التفاصيل البيبلوغرافية
| العنوان: |
Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1. |
| المؤلفون: |
Staedtke, Verena1 (AUTHOR) tgraybe1@jhmi.edu, Gray-Bethke, Tyler1 (AUTHOR), Riggins, Gregory J.2 (AUTHOR) griggin1@jhmi.edu, Bai, Ren-Yuan2 (AUTHOR) vstaedt1@jhmi.edu |
| المصدر: |
Genes. Jul2020, Vol. 11 Issue 7, p762. 1p. |
| مصطلحات موضوعية: |
*NEUROFIBROMATOSIS 1, *SCHWANNOMAS, *GUANOSINE triphosphate, *EXTRACELLULAR signal-regulated kinases, *BENIGN tumors |
| مستخلص: |
Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect of mebendazole, alone or in combination with cyclooxygenase-2 (COX-2) inhibitors, on the prevention of NF1-related malignancies in a cisNf1+/−;Tp53+/− (NPcis) mouse model of NF1. Our in vitro findings showed that mebendazole (MBZ) inhibits the growth of NF1-related malignant peripheral nerve sheath tumors (MPNSTs) through a reduction in activated guanosine triphosphate (GTP)-bound Ras. The daily MBZ treatment of NPcis mice dosed at 195 mg/kg daily, initiated 60 days after birth, substantially delayed the formation of solid malignancies and increased median survival (p < 0.0001). Compared to placebo-treated mice, phosphorylated extracellular signal-regulated kinase (pERK) levels were decreased in the malignancies of MBZ-treated mice. The combination of MBZ with COX-2 inhibitor celecoxib (CXB) further enhanced the chemopreventative effect in female mice beyond each drug alone. These findings demonstrate the feasibility of a prevention strategy for malignancy development in high-risk NF1 individuals. [ABSTRACT FROM AUTHOR] |
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