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Egfr kinase

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https://www.readbyqxmd.com/read/28934846/egfr-mutation-status-in-lung-adenocarcinoma-associated-malignant-pleural-effusion-and-efficacy-of-egfr-tyrosine-kinase-inhibitors
#1
Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han
Purpose: Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI-treated patients were analyzed retrospectively...
September 19, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28933590/rubcn-rubicon-and-egfr-regulate-lysosomal-degradative-processes-in-the-retinal-pigment-epithelium-rpe-of-the-eye
#2
Luis Muniz-Feliciano, Teresa A Doggett, Zhenqing Zhou, Thomas A Ferguson
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28932588/kras-mutation-positive-mucinous-adenocarcinoma-originating-in-the-thymus
#3
Ichiro Sakanoue, Hiroshi Hamakawa, Daichi Fujimoto, Yukihiro Imai, Kazuhiro Minami, Keisuke Tomii, Yutaka Takahashi
Thymic carcinoma is a rare, aggressive disease with a low 5-year survival rate. The most common histological neoplastic thymic tumor subtype is squamous cell. We describe an interesting case of a 39-year-old woman who presented with mucinous adenocarcinoma that originated in the thymus and was treated via radical resection and venoplasty of the superior vena cava (SVC). Macroscopically, the resected tumor contained a solid region and multiple cysts with abundant mucin. Microscopic examination showed a papillary growth pattern of goblet cells with round nuclei...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932544/the-detectability-of-the-pretreatment-egfr-t790m-mutations-in-lung-adenocarcinoma-using-cast-pcr-and-digital-pcr
#4
Tsutomu Tatematsu, Katsuhiro Okuda, Ayumi Suzuki, Risa Oda, Tadashi Sakane, Osamu Kawano, Hiroshi Haneda, Satoru Moriyama, Hidefumi Sasaki, Ryoichi Nakanishi
BACKGROUND: A gatekeeper T790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI. METHODS: We used a competitive allele-specific polymerase chain reaction (CAST-PCR) to analyze the incidence and clinical significance of T790M mutations in 153 lung adenocarcinomas with EGFR-activating mutations...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28927801/design-synthesis-and-antitumor-activity-of-novel-sorafenib-derivatives-bearing-pyrazole-scaffold
#5
Min Wang, Shan Xu, Huajun Lei, Caolin Wang, Zhen Xiao, Shuang Jia, Jia Zhi, Pengwu Zheng, Wufu Zhu
Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC50 value of compounds 8b on VEGFR-2 kinase was 0...
September 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#6
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924490/the-lauric-acid-activated-signaling-prompts-apoptosis-in-cancer-cells
#7
Rosamaria Lappano, Anna Sebastiani, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Giulia Raffaella Galli, Rosita Curcio, Roberta Malaguarnera, Antonino Belfiore, Anna Rita Cappello, Marcello Maggiolini
The saturated medium-chain fatty-acid lauric acid (LA) has been associated to certain health-promoting benefits of coconut oil intake, including the improvement of the quality of life in breast cancer patients during chemotherapy. As it concerns the potential to hamper tumor growth, LA was shown to elicit inhibitory effects only in colon cancer cells. Here, we provide novel insights regarding the molecular mechanisms through which LA triggers antiproliferative and pro-apoptotic effects in both breast and endometrial cancer cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28923853/adaptation-to-tki-treatment-reactivates-erk-signaling-in-tyrosine-kinase-driven-leukemias-and-other-malignancies
#8
Joshua K Bruner, Hayley S Ma, Li Li, Alice Can Ran Qin, Michelle A Rudek, Richard J Jones, Mark J Levis, Keith W Pratz, Christine A Pratilas, Donald Small
FLT3 tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia. We hypothesized that FLT3/ITD leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared to either drug alone...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28921872/first-line-therapy-with-dacomitinib-an-orally-available-pan-her-tyrosine-kinase-inhibitor-for-locally-advanced-or-metastatic-penile-squamous-cell-carcinoma-results-of-an-open-label-single-arm-single-center-phase-2-study
#9
A Necchi, S Lo Vullo, F Perrone, D Raggi, P Giannatempo, G Calareso, N Nicolai, L Piva, D Biasoni, M Catanzaro, T Torelli, S Stagni, E Togliardi, M Colecchia, A Busico, A Gloghini, A Testi, L Mariani, R Salvioni
OBJECTIVE: To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. PATIENTS AND METHODS: In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (TNM 2009), and no prior chemotherapy administration...
September 16, 2017: BJU International
https://www.readbyqxmd.com/read/28920960/long-noncoding-rna-egfr-as1-mediates-epidermal-growth-factor-receptor-addiction-and-modulates-treatment-response-in-squamous-cell-carcinoma
#10
Daniel S W Tan, Fui Teen Chong, Hui Sun Leong, Shen Yon Toh, Dawn P Lau, Xue Lin Kwang, Xiaoqian Zhang, Gopinath M Sundaram, Gek San Tan, Mei Mei Chang, Boon Tin Chua, Wan Teck Lim, Eng Huat Tan, Mei Kim Ang, Tony K H Lim, Prabha Sampath, Balram Chowbay, Anders J Skanderup, Ramanuj DasGupta, N Gopalakrishna Iyer
Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919784/durable-complete-remission-of-poor-performance-status-metastatic-lung-adenocarcinoma-patient-treated-with-second-line-erlotinib-a-case-report
#11
Dragana Jovanovic, Ruza Stevic, Marta Velinovic, Milica Kontic, Dragana Maric, Jelena Spasic, Davorin Radosavljevic
This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1 - almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28915719/genomic-analysis-of-exceptional-responder-to-regorafenib-in-treatment-refractory-metastatic-rectal-cancer-a-case-report-and-review-of-the-literature
#12
Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915658/oxidative-stress-mediates-an-increased-formation-of-vascular-endothelial-growth-factor-in-human-hepatocarcinoma-cells-exposed-to-erlotinib
#13
Nataliya Rohr-Udilova, Florian Klinglmüller, Martha Seif, Hubert Hayden, Martin Bilban, Matthias Pinter, Klaus Stolze, Wolfgang Sieghart, Markus Peck-Radosavljevic, Michael Trauner
The tyrosine kinase inhibitor erlotinib targets the receptor of epidermal growth factor (EGFR) involved in development of hepatocellular carcinoma (HCC). Although inefficient in established HCC, erlotinib has been recently proposed for HCC chemoprevention. Since Cyp3A4 and Cyp1A2 enzymes metabolize erlotinib in the liver, the insights into the mechanisms of erlotinib effects on liver cells with maintained drug metabolizing activity are needed. We applied erlotinib to both commercially available (SNU398, Huh7) and established in Austria HCC cell lines (HCC-1...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#14
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915624/microwave-ablation-combined-with-egfr-tkis-versus-only-egfr-tkis-in-advanced-nsclc-patients-with-egfr-sensitive-mutations
#15
Zhigang Wei, Xin Ye, Xia Yang, Aimin Zheng, Guanghui Huang, Wenhong Li, Jiao Wang, Xiaoying Han, Min Meng, Yang Ni
We conducted this retrospective study to investigate whether microwave ablation (MWA) of primary tumor sites plus epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could improve survival in advanced non small cell lung cancer (NSCLC) with EGFR mutations. MWA was conducted at the primary tumor sites, followed by EGFR-TKIs in the MWA plus EGFR-TKIs group. EGFR-TKIs were administered until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and objective response rate (ORR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#16
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915593/a-novel-egfr-tki-inhibitor-camp-h3bo3complex-combined-with-thermal-therapy-is-a-promising-strategy-to-improve-lung-cancer-treatment-outcomes
#17
Yongpeng Tong, Chunliu Huang, Junfang Zhang
PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912847/identification-of-micrornas-involved-in-gefitinib-resistance-of-non-small-cell-lung-cancer-through-the-insulin-like-growth-factor-receptor-1-signaling-pathway
#18
Wei Ma, Yanhong Kang, Lanlan Ning, Jie Tan, Hanping Wang, Yi Ying
Multiple clinical and experimental studies have suggested that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may be effective at treating advanced non-small cell lung cancer (NSCLC), however, the molecular basis of primary resistance to EGFR-TKIs in NSCLC remains unclear. In the current study, the insulin-like growth factor 1 receptor (IGF-1R) gene in the gefitinib-resistant human lung adenocarcinoma epithelial cell line A549 (A549/GR) was silenced using small interfering RNA (siRNA) in order to determine the role of microRNA (miRNA) in the development of resistance against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912511/outcomes-of-adjuvant-epithelial-growth-factor-receptor-tyrosine-kinase-inhibitors-egfr-tkis-treatment-for-egfr-mutant-non-small-cell-lung-cancer-a-propensity-score-analysis
#19
Shufen Zhao, Ge Ma, Jing Guo, Aiping Ding, Shasha Wang, Guohong Yu, Lei Chen, Yonggang Yuan, Wenjing Xiao
Small molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced non-small-cell lung cancer (NSCLC) harboring activating epithelial growth factor receptor (EGFR) mutations, while the efficacy of TKIs in the adjuvant setting remains unclear. We collected the data of 209 EGFR-mutant NSCLC patients receiving complete resection from 2010 to 2013. Study end points were disease-free survival (DFS) and overall survival (OS). Among the eligible patients, 41 (19.6%) received EGFR TKIs in the adjuvant treatment...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912396/-immune-checkpoint-inhibitors-for-lung-cancer-with-egfr-mutation
#20
Hidetoshi Hayashi, Tetsuya Mitsudomi
Recent clinical evidence that anti-PD-1/PD-L1 antibody therapy is superior to cytotoxic chemotherapy for patients with non-small cell lung cancer(NSCLC)that expresses PD-L1 has lead to a paradigm shift in treatment strategies for those patients. However, efficacy of anti-PD-1/PD-L1 antibodies for patients with NSCLC harboring EGFR mutation is generally poor. This lack ofresponse is at least partially attributed to suppression oftumor infiltrating lymphocytes caused by EGFR pathway activation or to low non-synonymous mutation load in NSCLC with EGFR mutation...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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