang, Weijing Yang, Liang Cheng, Fenghua Meng, Jian Zhang, Zhiyuan Zhong
Liver cancer is a globally leading malignancy that has a poor five-year survival rate of less than 20%. The systemic chemotherapeutics are generally ineffective for liver cancers partly due to fast clearance and low tumor uptake. Here, we report that GE11 peptide functionalized polymersomal doxorubicin (GE11-PS-DOX) effectively targets and inhibits epidermal growth factor receptor (EGFR)-positive SMMC7721 orthotopic human liver tumor xenografts in mice. GE11-PS-DOX with a GE11 surface density of 10% displayed a high drug loading of 15...
October 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29029530/which-treatment-is-preferred-for-advanced-non-small-cell-lung-cancer-with-wild-type-epidermal-growth-factor-receptor-in-second-line-therapy-a-meta-analysis-comparing-immune-checkpoint-inhibitor-tyrosine-kinase-inhibitor-and-chemotherapy
#19
Di Wu, Chongyang Duan, Fenfang Wu, Liyong Chen, Size Chen
BACKGROUND: The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy. PATIENTS AND METHODS: Randomized trials investigating two of the three treatments were searched and included...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029486/egf-stimulates-glioblastoma-metastasis-by-induction-of-matrix-metalloproteinase-9-in-an-egfr-dependent-mechanism
#20
Xing-Chen Chen, Xiang-Tai Wei, Jun-Hong Guan, Hong Shu, Duo Chen
Epidermal growth factor (EGF) and EGF receptor (EGFR) play prominent roles in the metastasis of glioblastoma (GBM). However, the molecular mechanisms for the function of EGF and EGFR in GBM metastasis have not been elucidated. Herein, we demonstrate that coactivation of EGF and EGFR drives tumor metastasis in a matrix metalloproteinase-9 (MMP-9)-dependent manner. Expression levels of EGF, EGFR, and MMP-9 were substantially upregulated in the GBM and edema zones of patients, compared with those of paired unaffected participants...
September 12, 2017: Oncotarget
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