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Martin Pool, Arjan Kol, Marjolijn N Lub-de Hooge, Christian A Gerdes, Steven de Jong, Elisabeth G E de Vries, Anton G T Terwisscha van Scheltinga
Preclinical positron emission tomography (PET) imaging revealed a mismatch between in vivo epidermal growth factor receptor (EGFR) expression and EGFR antibody tracer tumor uptake. Shed EGFR ectodomain (sEGFR), which is present in cancer patient sera, can potentially bind tracer and therefore influence tracer kinetics. To optimize EGFR-PET, we examined the influence of sEGFR levels on tracer kinetics and tumor uptake of EGFR monoclonal antibody 89Zr-imgatuzumab in varying xenograft models. Human cancer cell lines A431 (EGFR overexpressing, epidermoid), A549 and H441 (both EGFR medium expressing, non-small cell lung cancer) were xenografted in mice...
October 18, 2016: Oncotarget
Sally Maramotti, Massimiliano Paci, Gloria Manzotti, Cristian Rapicetta, Mila Gugnoni, Carla Galeone, Alfredo Cesario, Filippo Lococo
The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers...
April 19, 2016: International Journal of Molecular Sciences
Filippo Lococo, Massimiliano Paci, Cristian Rapicetta, Teresa Rossi, Valentina Sancisi, Luca Braglia, Silvio Cavuto, Alessandra Bisagni, Italia Bongarzone, Douglas M Noonan, Adriana Albini, Sally Maramotti
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered...
2015: International Journal of Molecular Sciences
Heng Hu, Lingling Gao, Cun Wang, Yan Li, Huiying Ma, Long Chen, Jie Qin, Binbin Liu, Yinkun Liu, Chunmin Liang
Hepatocellular carcinoma (HCC) is one of the most deadly cancers in the world due to its high metastatic potential. By using the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative N-glycoproteomic analysis, 26 differentially expressed serum glycoproteins derived from defined stages in orthotopic xenograft tumor model were identified. Among them, expression level of soluble EGFR (sEGFR) was verified in HCC cell lines. We found that non-metastasis HCC cell lines express significantly more sEGFR than HCC cell lines with metastasis potential both in cell lysates and culture media...
May 2015: Discovery Medicine
Elena Yaiza Romero-Ventosa, Sonia Blanco-Prieto, Ana Lourdes González-Piñeiro, Francisco Javier Rodríguez-Berrocal, Guadalupe Piñeiro-Corrales, María Páez de la Cadena
The aim of this study has been to investigate the potential of serum biomarkers used in clinical practice (CEA, CYFRA 21-1, SCC) together with the serum epidermal growth factor receptor (EGFR) and its associated ligands (EGF, TGF-α, HB-EGF) as outcome predictors of non-small cell lung cancer (NSCLC) patients treated with the TKI erlotinib. The pretreatment levels of these markers were evaluated through immunoassays carried out in 58 patients. The progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan-Meier method and differences between groups were compared by means of the Log-Rank test...
2015: SpringerPlus
Manuel Correia, Viruthachalam Thiagarajan, Isabel Coutinho, Gnana Prakash Gajula, Steffen B Petersen, Maria Teresa Neves-Petersen
The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. EGFR is activated upon binding to e.g. epidermal growth factor (EGF), leading to cell survival, proliferation and migration. EGFR overactivation is associated with tumor progression. We have previously shown that low dose UVB illumination of cancer cells overexpressing EGFR prior to adding EGF halted the EGFR signaling pathway. We here show that UVB illumination of the extracellular domain of EGFR (sEGFR) induces protein conformational changes, disulphide bridge breakage and formation of tryptophan and tyrosine photoproducts such as dityrosine, N-formylkynurenine and kynurenine...
2014: PloS One
I Flisiak, M Szterling-Jaworowska, A Baran, M Rogalska-Taranta
BACKGROUND: Epidermal growth factor receptors (EGFRs) are overexpressed in psoriatic keratinocytes, and regulate cell growth, proliferation and differentiation through binding to epidermal growth factor (EGF). The role of EGF and EGFRs in the pathogenesis of psoriasis and the contribution of their measurement to psoriasis management are still unknown. AIM: To evaluate serum concentrations of EGF, soluble (s)EGFRs and EGF content in psoriatic scales of patients with severe psoriasis, and to analyse their association with the clinical activity of the disease...
June 2014: Clinical and Experimental Dermatology
Y Hasegawa, M Takahashi, S Ariki, D Asakawa, M Tajiri, Y Wada, Y Yamaguchi, C Nishitani, R Takamiya, A Saito, Y Uehara, J Hashimoto, Y Kurimura, H Takahashi, Y Kuroki
Surfactant protein D (SP-D) is a member of the collectin family that has an important role in maintaining pulmonary homeostasis. In this study, we demonstrated that SP-D inhibited the proliferation, migration and invasion of A549 human lung adenocarcinoma cells. We found that SP-D suppressed epidermal growth factor (EGF) signaling in A549 cells, H441 human lung adenocarcinoma cells and human EGF receptor (EGFR) stable expression CHO-K1 cells. A binding study using (125)I-EGF demonstrated that SP-D downregulated the binding of EGF to EGFR...
February 12, 2015: Oncogene
Vehary Sakanyan, Marie Angelini, Mickael Le Béchec, Michèle Françoise Lecocq, Florence Benaiteau, Bénédicte Rousseau, Aram Gyulkhandanyan, Lusine Gyulkhandanyan, Cédric Logé, Eric Reiter, Christos Roussakis, Fabrice Fleury
Peptide ligand-induced dimerization of the extracellular region of the epidermal growth factor receptor (sEGFR) is central to the signal transduction of many cellular processes. A small molecule microarray screen has been developed to search for non-peptide compounds able to bind to sEGFR. We describe the discovery of nitro-benzoxadiazole (NBD) compounds that enhance tyrosine phosphorylation of EGFR and thereby trigger downstream signaling pathways and other receptor tyrosine kinases in cancer cells. The protein phosphorylation profile in cells exposed to NBD compounds is to some extent reminiscent of the profile induced by the cognate ligand...
2014: Scientific Reports
T Yamashita, H Kamada, S Kanasaki, Y Maeda, K Nagano, Y Abe, M Inoue, Y Yoshioka, Y Tsutsumi, S Katayama, M Inoue, S Tsunoda
Detection of drug-target proteins and biomarkers that are expressed in cancer tissue has significant potential for both diagnosis and treatment of cancer. However, current immuno-histochemical and cytogenetic analyses of biopsy specimens for pre-operational diagnosis are highly invasive and often difficult to apply to lung cancer patients. The purpose of this study was to evaluate the possible utility of determining epidermal growth factor receptor (EGFR) expression on exosomal membranes using a targeted ELISA with an anti-CD81 antibody as a capture antibody for lung cancer diagnosis...
December 2013: Die Pharmazie
Hatem A El-mezayen, Fatheya M Metwally, Hossam Darwish
Invasion and metastasis of solid tumors require proteolytic enzymes for degradation of the basal membrane and extracellular matrix. Currently, there are no reliable methodologies to predict the risk for metastatic disease. In this context, our aim has been focused on the development of a noninvasive score based on tumor-associated trypsin inhibitor (TATI) for the assessment of metastasis in patients with breast cancer. TATI, trypsin, and soluble epidermal growth factor receptor (sEGFR) were assayed by enzyme-linked immunosorbent assay...
March 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Benjamin Nisman, Luna Kadouri, Tanir Allweis, Bella Maly, Tamar Hamburger, Simon Gronowitz, Tamar Peretz
Previous studies indicated that BRCA haploinsufficiency was associated with activation of the EGF receptor (EGFR) signaling pathway and increased proliferative activity in mammary epithelial cells of healthy women. We hypothesized that these processes might be reflected in the expression of serologic soluble EGFR (sEGFR) and thymidine kinase 1 (TK1) activity, which signal the initial and final steps of the proliferative pathway, respectively. We found that healthy carriers of BRCA1/2 mutations (n = 80) showed a significantly higher TK1 activity than age-matched controls (P = 0...
November 2013: Cancer Epidemiology, Biomarkers & Prevention
Keiko Tawa, Mitsuo Umetsu, Hikaru Nakazawa, Takamitsu Hattori, Izumi Kumagai
The grating substrate covered with a metal layer, a plasmonic chip, and a bispecific antibody can play a key role in the sensitive detection of a marker protein with an immunosensor, because of the provision of an enhanced fluorescence signal and the preparation of a sensor surface densely modified with capture antibody, respectively. In this study, one of the tumor markers, a soluble epidermal growth factor receptor (sEGFR), was selected as the target to be detected. The ZnO- and silver-coated plasmonic chip with precise regularity and the appropriate duty ratio in the periodic structure further enhanced the fluorescence intensity...
September 11, 2013: ACS Applied Materials & Interfaces
Jason A Wilken, Marianela Perez-Torres, Rene Nieves-Alicea, Elsa M Cora, Trace A Christensen, Andre T Baron, Nita J Maihle
Soluble epidermal growth factor receptor (sEGFR) is a circulating serum biomarker in cancer patients. Recent studies suggest that baseline serum sEGFR concentrations may predict responsiveness to EGFR-targeted therapy. Here, we demonstrate that sEGFR is generated through proteolytic cleavage of a cell surface precursor of an alternately spliced EGF receptor isoform and that sEGFR binds to EGF with high affinity. Proteolytic cleavage is stimulated by an anti-α5/β1 integrin antibody and 4-aminophenylmercuric acetate, and inhibited by fibronectin...
July 2, 2013: Biochemistry
François Becher, Mathieu Dubois, François Fenaille, Eric Ezan
We present here an analytical protocol for the sensitive, specific, and accurate absolute quantification of cetuximab, a human:murine chimeric monoclonal antibody, using mass spectrometry. Extraction from human serum is performed with micrometric magnetized beads, functionalized with soluble epidermal growth factor receptor (sEGFR), the pharmacological target of cetuximab. This specific immunocapture step allows sample purification and, in parallel, assessment of the antibody's biological potency. The eluted mAb is digested with trypsin and specific peptides from light and heavy chains are monitored by liquid chromatography coupled with tandem mass spectrometry operated in the selected reaction monitoring (SRM) mode...
2013: Methods in Molecular Biology
Kimberly K Leslie, Michael W Sill, Edgar Fischer, Kathleen M Darcy, Robert S Mannel, Krishnansu S Tewari, Parviz Hanjani, Jason A Wilken, Andre T Baron, Andrew K Godwin, Russell J Schilder, Meenakshi Singh, Nita J Maihle
BACKGROUND: A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. METHODS: Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment...
June 2013: Gynecologic Oncology
Shiaw-Lin Wu, Allen D Taylor, Qiaozhen Lu, Samir M Hanash, Hogune Im, Michael Snyder, William S Hancock
We have used powerful HPLC-mass spectrometric approaches to characterize the secreted form of epidermal growth factor receptor (sEGFR). We demonstrated that the amino acid sequence lacked the cytoplasmic domain and was consistent with the primary sequence reported for EGFR purified from a human plasma pool. One of the sEGFR forms, attributed to the alternative RNA splicing, was also confirmed by transcriptional analysis (RNA sequencing). Two unusual types of glycan structures were observed in sEGFR as compared with membrane-bound EGFR from the A431 cell line...
May 2013: Molecular & Cellular Proteomics: MCP
George R Blumenschein, Martin Reck, Frank Fossella, David J Stewart, Chetan Lathia, Carol Peña
We investigated the relationship between plasma protein biomarker concentrations and clinical outcomes in 52 patients with relapsed/refractory advanced non-small cell lung cancer (NSCLC) treated with 400~mg bid sorafenib in a phase II trial. Blood samples were collected at baseline, on day 15 of cycle 1 (C1D15), and on day 1 of cycle 3 (C3D1), and plasma concentrations of total VEGF, VEGF-165, soluble (s) VEGFR-2, PDGF-BB, sPDGFR-β, sEGFR, sHER-2, uPA, PAI-1, uPAR, TIMP-1, and circulating Ras p21 were assayed by ELISA...
0: Cancer Biomarkers: Section A of Disease Markers
Edzard Spillner, Melanie Plum, Simon Blank, Michaela Miehe, Josef Singer, Ingke Braren
Monoclonal antibodies have become a mainstay for the targeted treatment of cancer today. Some of the most successful targets of monoclonal antibodies are constituted by the epidermal growth factor receptor family spearheaded by the epidermal growth factor receptor (EGFR). Prompted by studies indicating that IgE compared to IgG may harness alternate effector functions to eradicate malignant cells, we addressed the establishment, engineering, and the potential tumoricidal effects of recombinant anti-EGFR IgE...
September 2012: Cancer Immunology, Immunotherapy: CII
Angélique Guillaudeau, Karine Durand, Barbara Bessette, Alain Chaunavel, Isabelle Pommepuy, Fabrice Projetti, Sandrine Robert, François Caire, Hélène Rabinovitch-Chable, François Labrousse
The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a...
2012: PloS One
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