scholarly journals Neurofibromin Deficiency Causes Epidermal Growth Factor Receptor Upregulation through the Activation of Ras/ERK/SP1 Signaling Pathway in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheet Tumor

2021 ◽  
Vol 22 (24) ◽  
pp. 13308
Author(s):  
Gun-Hoo Park ◽  
Su-Jin Lee ◽  
Chang-Gun Lee ◽  
Jeonghyun Kim ◽  
Eunkuk Park ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Peripheral Nerve ◽  
Growth Factor Receptor ◽  
Neurofibromatosis Type ◽  
Sirna Treatment ◽  
Egfr Expression ◽  
Epidermal Growth

Neurofibromatosis type 1 (NF1) is an autosomal dominant human genetic disorder. The progression of benign plexiform neurofibromas to malignant peripheral nerve sheet tumors (MPNSTs) is a major cause of mortality in patients with NF1. Although elevated epidermal growth factor receptor (EGFR) expression plays a crucial role in the pathogenesis of MPNST, the cause of EGFR overexpression remains unclear. Here, we assessed EGFR expression levels in MPNST tissues of NF1 patients and NF1 patient-derived MPNST cells. We found that the expression of EGFR was upregulated in MPNST tissues and MPNST cells, while the expression of neurofibromin was significantly decreased. Manipulation of NF1 expression by NF1 siRNA treatment or NF1-GAP-related domain overexpression demonstrated that EGFR expression levels were closely and inversely correlated with neurofibromin levels. Notably, knockdown of the NF1 gene by siRNA treatment augmented the nuclear localization of phosphorylated SP1 (pSP1) and enhanced pSP1 binding to the EGFR gene promoter region. Our results suggest that neurofibromin deficiency in NF1-associated MPNSTs enhances the Ras/ERK/SP1 signaling pathway, which in turn may lead to the upregulation of EGFR expression. This study provides insight into the progression of benign tumors and novel therapeutic approaches for treatment of NF1-associated MPNSTs.

scholarly journals Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers

2018 ◽  
Vol 129 (3) ◽  
pp. 805-814 ◽  
Author(s):  
Eric D. Young ◽  
Davis Ingram ◽  
William Metcalf-Doetsch ◽  
Dilshad Khan ◽  
Ghadah Al Sannaa ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Peripheral Nerve ◽  
Tumor Cells ◽  
Tissue Microarray ◽  
Growth Factor Receptor ◽  
Nerve Sheath ◽  
Epidermal Growth

OBJECTIVEWhile sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS.METHODSPatients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121).RESULTSSPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor–β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor–2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018).CONCLUSIONSComplete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2–associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.

scholarly journals Epidermal growth factor receptor protein expression in lung cancer and survival analysis

2018 ◽  
Vol 5 (3) ◽  
pp. 550
Author(s):  
Shivalingaswamy Salimath ◽  
Jayaraj B. S. ◽  
Mahesh P. A. ◽  
M. D. Majeed Pasha ◽  
Lokesh K. S. ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Multivariate Analysis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Nsclc Patients

Background: Epidermal Growth Factor Receptor (EGFR) is one of the important molecules involved in lung cancer initiation and progression. Studies on over expression of EGFR and its survival in relation with Non-small cell lung cancer (NSCLC) patients have yielded controversial results. Prevalence of EGFR expression in NSCLC patients and 6-month survival in south Indian population is unknown.Methods: We carried out a prospective study in tertiary hospital. Diagnosed patients with NSCLC were included in the study and were interviewed with questionnaire containing demography and investigations like Chest X-ray, CT thorax, Bronchoscopy were recorded. EGFR expression analysis was done for all patients and were followed up monthly for 6 months and details of survival and treatment were collected. Cox regression analysis was used to assess their survival.Results: 50 patients with NSCLC were included. Forty-four (88%) were men, median age of study group was 65 years. Twenty-seven patients (54%) had Adenocarcinoma, 14 patients (28%) had Squamous cell carcinoma, 7 patients (14%) had poorly differentiated carcinoma and 2 patients (4%) had large cell carcinoma. Thirty-four (68%) samples were positive for EGFR expression. On multivariate analysis we found patients who took chemotherapy and with good performance status (Karnofsky score >65 and Eastern Cooperative Oncology Group >2.5) had better survival at 6 months.Conclusions: Patients with EGFR positivity had better survival with chemotherapy but worse with radiotherapy. Patients who took chemotherapy and had good performance status had better survival on multivariate analysis. We didn’t find any correlation between EGFR positivity and poor survival.

scholarly journals Inhibition of epidermal growth factor receptor (EGFR) expression by human cytomegalovirus correlates with an increase in the expression and binding of Wilms' Tumour 1 protein to the EGFR promoter

2009 ◽  
Vol 90 (7) ◽  
pp. 1569-1574 ◽  
Author(s):  
Insiya Jafferji ◽  
Mark Bain ◽  
Christine King ◽  
John H. Sinclair
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Cytomegalovirus ◽  
Growth Factor Receptor ◽  
Cell Surface Receptor ◽  
Wilms Tumour ◽  
Promote Cell Proliferation ◽  
Egfr Expression ◽  
Epidermal Growth

Infection with human cytomegalovirus (HCMV) modulates the expression of a number of cellular receptors and is known to inhibit expression of the epidermal growth factor receptor (EGFR), a cell surface receptor that can promote cell proliferation through a cascade of intracellular signalling events. We have examined the mechanisms by which HCMV mediates downregulation of EGFR expression and show that virus infection results in the profound upregulation of Wilms' Tumour 1 (WT1) protein, a transcription factor associated with the negative regulation of a number of growth factors and growth factor receptors, including EGFR. Moreover, chromatin immunoprecipitation experiments also show that HCMV infection results in increased binding of WT1 to the EGFR promoter. Finally, we show that depleting the cell of WT1 using small interfering RNA abrogates virus-mediated downregulation of EGFR. Taken together, our observations suggest that HCMV-mediated repression of EGFR expression results from a virus-mediated increase in cellular WT1, a known pleiotropic regulator of mitogenesis, apoptosis and differentiation.

Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer

2006 ◽  
Vol 24 (19) ◽  
pp. 3069-3074 ◽  
Author(s):  
Philip A. Philip ◽  
Michelle R. Mahoney ◽  
Cristine Allmer ◽  
James Thomas ◽  
Henry C. Pitot ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Skin Rash ◽  
Group Performance ◽  
Growth Factor Receptor ◽  
Locoregional Therapy ◽  
Biliary Cancer ◽  
Egfr Expression ◽  
Epidermal Growth

Purpose Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Methods Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Results Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Conclusion Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

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