scholarly journals Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models

2000 ◽  
Vol 105 (9) ◽  
pp. 1233-1241 ◽  
Author(s):  
Jeffrey E. DeClue ◽  
Sue Heffelfinger ◽  
Giovanna Benvenuto ◽  
Bo Ling ◽  
Shaowei Li ◽  
...  
2021 ◽  
Vol 22 (24) ◽  
pp. 13308
Author(s):  
Gun-Hoo Park ◽  
Su-Jin Lee ◽  
Chang-Gun Lee ◽  
Jeonghyun Kim ◽  
Eunkuk Park ◽  
...  

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.


Cancer ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 1234-1242 ◽  
Author(s):  
Mothaffar F. Rimawi ◽  
Priya B. Shetty ◽  
Heidi L. Weiss ◽  
Rachel Schiff ◽  
C. Kent Osborne ◽  
...  

2021 ◽  
pp. 107815522110382
Author(s):  
Rocío Díaz-Acedo ◽  
Silvia Artacho Criado ◽  
Rocío Jiménez Galán ◽  
Antonio Gutiérrez Pizarraya ◽  
Mercedes Galván Banqueri ◽  
...  

Background Eribulin’s clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. Patients and methods This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. Results A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1–11.4) and 2.8 months (95% confidence interval: 2.5–3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3–4.5) versus triple negative: 2.0 (95%confidence interval: 1.7–2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6–12.5 vs. 4.8 months, 95% confidence interval: 3.4–6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1–16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8–5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. Conclusion Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.


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