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( Jihyun An ),( Hyo Jeong Kang ),( Ju Hyun Shim ),( Gi-won Song ),( Gwang Hyun Choi ),( Han Chu Lee ),( Bora Oh ),( Naomi Park ),( Jihyun ),( Song Eunsil Yu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC). Methods: A total of 221 patients with HCC who underwent curative resection were included. Expression of Programmed-cell death ligand- 1 in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), Programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically. Results: Among the 221 patients, histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1% (n=71), 42.5% (n=94), 35.3% (n=78), and 14.9% (n=33), respectively. Multivariate logistic analyses revealed that male sex and tumor >5cm were variables related to iCTLA-4 positivity (odds ratios [ORs] 0.46 and 1.94 respectively; Ps<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (ORs 2.88 and 3.46, respectively; Ps<0.05). Microvascular invasion was significantly associated only with iPD-L1, whereas tPD-L1 was positively correlated with baseline elevation of serum alpha-fetoprotein (≥200 ng/ml) (ORs 2.24 and 2.45; Ps<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all Ps< 0.05), but not to time-to-recurrence or cancer-specific deaths (all Ps >0.05). Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively). Conclusions: Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.
Charcot Spinal Arthropathy without Any Risk Factors: A Case Report
Oh Jihyun,Kim Soo Yeon,Choe Woo Jin 대한말초신경학회 2020 The Nerve Vol.6 No.2
Charcot spinal arthropathy (CSA) is a rare progressive disorder that occurs after the loss of neuroprotective sensation and proprioceptive perception. Although its etiology is unclear, studies have suggested that it is primarily caused by spinal cord injuries, and diabetes mellitus, syringomyelia, tertiary syphilis, and Parkinson’s disease. Here, we describe a case of a 71-year-old woman with CSA without any risk factors. We report that CSA could occur without any prominent presentations or risk factors and may initially be misdiagnosed as pyogenic spondylitis.
Prognostic Molecular Signatures and S100P Expression in Resectable Hepatocellular Carcinoma
( Jihyun An ),( Hee Sang Hwang ),( Hyo Jeong Kang ),( Bora Oh ),( Yoo-Jin Oh ),( Ji-hye Oh ),( Wonkyung Kim ),( Deokhoon Kim ),( Chang Ohk Sung ),( Ju Hyun Shim ),( Eunsil Yu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Although hepatocellular carcinoma (HCC) is often recurred in patients undergoing curative hepatectomy, there are no faithful biomarkers to predict this undesirable events. Recent RNA-based efforts have developed valuable genetic markers or signatures prognostic of cancer outcomes. We aimed to discover molecular predictors of recurrence after HCC resection and to unveil the geno-molecular structure of the resected tumors in a series of Korean patients. Methods: Based on transcriptomic and genomic data of 206 HCC samples surgically resected at Asan Medical Center, we performed differential gene expression analysis to find quantitative markers associated with early recurrence; and used unsupervised clustering method to classify molecular subtypes. Public RNA-sequencing datasets from Japan (RIKEN) and China (GSE14520) were also used to validate original findings. Results: The results of differential gene expression analysis showed that S100P was identified as the highest-ranked overexpressed gene in HCCs with early recurrence within 2 years after surgery. This trend was also reproduced in immunohistochemical studies of the original and independent AMC cohorts. On multivariable competing risks modeling, S100P expression independently predicted HCC-specific mortality (adjusted hazard ratio, 1.09; P<0.05). Validation in the GSE14520 cohort and in vitro experiments confirmed the prognostic value of S100P for HCC recurrence. The c-statics of the S100P mRNA for predicting early recurrence confirmed that it had prognostic utility better than that of serum alpha-fetoprotein. We also identified five discrete molecular subtypes of HCC: the subtype with stem cell features (‘AMC-C4’) was associated with the worst prognosis both in our series and another two public datasets. S100P was most significantly upregulated in the subgroup C4 (P<0.05). Conclusions: We discovered a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and verified geno-molecular architecture of tumors affecting clinical outcomes particularly in Asian patients. These new insights into molecular mediators would help to tailor care for affected Asians.