Pathologic Predictive Factors for Late Recurrence of Hepatocellular Carcinoma in Chronic Hepatitis

( Ji Hae Nahm ),( Hye Sun Lee ),( Ju-seog Lee ),( Haeryoung Kim ),( Jeong Eun Yoo ),( Young Nyun Park ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Hepatocellular carcinoma (HCC) has poor outcome, with a cumulative 5-year recurrence rate > 70% even after curative resection. Late recurrence (> 2 years after resection) is regarded as de novo HCC that typically develops from chronic liver disease through a multistep process. It was recently reported that the molecular genetic profile of the background liver rather than HCC itself predicts late HCC recurrence. In this study, we developed and validated a predictive model based on histopathologic features and immunohistochemical marker expression, which is practically useful. Methods: The training (402 cases) and validation (243 cases) cohorts of patients who underwent curative resection for HCC were independently established. Histopathologic features including lobular and porto-periportal inflammatory activity, fibrosis stage, and small or large liver cell changes were evaluated. To evaluate changes in protein expression of genes related to late recurrence, 95 non-tumor liver tissue samples from HCC patients were screened by reverse phase microarray analysis. Expression of phosphorylated signal transducer and activator of transcription (pSTAT)3, phosphorylated extracellular signal-regulated kinase (pERK)1/2, plasminogen activator inhibitor (PAI)-1, and spleen tyrosine kinase (SYK) was detected by immunohistochemical staining. A predictive model was constructed using independent parameters selected by multiple Cox proportional hazards regression analysis. The same analysis was performed in the validation cohort to verify the reliability of the model for predicting late recurrence. Results: In the training cohort, late recurrence of HCC was observed in 74 (18%) patients, with a median follow-up period of 82 months. Late recurrence in HCC patients was correlated with cirrhosis (fibrosis stage 4), small and large liver cell changes, and upregulation of pSTAT3, pERK1/2, and PAI- 1 levels (P<0.05 for all). Cirrhosis (odds ratio [OR] = 2.0; 95% confidence interval [CI]: 1.2-3.2), moderate or severe lobular activity (OR = 21.4; 95% CI: 4.4-104.2), and expression of one or more of pSTAT3, pERK1/2, and SYK (OR = 6.0; 95% CI: 2.0-17.5) as detected by immunohistochemical staining were independently associated with late HCC recurrence according to the multivariate Cox regression analysis (P<0.05 for all). A nomogram was based on these variables to predict late recurrence of HCC, and Harrell’s c index was 0.701 (95% CI: 0.64- 0.75). In the validation cohort, 47 patients (19%) showed late recurrence with a median follow-up period of 56 months and the Harrell’s c index was 0.719 (95% CI: 0.64-0.79) for predicting late recurrence of HCC, demonstrating that the predictive model is highly reliable. Conclusions: Our predictive model based on cirrhosis (fibrosis stage 4), moderate or severe lobular activity, and expression of one or more of pSTAT3, pERK1/2, and SYK in non-tumoral tissue of background liver is useful for predicting late recurrence of HCC after curative resection.

간세포암종의 병리진단에 대한 최신 지견

남지해 ( Ji Hae Nahm ),박영년 ( Young Nyun Park ) 대한소화기학회 2021 대한소화기학회지 Vol.78 No.5

Hepatocellular carcinoma (HCC) has heterogeneous molecular and pathological features and biological behavior. Large-scale genetic studies of HCC were accumulated, and a pathological-molecular classification of HCC was proposed. Approximately 35% of HCCs can be classified into distinct histopathological subtypes according to their molecular characteristics. Among recently identified subtypes, macrotrabecular massive HCC, neutrophil-rich HCC, vessels encapsulating tumor clusters HCC, and progenitor phenotype HCC (HCC with CK19 expression) are associated with a poor prognosis, whereas the lymphocyte-rich HCC subtype is related to a better prognosis. This review provides up-to-date knowledge on the pathological diagnosis of HCC according to the updated World Health Organization Classification of Digestive System Tumors 5th ed. (Korean J Gastroenterol 2021;78:268-283)

LP9M80-H Isolated from Liriope platyphylla Could Help Alleviate Diabetic Symptoms via the Regulation of Glucose and Lipid Concentration

Ji Eun Kim(김지은),In Sik Hwang(황인식),Jun Seo Goo(구준서),So Hee Nam(남소희),Sun Il Choi(최선일),Hae Ryun Lee(이혜련),Young Ju Lee(이영주),Yoon Han Kim(김윤환),Se Jin Park(박세진),Nahm-Su Kim(김남수),Young Hwan Choi(최영환),Dae You 한국생명과학회 2012 생명과학회지 Vol.22 No.5

LP9M80-H는 맥문동(Liriope platyphylla)으로부터 메탄올과 헥산을 이용하여 추출한 새로운 추출물로서 ICR 마우스에서 인슐린분비를 촉진하며, 간과 뇌 조직에서 인슐린 신호경로를 활성화시키는 것으로 알려져 있다. 본 연구에 서는 LP9M80-H가 당뇨와 비만의 치료에 미치는 효과를 조사하기 위하여, OLETF 모델동물에 LP9M80-H를 2주간 투여한 후 당뇨와 비만과 관련된 주요인자의 변화를 관찰하였다. 비록 체중은 두 집단간에 차이가 없었으나 복부 지방량은 vehicle 투여군보다 LP9M80-H 투여군에서 적었다. 또한, 혈중 포도당농도는 LP9M80-H를 투여한 OLETF랫드가 대조군에 비하여 약간 낮았으나 인슐린의 농도는 유의적으로 크게 증가하였다. 혈청 내 3가지 주요 지질의 농도는 LP9M80-H를 투여한 OLETF 랫드에서 유의적으로 감소하였고, 지방의 산화를 촉진하는 아디포넥틴의 농도도 LP9M80-H를 투여한 OLETF 랫드에서 감소하였다. 더불어, 체내에 분비된 인슐린이 표적장기에 미치는 영향을 관찰하기 위하여 간조직에서 인슐린 수용체와 인슐린 수용체기질(IRS)의 발현을 관찰하였으며, 이러한 2가지 단백질은 LP9M80-H를 투여한 OLETF 랫드에서 vehicle 투여군에 비해 유의미하게 감소하였다. 또한, 인슐린 신호경로의 다운스트림에 위치하는 포도당 수송체 중에서 Glut-2와 Glut-3 발현은 LP9M80-H를 투여한 OLETF 랫드에서 유의미하게 감소하는 반면에, Glut-4 발현은 일정하게 유지되었다. 따라서 이러한 결과는 LP9M80-H는 포도당항상성과 지질농도의 조절을 통하여 당뇨와 비만의 증상을 완화시키는데 기여할 것으로 사료된다. It was reported that the novel compounds (LP9M80-H) of Liriope platyphylla regulate glucose transporter (Glut) biosynthesis by activating the insulin-signaling pathway in the liver and brain of ICR mice. To investigate the therapeutic effects of LP9M80-H on the pathology of diabetes and obesity, alterations of key factors related to symptoms were analyzed in the Otsuka Long Evans Tokushima Fatty (OLETF) rats treated with LP9M80-H for 2 weeks. The abdominal fat masses in the LP9M80-H-treated group were lower than the vehicle-treated group, although there was no difference in body weight between the two groups. Additionally, when compared to the vehicle-treated group, LP9M80-H treatment induced a significant decrease in glucose levels and an increase in the insulin concentration in the blood of OLETF rats. A high level of insulin protein was also detected in pancreatic β cells of LP9M80-H-treated OLETF rats. A significant reduction in the concentration of lipids and adiponectin was detected only in LP9M80-H-treated OLETF rats. Furthermore, the expression of insulin receptor β and the insulin receptor substrate (IRS) was dramatically decreased in LP9M80-H-treated OLETF rats compared to the vehicle-treated group. Of the glucose transporters located downstream of the insulin-signaling pathway, glucose transporters (Glut) -2 and -3 were significantly decreased in LP9M80-H-treated OLETF rats, while the level of Glut-4 was maintained under all conditions. Therefore, these results suggest that LP9M80-H may contribute to relieving symptoms of diabetes and obesity through glucose homeostasis and regulation of lipid concentration.

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors

Lee, Ji-Ho,Kim, Su-Chin,Choi, Hyunna,Jung, Chang-Gyu,Ban, Ga-Young,Shin, Yoo Seob,Nahm, Dong-Ho,Park, Hae-Sim,Ye, Young-Min KOREAN ACADEMY OF MEDICAL SCIENCE 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.7

<P>Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79–5.39; <I>P</I> < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21–2.72; <I>P</I> = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to <I>Dermatophagoides pteronyssinus</I> and <I>Dermatophagoides farinae</I> did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.</P>

Therapeutic Effect of Omalizumab in Severe Asthma: A Real-World Study in Korea

Lee, Ji-Ho,Lee, Hyun Young,Jung, Chang-Gyu,Ban, Ga-Young,Shin, Yoo Seob,Ye, Young-Min,Nahm, Dong-Ho,Park, Hae-Sim The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.2

<P><B>Purpose</B></P><P>Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, has proved to be effective for the treatment of severe asthma. However, there is no direct evidence of effectiveness of omalizumab in Korean patients with severe asthma. We sought to evaluate the real-world effectiveness of omalizumab in Korean adult patients suffering from severe asthma and to identify predictors of favorable response.</P><P><B>Methods</B></P><P>A retrospective analysis of electrical medical records was performed on severe allergic asthmatic patients with omalizumab treatment group (OT group) for more than 6 months between March 2008 and February 2016. Propensity score matching was applied to define the standardized treatment control group (STC group) treated without omalizumab. Asthma-related outcomes were compared between the 2 groups, and analyzed before and after omalizumab use in the OT group. Responders to treatment were defined as patients showing >50% reduction in asthma exacerbations and/or systemic steroid requirement during the outcome period.</P><P><B>Results</B></P><P>One hundred twenty-four patients with severe asthma (62 in the OT group; 62 in the STC group) were enrolled in the study. Proportion of patients having the reduction of asthma exacerbation (53.2% vs 35.5%, <I>P</I>=0.015) and the rate of responders (67.7% vs 41.9%, <I>P</I>=0.007) were significantly higher in the OT group than in the STC group. Significant reductions were noted in asthma exacerbation (<I>P</I>=0.006), hospitalization (<I>P</I>=0.009), hospitalization days (<I>P</I>=0.006), systemic corticosteroid requirements (<I>P</I>=0.027), and sputum eosinophil count (<I>P</I>=0.031) in OT group compared with STC group. There were no significant differences in changes of forced expiratory volume in the 1 second (FEV1) levels between the 2 groups. No predictors of responders were found for omalizumab treatment.</P><P><B>Conclusions</B></P><P>Omalizumab can reduce exacerbations/hospitalization/systemic steroid burst in Korean adult patients with severe asthma.</P>

A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen Immunotherapy With House Dust Mites for Allergic Rhinitis

Lee, Ji-Ho,Kim, Su-Chin,Choi, Hyunna,Jung, Chang-Gyu,Ban, Ga-Young,Shin, Yoo Seob,Nahm, Dong-Ho,Park, Hae-Sim,Ye, Young-Min The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.1

<P><B>Purpose</B></P><P>House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM.</P><P><B>Methods</B></P><P>We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes.</P><P><B>Results</B></P><P>The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; <I>P</I>=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; <I>P</I>=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; <I>P</I><0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed.</P><P><B>Conclusions</B></P><P>SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients.</P>

Properties of Acid Phosphatase from Pear

Mi-Hae Shin,Yur-Yang Yoon,Gi-Nahm Kim,Ji-Eun Kil,Inshik Park 한국식품과학회 1994 Food Science and Biotechnology Vol.3 No.1

Properties of Acid Phosphatase from Pear

Shin,Mi-Hae,Yoon,Yur-Yang,Kim,Gi-Nahm,Kil,Ji-Eun,Park,Inshik 東亞大學校附設遺傳工學硏究所 1995 遺傳工學硏究 Vol.- No.2

Acid phosphatase from pear has been partially purified by ammonium sulfate fractionation, Sephacryl S-200 gel filtration, CM-Sepharose CL-6B, and DEAE-Sephacel ion exchange chromatography. The optimum pH and temperature for the enzyme reaction with p-nitrophenyl phosphate as a substrate were pH 5.5 and 55℃, respectively. The enzyme was most stable at pH 7.0. It was inactivated completely when incubated at 70℃ for 20 min. The preferred substrate for the enzyme was identified as p-nitrophenyl phosphate, while 5´-GMP and 5´-IMP were poor substrates for the enzyme. The Michaelis-Menten constant of the enzyme with p-nitrophenyl phosphate was 1.53 mM. The enzyme activity was inhibited by molybdate, metavanadate, fluoride ions and L-phenylalanine.

Budd-Chiari syndrome with multiple large regenerative nodules

Kim, Haeryoung,Nahm, Ji Hae,Park, Young Nyun The Korean Association for the Study of the Liver 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.1

Liver Pathology : Budd-Chiari syndrome with multiple large regenerative nodules

( Haer Young Kim ),( Ji Hae Nahm ),( Young Nyun Park ) 대한간학회 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.1