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Gefitinib

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https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#1
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/29447084/binding-site-identification-of-anticancer-drug-gefitinib-to-hsa-and-dna-in-the-presence-of-five-different-probes
#2
Hamid Tanzadehpanah, Hanie Mahaki, Neda Hosseinpour Moghadam, Sadegh Salehzadeh, Omid Rajabi, Rezvan Najafi, Razieh Amini, Massoud Saidijam
This study was carried out to evaluate the binding interaction of gefitinib (GEF) with human serum albumin (HSA) and calf thymus DNA (ct-DNA) using fluorescence, UV-visible, zeta potential measurements and molecular docking methods in order to understand its pharmacokinetic mechanism. By increasing the temperature, a steady decrease in Stern-Volmer quenching constants was observed for HSA binding properties; this indicates a static type of fluorescence quenching. Negative values were calculated for Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) changes, indicating that the reaction is spontaneous and enthalpy-driven...
February 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29446042/the-clinical-features-of-squamous-cell-lung-carcinoma-with-sensitive-egfr-mutations
#3
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/29444555/significant-effect-of-anti-tyrosine-kinase-inhibitor-gefitinib-on-overall-survival-of-the-glioblastoma-gbm-patients-in-the-backdrop-of-mutational-status-of-egfr-and-pten-genes
#4
Sajad H Arif, Arshad A Pandith, Rehana Tabasum, Altaf U Ramzan, Sarabjeet Singh, Mushtaq A Siddiqi, Abdul R Bhat
INTRODUCTION: We aimed to assess the effect of antityrosine kinase inhibitors (Geftinib) in overall survival of the GBM patients in the backdrop of mutational status of EGFR and PTEN genes. MATERIALS AND METHODS: All the patients subjected to resection or biopsies were put on Geftinib and radiotherapy was delivered as per the hospital protocol. EGFR and PTEN mutational spectrum was performed by SSCP followed by DNA sequencing. RESULTS: In total, 50% GBM tumors had mutation either in EGFR or PTEN...
February 13, 2018: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/29440914/associations-between-abcg2-gene-polymorphisms-and-gefitinib-toxicity-in-non-small-cell-lung-cancer-a-meta-analysis
#5
Lina Tang, Chunling Zhang, Hairong He, Zhenyu Pan, Di Fan, Yinli He, Haisheng You, Yuanjie Li
Background: Gefitinib is frequently used to treat patients with non-small cell lung cancer (NSCLC) and is excreted out from cells via the ATP-binding cassette transporter ABCG2. ABCG2 gene polymorphisms have been suggested to be associated with ABCG2 protein expression and function and may influence the risk of gefitinib toxicity in NSCLC patients. Previous studies on the associations between ABCG2 gene polymorphisms and the toxicity of gefitinib in NSCLC patients have produced conflicting results...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29440861/eyelashes-trichomegaly-an-unusual-side-effect-of-gefitinib-therapy
#6
Chaturbhuj R Agrawal, Pankaj Goyal, Dinesh Chandra Doval, Kumardeep Dutta, Kshitij Domadia, Silky Kothiwal
Evolution of targeted therapy has changed the spectrum of treatment in oncology since the past two decades as lots of newer agents are being added to the pharmacologic armamentarium of cancer therapy. Epidermal growth factor receptor inhibitors form one such advancing field with many newer agents being investigated and they are used in wide variety of malignancies such as head and neck cancer, lung cancer, and even gastrointestinal malignancies such as pancreatic cancer. Various troublesome side effects of these agents include diarrhea, severe fatigability, severe skin rashes, and deranged liver function tests which may require treatment interruption or dose reduction resulting in decreased response to treatment...
January 2018: International Journal of Trichology
https://www.readbyqxmd.com/read/29435131/pd-l1-confers-resistance-to-egfr-mutation-independent-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-via-upregulation-of-yap1-expression
#7
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434916/epidermal-growth-factor-receptor-somatic-mutation-analysis-in-354-chinese-patients-with-non-small-cell-lung-cancer
#8
Xueping Quan, Hongjun Gao, Zhikuan Wang, Jie Li, Wentao Zhao, Wei Liang, Qiang Yu, Dongliang Guo, Zhanping Hao, Jingxin Liu
Lung cancer is one of the most common types of cancer worldwide, with the highest mortality rate of all types of cancer. In the present study, epidermal growth factor receptor (EGFR) mutations of 354 primary patients with non-small cell lung cancer (NSCLC) of Chinese ethnicity were detected following formalin-fixed and paraffin-embedded specimen DNA extraction, polymerase chain reaction amplification, and sanger sequencing. The total rate of occurrence of EGFR somatic mutation in these 354 patients was 48.02%...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434678/dynamic-changes-in-quality-of-life-after-three-first-line-therapies-for-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#9
Szu-Chun Yang, Chien-Chung Lin, Wu-Wei Lai, Sheng-Mao Chang, Jing-Shiang Hwang, Wu-Chou Su, Jung-Der Wang
Background: Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. Methods: From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29433983/common-co-activation-of-axl-and-cdcp1-in-egfr-mutation-positive-non-smallcell-lung-cancer-associated-with-poor-prognosis
#10
Niki Karachaliou, Imane Chaib, Andres Felipe Cardona, Jordi Berenguer, Jillian Wilhelmina Paulina Bracht, Jie Yang, Xueting Cai, Zhigang Wang, Chunping Hu, Ana Drozdowskyj, Carles Codony Servat, Jordi Codony Servat, Masaoki Ito, Ilaria Attili, Erika Aldeguer, Ana Gimenez Capitan, July Rodriguez, Leonardo Rojas, Santiago Viteri, Miguel Angel Molina-Vila, Sai-Hong Ignatius Ou, Morihito Okada, Tony S Mok, Trever G Bivona, Mayumi Ono, Jean Cui, Santiago Ramón Y Cajal, Peng Cao, Rafael Rosell
Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo...
February 5, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29430239/a-case-of-paraneoplastic-remitting-seronegative-symmetrical-synovitis-with-pitting-edema-syndrome-improved-by-chemotherapy
#11
Takahiko Sakamoto, Shuji Ota, Terunobu Haruyama, Masashi Ishihara, Maika Natsume, Yoko Fukasawa, Shigeru Tanzawa, Ryo Usui, Takeshi Honda, Yasuko Ichikawa, Kiyotaka Watanabe, Nobuhiko Seki
The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB)...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29429891/vinorelbine-potently-induces-placental-cell-death-does-not-harm-fertility-and-is-a-potential-treatment-for-ectopic-pregnancy
#12
Roxanne Hastie, Elgene Lim, Pavel Sluka, Lisa Campbell, Andrew Horne, Lenore Ellett, Natalie J Hannan, Fiona Brownfoot, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice...
February 2, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29427754/withanolide-a-extends-the-lifespan-in-human-egfr-driven-cancerous-caenorhabditis-elegans
#13
Bashir Akhlaq Akhoon, Laxmi Rathor, Rakesh Pandey
The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway. Up-regulation of IGF1 can transactivate EGFR which inturn reduces longevity and promotes tumor development in an organism. We examined the effects of Withanolide A on the lifespan of a human EGFR-driven C...
February 7, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29421153/nuclear-translocation-of-igf1r-by-intracellular-amphiregulin-contributes-to-the-resistance-of-lung-tumour-cells-to-egfr-tki
#14
Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin...
February 5, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29420112/low-dose-bevacizumab-as-an-effective-pre-treatment-for-peri-tumoral-brain-edema-prior-to-cyberknife-radiosurgery-a-case-report
#15
Meng Xiangying, Zhao Rugang, Ding Lijuan, Zhao Yaowei, Sun Bing, Wang Junliang, Li Dan, Wu Shikai
A 75-y-old Chinese female patient diagnosed with lung adenocarcinoma with brain metastasis suffered severe nausea and vomiting, and these symptoms were contraindications for CyberKnife treatment. Neither mannitol, nor dexamethasone, relieved the symptoms. However, after the patient received a single dose of bevacizumab (200 mg, 2.9 mg/kg), the patient's symptoms were significantly relieved. The patient subsequently completed a successful CyberKnife treatment. In addition, the patient received an oral treatment of gefitinib...
February 8, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29411527/heterogeneity-based-multiple-mechanisms-in-the-resistance-to-osimertinib-azd9291-a-case-report
#16
Yutao Liu, Xuezhi Hao, Xingsheng Hu, Junling Li, Yan Wang, Hongyu Wang, Puyuan Xing, Weihua Li, Jianming Ying, Xiaohong Han, Yuankai Shi
Osimertinib is a novel, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR-mutated lung adenocarcinoma who, after 23-month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c-Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism...
February 7, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29410323/egfr-t790m-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-dacomitinib
#17
Yoshihisa Kobayashi, Toshio Fujino, Masaya Nishino, Takamasa Koga, Masato Chiba, Yuichi Sesumi, Shuta Ohara, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
INTRODUCTION: Dacomitinib is superior to gefitinib in terms of progression-free survival in patients with EGFR-mutant lung cancer in a recent ARCHER 1050 trial. However, despite a marked initial response, lung cancers eventually acquire resistance to these inhibitors. This study aimed to elucidate the mechanisms of acquired resistance to dacomitinib in vitro. METHODS: Dacomitinib-resistant clones were established by exposure to fixed concentrations of dacomitinib using N-ethyl-N-nitrosurea (ENU) mutagenesis or by chronic exposure to increasing concentrations of dacomitinib without ENU...
February 1, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29408491/nod2-rip2-contributes-to-the-inflammatory-responses-of-mice-in-vivo-to-streptococcus-pneumoniae
#18
Yuan Zheng, Feng Shang, Li An, Hongyang Zhao, Xinjie Liu
The objectives of this study were to investigate the role of the NOD2-RIP2 pathway in host responses to the gram-positive bacteria Streptococcus pneumoniae and to evaluate the effect of the RIP2 inhibitor gefitinib in a mouse model of S. pneumoniae meningitis. Mice were randomly divided into a normal saline control group (NS group), an S. pneumoniae meningitis group (SP group), a gefitinib group and a vehicle group. Animals in the NS group were sham-infected with sterile saline. Mice in the other three groups were inoculated with S...
February 3, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29404164/treatment-after-first-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-in-non-small-cell-lung-cancer
#19
REVIEW
Seher Nazlı Kazaz, İlhan Öztop
Systemic treatment is the basic treatment approach to advanced-stage non-small-cell lung cancer (NSCLC), and chemotherapy and targeted treatments are commonly employed in these patients. Recently, positive results achieved with immunotherapy have led to a growing number of treatment options and prolonged survival time. Today, specific tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and the TKI crizotinib, which targets anaplastic lymphoma kinase gene rearrangement, have become the standard treatment among targeted therapies for patients with sensitive molecular anomalies...
July 2017: Turkish Thoracic Journal
https://www.readbyqxmd.com/read/29403559/synergistic-effect-of-targeting-dishevelled-3-and-the-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-on-mesothelioma-cells-in-vitro
#20
Gaku Moriyama, Maya Tanigawa, Kosuke Sakai, Yusuke Hirata, Satoshi Kikuchi, Yuriko Saito, Hiroyuki Kyoyama, Kuniko Matsuda, Masahiro Seike, Akihiko Gemma, Kazutsugu Uematsu
It was previously revealed that Wnt signaling is activated in mesothelioma cells. Although epidermal growth factor receptor (EGFR) is expressed in mesothelioma cells, EGFR-tyrosine kinase inhibitors (TKIs) are not effective for mesothelioma treatment. However, in non-small cell lung cancer, the blocking of Wnt signaling has been identified to enhance the anticancer effect of EGFR-TKIs. To confirm the anticancer effect of blocking Wnt signaling in combination with EGFR-TKI treatment in mesothelioma, the present study evaluated the effect of simultaneous suppression of human dishevelled-3 (Dvl-3) expression with Dvl-3 small interfering RNA (siRNA) and of EGFR inhibition with gefitinib on mesothelioma cell viability...
January 2018: Oncology Letters
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