Department of Biochemistry

Background/Objectives: The purpose of this study was to investigate preoperative interhemispheric differences of the FAT in relation to the onset of postoperative SMA syndrome. Methods: This was a single-center retrospective analysis of patients who underwent surgical resection of diffuse gliomas involving the SMA between 2018 and 2022. Inclusion criteria were availability of preoperative and postoperative Magnetic Resonance Imaging, no previous surgery, and no neurological deficits at presentation. Diffusion-weighted data were processed by spherical deconvolution (SD) and diffusion tensor imaging tractography algorithms, and TrackVis was used to dissect the FAT of both hemispheres. The FAT data were analyzed for correlation with postoperative SMA syndrome onset. Results: N = 25 cases were included in the study, among which n = 23 had preoperative bilaterally identifiable FAT by SD. N = 12 developed an SMA syndrome, 6 demonstrated a motor-only syndrome, 4 had a verbal-only syndrome, and 2 had mixed verbal and motor features. The SMA syndrome incidence was significantly more frequent in lower-grade gliomas (p = 0.005). On the tumor side, the FAT identified by SD was smaller than the contralateral (mean volume 6.53 cm3 and 13.33 cm3, respectively, p < 0.001). In the 6 cases that developed a verbal SMA syndrome, a normalized FAT volume asymmetry (FAT-VA) demonstrated an asymmetry shifted towards the non-dominant side (mean FAT-VA = −0.68), while the cases with no postoperative verbal impairment had opposite asymmetry towards the dominant side (mean FAT-VA = 0.42, p = 0.010). Conclusions: Preoperative interhemispheric FAT volume asymmetry estimated according to functional dominance can predict postoperative onset of verbal SMA syndrome, with proportionally smaller FAT on the affected dominant hemisphere.

Background: The aim of this study was to determine the differences in diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) parameters between patients with peritoneal high-grade serous ovarian cancer (HGSOC) recurrence with BRCA mutations (BRCAmut) or BRCA wild type (BRCAwt). Materials and Methods: We retrospectively analyzed the abdominal and pelvic magnetic resonance (MR) images of 43 patients suspected of having recurrent HGSOC, of whom 18 had BRCA1/2 gene mutations. Patients underwent MRI examination via a 1.5 T MRI scanner, and the analyzed parameters were as follows: apparent diffusion coefficient (ADC), time to peak (TTP) and perfusion maximum enhancement (Perf. Max. En.). Results: The mean ADC in patients with BRCAwt was lower than that in patients with BRCAmut: 788.7 (SD: 139.5) vs. 977.3 (SD: 103), p-value = 0.00002. The average TTP value for patients with BRCAwt was greater than that for patients with mutations: 256.3 (SD: 50) vs. 160.6 (SD: 35.5), p-value < 0.01. The Perf. Max. En. value was lower in the BRCAwt group: 148.6 (SD: 12.3) vs. 233.6 (SD: 29.2), p-value < 0.01. Conclusion: Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.

Background and Objectives: Lung nodules detected by chest computed tomography (CT) often require invasive biopsies for definitive diagnosis, leading to unnecessary procedures for benign lesions. A blood-based biomarker test that predicts lung cancer risk in CT-detected nodules could help stratify patients and direct invasive diagnostics toward high-risk individuals. Methods: In this multicenter, single-blinded clinical trial, we evaluated a test measuring plasma levels of p53, anti-p53 autoantibodies, CYFRA 21-1, and anti-CYFRA 21-1 autoantibodies in patients with CT-detected lung nodules. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and subgroup analyses by gender, age, and smoking status were performed. A total of 1132 patients who had CT-detected lung nodules, including 885 lung cancer cases and 247 benign lesions, were enrolled from two academic hospitals in South Korea. Results: The test demonstrated a sensitivity of 78.4% (95% CI: 75.7–81.1) and specificity of 93.1% (95% CI: 90.0–96.3) in predicting lung cancer in CT-detected nodules. The PPV was 97.6%, and the NPV was 54.6%. Performance was consistent across gender (sensitivity 79.3% in men and 76.8% in women) and age groups, with a specificity of 93.4% in men and 92.7% in women. Stage I lung cancer was detected with a sensitivity of 80.6%. Conclusions: The Lung Cancer test based on 9G technology presented here offers a non-invasive method for stratifying lung cancer risk in patients with CT-detected nodules. Its integration into clinical practice could reduce unnecessary interventions and foster earlier detection.

Glioblastoma (GBM) is the most common primary brain malignancy in the U.S. with a 5-year overall survival < 5% despite an aggressive standard of care. Laser interstitial thermal therapy (LITT) is a surgical approach to treating GBM that has gained traction, providing a safe option for reducing intracranial tumor burden. LITT is believed to potentially modulate GBM immune responses; however, the biochemical mechanisms underlying the modulation of immune checkpoints in GBM cells have been poorly characterized. The present study aimed to preliminarily evaluate the effects of thermal therapy and radiation on PD-L1 modulation in vitro, as a function of IDH mutational status. U87 cells and their IDH-mutant counterpart (U87R132H), which was generated using a crispr-cas9 knock-in approach, were utilized for this preliminary evaluation. Cell heating was achieved by harvesting with trypsin centrifugation where the cell pellets were treated on a heat block for the associated time and temperature. Following thermal therapy, cells were resuspended and irradiated using a 37-Cesium irradiator at 0.6 Gy min−1. Immediately following treatment, cells were either plated as single cells to allow colonies to form, and stained with Coomassie blue to be counted approximately 10–14 days later or harvested for Western blot analysis. Cell lysates were analyzed for PD-L1 expression with respect to various iron metabolic parameters (mortalin (HSPA9), transferrin receptor, and ferritin heavy chain) using a Western blotting approach. In both U87 and U87R132H cell lines, thermal therapy showed a temperature-dependent cell-killing effect, but U87R132H cells appeared more sensitive to thermal treatment when treated at 43 °C for 10 min. Moreover, thermal therapy had minimal effects on cell responses to 2 Gy irradiation. Treatment with thermal therapy downregulated PD-L1 expression in U87R132H cells, which was associated with increased expression of the mitochondrial iron metabolic enzyme, HSPA9. Thermal therapy reversed the radiation-induced overexpression of PD-L1, transferrin receptor, and ferritin heavy chain in U87R132H cells. No effects were observed in wild-type U87 cells. Moreover, Ga(NO3)3 depleted mitochondrial iron content which, in turn, significantly enhanced the sensitivity of U87R132H cells to thermal therapy and 2 Gy irradiation and caused a significant increase in PD-L1 expression. These results suggest that thermal therapy alone can modulate the immune checkpoint PD-L1. This effect was more pronounced when thermal therapy was combined with radiation. Mechanistically, mitochondrial iron trafficking through HSPA9 may coordinate the regulation of PD-L1 in the context of thermal therapy and ionizing radiation, which can be targeted with gallium-based therapy. These novel, preliminary findings warrant further mechanistic investigations in pre-clinical models of LITT.