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Glioblastoma stem-like cells dynamically transition between a chemoradiation-resistant state and a chemoradiation-sensitive state. However, physical barriers in the tumour microenvironment restrict the delivery of chemotherapy to tumour compartments that are distant from blood vessels. Here, we show that a massively parallel computational model of the spatiotemporal dynamics of the perivascular niche that incorporates glioblastoma stem-like cells and differentiated tumour cells as well as relevant tissue-level phenomena can be used to optimize the administration schedules of concurrent radiation and temozolomide-the standard-of-care treatment for glioblastoma. In mice with platelet-derived growth factor (PDGF)-driven glioblastoma, the model-optimized treatment schedule increased the survival of the animals. For standard radiation fractionation in patients, the model predicts that chemotherapy may be optimally administered about one hour before radiation treatment. Computational models of the spatiotemporal dynamics of the tumour microenvironment could be used to predict tumour responses to a broader range of treatments and to optimize treatment regimens.
Glioblastoma stem-like cells dynamically transition between a chemoradiation-resistant state and a chemoradiation-sensitive state. However, physical barriers in the tumour microenvironment restrict the delivery of chemotherapy to tumour compartments that are distant from blood vessels. Here, we show that a massively parallel computational model of the spatiotemporal dynamics of the perivascular niche that incorporates glioblastoma stem-like cells and differentiated tumour cells as well as relevant tissue-level phenomena can be used to optimize the administration schedules of concurrent radiation and temozolomide-the standard-of-care treatment for glioblastoma. In mice with platelet-derived growth factor (PDGF)-driven glioblastoma, the model-optimized treatment schedule increased the survival of the animals. For standard radiation fractionation in patients, the model predicts that chemotherapy may be optimally administered about one hour before radiation treatment. Computational models of the spatiotemporal dynamics of the tumour microenvironment could be used to predict tumour responses to a broader range of treatments and to optimize treatment regimens.
Abstract. The aim of the present study was to examine the expression of microRNA (miRNA)-184 in gliomas with different pathological grades, and its effect on survival prognosis. For the present study, 40 participants were selected with different pathological grades of glioma tissues with grade I (n=10), grade II (n=8), grade III (n=16), and grade IV (n=6). In addition, 10 cases of normal brain tissue (obtained by decompression because of traumatic brain injury) were selected. RT-PCR and immunohistochemical techniques were used to detect the expression level and intensity of miRNA-184 in different grades of glioma tissues. The length of survival of miRNA-184-positive patients was analyzed. miRNA-184 mRNA expression was found in normal tissues and tumor tissues, and the expression in tumor tissues was significant (P<0.05). Statistically significant differences of miRNA-184 expression were observed among different grades (P<0.05). miRNA-184 expression increased with the increase of grade level. The differences in expression across grade levels was statistically significant (P<0.05). A positive expression was not related to the pathological types of glioma cells. The median survival time of patients with miRNA-184-positive expression was significantly shorter than that of the negative expression group (P<0.05). miRNA-184 is highly expressed in gliomas, which is positively correlated with pathological grade, and is not correlated with pathological type, and negatively correlated with survival time. Thus, miRNA-184 is a potentially important molecular marker for glioma.
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