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Kyeongmin Kim,Se Hoon Kim,Jung-Yun Lee,Yoo-Na Kim,Seung-Tae Lee,박은향 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.4
Objective: The RAD51 assay is a recently developed functional assay for homologous recombination deficiency (HRD) that reflects real-time HRD status. We aimed to identify the applicability and predictive value of RAD51 immunohistochemical expression in pre- and post-neoadjuvant chemotherapy (NAC) samples of ovarian high-grade serous carcinoma (HGSC). Methods: We evaluated the immunohistochemical expression of RAD51/geminin/γH2AX in ovarian HGSC before and after NAC. Results: In pre-NAC tumors (n=51), 74.5% (39/51) showed at least 25% of γH2AX-positive tumor cells, suggesting endogenous DNA damage. The RAD51-high group (41.0%, 16/39) showed significantly worse progression-free survival (PFS) compared to the RAD51-low group (51.3%, 20/39) (p=0.032). In post-NAC tumors (n=50), the RAD51-high group (36.0%, 18/50) showed worse PFS (p=0.013) and tended to present worse overall survival (p=0.067) compared to the RAD51-low group (64.0%, 32/50). RAD51-high cases were more likely to progress than RAD51-low cases at both 6 months and 12 months (p=0.046 and p=0.019, respectively). Of 34 patients with matched pre- and post-NAC RAD51 results, 44% (15/34) of pre-NAC RAD51 results were changed in the post-NAC tissue, and the RAD51 high-to-high group showed the worst PFS, while the low-to-low group showed the best PFS (p=0.031). Conclusion: High RAD51 expression was significantly associated with worse PFS in HGSC, and post-NAC RAD51 status showed higher association than pre-NAC RAD51 status. Moreover, RAD51 status can be evaluated in a significant proportion of treatment-naïve HGSC samples. As RAD51 status dynamically changes, sequential follow-up of RAD51 status might reflect the biological behavior of HGSCs.
Jung Kyeongmin,Yoon Joohyun,Ahn Yeeun,Kim Soyeon,Shim Injeong,Ko Hyunwoong,Jung Sang-Hyuk,Kim Jaeyoung,Kim Hyejin,Lee Dong June,Cha Soojin,Lee Hyewon,Kim Beomsu,Cho Min Young,Cho Hyunbin,Kim Dan Say,K 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Irritability is a heritable core mental trait associated with several psychiatric illnesses. However, the genomic basis of irritability is unclear. Therefore, this study aimed to 1) identify the genetic variants associated with irritability and investigate the associated biological pathways, genes, and tissues as well as single-nucleotide polymorphism (SNP)-based heritability; 2) explore the relationships between irritability and various traits, including psychiatric disorders; and 3) identify additional and shared genetic variants for irritability and psychiatric disorders. We conducted a genome-wide association study (GWAS) using 379,506 European samples (105,975 cases and 273,531 controls) from the UK Biobank. We utilized various post-GWAS analyses, including linkage disequilibrium score regression, the bivariate causal mixture model (MiXeR), and conditional and conjunctional false discovery rate approaches. This GWAS identified 15 independent loci associated with irritability; the total SNP heritability estimate was 4.19%. Genetic correlations with psychiatric disorders were most pronounced for major depressive disorder (MDD) and bipolar II disorder (BD II). MiXeR analysis revealed polygenic overlap with schizophrenia (SCZ), bipolar I disorder (BD I), and MDD. Conditional false discovery rate analyses identified additional loci associated with SCZ (number [n] of additional SNPs = 105), BD I (n = 54), MDD (n = 107), and irritability (n = 157). Conjunctional false discovery rate analyses identified 85, 41, and 198 shared loci between irritability and SCZ, BD I, and MDD, respectively. Multiple genetic loci were associated with irritability and three main psychiatric disorders. Given that irritability is a cross-disorder trait, these findings may help to elucidate the genomics of psychiatric disorders.
( Kyeongmin Kim ),( Songmi Noh ),( Jae-ho Cheong ),( Hyunki Kim ) 대한소화기학회 2021 Gut and Liver Vol.15 No.5
Background/Aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Methods: In total, 1,158 cases of advanced GC were investigated using immunohistochemical staining and tissue microarrays for CDX-1 and -2 expression, and survival analysis was performed according to different histological and molecular subtypes. Results: Of the 915 GCs with CDX-1 expression, 163 (17.8%) were Epstein-Barr virus (EBV)- positive or mismatch repair deficient (MMR-d), and the remaining 752 (82.2%) were EBV-negative or MMR-proficient (MMR-p). Of the 1,008 GCs with CDX-2 expression, 177 (17.5%) were EBV-positive or MMR-d, and the remaining 831 (82.5%) were EBV-negative or MMR-p. In the EBV-positive and MMR-d groups, CDX expression had no relationship with patient outcomes. In the EBV-negative and MMR-p groups, 404 (53.7%) and 523 (62.9%) samples were positive for CDX-1 and CDX-2 expression, respectively. Survival analysis demonstrated that CDX-1 and CDX-2 expression in all patients was correlated with favorable outcomes in terms of overall survival (multivariate analysis; p=0.018 and p=0.028, respectively). In the subgroup analysis, CDX-1 expression and CDX-2 expression were associated with favorable outcomes in EBV-negative and MMR-p intestinal (p=0.015 and p=0.010), and mixed and diffuse-type (p=0.019 and p=0.042) GCs, respectively. Conclusions: The expression of CDX-1 and CDX-2 is a favorable prognostic factor in EBVnegative, MMR-p advanced GC. (Gut Liver 2021;15:694-704)
Kim, Kyeongmin,Nam, Ki-Ho,Lee, Jaekwan,Kim, Ho-Joong,Goh, Munju,Ku, Bon-Cheol,You, Nam-Ho Elsevier 2017 Carbon Vol.122 No.-
<P>We report an effective method for fabricating graphene-based multifunctional polyimide (PI) nano-composites via in situ polymerization, by the chemical defect-healing of pyridine functionalized reduced graphene oxide (H-Py-RGO). H-Py-RGO was successfully obtained through intramolecular cross-dehydrogenative coupling (ICDC). The mechanical properties, and thermal stability of the PI/H-Py-RGO nanocomposites were significantly improved compared with those of pristine PI film due to the restoration of the defect sites on the graphene surface, and the resulting high compatibility between the H-Py-RGO and the PI matrix. The tensile strength and modulus of the PI/H-Py-RGO nanocomposites with 1 wt% of added H-Py-RGO were increased by about 598% (883.5 MPa) and 535% (39.4 GPa) compared to those of pristine PI, respectively. Furthermore, 5 wt% H-Py-RGO loading resulted in a 91% reduction in the coefficient of thermal expansion (CTE) of the PI/H-Py-RGO nanocomposite. (C) 2017 Elsevier Ltd. All rights reserved.</P>