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Receptor tyrosine kinase

Robert Campbell, Geoffrey Chong, Eliza A Hawkes
Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies...
March 21, 2018: Journal of Clinical Medicine
Jorge A Avila, Roseanna M Zanca, Denis Shor, Nicholas Paleologos, Amber A Alliger, Maria E Figueiredo-Pereira, Peter A Serrano
Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA...
February 2018: Heliyon
Fang Hu, Xiaowei Mao, Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan Zhang
Purpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients. Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve...
2018: OncoTargets and Therapy
Yoon Hee Park, Soyeon Cho, Jeong Yee, Jae Youn Kim, Sandy Jeong Rhie, Hye Sun Gwak
Gefitinib is an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for non-small-cell lung cancer with EGFR mutations. Although a few studies have analyzed the causes of gefitinib-induced hepatotoxicity, research focusing on the time intervals before and after hepatotoxicity has yet to be reported. Therefore, this study investigated two types of factors: the time to reach gefitinib-induced hepatotoxicity and the time for recovery. From January 2013 to December 2014, a retrospective study was carried out on 473 non-small-cell lung cancer patients who were treated with gefitinib...
March 19, 2018: Anti-cancer Drugs
Zeanap A Mabruk, Samrein B M Ahmed, Asha Caroline Thomas, Sally A Prigent
Preliminary screening data showed that the ShcD adaptor protein associates with the proto-oncogene RET receptor tyrosine kinase. In the present study, we aimed to investigate the molecular interaction between ShcD and RET in human neuroblastoma cells and study the functional impact of this interaction. We were able to show that ShcD immunoprecipitated with RET from SK-N-AS neuroblastoma cell lysates upon GDNF treatment. This result was validated by ShcD-RET co-localization, which was visualized using a fluorescence microscope...
March 2018: Biochemistry and Biophysics Reports
Hitendra S Solanki, Remya Raja, Alex Zhavoronkov, Ivan V Ozerov, Artem V Artemov, Jayshree Advani, Aneesha Radhakrishnan, Niraj Babu, Vinuth N Puttamallesh, Nazia Syed, Vishalakshi Nanjappa, Tejaswini Subbannayya, Nandini A Sahasrabuddhe, Arun H Patil, T S Keshava Prasad, Daria Gaykalova, Xiaofei Chang, Rachana Sathyendran, Premendu Prakash Mathur, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Evgeny Izumchenko, Harsha Gowda, Aditi Chatterjee
EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells. SILAC-based mass-spectrometry approach was used to study altered signaling in H358-S cell line. Importantly, among the top phosphosites in H358-S cells we observed hyperphosphorylation of EGFR (Y1197) and non-receptor tyrosine kinase FAK (Y576/577)...
January 2018: Oncoscience
Raffaele Altara, Fouad A Zouein, Rita Dias Brandão, Saeed N Bajestani, Alessandro Cataliotti, George W Booz
Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences...
2018: Frontiers in Cardiovascular Medicine
Jiang-Kai Dong, Hui-Min Lei, Qian Liang, Ya-Bin Tang, Ye Zhou, Yang Wang, Shengzhe Zhang, Wen-Bin Li, Yunguang Tong, Guanglei Zhuang, Liang Zhang, Hong-Zhuan Chen, Liang Zhu, Ying Shen
How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients...
2018: Theranostics
Ruilian Xu, Guolin Zhong, Tanxiao Huang, Wan He, Cheng Kong, Xiaoni Zhang, Ying Wang, Ming Liu, Mingyan Xu, Shifu Chen
Lung cancer is the most commonly occurring type of cancer worldwide and also has the highest mortality rate. Although targeted therapy of non-small cell lung carcinoma (NSCLC) has become common, the majority of patients receiving first-line epithelial growth factor receptor (EGFR)-TKI treatment develop drug resistance. The EGFR T790M (NM_005228.4(EGFR):c.2369C>T (p.Thr790Met)) mutation accounts for half of all reported resistance cases; however, the molecular mechanism resulting in the drug resistance remains to be characterized...
March 2018: Oncology Letters
Mark W Cunningham, Javier Castillo, Tarek Ibrahim, Denise C Cornelius, Nathan Campbell, Lorena Amaral, Venkata Ramana Vaka, Nathan Usry, Jan M Williams, Babbette LaMarca
Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...
March 19, 2018: Hypertension
Julie A Lynch, Brygida Berse, Merry Rabb, Paul Mosquin, Rob Chew, Suzanne L West, Nicole Coomer, Daniel Becker, John Kautter
BACKGROUND: Tumor testing for mutations in the epidermal growth factor receptor (EGFR) gene is indicated for all newly diagnosed, metastatic lung cancer patients, who may be candidates for first-line treatment with an EGFR tyrosine kinase inhibitor. Few studies have analyzed population-level testing. METHODS: We identified clinical, demographic, and regional predictors of EGFR & KRAS testing among Medicare beneficiaries with a new diagnosis of lung cancer in 2011-2013 claims...
March 20, 2018: BMC Cancer
Michele Fiore, Rolando Maria D Apos Angelillo, Carlo Greco, Iacopo Fioroni, Edy Ippolito, Daniele Santini, Sara Ramella
Treatment of metastatic renal cell carcinoma (mRCC) has seen substantial progress over the last decade. A number of targeted therapies have been shown to improve clinical outcome. Vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) are an effective option in treating mRCC. RCC is traditionally perceived to be a radioresistant malignancy with a limited role of radiotherapy (RT) in the management of localized disease. While RCC appears to be radioresistant using conventionally fractionated RT, preclinical data suggest increased radiosensitivity when an ablative, hypofractionated schedule is used...
March 19, 2018: Chemotherapy
Cinthia C Amaya Ramirez, Petra Hubbe, Nicolas Mandel, Julien Béthune
Initially identified as a factor involved in tyrosine kinase receptor signaling, Grb10-interacting GYF protein 2 (GIGYF2) has later been shown to interact with the 5' cap-binding protein 4EHP as part of a translation repression complex, and to mediate post-transcriptional repression of tethered reporter mRNAs. A current model proposes that GIGYF2 is indirectly recruited to mRNAs by specific RNA-binding proteins (RBPs) leading to translation repression through its association with 4EHP. Accordingly, we recently observed that GIGYF2 also interacts with the miRNA-induced silencing complex and probably modulates its translation repression activity...
March 15, 2018: Nucleic Acids Research
Hyojin Eom, Neha Kaushik, Ki-Chun Yoo, Jin-Kyoung Shim, Munjin Kwon, Mi-Young Choi, Taeyoung Yoon, Seok-Gu Kang, Su-Jae Lee
Receptor tyrosine kinase Mer (MerTK) has been shown to be highly expressed in Glioblastoma multiforme (GBM) in comparison to its healthy counterpart and is implicated in brain tumorigenesis. Clarifying the underlying mechanism of MerTK induced invasiveness would result in novel strategies to improve patient's response to chemotherapeutics. In vitro and in vivo assays were performed to examine the functional role of cancer stem sell (CSC) maintenance in MerTK associated invasiveness. In this article, we demonstrate that apart from GBM cells, MerTK is also upregulated in GBM stem-like cells and associated with an increased infiltrative potential of brain tumors in vivo...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Yasuhiro Fujisawa, Koji Yoshino, Taku Fujimura, Yoshiyuki Nakamura, Naoko Okiyama, Yosuke Ishitsuka, Rei Watanabe, Manabu Fujimoto
The most widely accepted treatment for cutaneous angiosarcoma (CAS) is wide local excision and postoperative radiation to decrease the risk of recurrence. Positive surgical margins and large tumors (T2, >5 cm) are known to be associated with poor prognosis. Moreover, T2 tumors are known to be associated with positive surgical margins. According to previous reports, the majority of CAS patients in Japan had T2 tumors, whereas less than half of the patients in the studies from western countries did so. Consequently, the reported 5-year overall survival of Japanese CAS patients without distant metastasis was only 9%, lower than that for stage-IV melanoma...
2018: Frontiers in Oncology
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Yuko Saito
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of either triggering receptor expressed on myeloid cells 2 ( TREM2 ) or TYRO protein tyrosine kinase binding protein ( TYROBP ), alternatively named DNAX-activation protein 12 ( DAP12 ), both of which are expressed on microglia in the brain and form the receptor-adaptor complex that chiefly recognizes anionic lipids. TREM2 transmits the signals involved in microglial survival, proliferation, chemotaxis, and phagocytosis...
February 2018: Intractable & Rare Diseases Research
Chiawen Hsieh, Yun-Wei Lin, Ching-Hsein Chen, Wenjun Ku, Fuching Ma, Hanming Yu, Chishih Chu
Natural compounds have been candidates for anticancer medicine over the last 20 years. During the process of isolating seed oil from Calophyllum inophyllum L., yellow and green pigments containing multiple compounds with an aromatic structure were identified. High-performance liquid chromatography and nuclear magnetic resonance analysis of these pigments revealed that the compounds present were identical, but the concentration of the compounds was different. Treatment with the pigments was able to induce the death of DLD-1 human colon cancer cells and increase the percentage of the cells in the sub-G1 and sub-G2 /M phases in a dose-dependent manner...
April 2018: Oncology Letters
Hongyang Lu, Bo Chen, Jing Qin, Fajun Xie, Na Han, Zhiyu Huang
The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology...
April 2018: Oncology Letters
Danmei Zhou, Kehan Ren, Jigang Wang, Hong Ren, Wenlin Yang, Wenjuan Wang, Qiong Li, Xiuping Liu, Feng Tang
Erythropoietin-producing hepatocellular A6 (EphA6) is a member of the Eph receptor tyrosine kinase family, which has been implicated in tumorigenesis. However, little is known about the expression and function of EphA6 in breast cancer. The aim of the present study was to investigate the expression of EphA6 and the possible association between EphA6 and clinicopathological characteristics in breast cancer. In the present study, EphA6 mRNA expression was measured in 26 paired breast cancer tissues and adjacent non-cancerous tissues by reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Ling Fu, Liang Guo, Yi Zheng, Zhenyu Zhu, Mingyue Zhang, Xiaohua Zhao, Hongxue Cui
Sorafenib is a multikinase inhibitor that is frequently used to treat various types of malignant tumors. However, it has been demonstrated that Sorafenib only has a moderate antitumor efficacy and is associated with numerous side effects in non-small cell lung cancer (NSCLC), which greatly limits its clinical application. The present study aimed to examine the effects of a combination of Sorafenib and low-dose PF-2341066, a selective c-Met tyrosine kinase inhibitor, on the proliferation, apoptosis and migration of the NSCLC cell line NCI-H1993...
April 2018: Oncology Letters
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