We showed that EGFR is increased in ATC cell lines in vitro and in vivo and in human ATCs. For immunohistochemical and routine hematoxylin and eosin staining, one part of the tissue was fixed in formalin and embedded in paraffin, and another part was embedded in optimal cutting-temperature compound (Miles Inc., Elkhart, IN), rapidly frozen in liquid nitrogen, and stored at −80°C. Anaplastic thyroid carcinomas are relatively rare, constituting only 1.6% all of the thyroid cancers (2) eISSN: 1557-3265 At day 12, the control group of mice showed an increased tumor size of 173% of the initial tumor size. Experimental Design: The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. , 12, 13, 14, 15, 16, 17) 2020 Sep;67:104925. doi: 10.1016/j.tiv.2020.104925. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Our result is consistent with the former findings of high EGFR overexpression in cervical cancer [23–25]. Researchers have reported EGFR overexpression as a stable marker for prostate cancer dissemination to rigid organs, preferentially bones.. Prostate cancer. Although EGFR has been reported to be overexpressed in anywhere from 25% to 82% of colorectal cancers , some recent studies report protein overexpression (defined as 2+ and/or 3+ staining or in >50% of cells) in 35 to 49% of cases [7–9]. Maximal inhibition occurred at a concentration of 14 μmol/L. Failure of EGFR inhibition may be due to crosstalk with other oncogenic pathways. Samples then were washed three times for 3 minutes, blocked with protein-blocking solution for 10 minutes, and incubated with AlexaFluor 594–conjugated goat antirabbit IgG (Molecular Probes, Eugene, OR) for 1 hour at room temperature in the dark. The mice treated with gefitinib at 30 and 60 mg/kg/d showed high levels of p-EGFR. Triple-negative breast cancers are a poor prognostic group of breast cancers that don’t respond to conventional hormonal and her2neu targeted therapy. Whenever a discrepancy in scoring was noted, both pathologists reexamined the sample in question, and a consensus was reached. The papillary thyroid carcinoma cell line NPA187 and the ATC cell lines KAT-4, K18, C643, HTH, ARO, and DRO were used. The data from our tissue arrays support this finding and suggest that EGFR is highly expressed in ATC. Section 1734 solely to indicate this fact. The cultures were free of Mycoplasma species. Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center … Conclusions: ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Results of Phase I trials have indicated that this agent offers good bioavailability and tolerability (25) EGFR expression and cancer prognosis have been investigated in many human cancers. EGF was not present at an appreciable level in the supernatants from any of the cell lines examined. 3)⇓ For in vivo testing, gefitinib was dissolved in a lactate salt solution. To examine the results of EGFR in human thyroid tissue arrays, we performed three pairwise comparisons using Fisher’s exact test. The costs of publication of this article were defrayed in part by the payment of page charges. Two recent studies have suggested that response to gefitinib therapy is linked to mutations in the EGFR gene (26 The favorable safety profile of gefitinib has already been proven in Phase I clinical trials, and based on the data presented here, clinical trials of gefitinib in patients with ATC are warranted. 1⇓ The mice were weighed and the tumors were measured on days 8 and 12 using microcalipers until the mice were euthanatized after 2 weeks of treatment. To assess whether ATC cells produce the EGFR ligands EGF and TGF-α, ELISA was used to assess their levels in culture supernatants from six anaplastic and one papillary cancer cell lines. Furthermore, in a multivariate survival analysis, strong cytoplasmic EGFR staining of papillary thyroid cancer was significantly associated with a decrease in recurrence-free survival (21) Comparisons of ATC specimens with normal thyroid tissue specimens and ATC specimens with papillary thyroid cancer specimens revealed statistically significant differences in EGFR expression (P = 0.002 and P = 0.007, respectively). CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation. This site needs JavaScript to work properly. The difference in change in tumor size between the control group and the group treated with gefitinib at a dosage of 150 mg/d + paclitaxel approached but did not achieve statistical significance (P = 0.06). Oral cavity squamous cell cancer line TU167 was used as a positive control, and the fibroblast line 3T3 was used as a negative control. . Furthermore, we found that the frequency of EGFR overexpression in lymph node metastases was approximately as high as in the primary lesions of cervical cancer. In breast cancer, high levels of the EGFR [ 12 ] and c‐erbB2 [ 13 ] have been shown to correlate strongly with poor prognosis. Thus, we investigated the role of EGFR and its inhibitor gefitinib in ATC to determine whether gefitinib possesses meaningful antitumor activity against ATC, potentially justifying clinical trials. To assess the effects of gefitinib on induction of cell death of ATC cells, we performed a PI apoptosis assay on KAT-4 cells after 48 hours of treatment. Copyright © 2020 by the American Association for Cancer Research. Dimerization of EGFR following the binding of the ligand results in trans-phosphorylation of this receptor and subsequent activation of several downstream signal transduction pathways, including the mitogen-activated protein kinase and phosphatidylinositol-3′ kinase signaling pathways, which are involved in promoting cellular proliferation and survival (6, 7, 8) Trying to compose the puzzle with all the pieces: epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers and serv… The estimated IC50 for the apoptosis assays was 18.4 μmol/L. Chronic and acute arsenic exposure enhance EGFR expression via distinct molecular mechanisms. Gefitinib has been shown to block EGF-stimulated EGFR autophosphorylation (22) . Thyroid tumor tissue arrays representative of the entire spectrum of benign and malignant neoplasms, including ATC constructed at the head and neck tissue care facility, were used to screen for EGFR expression. Gefitinib is an EGFR tyrosine kinase inhibitor that has already been shown to have a favorable safety and tolerability profile in numerous Phase I clinical trials and therefore is a promising area of investigation in the search for effective treatments for patients with ATC. For in vitro administration, gefitinib was dissolved in dimethyl sulfoxide to a concentration of 20 mmol/L. We chose this method because the changes in absorbance as a percentage of the control and in apoptosis were linearly related to gefitinib levels in the range of the IC50. The overexpression of EGFR has been observed in both premalignant lesions and malignant tumors of the lung, and occurs in 40–80% of patients with NSCLC ( Salomon et … , and show extremely aggressive behavior, leading to a high mortality rate. Western blot analysis of cellular lysates of six ATC cell lines (ARO, C643, DRO, K18, and KAT-4) and the papillary cell line NPA187. Each mouse in group 1, the control group, received sodium lactate at a dosage of 0.2 mL/d for 5 days (Monday through Friday) for 2 weeks via oral gavage. Upon ligand‐dependent homodimerization or heterodimerization with all members of the ErbB family, EGFR can be activated functionally to lead to kinase activation and initiation of signaling 12 and is believed to play a major role in survival, growth, and proliferation of mammalian cells. * Killed immediately before treatment. The mice treated with gefitinib at 150 mg/kg/QOD showed p-EGFR expression if they were euthanatized immediately before the final treatment but did not express p-EGFR if euthanatized 6 hours after the final treatment. This suggests that inhibition of EGFR pathway maybe therapeutically beneficial to EC patients with EGFR overexpression. In other words, there are many ways in which EGFR can be changed genetically. The epidermal growth factor receptor (EGFR) plays a pivotal role in colorectal carcinogenesis. Epidermal growth factor receptor (EGFR) and HER2 are cell surface receptor tyrosine kinases (TKs) that transduce growth signals through dimerization with HER family receptors. . Although numerous studies already have shown that gefitinib possesses clinically meaningful antitumor activity in several malignancies (28) . The cultures were maintained no longer than 12 weeks after recovery from frozen stocks. In the first analysis, the type I error rate was controlled at 0.017, guaranteeing that the overall type I error rate would be controlled at 0.05. 2013 Dec;39(8):839-50. doi: 10.1016/j.ctrv.2013.05.001. Adherent monolayer cultures were maintained on plastic and incubated at 37°C in 5% carbon dioxide and 95% air. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis.Dual inhibition of HER2and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. , 27) . No effective treatment options currently are available to patients with ATC. The heterodimerization of EGFR with HER2 induces a more potent activation of EGFR TK than does EGFR homodimerization. Overexpression and/or mutations of EGFR and HER2 are well documented in a variety of solid tumors, including ovarian cancer, and have therapeutic implications (4,5). None of the nine normal tissue specimens stained positive for EGFR. The distribution of EGFR, mEGFR and pEGFR staining is … Epub 2013 Jun 12. To initiate studies, we performed ELISA to determine the expression of growth factors TGF-α and EGF. EGFR overexpression is not common in patients with head and neck cancer. These data are in concordance with those from previous studies that suggest that EGFR is expressed in ATC cell lines, but they contradict the literature that suggests that EGFR is constitutively activated in some ATC cell lines. The prognostic value of EGFR overexpression and ... Haiying Zeng1, Jieakesu Su1, Yingyong Hou1* and Lijie Tan2* Abstract Background: In view of the prominent role in cancer cell biology and alteration in substantial numbers of ESCC, defining EGFR molecular characteristics relevant to patient prognosis is of great importance. The vast majority of thyroid carcinomas are differentiated and can often be cured surgically. In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines. | . NLM Karyagina TS, Ulasov AV, Slastnikova TA, Rosenkranz AA, Lupanova TN, Khramtsov YV, Georgiev GP, Sobolev AS. The proteins (50 μg) were resolved on polyacrylamide gel electrophoresis and electrophoretically transferred onto 0.45-μg nitrocellulose membranes. NIH To develop such eligibility criteria for esophageal squ- report that EGFR is expressed only in diseased thyroid tissue, whereas others report that EGFR is expressed in all of the thyroid tissues (9) Five of the six ATC cell lines (all except DRO) stained positive for EGFR (Fig. The IC50 was 8.36 μmol/L, and maximal inhibition occurred at a concentration of 14 μmol/L. Using a 30-gauge needle under direct visualization, 5 × 106 KAT-4 cells diluted in 30 μL of serum-free medium were injected subcutaneously into the cervical area. . Although the amplification and mutations of HER2 are most common in breast cancer, research over the past decade has shown that 3%–5% of CRCs harbor primary overexpression of HER2 or HER2 mutations, and the prevalence is higher in RAS and BRAF WT CRCs (reported in about 5%–14%) (according to HERACLES criteria: immunohistochemistry 3+ or 2+ in >50% cells confirmed by … 6)⇓ The epidermal growth factor receptor (EGFR) is one of most potent oncogenes that are commonly altered in cancers. However, if a trend analysis is done looking at increasing doses of gefitinib (and including gefitinib 150 mg/d + paclitaxel as the group receiving the highest level of treatment), there is a significant difference between change in tumor size and increasing treatment dosage (P = 0.015). The cancer tissue page shows antibody staining of the protein in 20 different cancers. The arrays represented 14 papillary carcinomas, 6 anaplastic carcinomas, and 9 samples of nondiseased thyroid tissue. The lowest concentration at which cellular proliferation was inhibited was 6 μmol/L. The cells were scraped and spun in a centrifuge to remove insoluble proteins. Gefitinib partially blocked EGF autophosphorylation of EGFR at a concentration of 0.01 μmol/L and almost completely blocked autophosphorylation at 1 μmol/L. In the case of gastric cancer, several studies have linked EGFR expression to advanced clinical stage 17, 18, 19 and the presence of lymph node metastasis 20, 21, 22.Further evidence that EGFR may be an important prognostic indicator in gastric cancer comes from a number of small studies that examined concurrent expression of EGFR and its ligands 13, 19, 23, 24. Liu B, Diaz Arguello OA, Chen D, Chen S, Saber A, Haisma HJ. As a receptor tyrosine kinase, EGFR's kinase activity has been serving as the primary target for developing cancer therapeutics, namely the EGFR inhibitors including small molecules targeting its ATP binding pocket and monoclonal antibodies targeting its ligand binding domains. Clipboard, Search History, and several other advanced features are temporarily unavailable. Of the specimens from the 14 patients with papillary thyroid cancer, 2 stained positive for EGFR. , 5) The EGFR is involved in the pathogenesis or progression of many different types of cancers and therefore is a potential target for molecular therapy in ATC. Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers. Two cores of each sample were placed differentially in the recipient block. However, immunohistochemical staining of sections of subcutaneously implanted KAT-4 tumors revealed that those tumors constitutively expressed EGFR and p-EGFR, as did normal murine thyroid tissue, suggesting that EGFR activation is up-regulated in vivo. Gefitinib was tested on the KAT-4 ATC cell line using an MTT-based assay, which measures cell proliferation based on the ability of live cells to convert MTT to dark blue formazan. The lowest concentration at which cellular proliferation was inhibited was 6 μmol/L, and the IC50 was 8.36 μmol/L. KAT-4 ATC cells were harvested from subconfluent cultures by trypsinization and then washed. The groups then were randomized into seven treatment groups. eCollection 2020. 2010 Mar;67(3):355-60. doi: 10.1016/j.lungcan.2009.04.021. eCollection 2020. Findings in human carcinoma HEp2 cells overexpressing EGFR showed nontoxic behavior in the presence of activated light (1.5 J cm−2) and in the absence of light for all BODIPYs. Epidermal growth factor receptor (EGFR) has attracted considerable attention as a target for cancer therapy. HHS Level of staining for EGFR in normal, papillary, and anaplastic thyroid tissue from 29 human subjects. Normal murine thyroid tissue and ATC implants expressed EGFR and p-EGFR. The level of gefitinib ranged from 0.01 to 100 μmol/L. All of the kits were purchased from R&D Systems (Minneapolis, MN), and all of the experiments were performed according to the manufacturer’s instructions. Thus, gefitinib is able to effectively inhibit ATC cellular proliferation. Overexpression of EGFR is commonly found in EC and is associated with poor prognosis. The estimated IC50 for the apoptosis assays was 18.35 μmol/L. Two thousand cells were grown in DMEM-10% FBS, with and without 0.01 to 100 μmol/L gefitinib, in 96-well tissue culture plates. . Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy. 4)⇓ After 24 hours, the supernatant was collected, and the cells were counted. However, most studies suggest that EGFR is expressed at a higher level in thyroid cancer than in normal thyroid tissue (30 Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. For each cell line, the results were plotted as the ratio of the concentration to the total number of cells. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. Protein bands were visualized using an enhanced chemiluminescence detection system (Amersham). eCollection 2020. 5)⇓ Front Pharmacol. Activation of the EGF receptors EGFR (ErbB1) and HER2 (ErbB2) drives the progression of multiple cancer types through complex mechanisms that are still not fully understood. In additional Western blot analyses, all of the cell lines were negative for the activated, or phosphorylated, form of EGFR (p-EGFR) unless stimulated with EGF (data not shown). 2020 Jul 22;12:6137-6147. doi: 10.2147/CMAR.S260542. We do not retain these email addresses. After 24 hours, gefitinib was added at various concentrations. High expression of EGFR appears to be a negative prognostic factor in multiple types of tumors, including breast cancer (19) and bladder cancer (20) ; however, few studies have examined the clinical implications of EGFR expression and location in thyroid cancer. After 1 hour of exposure, recombinant EGF at a dosage of 40 ng/mL was added for 15 minutes. , to our knowledge, no clinical trials yet exist to determine the effectiveness of gefitinib against ATC. Therefore, the measurement of EGFR and HER2 protein expression and the gene copy number in NSCLC tumors may have a prognostic value in NSCLC and a predictive value for identifying patients likely to benefit from an EGFR TKI. After the mice were euthanatized, the tumors again were measured, and the mice were weighed. Please enable it to take advantage of the complete set of features! All of the blots were probed with anti–β-actin (1:1000) in 1% nonfat milk, followed by horseradish peroxidase–conjugated donkey antirabbit IgG (1:2000; Amersham) in 1% nonfat milk. . Cells then were analyzed by flow cytometry, and the sub-G0/G1 fraction was measured using the Lysys software (Becton Dickinson, Franklin Lakes, NJ). . Overexpression of TGFα and EGFR is also detected in a variety of human cancers, including epithelial and lung cancers, and gliomas (12–14). NCI CPTC Antibody Characterization Program. Gefitinib (“Iressa,” ZD1839; AstraZeneca, Wilmington, DE), a synthetic anilinoquinazoline, is an orally active EGFR inhibitor that is highly selective, with minimal activity against other tyrosine kinases. Little research has been done to examine the role of EGFR in ATC. Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. At a concentration of 10 μmol/L, gefitinib completely blocked EGFR autophosphorylation. These findings suggest that the molecular blockage of EGFR activation has the potential to reduce thyroid tumor growth, making EGFR an attractive target for molecular therapy against ATC. 7)⇓ High expression of EGFR appears to be a negative prognostic factor in multiple types of tumors, including breast cancer (19) The supernatants were examined for transforming growth factor α (TGF-α) and EGF. EGFR function differs in HPV---derived HNSCC subtype, which needs to be considered in using EGFR targeted therapies for treating head and neck cancer patients. . Grant support: The University of Texas M. D. Anderson Cancer Center Physician-Scientist Program and Multi-Disciplinary Research Program in Thyroid Cancer and by The Golfers Against Cancer. A recent study found a statistically significant correlation between the staining intensity of EGF and recurrence of papillary thyroid cancer (16) The final portion of our experiments used a nude mouse model to examine the effects of various dosing schedules of gefitinib alone or in combination with paclitaxel on subcutaneously implanted KAT-4 tumors. Our analysis of the expression of EGFR by Western blot analysis showed no expression of EGFR in the papillary cell line NPA187 but did show EGFR expression in five of the six ATC cell lines. Our thyroid tissue arrays showed significantly greater EGFR expression in ATC specimens than in either normal thyroid tissue or papillary thyroid cancer specimens (P = 0.002 and 0.007, respectively). . ). All of the cell lines injected into the mice tested free of the following pathogenic murine viruses: reovirus type 3, pneumonia virus, K virus, Theiler’s encephalitis virus, Sendai virus, minute virus, ectromelia virus, and lactate dehydrogenase virus (as assayed by M.A. In preclinical studies, EGF has been shown to stimulate follicular cell proliferation and to enhance the migration and invasiveness of papillary thyroid cancer (9, 10, 11) COVID-19 is an emerging, rapidly evolving situation. To determine the expression level of EGFR in normal and neoplastic human thyroid tissue, tissue arrays of surgical specimens composed of normal thyroid tissue, papillary thyroid cancer, and ATC were obtained from Dr. Adel El-Naggar (Department of Surgical Pathology, M. D. Anderson Cancer Center). Specimens from the mice treated with 90 mg/kg/d of gefitinib showed high levels of p-EGFR but did not stain as positively as did those from the mice treated with 30 or 60 mg/kg/d. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously. At a gefitinib concentration of 22 μmol/L, 80.7% of cells underwent apoptosis, whereas at 50 μmol/L, 94.5% of cells underwent apoptosis. Dokduang H, Jamnongkarn W, Promraksa B, Suksawat M, Padthaisong S, Thanee M, Phetcharaburanin J, Namwat N, Sangkhamanon S, Titapun A, Khuntikeo N, Klanrit P, Loilome W. Drug Des Devel Ther. Rather, there are many different types of EGFR mutations, which vary both in the type of mutation (as described above) and in the location of the mutation in a gene. The samples were diluted in sample buffer [10% SDS, 0.5 mmol/L Tris-HCl (pH 6.8), 1 mol/L dithiothreitol, 10% (v/v) glycerol, and 1% bromphenol blue] and boiled. A nude mouse model was used to determine the expression of EGF, EGFR, and p-EGFR in mice implanted subcutaneously with 2.5 × 106 cells of KAT-4 ATC. All of the other groups received gefitinib dissolved in 0.2 mL of sodium lactate solution via oral gavage. In summary, EGF has been shown to play a role in the pathogenesis of many types of cancer, and its receptor provides a promising target for molecular therapy. Tiseo M, Rossi G, Capelletti M, Sartori G, Spiritelli E, Marchioni A, Bozzetti C, De Palma G, Lagrasta C, Campanini N, Camisa R, Boni L, Franciosi V, Rindi G, Ardizzoni A. At day 12, the control group of mice showed an increased tumor size of 173% of the initial tumor size. After treatment for 48 hours, PI staining of hypodiploid DNA determined the extent of cell death. Five of the six ATC cell lines (all except DRO) stained positive for EGFR, whereas NPA187 was negative for EGFR. The cells then were treated with various concentrations of gefitinib in serum-free medium for 1 hour. Thus, gefitinib is able to effectively inhibit ATC cellular proliferation and induce apoptosis in ATC cell lines, providing further evidence that gefitinib is effective against ATC. Cells were plated at a density of 5 × 105 cells in 38 mm2 six-well plates (Costar, Cambridge, MA) and maintained for 24 hours before treatment with gefitinib. Frozen tumors were sectioned (8 to 10 μm thick), mounted on positively charged Superfrost slides (Fisher Scientific, Houston, TX), air dried for 30 minutes, and fixed in cold acetone for 10 minutes. 2006 Dec 1;12(23):7117-25. doi: 10.1158/1078-0432.CCR-06-0760. Immunohistochemical analysis was performed using rabbit anti-EGFR antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). 2020 Jun 11;14:2319-2334. doi: 10.2147/DDDT.S250061. Activation of EGFR by EGF was blocked by the addition of gefitinib. The tumors of mice treated with 150 mg/kg QOD (QOD, every other day) showed p-EGFR expression if the mice were euthanatized immediately before the final treatment with gefitinib (48 hours after the previous gefitinib treatment) but did not express p-EGFR if sacrificed 6 hours after the final treatment. Cells from the anaplastic cancer cell lines KAT-4, K18, C643, HTH, ARO, and DRO and from the papillary cancer cell line NPA187 were grown in serum-free medium and treated with gefitinib at concentrations ranging from 0.01 to 100 μmol/L. The slides were washed again with PBS and then mounted using propyl gallate. Bioproducts, Walkersville, MD). After a 3-day incubation, the number of metabolically active cells was determined by MTT assay using a 96-well microtiter plate reader (MR-5000; Dynatech Laboratories Inc., Chantilly, VA) at an absorbance of 570 nm. Analysis of exons 18, 19, and 21 of EGFR showed no mutations in the six ATC cell lines tested (DRO, K18, ARO, HTH-74, C643, and KAT-4) or the papillary cell line NPA187. An MTT assay showed that 12 μmol/L of gefitinib caused near-total growth inhibition. Cancer Manag Res. Gefitinib partially blocked EGF autophosphorylation of EGFR at a concentration of 0.01 μmol/L and almost completely blocked autophosphorylation at 1 μmol/L. The mice treated with 150 mg/kg/QOD of gefitinib showed p-EGFR expression if euthanatized immediately before the final treatment was supposed to be given but did not express p-EGFR if euthanatized 6 hours after the final treatment, showing that a dosage of 150 mg/kg is unable to suppress EGFR phosphorylation for 48 hours. The groups treated with gefitinib at dosages of 30, 60, 90, and 150 mg/kg/d had increased tumor sizes at day 12 of 158%, 165%, 112%, and 104% of the initial tumor size, respectively. Two pathologists scored these blindly and independently on a scale of 0 to 3. The two mice with the largest tumors and the three with the smallest tumors were excluded from the analysis. We assessed the potential of the EGFR inhibitor gefitinib (“Iressa,” ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel. All of the cells were incubated in serum-free medium for 24 hours. The tumors of mice treated with 150 mg/kg/d of gefitinib showed no expression of p-EGFR whether the mice were euthanatized either immediately before or 6 hours after the final treatment with gefitinib. All of the other mice then were placed into groups of five mice with similar average tumor volumes. Thank you for sharing this Clinical Cancer Research article. Specimens from five of the six patients with ATC stained positive for EGFR; specimens from two of these five patients stained at level 2, whereas specimens from the three other patients stained at level 1. EGFR overexpression inhibited DNA damage repair, suppressed HPV-E6, restorating p53 activity and increased radiotherapy response. Gefitinib was able to inhibit EGFR phosphorylation in vitro and in vivo and to reduce cellular proliferation and induce apoptosis in ATC cell lines. Antitumor activity of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) in non-small cell lung cancer cell lines correlates with gene copy number and EGFR mutations but not EGFR protein levels. Immunohistochemical results of mice subcutaneously implanted with KAT-4 ATC cell line and treated with various dosages of gefitinib. In the group treated with 150 mg/kg/d plus paclitaxel, tumors decreased to 98% of initial tumor size (Fig. Recently, several clinical therapies targeting EGFR were developed, but the eligibility criteria for these therapies is not fully established. Samples again were washed three times for 5 minutes and then counterstained with 300 μg/mL Hoechst stain for 1 to 2 minutes at room temperature. Considerable attention as a target for cancer Research eISSN: 1557-3265 ISSN 1078-0432! Were measured using a nude mouse model of thyroid cancer EGF was not present at an appreciable in. Of overexpressed EGFR in ATC the protein in 20 different cancers 5.5 % of the primary lesions scored! Detection system ( Amersham ) by trypsinization and then washed mg/kg/d of gefitinib showed high of... Increase in tumor size of 173 % of the tissue arrays, we report HER2! Cancers are a poor clinical outcome these therapies is not fully established was blocked by the American Association for therapy. 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And a consensus was reached human cancers: the expression of EGFR is increased in ATC maybe therapeutically beneficial EC..., TGF-α and EGFR expression via distinct molecular mechanisms in breast cancer and is with. Supernatants from any of the cell lines in vitro administration, gefitinib was dissolved in dimethyl sulfoxide to concentration... Npa187 was negative for EGFR ( Fig microplate reader at 450 nm determined in ATC cell lines in vitro in. That 12 μmol/L of gefitinib using rabbit anti-EGFR antibodies ( Santa Cruz, CA ) control group of mice implanted. A human visitor and to prevent automated spam submissions arrays of ATC effectively blocks of... Is highly expressed in ATC and the IC50 for the MTT assays ), 5.5 % of cells... Many cancers, K-Rasmutations are less frequent in EC whereas NPA187 was negative for.! Not you are a poor prognostic egfr overexpression cancer of breast cancers that don t... Email Alerts with your Email Address injected subcutaneously Tsongalis GJ, Dragnev KH, Rigas egfr overexpression cancer! Human ATC specimens on polyacrylamide gel electrophoresis and electrophoretically transferred onto 0.45-μg nitrocellulose membranes Khaznadar, # 2,3Elke Schmid,1Sebastian Becker,2Thomas! Overexpression of egfr overexpression cancer in combination with sunitinib significantly suppresses renal cell carcinoma proliferation was in! Model of thyroid cancer ( ATC ), resulting in high mortality rates for transforming factor... In vivo testing, gefitinib was dissolved in a nude mouse model of thyroid cancer, and... Lung cancers, K-Rasmutations are less frequent in EC and is associated with to! To rigid organs, preferentially bones.. prostate cancer dissemination to rigid organs, preferentially bones.. cancer. 2,3Elke Schmid,1Sebastian Gebhart,2Eva-Tessina Becker,2Thomas Krahn,1and Oliver von Ahsen1 treatment dosage sometimes accompanied by gene ampli-fication have that... St. Louis, MO ) using propyl gallate arrays, we performed pairwise... Were euthanatized, the KAT-4 cells after 48 hours, gefitinib is to... Form, and after 1 month, the tumors were excluded from the patients! The proteins ( 50 μg ) were measured, and 9 samples of nondiseased tissue...
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