연속적으로 시행한 정유공장 근로자 건강검진에서 간기능검사 이상자의 유병률 변화와 위험인자에 대한 연구

학위논문(석사)--서울대학교 보건대학원 :환경보건학과 산업보건전공,2003.Maste

간성상세포에서 chenodeoxycholate에 의한 항자멸사 신호로서 cyclooxygenase-2와 Mcl-1의 발현 증가

Thesis(doctoral)--서울대학교 대학원 :의학과 분자유전체의학전공,2005.Thesis(doctoral)-

Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection

The majority of patients with hepatocellular carcinoma (HCC) undergoing curative resection experience tumor recurrence. To examine the association between preoperative serum sorbitol dehydrogenase (SORD), a liver-derived enzyme that reflects liver damage, and recurrence of HCC after curative resection, 92 patients were randomly selected who underwent curative resection for HCC between 2011 and 2012 from a prospective registry. Recurrence-free survival (RFS) was compared based on serum SORD levels. Cox proportional hazard models were used to investigate prognostic factors for RFS. During a median follow-up duration of 57.1 months, 43 patients experienced HCC recurrence. Patients with serum SORD ≥15 ng/mL (HR, 3.46; 95% CI, 1.76?6.81; p < 0.001) had worse RFS compared with patients with serum SORD <15 ng/mL. Serum AFP and SORD levels were two independent prognostic factors for RFS. When patients were stratified by baseline serum SORD and AFP levels, patients with serum AFP levels ≥400 ng/mL and serum SORD levels ≥15 ng/mL had a distinctly poor prognosis with the lowest RFS rates (HR, 22.08; 95% CI, 6.91?70.50; p < 0.001). Baseline serum SORD is an effective prognostic factor for HCC after resection. It may help guide patient selection for surgery, especially when combined with serum AFP levels

Liver-to-Spleen Volume Ratio Automatically Measured on CT Predicts Decompensation in Patients with B Viral Compensated Cirrhosis

Abstract Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosi

Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2 alpha/ATF4/CHOP axis in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids. Methods Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model. Results Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2 alpha/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism. Conclusions These results demonstrate the critical functional roles for the arginine metabolism-independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression

Kinetics of the neutrophil-lymphocyte ratio during PD-1 inhibition as a prognostic factor in advanced hepatocellular carcinoma

Background and Aims Programmed death 1 (PD-1) inhibitors have improved survival outcomes and produced durable responses in advanced hepatocellular carcinoma (HCC) for some patients. Here, we evaluated the relationship between the baseline and kinetics of the neutrophil-lymphocyte ratio (NLR) and clinical outcomes in nivolumab-treated HCC patients. Methods All consecutive HCC patients treated with nivolumab between July 2017 and June 2020 were screened for the eligibility. The NLRs were calculated before and at 2, 4 and 6 weeks after treatment. Survival outcomes were compared based on the baseline and kinetics of NLR. We additionally analysed the association of the baseline and dynamic changes in the NLR with hyperprogression (HPD). Results Among the 194 included cases, most patients were male (82.0%) and had a Child-Pugh Class A disease (70.6%). Patients with a baseline NLR >= 3 (hazard ratio [HR] 2.46; 95% CI 1.63-3.71) had a poorer overall survival than patients with baseline NLR < 3. During the treatment, the NLR increased rapidly in patients developing HPD, and only a Delta NLR at 4 weeks was predictive of HPD. The risk of HPD increased by 20% for every 20% increase in the Delta NLR at 4 weeks. Accordingly, an NLR increase at 4 weeks (HR 1.79; 95% CI 1.19-2.68) was associated with an increased risk of death, especially among patients with a baseline NLR >= 3. Conclusions The baseline and on-treatment kinetics for the NLR are effective prognostic indicators in nivolumab-treated patients with HCC. This may help to guide patient selection and on-treatment strategies for immunotherapies in advanced HCC