PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs)
| العنوان: | PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs) |
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| المؤلفون: | Lin Shen, Jian Li, Jianling Zou, Yun-zhi Dang, Jing Gao, Yanyan Li |
| المصدر: | Medical Oncology. 32 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Cancer Research, medicine.medical_specialty, Gastrointestinal Stromal Tumors, Polymerase Chain Reaction, Immunoenzyme Techniques, Phosphatidylinositol 3-Kinases, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, PTEN, Gastrointestinal stromal tumors (GISTs), Phosphorylation, Protein Kinase Inhibitors, neoplasms, Protein kinase B, PI3K/AKT/mTOR pathway, Neoplasm Staging, biology, GiST, business.industry, TOR Serine-Threonine Kinases, PTEN Phosphohydrolase, Imatinib, Hematology, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Rate, Proto-Oncogene Proteins c-kit, Endocrinology, Oncology, Drug Resistance, Neoplasm, Tumor progression, Lymphatic Metastasis, Mutation, Imatinib Mesylate, Cancer research, biology.protein, Immunohistochemistry, Female, Neoplasm Recurrence, Local, business, Proto-Oncogene Proteins c-akt, Follow-Up Studies, Signal Transduction, medicine.drug |
| الوصف: | Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway activation may be related to imatinib resistance; however, no study has focused on whether signal conduction of this pathway will change after imatinib resistance. A total of 111 GIST samples from 91 patients were used in this study, including 20 pairs of samples before and after imatinib treatment. Immunohistochemistry was performed on tissue for p-KIT (phospho-KIT), PTEN (phosphatase and tensin homolog deleted on chromosome ten), PI3K, phospho-AKT (p-AKT), phospho-4EBP1 (p-4EBP1) and phospho-S6 (p-S6RP). The activation of AKT/mTOR was significantly higher in imatinib secondary resistant GIST (53.1 %) than in imatinib-sensitive (27.1 %) and primary resistant GIST (33.3 %) (P = 0.049). In the analysis of 20 pairs of samples, comparing pre-imatinib GIST with on-treatment ones, the PI3K status was changed from inactivated to activated in four cases each in eight patients with effective imatinib and 12 patients whose secondary resistance happened, respectively. AKT/mTOR status was inactivated in pre-imatinib and on-treatment samples in eight patients with effective imatinib; however, the status of six patients was changed from inactivated to activated in 12 patients at the time of tumor progression. The negative expression of p-KIT was accompanied with PI3K pathway and/or AKT/mTOR pathway activity in some GISTs with secondary resistance. PI3K/AKT/mTOR pathway can be partly activated after imatinib secondary resistance in GIST. In this pathway, activation of AKT/mTOR is a more crucial factor, and PI3K activation may be the early part of secondary resistance. |
| تدمد: | 1559-131X 1357-0560 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c698d24578086ea834fca3658ad12f0d https://doi.org/10.1007/s12032-015-0554-6 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....c698d24578086ea834fca3658ad12f0d |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1559131X 13570560 |
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