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EGFR and cancer

Kasturi Chatterjee, Sayantan Jana, Pramathes DasMahapatra, Snehasikta Swarnakar
Endometriosis, characterized by extrauterine development of endometrial glands and stroma, is associated with increased risk of ovarian cancer development. In the present study, we investigated the role of matrix metalloproteinase-7 (MMP-7) on epithelial-mesenchymal transition (EMT) during ovarian endometriosis ( N = 40) progression. We found that the expressions of EMT markers such as vimentin, slug, and N-cadherin were significantly elevated in late stages of ovarian endometriosis compared with those found in early stages...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Oğuz Ahmet Hasdemir, Serhat Tokgöz, Fulya Köybaşıoğlu, Harun Karabacak, Cüneyt Yücesoy, Gökşen İnanç İmamoğlu
BACKGROUND: Metaplastic carcinoma of the breast (MpBC) is defined as a group of heterogeneous malignant neoplasms that contain glandular and non-glandular components with mixed epithelial and mesenchymal differentiations. OBJECTIVES: The aim of this study was to research the clinical and pathological characteristics of MpBC determining its rank among all breast cancers. MATERIAL AND METHODS: Metaplastic carcinoma of the breast was found in 7 out of 1,164 patients who had been diagnosed with breast cancer within the period of 12 years in our hospital...
March 19, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
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
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
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
Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
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
Ludovic Ménard, Nicolas Floc'h, Matthew J Martin, Darren Ae Cross
Tyrosine kinase inhibitors (TKIs) targeting mutant-EGFR in NSCLC have been successful to control cancer growth, but acquired resistance inevitably occurs, including mutations directly on EGFR e.g. T790M and C797S. Strategies to prevent such acquired mutations by reducing mutant-EGFR expression have met limited success. Here we propose a new model of mutant-EGFR trafficking and demonstrate that clathrin inhibition induces rapid degradation across a large panel of endogenous mutant-EGFR (Ex19del, L858R, Ex20Ins)...
March 19, 2018: Cancer Research
Ibrahim O Alanazi, Sami A AlYahya, Esmaeil Ebrahimie, Manijeh Mohammadi-Dehcheshmeh
Exponentially growing scientific knowledge in scientific publications has resulted in the emergence of a new interdisciplinary science of literature mining. In text mining, the machine reads the published literature and transfers the discovered knowledge to mathematical-like formulas. In an integrative approach in this study, we used text mining in combination with network discovery, pathway analysis, and enrichment analysis of genomic regions for better understanding of biomarkers in lung cancer. Particular attention was paid to non-coding biomarkers...
March 16, 2018: Gene
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
Catherine L Forse, Dushanthi Pinnaduwage, Shelley B Bull, Anna Marie Mulligan, Irene L Andrulis
The proper handling of unstained paraffin slides for immunohistochemistry has been a matter of debate, with several studies demonstrating loss of antigenicity with prolonged storage at room temperature, 4°C and -20°C. The purpose of this study was to determine whether long-term storage of unstained slides at -80°C would impact the staining intensity and expression distribution of markers used to molecularly subtype breast cancer specimens [estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), and Ki67]...
March 17, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Steven Quinn, Shwetha Srinivasan, Jesse Gordon, Wei He, Kermit L Carraway, Matthew A Coleman, Gabriela S Schlau-Cohen
The epidermal growth factor receptor (EGFR) is critical to normal cellular signaling pathways. Moreover, it has been implicated in a range of pathologies, including cancer. As a result, it is the primary target of many anti-cancer drugs. One limitation to the design and development of these drugs has been the lack of molecular-level information about the interactions and conformational dynamics of EGFR. To overcome this limitation, this work reports the development and characterization of functional fluorescently-labeled full-length EGFR in model membrane nanolipoprotein particles (NLPs) for in vitro fluorescence studies...
March 19, 2018: Biochemistry
Rong Biaoxue, Yang Shuanying
BACKGROUND: Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference. We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. METHODS: Investigations that provided data on EGFR mutation status in blood were searched in the databases of Medline, Embase, Ovid Technologies and Web of Science. The detect efficiency of EGFR mutations in paired blood and tissues was compared using a random-effects model of meta-analysis...
January 2018: International Journal of Biological Markers
Anna Mouzakiti, Constantinos Nastos, Dimitrios Vlachodimitropoulos, Constantinos Gennatas, Agathi Kondi-Pafiti, Dionisios Voros
PURPOSE: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. METHODS: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
Mengfan Qi, Ye Tian, Wang Li, Dan Li, Tian Zhao, Yuxin Yang, Qiwen Li, Sujun Chen, Yan Yang, Zhixiong Zhang, Liang Tang, Zhonghua Liu, Bo Su, Fei Li, Yonghong Feng, Ke Fei, Peng Zhang, Fan Zhang, Lei Zhang
Gefitinib, an EGFR tyrosine kinase inhibitor, is used to treat non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the resistance to gefitinib eventually emerges in most of the patients. To understand its mechanism, we generated two acquired gefitinib-resistant NSCLC cell lines. The resistant cells have slower growth rates, but are more resistant to apoptosis in the presence of gefitinib, compared with their sensitive counterparts. In addition, our genome-wide transcriptome analysis reveals unexpected pathways, particularly autophagy, are dysregulated in the gefitinib-resistant cells...
February 23, 2018: Oncotarget
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
Yanhong Yang, Wenwen Zhou, Jiandong Wu, Lixin Yao, Lei Xue, Qianyi Zhang, Zhenzhen Wang, Xiaoyu Wang, Shu Dong, Jiangman Zhao, Duanduan Yin
Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin...
April 2018: Oncology Letters
Ping Zhou, Jian Hu, Xiaoqin Wang, Jingyuan Wang, Yong Zhang, Cong Wang
The present study assessed the function of epidermal growth factor receptor (EGFR) and its molecular targets in non-small cell lung cancer. The results of the present study demonstrated that EGFR protein and mRNA expression in the normal adjacent tissue specimens was decreased compared with that in the lung cancer tissue samples. Compared with the BEAS-2B normal bronchial epithelial cells, EGFR and phosphorylated (p)-extracellular signal-regulated kinase (ERK) protein expression in the SW-900 and A549 lung cancer cells was increased and microRNA (miR)200a expression in the SW-900 and A549 cells was inhibited compared with the BEAS-2B cells...
April 2018: Oncology Letters
Yajie Zhao, Lin Shen, Xinqiong Huang, Yuxiang He, Jun Fu, Yujie Qian, Shan Li, Na Zhao, Liangfang Shen
The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively...
April 2018: Oncology Letters
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