과학 수업과 과학논술 지도에서 개념체계도 활용이 중학생의 과학논술 작성에 미치는 영향

학위논문(석사) --서울대학교 대학원 :과학교육과(생물전공),2008. 8.Maste

한국인 폐암 임상상의 경시적 추이에 관한 연구

학위논문(석사)--서울대학교 대학원 :의학과 내과학전공,1998.Maste

Expression of the immune checkpoint molecule V-set immunoglobulin domain-containing 4 is associated with poor prognosis in patients with advanced gastric cancer

Abstract Background: Recent clinical studies on immune checkpoint (IC) inhibitors in the context of advanced gastric cancer (AGC) have failed to show significant survival benefits but have suggested the possible role of IC inhibitors in anti-AGC immunity. Considering the low efficacy of targeted drugs in AGC, there is an urgent need for the discovery of new targets for the development of immunotherapeutics and prognostic markers for patient selection. This study aimed to investigate the expression of a new IC molecule, V-set Ig domain-containing 4 (VSIG4), and its clinical significance in AGC and other major cancers. Methods: We analyzed the expression of VSIG4 and its correlation with survival in various carcinomas, including 882 surgically resected samples from patients with stage II-III AGC (two academic hospitals). Results: VSIG4 positivity in AGC was significantly associated with overall survival (OS; Hazard ratio (HR) = 2.661, 95% confidence interval [CI] = 2.012-3.519, P < 0.001) and event-free survival (HR = 2.8, 95% CI = 2.18-3.72, P < 0.001). These findings were successfully validated in independent cohorts. VSIG4 expression was also significantly correlated with low intratumoral CD8 + T-cell infiltration (CD8i) (P = 0.029) and high Foxp3 + /CD8i ratio (P = 0.026), which is consistent with the previously reported immunological function of VSIG4. However, VSIG4 expression was not associated with survival in other cancers (colon, P = 0.459; lung, P = 0.275; kidney, P = 0.121; breast, P = 0.147). Conclusion: Our results suggest that VSIG4 is an independent prognostic factor in AGC and also implies that VSIG4 is a second-tier IC molecule in AGC, thus, providing an important basis for the development of gastric cancer-specific immunotherapeutics. Keywords: Advanced gastric cancer; Immune checkpoint molecule; Immunotherapy; Tumor microenvironment; V-set Ig domain-containing 4

Comparison of PD-L1 immunohistochemical assays in advanced gastric adenocarcinomas using endoscopic biopsy and paired resected specimens

Immunohistochemical (IHC) assays for programmed death ligand 1 (PD-L1) expression are crucial for guiding immune checkpoint inhibitor therapies in advanced gastric adenocarcinoma (AGC). The results from clinical trials of various PD-L1 antibody clones are variable and the exchangeability of these assays is a highly sought goal. The aim of this study was to determine whether three different PD-L1 assays (SP263 and 22C3 on the Dako and Ventana platforms) are interchangeable through analysis of their concordance rate within samples between biopsy and paired resected specimens. One hundred pairs of biopsied and resected AGC specimens were collected and stained for PD-L1. The combined positive score (CPS) was used for the IHC analysis and a four tiered system was applied, i.e., <1, 1 to < 5, 5 to 50, and >50. The agreement for the different IHC assays was low across all cut-offs with the biopsied or resected specimens (biopsy, kappa=0.17-0.453; resection, kappa=0.02-0.311). The overall positive agreement (OPA) for the PD-L1 results from the biopsy and resection tissues was 100% (SP263, kappa=1), 86% (22C3 on the Dako platform, kappa=0.693) and 93% (22C3 on the Ventana platform, kappa=0.82) at the CPS1 cutoff. The low concordances among the three PD-L1 IHC assays indicated that they cannot be used interchangeably in clinical practice. The results of the SP263 assay using CPS1 showed the highest agreement between the biopsy and resection specimens, suggesting SP263 may provide the most representative approach for the evaluation of PD-L1 status in gastric cancer