Epigenetic Regulation of the Expression of T Cell Stimulatory and Inhibitory Factors by Histone H3 Lysine Modification Enzymes and Its Prognostic Roles in Glioblastoma.

BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed. Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. RESULTS: The mean follow-up duration was 27.5 months (range, 4.1-43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3-20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = -1.746) and those of PD-L1 and EZH1 (R2 linear = -2.118); these relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. CONCLUSION: These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.

Video-assisted thoracoscopic surgical wedge resection using multiplanar computed tomography reconstruction-fluoroscopy after CT guided microcoil localization.

BACKGROUND: When early-stage lung cancer is diagnosed, the recommended treatment is anatomical resection using video-assisted thoracoscopic surgery (VATS) or robotic lobectomy. However, nonanatomical resection, known as wedge resection (WR), which is performed to diagnose pulmonary nodules, can be problematic for clinicians performing VATS or robotic-assisted thoracic surgery (RATS). The purpose of this study was to evaluate the safety and effectiveness of VATS WR using multiplanar computed tomography reconstruction (CT MPR)-fluoroscopy after CT guided microcoil localization to achieve complete pulmonary nodule resection. METHODS: Between January 2016 to December 2020, the medical records of patients who underwent CT-guided microcoil localization for suspicious malignant pulmonary nodules and VATS WR with CT MPR and intraoperative fluoroscopy were retrospectively reviewed. RESULTS: All 130 patients successfully underwent CT-guided localization. The success rate of VATS WR with CT MPR-intraoperative fluoroscopy was 98.5%. Mean operation time was 58 min (range 50-84 min). The postoperative complication rate was 3.1%, and no major postoperative complications were reported. The mean postoperative length of hospital stay was 4.7 days (range 4-8 days). CONCLUSIONS: VATS WR using CT MPR-fluoroscopy after CT guided microcoil localization is a safe and highly effective approach for complete pulmonary nodule resection. However, even in uniport VATS or recently performed robotic surgery, localization and resection of nonvisible, nonpalpable pulmonary nodules is a challenging problem. Consequently, satisfactory outcomes can be expected if this technique is used for suspicious malignant pulmonary nodule resection.