Fibroblast growth factor 13 regulates glioma cell invasion and is important for bevacizumab-induced glioma invasion.

Glioblastoma has the poorest prognosis, and is characterized by excessive invasion and angiogenesis. To determine the invasive mechanisms, we previously used two glioma cell lines (J3T-1 and J3T-2) with different invasive phenotypes. The J3T-1 showed abundant angiogenesis and tumor cell invasion around neovasculature, while J3T-2 showed diffuse cell infiltration into surrounding healthy parenchyma. Microarray analyses were used to identify invasion-related genes in J3T-2 cells, and the expressed genes and their intracellular and intratumoral distribution patterns were evaluated in J3T-2 cell lines, human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens. To determine the role of the invasion-related genes, invasive activities were evaluated in vitro and in vivo. Fibroblast growth factor 13 (FGF13) was overexpressed in J3T-2 cells compared to J3T-1 cells, and in human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens, when compared to that of normal human astrocytes. Immunohistochemical staining and the RNA-seq (sequencing) data from the IVY Glioblastoma Atlas Project showed FGF13 expression in glioma cells in the invasive edges of tumor specimens. Also, the intracellular distribution was mainly in the cytoplasm of tumor cells and colocalized with tubulin. Overexpression of FGF13 stabilized tubulin dynamics in vitro and knockdown of FGF13 decreased glioma invasion both in vitro and in vivo and prolonged overall survival of several xenograft models. FGF13 was negatively regulated by hypoxic condition. Silencing of FGF13 also decreased in vivo bevacizumab-induced glioma invasion. In conclusion, FGF13 regulated glioma cell invasion and bevacizumab-induced glioma invasion, and could be a novel target for glioma treatment.

Analysis of Associated Spinal Fractures in Cases of Traumatic Intracranial Hemorrhage or Skull Fracture.

Introduction: Patients with traumatic intracranial hemorrhage (ICH) or skull fracture are typically admitted to the Department of Neurosurgery for fear of delayed neurological deterioration. Neurosurgeons, therefore, must be careful not to overlook a spinal fracture in these patients. In this study, we investigated the occurrence and risk factor of spinal fracture in patients with traumatic ICH or skull fracture. Patients and methods: We retrospectively analyzed the hospital records of 134 patients admitted to the Department of Neurosurgery at Kagawa Rosai Hospital for traumatic ICH or skull fracture. The etiology of trauma, level of consciousness, presence or absence of ICH, skull fracture, craniotomy and spinal surgery were investigated. Furthermore, in cases of spinal fracture, its type, neurological symptoms, treatment were investigated. Results: In an analysis of 134 patients, Ground level fall and traffic accident were the most frequent etiologies of trauma (47.0% and 23.9% respectively). Glasgow coma scale on admission was 15-13 for 106 patients (79.1%). spinal fracture was identified in 10 of 134 patients (7.5%). Two patients had cervical, 8 had thoracolumbar fractures. In the analysis of risk factors, an accidental fall and skull fracture was observed significantly more in the spinal fracture cases. Conclusion: The majority of traumatic ICH or skull fracture cases treated in the Department of Neurosurgery were caused by minor head impacts. When treating these patients, it is necessary to investigate not only the cervical, but also the thoracolumbar spine, especially when the cause of injury is an accidental fall and a skull fracture is identified.