Relevance of the Foramen of Vesalius for Preoperative Tumor Embolization in Skull Base Meningioma.

OBJECTIVE: The objective of this study was to investigate the role of the foramen of Vesalius (FV) in the pathogenesis of skull base meningioma by analyzing data from various multi-image modalities. METHODS: For this single-center retrospective study, 39 consecutive patients with skull base meningioma who underwent tumor resection between January 2020 and March 2023 were enrolled. The anatomical and pathological characteristics of the FV were evaluated using computed tomography and 3-dimensional digital subtraction angiography. The clinical significance of the FV in tumor hemodynamics and treatment, such as preoperative tumor embolization, was investigated using the 3-dimensional digital subtraction angiography/computed tomography fusion images. RESULTS: We identified FV in 52% (17/27) of the finally included patients. In 10 (30%) patients, the FV was found bilaterally with no significant variation in appearance between the healthy and tumor-affected sides (P = 0.786). The mean FV diameter was significantly larger on the tumor-affected side (P = 0.010). No significant anatomical differences, like duplication and partial assimilation with the foramen ovale, were observed between the 2 sides. The FV was involved in venous skull base perfusion around the tumor in 9 cases. In 4 cases where it was the pathway for tumor feeders, preoperative tumor embolization via the FV resulted in disappearance of the tumor stain. No complications associated with endovascular treatment were observed. CONCLUSIONS: This study elucidated the anatomical asymmetry of the FV and its role in the hemodynamics of skull base meningioma. Our findings highlight the significance of performing anatomical and pathological evaluations of the FV in determining treatment strategies, including preoperative embolization, for skull base lesions.

Improvement of the dP-nucleoside-mediated herpes simplex virus thymidine kinase negative-selection system by manipulating dP metabolism genes.

A variety of positive/negative selection systems have been exploited as genome engineering tools and screening platforms for genetic switches. While numerous positive-selection systems are available, only a handful of negative-selection systems are useful for such applications. We previously reported a powerful negative-selection system using herpes simplex virus thymidine kinase (HsvTK) and the mutagenic nucleoside analog 6-(ß-d-2-deoxyribofuranosyl)-3,4-dihydro-8H-pyrimido [4,5-c][1,2] oxazin-7-one (dP). Upon addition of 1000 nM dP, cells expressing HsvTK quickly die, with unprecedented efficacy. However, this selection procedure elevates the spontaneous mutation rate of the host cells by 10-fold due to the mutagenic nature of dP. To decrease the operative concentration of dP required for negative selection, we systematically created the strains of Escherichia coli either by removing or overexpressing genes involved in DNA/RNA metabolism. We found that over-expression of NupC and NupG (nucleoside uptake-related inner membrane transporters), Tsx (outer membrane transporter), NdK (nucleotide kinase) sensitized E. coli cells to dP. Simultaneous overexpression of these three genes (ndk-nupC-tsx) significantly improved the dP-sensitivity of E. coli, lowering the necessary operative concentration of dP for negative selection by 10-fold. This enabled robust and selective elimination of strains harboring chromosomally-encoded hsvtk simply by adding as low as 100 nM dP, which causes only a modest increase in the spontaneous mutation frequency as compared to the cells without hsvtk.

Rapid Diversification of BetI-Based Transcriptional Switches for the Control of Biosynthetic Pathways and Genetic Circuits.

Synthetic biologists are in need of genetic switches, or inducible sensor/promoter systems, that can be reliably integrated in multiple contexts. Using a liquid-based selection method, we systematically engineered the choline-inducible transcription factor BetI, yielding various choline-inducible and choline-repressive promoter systems with various input-output characteristics. In addition to having high stringency and a high maximum induction level, they underwent a graded and single-peaked response to choline. Taking advantage of these features, we demonstrated the utility of these systems for controlling the carotenoid biosynthetic pathway and for constructing two-input logic gates. Additionally, we demonstrated the rapidity, throughput, robustness, and cost-effectiveness of our selection method, which facilitates the conversion of natural genetic controlling systems into systems that are designed for various synthetic biology applications.