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Purpose. Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods. Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results. Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion. G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma. [ABSTRACT FROM AUTHOR]

Endovascular thrombectomy (EVT) is the preferred treatment strategy for patients with acute ischemic stroke (AIS). However, clinical outcome and prognosis in patients who undergo EVT in response to AIS with concomitant malignancy have not been fully elucidated. Data of patients with malignancy who underwent EVT at participating institutions between January 2015 and April 2019 were retrospectively analyzed. Patient characteristics, treatment methods, posttreatment strategy, and long-term prognosis were evaluated in 12 patients with prediagnoses of malignancy. Good revascularization (TICI 2b or higher) was achieved in 10 of 12 patients. Among the eight patients who survived more than 2 weeks from onset, four patients showed good clinical outcome [modified Rankin Scale (mRS) <2] at 60 days posttreatment and were able to continue treatment for malignancy. However, seven of eight patients died within a year of EVT (median survival, 83 days) due to progression of malignancy. One-year survival was achieved in only one patient whose etiology of stroke was determined as infectious endocarditis and not Trousseau syndrome. Even after successful revascularization and good short-term clinical outcome, the long-term prognosis after thrombectomy in patients with malignancy was poor. Thrombectomy for concomitant malignancy requires judicious decision, and further studies are necessary to fully elucidate its efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole ( 18 F-FMISO) and fluorine-18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism., Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma ( n = 33) who underwent preoperative 18 F-FMISO and 18 F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort ( n = 17) and validated by The Cancer Genome Atlas (TCGA) database ( n = 167)., Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 ( G6PC3 ) correlated with 18 F-FDG LNR ( P = 0.03). In addition, G6PC3 mRNA expression in 18 F-FMISO high-accumulated glioblastomas was significantly higher than that in 18 F-FMISO low-accumulated glioblastomas ( P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database., Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18 F-FDG and 18 F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 Michinari Okamoto et al.)