Although temozolomide （TMZ） is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to id...Although temozolomide （TMZ） is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to identity prognostic markers for outcome prediction and to develop chemo-sensitizing agents. Here, the gene expression profiles of TMZ-resistant and TMZ-sensitive samples were compared by microarray analysis, and mitogen-activated protein kinase kinase 2 （MEK2） was upregulated specifically in resistant glioma cells but not in sensitive tumor cells or non-tumor tissues. Moreover, a comprehensive analysis of patient data revealed that the increased level of MEK2 expression correlated well with the advancement of glioma grade and worse prognosis in response to TMZ treatment. Furthermore, reducing the level of MEK2 in U251 glioma cell lines or xenografted glioma models through shRNA-mediated gene knockdown inhibited cell proliferation and enhanced the sensitivity of cells toward TMZ treatment. Further analysis of tumor samples from glioma patients by real-time PCR indicated that an increased MEK2 expression level was closely associated with the activation of many drug resistance genes. Finally, these resistance genes were downregulated after MEK2 was silenced in vitro, suggesting that the mechanism of MEK2-induced chemo-resistance could be mediated by the transcriptional activation of these resistance genes. Collectively, our data indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ.展开更多
Background:Classical pterional appoach for temporal surgeries may cause atrophy and dysfunction of temporalis,injury to the facial nerve,and unnecessary cortical exposure.As an alternative to the classical pterional a...Background:Classical pterional appoach for temporal surgeries may cause atrophy and dysfunction of temporalis,injury to the facial nerve,and unnecessary cortical exposure.As an alternative to the classical pterional approach for such surgeries,we hereby describe an mini-temporal approach which reduces these risks and proven to be practical in neurological surgeries.Material and methods:In the mini-temporal incision design,the frontal end of the incision never surpassed the hairline at the level of temporal line,and a one-layer skin-galea-muscle flap was detached from the cranium,effectively avoiding the injuries of facial nerve.The surgical bone window was completely located underneath the temporalis muscle,allowing it to be completely repositioned postoperatively.Results:We demonstrated the application of mini-temporal approach in a variety of temporal region tumors,which can be applied to complete successful resective surgeries while effectively reducing injuries to extra-temporal cortex,temporalis,and facial nerve.There were no postoperative complications related to extra-temporal cortical damage,atrophy of temporalis,or injury to the facial nerve.Conclusion:The mini-temporal approach can effectively shorten the time of craniotomy and closure,decrease the size of bony removal,increase the restoration of temporalis during closure,and lower the chance of facial nerve injury.Therefore,it improves cosmetic outcomes and reduces the risk of unintentional extra-temporal cortical injury,which fully embodies the minimally invasive principle in neurosurgery.展开更多
文摘Although temozolomide （TMZ） is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to identity prognostic markers for outcome prediction and to develop chemo-sensitizing agents. Here, the gene expression profiles of TMZ-resistant and TMZ-sensitive samples were compared by microarray analysis, and mitogen-activated protein kinase kinase 2 （MEK2） was upregulated specifically in resistant glioma cells but not in sensitive tumor cells or non-tumor tissues. Moreover, a comprehensive analysis of patient data revealed that the increased level of MEK2 expression correlated well with the advancement of glioma grade and worse prognosis in response to TMZ treatment. Furthermore, reducing the level of MEK2 in U251 glioma cell lines or xenografted glioma models through shRNA-mediated gene knockdown inhibited cell proliferation and enhanced the sensitivity of cells toward TMZ treatment. Further analysis of tumor samples from glioma patients by real-time PCR indicated that an increased MEK2 expression level was closely associated with the activation of many drug resistance genes. Finally, these resistance genes were downregulated after MEK2 was silenced in vitro, suggesting that the mechanism of MEK2-induced chemo-resistance could be mediated by the transcriptional activation of these resistance genes. Collectively, our data indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ.
基金Matthias Mäurer and Marcel Kamp were funded by the Stifterverband in cooperation with the Thuringian Ministry of Economics,Science and Digital Society within the framework of the"Fellowship for Innovations in Digital University Teaching"(GZ:5508/78-15-25)Matthias Mäurer was funded by the Deutsche Forschungsgemsinschaft(DFG,German Research Foundation)Clinician Scientist Program OrganAge(funding number 413668513)by the Interdisciplinary Center of Clinical Research of the Medical Faculty Jena.Irina Mäurer was supported by funding from the Foundation"Else-Kröner-Fresenius-Stiftung"within the Else Kröner Research School for Physicians"AntiAge".
文摘Background:Classical pterional appoach for temporal surgeries may cause atrophy and dysfunction of temporalis,injury to the facial nerve,and unnecessary cortical exposure.As an alternative to the classical pterional approach for such surgeries,we hereby describe an mini-temporal approach which reduces these risks and proven to be practical in neurological surgeries.Material and methods:In the mini-temporal incision design,the frontal end of the incision never surpassed the hairline at the level of temporal line,and a one-layer skin-galea-muscle flap was detached from the cranium,effectively avoiding the injuries of facial nerve.The surgical bone window was completely located underneath the temporalis muscle,allowing it to be completely repositioned postoperatively.Results:We demonstrated the application of mini-temporal approach in a variety of temporal region tumors,which can be applied to complete successful resective surgeries while effectively reducing injuries to extra-temporal cortex,temporalis,and facial nerve.There were no postoperative complications related to extra-temporal cortical damage,atrophy of temporalis,or injury to the facial nerve.Conclusion:The mini-temporal approach can effectively shorten the time of craniotomy and closure,decrease the size of bony removal,increase the restoration of temporalis during closure,and lower the chance of facial nerve injury.Therefore,it improves cosmetic outcomes and reduces the risk of unintentional extra-temporal cortical injury,which fully embodies the minimally invasive principle in neurosurgery.
