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Epidermal growth factor receptor

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https://www.readbyqxmd.com/read/29909520/lapatinib-in-combination-with-paclitaxel-plays-synergistic-antitumor-effects-on-esophageal-squamous-cancer
#1
Xiao-Fang Guo, Sai-Sai Li, Xiao-Fei Zhu, Qiao-Hua Dou, Duan Liu
PURPOSE: Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), combined with paclitaxel on the esophageal squamous cancer. METHODS: MTT assays were used to evaluate the effects of the combination of lapatinib and paclitaxel on the growth of esophageal squamous cancer cell lines (KYSE150, KYSE450, KYSE510 and TE-7)...
June 16, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29909387/paraneoplastic-cerebellar-degeneration-in-a-patient-with-anaplastic-non-hodgkin-s-lymphoma
#2
Nadir Khan
A 31-year-old man presented with a subacute cerebellar syndrome of unknown aetiology. Investigations including a paraneoplastic antibody screen were negative and a working diagnosis of possible vasculitis was concluded. After 1 month, he re-presented with worsening of his symptoms and a neck lump. He was diagnosed with anaplastic lymphoma kinase, negative non-Hodgkin's lymphoma and paraneoplastic cerebellar syndrome. A more extensive paraneoplastic antibody screen found patient to be Tr (delta/notch-like epidermal growth factor-related receptor) antibody positive...
June 15, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29909039/integrin-%C3%AE-6-and-egfr-signaling-converge-at-mechanosensitive-calpain-2
#3
A D Schwartz, C L Hall, L E Barney, C C Babbitt, S R Peyton
Cells sense and respond to mechanical cues from the extracellular matrix (ECM) via integrins. ECM stiffness is known to enhance integrin clustering and response to epidermal growth factor (EGF), but we lack information on when or if these mechanosensitive growth factor receptors and integrins converge intracellularly. Towards closing this knowledge gap, we combined a biomaterial platform with transcriptomics, molecular biology, and functional assays to link integrin-mediated mechanosensing and epidermal growth factor receptor (EGFR) signaling...
June 2, 2018: Biomaterials
https://www.readbyqxmd.com/read/29909007/early-emergence-of-de-novo-egfr-t790-m-gatekeeper-mutations-during-erlotinib-treatment-in-pc9-non-small-cell-lung-cancer-cells
#4
Sujin Kim, Angela Kj Park, Jeonghee Cho
The emergence of the T790 M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) gene is an important mechanism that can lead to the acquired resistance to EGFR-targeted tyrosine kinase inhibitors such as erlotinib or gefitinib. These drugs have been used in treating a subset of non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Here we investigated the paths leading to the acquisition of the T790 M mutation by establishing an erlotinib resistant PC9 cell model harboring ectopically introduced EGFR cDNA...
June 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29908541/construction-of-a-recombinant-phage-vaccine-capable-of-reducing-the-growth-rate-of-an-established-ll2-tumor-model
#5
Majid Asadi-Ghalehni, Mohamad Javad Rasaee, Nabiollah Namvar Asl, Masood Khosravani, Masoumeh Rajabibazl, Saeed Khalili, Helmout Modjtahedi, Esmaeil Sadroddiny
Over expression of the epidermal growth factor receptor (EGFR) in many human epithelial tumors has been correlated with disease progression and poor prognosis. EGFR-inhibiting immunotherapy has already been introduced in cancer therapy. Peptide displaying phage particles in eukaryotic hosts can behave as antigen carriers, able to activate the innate immune system and to elicit adaptive immunity. Herein, the M13-pAK8-VIII phagemid plasmid was engineered to contain the sequences for an EGFR mimotope along with the L2 extracellular domain of EGFR (EM-L2) which would produce the final peptide-phage vaccine...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29907952/bim-deletion-polymorphism-confers-resistance-to-osimertinib-in-egfr-t790m-lung-cancer-a-case-report-and-literature-review
#6
REVIEW
Xuanzong Li, Shijiang Wang, Butuo Li, Zhen Wang, Shuheng Shang, Yang Shao, Xindong Sun, Linlin Wang
The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations...
June 16, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29907942/distribution-of-21-gene-recurrence-scores-in-male-breast-cancer-in-the-united-states
#7
Ariella M Altman, Scott Kizy, Jianling Yuan, Jason W Denbo, Eric H Jensen, Jane Y C Hui, Todd M Tuttle, Schelomo Marmor
BACKGROUND: The 21-gene recurrence score (RS) is a RT-PCR assay estimating risk of distant recurrence in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2) breast cancer (BC). Studies validating RS are limited to women. Our objective was to assess RS distribution and factors associated with high-risk RS in male BC. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified men and women with ER+/HER2- BC from 2010 to 2013...
June 15, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29906411/dermal-fibroblast-slc3a2-deficiency-leads-to-premature-aging-and-loss-of-epithelial-homeostasis
#8
Floriane S Tissot, Soline Estrach, Etienne Boulter, Laurence Cailleteau, Lionel Tosello, Laetitia Seguin, Sabrina Pisano, Stéphane Audebert, Olivier Croce, Chloé C Féral
Skin homeostasis relies on fine tuning of epidermis/dermis interactions and is affected by aging. While extracellular matrix (ECM) proteins, such as integrins, are involved in aging, the molecular basis of the skin changes need to be further investigated. Here, we showed that integrin co-receptor, SLC3A2, required for cell proliferation, is expressed at the surface of resting dermal fibroblasts (DF) in young patients, and drastically reduced with aging. In vivo SLC3A2 DF deletion induced major skin phenotypes resembling premature aging...
June 12, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29906246/o-glycosylation-mediated-signaling-circuit-drives-metastatic-castration-resistant-prostate-cancer
#9
Sheue-Fen Tzeng, Chin-Hsien Tsai, Tai-Kuang Chao, Yu-Ching Chou, Yu-Chih Yang, Mong-Hsun Tsai, Tai-Lung Cha, Pei-Wen Hsiao
Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29906114/design-synthesis-and-biological-evaluation-of-pyrimido-4-5-d-pyrimidine-2-4-1-h-3-h-diones-as-potent-and-selective-epidermal-growth-factor-receptor-egfr-inhibitors-against-l858r-t790m-resistance-mutation
#10
Yongjia Hao, Jiankun Lyu, Rong Qu, Yi Tong, Deheng Sun, Fang Feng, Linjiang Tong, Tingyuan Yang, Zhenjiang Zhao, Lili Zhu, Jian Ding, Yufang Xu, Hua Xie, Honglin Li
First-generation epidermal growth factor receptor (EGFR) inhibitors, gefitinib and erlotinib have achieved initially marked clinical efficacy for non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, their clinical benefit was limited by the emergence of acquired resistance mutations. In most cases (approximately 60%), the resistance was caused by the secondary EGFR T790M gatekeeper mutation. Thus, it is still desirable to develop novel third-generation EGFR inhibitors to overcome T790M mutation while sparing wild-type (WT) EGFR...
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29905778/predictive-biomarkers-for-response-to-egfr-directed-monoclonal-antibodies-for-advanced-squamous-cell-lung-cancer
#11
P D Bonomi, D Gandara, F R Hirsch, K M Kerr, C Obasaju, L Paz-Ares, C Bellomo, J D Bradley, P A Bunn, M Culligan, J R Jett, E S Kim, C J Langer, R B Natale, S Novello, M Pérol, S S Ramalingam, M Reck, C H Reynolds, E F Smit, M A Socinski, D R Spigel, J F Vansteenkiste, H Wakelee, N Thatcher
Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs...
June 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29904737/serum-cytokine-profiles-and-metabolic-tumor-burden-in-patients-with-non-small-cell-lung-cancer-undergoing-palliative-thoracic-radiation-therapy
#12
Hanne A Eide, Ingerid Skjei Knudtsen, Vandana Sandhu, Ayca M Løndalen, Ann Rita Halvorsen, Azadeh Abravan, Elin H Kure, Trond V Bogsrud, Odd Terje Brustugun, Jon Amund Kyte, Eirik Malinen, Åslaug Helland
Purpose: Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (18 F-FDG) positron emission tomography (PET). Methods and materials: Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor...
April 2018: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29904688/data-on-mass-spectrometry-based-proteomics-for-studying-the-involvement-of-cyld-in-the-ubiquitination-events-downstream-of-egfr-activation
#13
Virginia Sanchez-Quiles, Nerea Osinalde, Vyacheslav Akimov, Irina Kratchmarova, Blagoy Blagoev
The present data article corresponds to the proteomic data of the involvement of Cylindromatosis protein (CYLD) in the ubiquitination signaling initiated by EGF stimulation. CYLD tumor suppressor protein has Lys63-chain deubiquitinase activity that has been proved essential for the negative regulation of crucial signaling mechanisms, namely the NFkB pathway. Previous results have suggested the involvement of CYLD in the EGF-dependent signal transduction as well, showing its engagement within the tyrosine-phosphorylated complexes formed following the addition of the growth factor...
June 2018: Data in Brief
https://www.readbyqxmd.com/read/29904427/association-of-serum-interleukin-10-interleukin-17a-and-transforming-growth-factor-%C3%AE-levels-with-human-benign-and-malignant-breast-diseases
#14
Zhuangwei Lv, Min Liu, Jinghui Shen, Dong Xiang, Yunfeng Ma, Yanhong Ji
Interleukin-10 (IL-10), interleukin-17A (IL-17A) and transforming growth factor α (TGF-α) have been implicated in the progression of breast cancer. However, the diagnostic and prognostic roles of these cytokines in ductal carcinoma remain unclear. The present study therefore aimed to determine the serum levels of IL-10, IL-17 and TGF-α in subjects with benign and malignant breast diseases and to evaluate the clinical significance of these cytokines in ductal carcinoma. Pre-operative serum samples were collected from 378 patients with breast disease and 70 healthy subjects...
June 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29904349/an-in-vitro-assay-of-herg-k-channel-potency-for-a-new-egfr-inhibitor-fhnd004
#15
Tao Jin, Bingxue Hu, Shanshan Chen, Qiang Wang, Xue Dong, Yin Zhang, Yongqiang Zhu, Zhao Zhang
FHND004 is a newly synthesized epidermal growth factor receptor (EGFR) inhibitor for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the impacts of FHND004 on human ether-à-go-go- related gene (hERG) K+ channels and the molecular mechanisms underlying of its action. Whole-cell patch clamp recording was performed on wild type (WT), mutant hERG channels heterologously expressed in human embryonic kidney (HEK) 293 cells or I Kr endogenously expressed in HL-1 cells, respectively...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29904166/pharmacological-activation-of-epidermal-growth-factor-receptor-signaling-inhibits-colitis-associated-cancer-in-mice
#16
Philip E Dubé, Cambrian Y Liu, Nandini Girish, M Kay Washington, D Brent Polk
Current treatments for inflammatory bowel disease (IBD) target the overactive immune response of the intestinal mucosa. However, epidermal growth factor (EGF), an activating ligand of the EGF receptor (EGFR), has been shown to induce disease remission through direct targeting of intestinal mucosal healing. Despite promising preclinical and clinical results, this EGFR-activating therapy has not progressed, in part due to the potential for carcinogenesis associated with long-term use and the increased risk of colitis-associated cancer (CAC) in IBD...
June 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29903766/cytoprotective-and-pro-angiogenic-functions-of-thrombomodulin-are-preserved-in-the-c-loop-of-the-fifth-epidermal-growth-factor-like-domain
#17
Xiangmin Wang, Bin Pan, Goichi Honda, Xintao Wang, Yuko Hashimoto, Hiroshi Ohkawara, Kailin Xu, Lingyu Zeng, Takayuki Ikezoe
We previously found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) exerts cytoprotective and pro-angiogenic functions via G-protein coupled receptor 15 (GPR15). TME5 is comprised of three S-S bonds that divide it into three loops: A (TME5A), B (TME5B), and C (TME5C). Here, we identified the minimum structure of TME5 that produces favorable effects in vascular endothelial cells (ECs). We found that TME5C, composed of 19 amino acids, but not TME5A or TME5B, stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs)...
June 14, 2018: Haematologica
https://www.readbyqxmd.com/read/29903662/synthesis-and-antitumor-activity-of-novel-6-7-8-trimethoxy-n-aryl-substituted-4-aminoquinazoline-derivatives
#18
Fang Liu, Ziyou Huai, Guotai Xia, Liuping Song, Sha Li, Yulan Xu, Kangjun Hong, Mingyue Yao, Gang Liu, Yinjiu Huang
A series of 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives were synthesized as epidermal growth factor receptor (EGFR) inhibitors, and their antitumor activities were assessed in the gastric cancer cell line SGC7901 using MTT assay. All compounds of Tg1-14 were found to inhibit SGC7901 cell proliferation, and compound Tg11 (IC50  = 0.434 μM) was found to be slightly more effective against SGC7901 cells than epirubicin (IC50  = 5.16 μM). This suggests that compound Tg11 can be used as a new substitution structure to develop more efficacious antitumor agents...
May 18, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29902802/relationship-between-paronychia-and-drug-concentrations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#19
Katsuhiro Masago, Kei Irie, Shiro Fujita, Fumiko Imamichi, Yutaka Okada, Nobuyuki Katakami, Shoji Fukushima, Yasushi Yatabe
PURPOSE: The purpose of the study was to evaluate the site of paronychia in patients with non-small cell lung cancer harboring an epidermal growth factor receptor (EGFR) gene activating mutation who were treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). PATIENTS AND METHODS: The study included 55 patients with non-small-cell lung cancer who were treated with an EGFR TKIs. Resulting all toxicities were graded using the Common Terminology Criteria for Adverse Events version 4...
June 14, 2018: Oncology
https://www.readbyqxmd.com/read/29902673/revealing-the-molecular-interactions-of-aptamers-that-specifically-bind-to-the-extracellular-domain-of-her2-cancer-biomarker-protein-an-in-silico-assessment
#20
Sarfaraj Niazi, Madhusudan Purohit, Archana Sonawani, Javed H Niazi
Single-stranded (ss) oligonucleotide aptamers are emerging as the promising substitutes for monoclonal antibodies because of their low production cost and good batch-to-batch consistency. Aptamers vividly bind to a variety of cellular targets and alter their functions with a remarkable degree of specificities. In this study, the positive clones of human epidermal growth factor receptor 2 (HER2) specific binding ssDNA aptamers which were previously identified by in vitro Systematic Evolution of Ligands by EXponential enrichment (SELEX) process, hitherto lacking the putative binding site information and residues crucial for aptamer recognition are studied...
June 6, 2018: Journal of Molecular Graphics & Modelling
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