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Epidermal growth factor receptor

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https://www.readbyqxmd.com/read/29234489/molecular-insights-suppression-of-egfr-and-akt-activation-by-a-small-molecule-in-non-small-cell-lung-cancer
#1
Balaji Chandrasekaran, Ashish Tyagi, Arun K Sharma, Lu Cai, Murali Ankem, Chendil Damodaran
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549)...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29234247/pi3k-mtor-inhibitors-in-the-treatment-of-luminal-breast-cancer-why-when-and-to-whom
#2
REVIEW
Francesco Schettini, Giuseppe Buono, Meghana V Trivedi, Sabino De Placido, Grazia Arpino, Mario Giuliano
Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in luminal breast cancer (BC). Despite the efficacy of endocrine agents, many patients with luminal BC do not respond to endocrine therapy and many others develop endocrine resistance over time, due to the activation of escape pathways such as the PI3K/AKT/mTOR signaling. Several clinical trials have demonstrated the efficacy of mTOR and PI3K inhibitors in overcoming endocrine resistance in hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic BC (MBC) patients...
October 2017: Breast Care
https://www.readbyqxmd.com/read/29233606/staphylococcus-aureus-and-atopic-dermatitis-a-complex-and-evolving-relationship
#3
REVIEW
Joan A Geoghegan, Alan D Irvine, Timothy J Foster
Staphylococcus aureus is frequently isolated from the skin of atopic dermatitis (AD) patients during flares. The normal microbiota is disrupted and the diversity of the microorganisms on the skin is reduced. Many species that produce inhibitors of S. aureus growth decline. Strains from S. aureus clonal complex 1 are enriched among AD sufferers whereas the CC30 strains most frequently isolated from nasal carriers in the normal population are much rarer in AD. S. aureus expresses several molecules that contribute to the intensity of symptoms, including δ-toxin which stimulates mast cells, α-toxin which damages keratinocytes, phenol-soluble modulins which stimulate cytokine release by keratinocytes, protein A which triggers inflammatory responses from keratinocytes, superantigens which trigger B cell expansion and cytokine release, and proinflammatory lipoproteins...
December 9, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29232915/histologic-grade-is-predictive-of-incidence-of-epidermal-growth-factor-receptor-mutations-in-metastatic-lung-adenocarcinoma
#4
Michelle Levy, Liisa Lyon, Erika Barbero, John Wong, Marie Suga, Danny Sam, Minggui Pan
Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations...
December 11, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29232766/combined-erlotinib-and-pf-03084014-treatment-contributes-to-synthetic-lethality-in-head-and-neck-squamous-cell-carcinoma
#5
Yang Zheng, Zhao Wang, Xu Ding, Yibo Dong, Wei Zhang, Wei Zhang, Yi Zhong, Wenyi Gu, Yunong Wu, Xiaomeng Song
OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is characterized by high mortality and low survival rates. As an epidermal growth factor receptor (EGFR) inhibitor, Erlotinib has been approved for treatment of various tumours. PF-03084014 is a selective inhibitor of Notch1 signalling. This study aimed to explore new approaches for simultaneously targeting EGFR and Notch1 signalling to attenuate tumour growth and improve survival. MATERIALS AND METHODS: Cell proliferation was determined by CCK-8 assay and Flow cytometry...
December 12, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29232309/a-bispecific-antibody-based-on-pertuzumab-fab-has-potent-antitumor-activity
#6
Wentong Deng, Jiayu Liu, Haitao Pan, Li Li, Changhua Zhou, Xiaojuan Wang, Rui Shu, Bin Dong, Donglin Cao, Qing Li, Zhong Wang
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody...
January 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29231994/nes1-klk10-promotes-trastuzumab-resistance-via-activation-of-pi3k-akt-signaling-pathway-in-gastric-cancer
#7
Laiqin Tang, Zhiguo Long, Guangjia Feng, Xianzhi Guo, Minghua Yu
Trastuzumab, a humanized antibody targeting human epidermal growth factor receptor 2 (HER2), exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. Acquired resistance to trastuzumab remains a barrier to patient survival and the mechanisms underlying this are still not well understood. The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognized as a potential therapeutic target for reversing trastuzumab resistance. The aim of this study was to explore the potential role of KLK10 in trastuzumab resistance (TR) gastric cancer cells...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29231907/activated-hgf-c-met-axis-in-head-and-neck-cancer
#8
REVIEW
Levi Arnold, Jonathan Enders, Sufi Mary Thomas
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent's pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy...
December 12, 2017: Cancers
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a%C3%A2-systematic-review%C3%A2
#9
Rebecca Madden, Sam Kosari, Gregory M Peterson, Nasser Bagheri, Jackson Thomas
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine...
December 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29230689/the-combination-of-curcumin-and-5-fluorouracil-in-cancer-therapy
#10
REVIEW
Yumeng Wei, Panjing Yang, Shousong Cao, Ling Zhao
5-Fluorouracil (5-FU) alone or in combination with other therapeutic drugs has been widely used for clinical treatment of various cancers. However, 5-FU-based chemotherapy has limited anticancer efficacy in clinic due to multidrug resistance and dose-limiting cytotoxicity. Some molecules and genes in cancer cells, such as nuclear factor kappa B, insulin-like growth factor-1 receptor, epidermal growth factor receptor, cyclooxygenase-2, signal transducer and activator of transcription 3, phosphatase and tensin homolog deleted on chromosome ten and Bcl-2 etc...
December 11, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29230390/her2-overexpression-in-retinoblastoma-a-potential-therapeutic-target
#11
David Cordeiro Sousa, Pablo Zoroquiain, Maria Eugenia Orellana, Ana Beatriz Dias, Evangelina Esposito, Miguel N Burnier
Background: Retinoblastoma (RB) is the most common primary intraocular malignancy. Current therapies are associated with high morbidity in the short- and long-term. Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein detected in 15-30% of breast cancers, but it has also been described in other malignancies. Recently, it has been claimed that a truncated version of this protein is expressed in RB, responsive to directed therapies in vitro. We scored HER2 overexpression in RB tissue samples and discussed its potential clinical utility...
September 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29230123/molecular-targets-in-non-small-cell-lung-cancer
#12
REVIEW
Ryan Griffin, Robert A Ramirez
Background: Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These driver mutations render a cancer dependent on that specific mutation's biochemical pathway for its growth and survival...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29230122/the-role-of-checkpoint-inhibition-in-non-small-cell-lung-cancer
#13
REVIEW
Jonathan Lu, Robert A Ramirez
Background: The development of immune checkpoint inhibitors has revolutionized the treatment of cancer. Their use in non-small cell lung cancer (NSCLC) remains in its infancy, but rapid progress has been made in treating metastatic NSCLC. Methods: This article outlines the role of immune checkpoint inhibitors in the treatment of malignancy and reviews clinical trials of novel immunotherapies in the setting of metastatic NSCLC. Results: Traditional chemotherapy with a platinum-based doublet has long been the backbone in the treatment of metastatic NSCLC...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#14
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29230043/nanoparticle-orientation-to-control-rna%C3%A2-loading-and-ligand-display-on-extracellular-vesicles-for-cancer-regression
#15
Fengmei Pi, Daniel W Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M Croce, Bin Guo, B Mark Evers, Peixuan Guo
Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle...
December 11, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/29229979/near-infrared-plasmonic-assemblies-of-gold-nanoparticles-with-multimodal-function-for-targeted-cancer-theragnosis
#16
Seong-Eun Kim, Bo-Ram Lee, Hohyeon Lee, Sung Duk Jo, Hyuncheol Kim, You-Yeon Won, Jeewon Lee
Here we report a novel assembly structure of near-infrared plasmonic gold nanoparticles (AuNPs), possessing both photoacoustic (PA) and photothermal (PT) properties. The template for the plasmonic AuNP assembly is a bioconjugate between short double-strand DNA (sh-dsDNA) and human methyl binding domain protein 1 (MBD1). MBD1 binds to methylated cytosine-guanine dinucleotides (mCGs) within the sequence of sh-dsDNA. Hexahistidine peptides on the engineered MBD1 function as a nucleation site for AuNP synthesis, allowing the construction of hybrid conjugates, sh-dsDNA-MBD1-AuNPs (named DMAs)...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229958/egfr-feedback-inhibition-by-ran-binding-protein-6-is-disrupted-in-cancer
#17
Barbara Oldrini, Wan-Ying Hsieh, Hediye Erdjument-Bromage, Paolo Codega, Maria Stella Carro, Alvaro Curiel-García, Carl Campos, Maryam Pourmaleki, Christian Grommes, Igor Vivanco, Daniel Rohle, Craig M Bielski, Barry S Taylor, Travis J Hollmann, Marc Rosenblum, Paul Tempst, John Blenis, Massimo Squatrito, Ingo K Mellinghoff
Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29229933/evaluation-of-serum-epidermal-growth-factor-receptor-egfr-in-correlation-to-circulating-tumor-cells-in-patients-with-metastatic-breast-cancer
#18
Malgorzata Banys-Paluchowski, Isabell Witzel, Sabine Riethdorf, Brigitte Rack, Wolfgang Janni, Peter A Fasching, Erich-Franz Solomayer, Bahriye Aktas, Sabine Kasimir-Bauer, Klaus Pantel, Tanja Fehm, Volkmar Müller
Overexpression of epidermal growth factor receptor in breast cancer is associated with estrogen receptor negativity, higher histological grade and larger tumors. The aim of the present study was to evaluate the clinical significance of serum EGFR (sEGFR) in relation to circulating tumor cells (CTCs) in metastatic breast cancer. 252 patients were enrolled in this prospective multicentre study. Blood was drawn before start of a new line of therapy. sEGFR was determined using a sandwich-type ELISA. CTCs were detected using CellSearch...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229632/activation-of-the-aryl-hydrocarbon-receptor-leads-to-resistance-to-egfr-tkis-in-non-small-cell-lung-cancer-by-activating-src-mediated-bypass-signaling
#19
Mingxiang Ye, Yong Zhang, Hongjun Gao, Yan Xu, Pengyu Jing, Jianxiong Wu, Xinxin Zhang, Jie Xiong, Chenfang Dong, Libo Yao, Jian Zhang, Jian Zhang
PURPOSE: The aryl hydrocarbon receptor (AhR) has been generally recognized as a ligand-activated transcriptional factor that responds to xenobiotic chemicals. Recent studies have suggested that the expression of AhR varies widely across different cancer types and cancer cell lines, but its significance in cancer treatment has yet to be clarified. EXPERIMENTAL DESIGN: AhR expression in non-small-cell lung cancer (NSCLC) was determined by Western blotting and IHC staining...
December 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29229152/omission-of-radiotherapy-after-breast-conservation-surgery-in-the-postneoadjuvant-setting
#20
Andrew C Esposito, James Crawford, Elin R Sigurdson, Elizabeth A Handorf, Shelly B Hayes, Marcia Boraas, Richard J Bleicher
BACKGROUND: Breast conservation therapy (BCT) consists of breast conservation surgery (BCS) and radiotherapy (RT). Neoadjuvant chemotherapy (NACT) can downstage tumors, broadening BCS eligibility in patients requiring mastectomy. However, tumor downstaging does not obviate need for RT. This study evaluated factors that predict RT omission after NACT and BCS. METHODS: The National Cancer Database was queried for women with unilateral, clinical stage II-III breast cancer, treated with NACT and BCS between 2008 and 2012...
January 2018: Journal of Surgical Research
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