Central nervous system(CNS)tumors represent the most deadly cancer in pediatric age group.In China,thousands of children are diagnosed with CNS tumors every year.Despite the improving socioeconomic status and availabi...Central nervous system(CNS)tumors represent the most deadly cancer in pediatric age group.In China,thousands of children are diagnosed with CNS tumors every year.Despite the improving socioeconomic status and availability of medical expertise within the country,unique challenges remain for the delivery of pediatric neuro-oncology service.In this review,we discuss the existing hurdles for improving the outcome of children with CNS tumors in China.Need for precise disease burden estimation,lack of intra-and inter-hospital collaborative networks,high probability of treatment abandonment,along with financial toxicities from treatment represent the key challenges that Chinese healthcare providers encounter.The tremendous opportunities for advancing the status of pediatric neuro-oncology care in and beyond the country are explored.展开更多
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
文摘Central nervous system(CNS)tumors represent the most deadly cancer in pediatric age group.In China,thousands of children are diagnosed with CNS tumors every year.Despite the improving socioeconomic status and availability of medical expertise within the country,unique challenges remain for the delivery of pediatric neuro-oncology service.In this review,we discuss the existing hurdles for improving the outcome of children with CNS tumors in China.Need for precise disease burden estimation,lack of intra-and inter-hospital collaborative networks,high probability of treatment abandonment,along with financial toxicities from treatment represent the key challenges that Chinese healthcare providers encounter.The tremendous opportunities for advancing the status of pediatric neuro-oncology care in and beyond the country are explored.
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.
