Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1
| العنوان: | Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1 |
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| المؤلفون: | Ren Yuan Bai, Gregory J. Riggins, Tyler Gray-Bethke, Verena Staedtke |
| المصدر: | Genes Volume 11 Issue 7 Genes, Vol 11, Iss 762, p 762 (2020) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Neurofibromatosis 1, sarcoma, lcsh:QH426-470, Mebendazole, Antineoplastic Agents, RASopathy, Malignancy, Article, Nerve Sheath Neoplasms, 03 medical and health sciences, Mice, 0302 clinical medicine, MPNST, Cell Line, Tumor, Genetics, Medicine, Animals, Humans, chemoprevention, Neurofibromatosis, COX-2 inhibitor, Extracellular Signal-Regulated MAP Kinases, Genetics (clinical), Neurofibromin 1, Cyclooxygenase 2 Inhibitors, business.industry, Kinase, neurofibromatosis 1 (NF1), medicine.disease, Mice, Inbred C57BL, lcsh:Genetics, 030104 developmental biology, Celecoxib, 030220 oncology & carcinogenesis, Cancer research, ras Proteins, Female, Sarcoma, Tumor Suppressor Protein p53, mebendazole (MBZ), business, medicine.drug, Signal Transduction, malignancy |
| الوصف: | 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 cis Nf1+/ 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4425 |
| DOI: | 10.3390/genes11070762 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ed0ea7fb841a585850943052bfbee3eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7ed0ea7fb841a585850943052bfbee3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734425 |
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| DOI: | 10.3390/genes11070762 |