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Epidermal growth factor receptor

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https://www.readbyqxmd.com/read/29453963/significance-of-spread-through-air-spaces-in-resected-pathological-stage-i-lung-adenocarcinoma
#1
Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer, which spreads within air spaces beyond the edge of the main tumor. In the current study, we investigated the significance of STAS in patients with pathological stage I adenocarcinoma. METHODS: STAS was assessed in a total of 276 patients with resected pathological stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens...
February 14, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29452913/photo-immobilized-egf-chemical-gradients-differentially-impact-breast-cancer-cell-invasion-and-drug-response-in-defined-3d-hydrogels
#2
Stephanie A Fisher, Roger Y Tam, Ana Fokina, M Mohsen Mahmoodi, Mark D Distefano, Molly S Shoichet
Breast cancer cell invasion is influenced by growth factor concentration gradients in the tumor microenvironment. However, studying the influence of growth factor gradients on breast cancer cell invasion is challenging due to both the complexities of in vivo models and the difficulties in recapitulating the tumor microenvironment with defined gradients using in vitro models. A defined hyaluronic acid (HA)-based hydrogel crosslinked with matrix metalloproteinase (MMP) cleavable peptides and modified with multiphoton labile nitrodibenzofuran (NDBF) was synthesized to photochemically immobilize epidermal growth factor (EGF) gradients...
February 13, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452408/genome-wide-association-study-identifies-seven-novel-susceptibility-loci-for-primary-open-angle-glaucoma
#3
Yukihiro Shiga, Masato Akiyama, Koji M Nishiguchi, Kota Sato, Nobuhiro Shimozawa, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Matsuda Koichi, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Isao Oze, Haruo Mikami, Mariko Naito, Kenji Wakai, Munemitsu Yoshikawa, Masahiro Miyake, Kenji Yamashiro, Kenji Kashiwagi, Takeshi Iwata, Fumihiko Mabuchi, Mitsuko Takamoto, Mineo Ozaki, Kazuhide Kawase, Makoto Aihara, Makoto Araie, Tetsuya Yamamoto, Yoshiaki Kiuchi, Makoto Nakamura, Yasuhiro Ikeda, Koh-Hei Sonoda, Tatsuro Ishibashi, Koji Nitta, Aiko Iwase, Shiroaki Shirato, Yoshitaka Oka, Mamoru Satoh, Makoto Sasaki, Nobuo Fuse, Yoichi Suzuki, Ching-Yu Cheng, Chiea Chuen Khor, Mani Baskaran, Shamira Perera, Tin Aung, Eranga N Vithana, Jessica N Cooke Bailey, Jae H Kang, Louis R Pasquale, Jonathan L Haines, Janey L Wiggs, Kathryn P Burdon, Puya Gharahkhani, Alex W Hewitt, David A Mackey, Stuart MacGregor, Jamie E Craig, R Rand Allingham, Micheal Hauser, Adeyinka Ashaye, Donald L Budenz, Stephan Akafo, Susan E I Williams, Yoichiro Kamatani, Toru Nakazawa, Michiaki Kubo
Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7,378 POAG cases and 36,385 controls from a Japanese population. After combining the GWAS and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (p < 5...
February 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#4
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29450946/down-regulation-of-lrig1-by-microrna-20a-modulates-gastric-cancer-multidrug-resistance
#5
Lin Zhou, Xiaowei Li, Fan Zhou, Zhi'an Jin, Di Chen, Pin Wang, Shu Zhang, Yuzheng Zhuge, Yulong Shang, Xiaoping Zou
Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells...
February 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29450620/targeting-the-neddylation-pathway-in-cells-as-a-potential-therapeutic-approach-for-diseases
#6
REVIEW
Jie Ying, Miaomiao Zhang, Xiaoyan Qiu, Yu Lu
The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding...
February 15, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29450468/activity-and-safety-of-cetuximab-plus-modified-folfoxiri-followed-by-maintenance-with-cetuximab-or-bevacizumab-for-ras-and-braf-wild-type-metastatic-colorectal-cancer-a-randomized-phase-2-clinical-trial
#7
Chiara Cremolini, Carlotta Antoniotti, Sara Lonardi, Giuseppe Aprile, Francesca Bergamo, Gianluca Masi, Roberta Grande, Giuseppe Tonini, Claudia Mescoli, Giovanni Gerardo Cardellino, Luigi Coltelli, Lisa Salvatore, Domenico Cristiano Corsi, Cristiana Lupi, Donatello Gemma, Monica Ronzoni, Emanuela Dell'Aquila, Federica Marmorino, Francesca Di Fabio, Maria Laura Mancini, Lorenzo Marcucci, Gabriella Fontanini, Vittorina Zagonel, Luca Boni, Alfredo Falcone
Importance: The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. Objectives: To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC...
February 15, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29450147/lemongrass-cymbopogon-flexuosus-essential-oil-demonstrated-anti-inflammatory-effect-in-pre-inflamed-human-dermal-fibroblasts
#8
Xuesheng Han, Tory L Parker
Lemongrass ( Cymbopogon flexuosus ) essential oil (LEO), which has citral as its main component, has exhibited anti-inflammatory effect in both animal and human cells. In this study, we evaluated the anti-inflammatory activity of a commercially available LEO in pre-inflamed human dermal fibroblasts. We first studied the impact of LEO on 17 protein biomarkers that are critically associated with inflammation and tissue remodeling. LEO significantly inhibited production of the inflammatory biomarkers vascular cell adhesion molecule 1 (VCAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG); decreased levels of the tissue remodeling biomarkers collagen-I and III, epidermal growth factor receptor (EGFR), and plasminogen activator inhibitor (PAI-1); and inhibited the immunomodulatory biomarker macrophage colony-stimulating factor (M-CSF)...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29450144/anti-inflammatory-tissue-remodeling-immunomodulatory-and-anticancer-activities-of-oregano-origanum-vulgare-essential-oil-in-a-human-skin-disease-model
#9
Xuesheng Han, Tory L Parker
The use of oregano ( Origanum vulgare ) essential oil (OEO) has become popular in skin care products. However, scientific research regarding its effects on human skin cells is scarce. In this study, we investigated the biological activity of a commercially available OEO, which is high in carvacrol content, in a human skin cell disease model. OEO induced marked antiproliferative effects and significantly inhibited several inflammatory biomarkers, including monocyte chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), intracellular cell adhesion molecule 1 (ICAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG)...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#10
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449544/peak1-acting-as-a-tumor-promoter-in-colorectal-cancer-is-regulated-by-the-egfr-kras-signaling-axis-and-mir-181d
#11
Lanlan Huang, Chuangyu Wen, Xiangling Yang, Qiong Lou, Xiaoyan Wang, Jia Che, Junxiong Chen, Zihuan Yang, Xiaojian Wu, Meijin Huang, Ping Lan, Lei Wang, Aikichi Iwamoto, Jianping Wang, Huanliang Liu
PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis, but little is known about the role of PEAK1 in colorectal cancer (CRC) progression. We investigated the expression pattern, function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is overexpressed in CRC tissues and that high PEAK1 expression predicts poor survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1 inhibits cell proliferation, migration, and invasion in vitro and inhibits the growth of tumor xenografts in nude mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#12
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29448920/the-t790m-resistance-mutation-in-egfr-is-only-found-in-cfdna-from-erlotinib-treated-nsclc-patients-that-harbored-an-activating-egfr-mutation-before-treatment
#13
Christina Demuth, Anne Tranberg Madsen, Britta Weber, Lin Wu, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample...
February 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29448628/functionalized-magnetic-plga-nanospheres-for-targeting-and-bioimaging-of-breast-cancer
#14
Seung-Jun Lee, Hee-Jin Kim, Yong-Min Huh, Il Won Kim, Jae Hyun Jeong, Jin-Chul Kim, Jong-Duk Kim
Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers...
March 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29448311/enhancing-decision-making-about-adjuvant-chemotherapy-in-early-breast-cancer-following-endopredict-testing
#15
Lesley Fallowfield, Lucy Matthews, Shirley May, Valerie Jenkins, David Bloomfield
Chemotherapy side-effects can be substantial. There is increasing recognition that some oestrogen receptor positive (ER+ve), human epidermal growth factor receptor 2 negative (HER2-ve) patients with breast cancer derive no benefit from chemotherapy and experience only iatrogenic harm. Gene expression profiling tests help refine recurrence risk and likely chemotherapy benefit. EndoPredict® is one such test, which classifies risks of distant recurrence as low or high in patients treated with surgery and adjuvant endocrine therapy alone...
February 15, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29448072/a-phase-iii-study-comparing-sb3-a-proposed-trastuzumab-biosimilar-and-trastuzumab-reference-product-in-her2-positive-early-breast-cancer-treated-with-neoadjuvant-adjuvant-treatment-final-safety-immunogenicity-and-survival-results
#16
X Pivot, I Bondarenko, Z Nowecki, M Dvorkin, E Trishkina, J-H Ahn, S-A Im, T Sarosiek, S Chatterjee, M Z Wojtukiewicz, Y Shparyk, V Moiseyenko, M Bello, V Semiglazov, Y Lee, J Lim
BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide)...
February 12, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29447132/role-of-gpcr-mu-opioid-receptor-tyrosine-kinase-epidermal-growth-factor-crosstalk-in-opioid-induced-hyperalgesic-priming-type-ii
#17
Dionéia Araldi, Luiz F Ferrari, Jon D Levine
Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors...
January 11, 2018: Pain
https://www.readbyqxmd.com/read/29446042/the-clinical-features-of-squamous-cell-lung-carcinoma-with-sensitive-egfr-mutations
#18
Yuri Taniguchi, Yoko Matsumoto, Ryutaro Furukawa, Sayaka Ohara, Kazuhiro Usui
BACKGROUND: The process of selecting patients on the basis of epidermal growth factor receptor (EGFR) mutations would likely result in a patient population with greater sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, EGFR mutation status is not routinely examined in patients with squamous cell lung cancer (Sq) because of the low incidence of EGFR mutations and the poor clinical response to EGFR-TKIs. METHODS: We retrospectively reviewed the clinical features of patients at our hospital with Sq who carried EGFR-TKI-sensitive EGFR mutations and assessed their responses to EGFR-TKIs...
February 14, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29445301/comparative-effectiveness-of-early-line-nab-paclitaxel-vs-paclitaxel-in-patients-with-metastatic-breast-cancer-a-us-community-based-real-world-analysis
#19
Reshma L Mahtani, Monika Parisi, Stefan Glück, Quanhong Ni, Siyeon Park, Corey Pelletier, Claudio Faria, Fadi Braiteh
Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab -paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA. Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab -paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29445288/prognostic-significance-of-epidermal-growth-factor-receptor-expression-in-glioma-patients
#20
Junhong Li, Ruofei Liang, Chen Song, Yufan Xiang, Yanhui Liu
Purpose: There is a great controversy regarding the prognostic significance of epidermal growth factor receptor (EGFR) in glioma patients. The current meta-analysis was conducted to evaluate the effect of abnormal EGFR expression on overall survival in glioma patients. Materials and methods: A comprehensive literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Cochrane Library was conducted. The combined hazard ratio (HR) and its 95% confidence intervals (CIs) were used to evaluate the association between EGFR expression and survival in glioma...
2018: OncoTargets and Therapy
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