Risk Assessment and Suitability of Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma with or without Impaired Hepatic Function

( A Reum Choe ),( Joon Yeul Nam ),( Jeong-hoon Lee ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung-hwan Yoon ),( Hyo-cheol Kim ),( Jin Wook Chung ),( Hye Ah Lee ),( Tae Hun Kim ),( Kwon Yoo ),( Hwi Young Kim 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The decision of initiation or repetition of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) still remains challenging, especially in patients with impaired hepatic function. The aims: were (i) to identify prognosticators in patients undergoing TACE, (ii) to develop a risk prediction model, and (iii) to investigate the outcomes according to the scores in patients undergoing TACE with or without impaired hepatic functional reserve. Methods: A total of 597 consecutive patients were enrolled who underwent TACE as their initial treatment for unresectable HCC without macrovascular invasion or extrahepatic spread from two university hospitals in Korea. The entire cohort was randomly divided into two groups with 7:3 ratio to derive and validate a risk prediction model. Tumor- and liver function-related risk factors for overall survival were explored using Cox proportional-hazards model. Results: Median age was 64.0 years, and 474 patients were male (79.4%). Etiologies of underlying liver diseases were mostly viral (HBV, 386 [64.7%]; HCV, n=82 [13.7%]) or alcoholic (n=60, 10.1%). Multiple tumors were found in 379 patients (63.6%), and median maximal tumor diameter was 3.2 cm (interquartile range [IQR], 2.2-5.2). Median alpha-fetoprotein (AFP) was 16.0 ng/mL (IQR, 6.0-153.0). Child-Pugh classes were A in 479 patients (80.2%) and B in 118 (19.8%), respectively. Hepatoma arterial-embolisation prognostic (HAP) score D and modified HAP score D were in 95 patients (15.9%) and in 43 (7.2%), respectively. Albumin-bilirubin (ALBI) grades were 1 in 204 patients (34.2%), 2 in 363 (60.8%) and 3 in 30 (5.0%), respectively. Multivariable Cox model with stepwise selection identified the following four relevant prognostic factors: ALBI grade (hazards ratio [HR], 2.299; 95% confidence interval[CI], 1.694-3.119; P<0.001); AFP (HR, 1.583; 95% CI, 1.164-2.154; P=0.003); maximal tumor diameter (HR, 1.704; 95% CI, 1.424- 2.038; P<0.001); tumor response (HR, 1.915; 95% CI, 1.431- 2.563; P<0.001). A scoring system (ASAR) based on these risk factors was developed by assigning points as shown in Table 1. C-index for the prediction of overall survival (OS) was 0.73 (95% CI, 0.70-0.77). The 1-year and 3-year survival rates were 92.1% and 69.7% in patients with ASAR<4, and 52.4% and 23.7% in those with ASAR≥4, respectively (P<0.001). The 1-year and 3-year survival rates in subgroups according to the hepatic function and ASAR scores were as follows (all P<0.001): i) 93.6% and 73.3% in Child-Pugh class A and ASAR <4; ii) 54.4% and 29.0% in Child-Pugh A and ASAR≥4,; iii) 85.2% and 53.4% in Child-Pugh B and ASAR <4; iv) 46.3% and 6.6% in Child-Pugh B and ASAR ≥4. However, no significant differences were observed in Child-Pugh class B patients using HAP score (P=0.523) or modified HAP score (P=0.298). Conclusions: A novel scoring system (ASAR) may be helpful in patient selection undergoing TACE for unresectable HCC, especially those with impaired hepatic function.

Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT.

Park, A-Reum,Oh, Daeyoung,Lim, So-Hee,Choi, Jeonghoon,Moon, Jeonghee,Yu, Dae-Yeol,Park, Sung Goo,Heisterkamp, Nora,Kim, Eunjoon,Myung, Pyung-Keun,Lee, Jae-Ran Cambridge University Press 2012 Journal of cell science Vol.125 No.19

<P>Dendritic arborization is important for neuronal development as well as the formation of neural circuits. Rac1 is a member of the Rho GTPase family that serve as regulators of neuronal development. Breakpoint cluster region protein (BCR) is a Rac1 GTPase-activating protein that is abundantly expressed in the central nervous system. Here, we show that BCR plays a key role in neuronal development. Dendritic arborization and actin polymerization were attenuated by overexpression of BCR in hippocampal neurons. Knockdown of BCR using specific shRNAs increased the dendritic arborization as well as actin polymerization. The number of dendrites in null mutant BCR(-/-) mice was considerably increased compared with that in wild-type mice. We found that the function of the BCR GTPase-activating domain could be modulated by protein tyrosine phosphatase receptor T (PTPRT), which is expressed principally in the brain. We demonstrate that tyrosine 177 of BCR was the main target of PTPRT and the BCR mutant mimicking dephosphorylation of tyrosine 177 alleviated the attenuation of dendritic arborization. Additionally the attenuated dendritic arborization found upon BCR overexpression was relieved upon co-expression of PTPRT. When PTPRT was knocked down by a specific shRNA, the dendritic arborization was significantly reduced. The activity of the BCR GTPase-activating domain was modulated by means of conversions between the intra- and inter-molecular interactions, which are finely regulated through the dephosphorylation of a specific tyrosine residue by PTPRT. We thus show conclusively that BCR is a novel substrate of PTPRT and that BCR is involved in the regulation of neuronal development via control of the BCR GTPase-activating domain function by PTPRT.</P>

The Antifungal Activity of Bee Venom against Dermatophytes

( A Reum Yu ),( Jum Ji Kim ),( Gil Sun Park ),( Su Mi Oh ),( Chung Sub Han ),( Mi Young Lee ) 한국응용생명화학회 2012 Journal of Applied Biological Chemistry (J. Appl. Vol.55 No.1

The antifungal activities of the bee venom against Trichophyton mentagrophytes and Trichophyton rubrum were determined by using modified broth dilution assay. The most common dermatophytes, named T. mentagrophytes and T. rubrum, were known to cause a variety of cutaneous infections in humans and animals. The bee venom exhibited prominent antifungal activities against the two dermatophytes tested in this investigation. Moreover, the antifungal activities of the bee venom were much stronger than that of fluconazole, one of the commercial antifungal drugs used in the treatment and prevention of superficial and systemic fungal infections. The result suggests that bee venom could be developed as a natural antifungal drug.

식품 가공기술과 포장기술을 활용한 가정대용식 제품 개발

유아름(A-Reum Yu),최윤상(Yun-Sang Choi),홍정선(Jung Sun Hong),최희돈(Hee-Don Choi) 한국식품과학회 2017 식품과학과 산업 Vol.50 No.3

In order to secure competitiveness of the home meal replacement (HMR) industry from a long-term perspective, development of packaging and processing technologies must be achieved. The development of technology that can secure freshness, nutrition, and taste but secures the shelf life is the key to the future growth of HMR. The future of HMR can be considered in terms of nutrition, environment and safety. From the nutritional point of view, it is expected that development of healthy HMR such as low-salt, low-sugar, low-fat, and high fiber and premium HMR with functional ingredient enhanced, and personalized HMR for silver, infant and patients will be done. And it is expected that development of HMR utilizing environmentally friendly food or local food, development of energy reduction and environmentally friendly disinfection technology, development of environmentally friendly packaging material, and providing information on HMR preparation using QR code and RFID from the environmental and safe point of view.

종자 추출물의 RAW 264.7 세포에 대한 면역증강 효과

유아름(A-Reum Yu),박호영(Ho-Young Park),김윤숙(Yun-Sook Kim),하상근(Sang-Keun Ha),홍희도(Hee-Do Hong),최희돈(Hee-Don Choi) 한국식품영양과학회 2012 한국식품영양과학회지 Vol.41 No.12

9 종류의 종자 중 대식세포를 자극하여 NO 생성능이 높은 메밀, 민들레, 봉선화, 해바라기 4종의 종자를 선별하였다. 선별된 4종의 종자 추출물이 RAW 264.7 세포를 활성화시켜 면역을 증진시키는 효과를 알아보기 위해 RAW 264.7 세포와 T세포를 이용하여 면역 활성능 관련 지표를 조사하였다. 4종의 종자를 대식세포에 처리하였을 때 면역 활성의 지표가 되는 NO, cytokine(TNF-α, IL-1β, IL-6, IL-10)의 생성이 추출물을 처리하지 않은 대조군에 비해 증가되었고, Molt-4 세포에 처리하였을 때 대조군에 비해 세포가 증식되었다. 이와 같은 결과는 종자 추출물을 섭취하였을 때 외부로부터의 어떠한 자극이 있기 이전에 체내의 모든 조직에 분포하면서 1차적으로 이물질을 제거하는 대식세포를 자극하여 cytokine 등의 면역매개물질을 생성하여 인체의 비특이적 면역반응을 증가시킴으로써 항원을 공격, 제거하는 등의 작용을 통해 자연 면역반응에 있어 중요한 역할을 할 수 있을 것으로 판단된다. In this study, the immuno-enhancing activity of seed extracts were studied on the macrophage cell lines. We examined the effect of nine seed extracts on nitric oxide (NO) production in RAW 264.7 cells and selected four highly-effective seed candidates (Fagopyrum esculentum, Taraxacum platycarpum, Impatiens balsamina, Helianthus annuus) for further immune-related studies. The effects of the four seed extracts on the production of immune-related cytokines in the RAW 264.7 macrophage cell line and proliferation of Molt-4 as a T cell line were investigated. The secretion of NO from the RAW 264.7 cells was increased up to 39 μM by adding the seed extracts (25 μg/mL) compared to the control. Also, the secretion of tumor necrosis factor-alpha (TNF-α) was also increased up to 32 times by adding the seed extracts (25 μg/mL). Secretion of cytokines such as interleukin- 1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) was also increased and induced the proliferation of T cells compared to the control. In conclusion, these results suggest that four seed extracts provide beneficial immuno-enhancing effects for human health.

Suppressive effect of electrolyzed reduced water on the paraben-induced DNA damage in human dermal fibroblast cells

유아름(Yu, A-Reum),류근걸(Ryoo Kun-kul),이미영(Lee Mi-Young) 한국산학기술학회 2010 한국산학기술학회논문지 Vol.11 No.11

파라벤은 낮은 독성과 안전성으로 인해 화장품 보존제로 널리 사용되어 왔다. 그러나 최근 파라벤의 잠재적 독성이 알려지고 있다. 본 연구에서는 환원전리수가 널리 사용되는 메틸파라벤에 의한 사람 피부섬유아 세포의 DNA 산화손상을 억제할 수 있는지 알아보기 위하여 코멧어세이를 실시하였다. 그 결과 흥미롭게도 환원전리수는 파라벤에 의한 피부섬유아세포 DNA의 산화손상을 억제할 수 있었다. Parabens have been widely used as preservatives in cosmetics due to the presumed low toxicity and long history of safe use. However, recent studies have shown the potent toxicity of parabens. In order to know if electrolyzed reduced water could suppress the oxidative DNA damage of HDF cell by methylparaben, one of the frequently used parabens, we performed comet assay in this study. As a result, interestingly, electrolyzed reduced water could suppress methylparaben-induced oxidative DNA damage in HDF cells.

Sword Bean Pods (Canavalia gladiata) Inhibit Adipogenesis in Mice with High Fat Diet-Induced Obesity

Kyung-A Hwang,Hye-Jeong Hwang,Yu-Jin Hwang,Pu Reum Im,Jeong Yeon Im 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Obesity is a chronic disorder that is a significant risk factor for diabetes, malignancy, and other chronic diseases. Obesity treatment methods include lifestyle modifications such as diet and exercise. However, it is not easy to change the lifestyle, so drug treatment and surgery are selected. In particular, drug treatment has been constantly developed to date, but the effect of the drug is insufficient or side effects are caused by long-term use. Therefore, we need to focus on the development of anti-obesity drugs based on natural food materials. As such, we propose that natural food materials for safe and effective obesity treatment should be discovered and developed. Thus, we evaluated the anti-obesity effect using the sword bean pods(SBP; Canavalia gladiata) that were recently registered as food materials and lack scientific research on various physiological activities. As a result, SBP confirmed the anti-obesity effect by reducing production of obesity major factor. These results suggest that SBP is a material with potential effects on anti-obesity, and it is expected that it can be developed as a functional material for health functional food in the future.

경기 일부지역 유아의 식생활관련 지식, 자아효능감, 식품선호도 및 식행동 실태

이아름(A Reum Lee),유예리(Ye Lee Yu),김혜진(Hye Jin Kim),김경아(Kyung A Kim),김경원(Kyung Won Kim) 대한지역사회영양학회 2016 대한지역사회영양학회지 Vol.21 No.3

발아 전후 보리 당단백질 추출물의 영양성분 및 면역 활성 변화

유아름(A-Reum Yu),박호영(Ho-Young Park),홍희도(Hee-Do Hong),민진영(Jin-Young Min),최희돈(Hee-Don Choi) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.4

발아 전후 보리 당단백질 추출물에 대한 영양성분 변화와 RAW 264.7 세포에 처리 후 생성하는 산화질소 II와 사이토카인(인터류킨-6, 종양괴사인자-α) 양을 측정하여 면역 증진 효능을 예측하였다. 보리의 발아가 진행됨에 따라 당단백질 추출물의 단백질과 지방질 함량은 감소하고 총당 함량은 증가하는 추세를 확인하였다. 주요 중성당은 아라비노스, 포도당, 자일로스이며 발아함에 따라 6탄당인 포도당은 감소한 반면, 5탄당인 아라비노스와 자일로스는 증가하였다. 아미노산 함량은 GEB에 비해 24-GEGB와 48-GEGB에서 각각 1.03, 1.24배 증가하였다. 면역 활성을 측정하기 위하여 RAW 264.7 세포에 24-GEGB와 48-GEGB를 처리한 결과 GEB에 비해 더 높은 산화질소 II와 사이토카인(인터류킨-6, 종양괴사인자-α)을 생성하였다. 결론적으로, 보리 종자가 발아하면 종자 내 단백질, 지방질 및 당질 등의 영양성분 조성이 변하고, 그 결과 발아보리 당단백질 추출물은 외부 침입에 대해 1차적으로 방어하는 대식세포를 자극하여 세포에 독성을 미치지 않는 범위의 면역매개물질 생성하여 면역 증진 효과를 기대할 수 있는 것으로 판단된다. In the present study, we investigated changes in the nutritional components of pre- and post-germinated barley seeds and also investigated their immune-enhancing effects such as production of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α on the RAW 264.7 macrophage cell line. Protein and total sugar contents increased slightly with increase in germination time. The major neutral sugars of germinated balrey seeds were arabinose, glucose, and xylose. Glucose content decreased during germination, whereas arabinose and xylose contents increased during germination. Amino acid contents of barley germinated for 24 and 48 hours increased 1.03-fold and 1.24-fold, respectively, compared to that of pre-germinated barley. Moreover, RAW 264.7 macrophages stimulated with barley germinated for 24 and 48 hours showed higher production of NO, IL-6, and TNF-α compared to that observed in pre-germinated barley. The results of the present study indicate that germinated barley may have immune-enhancing effects derived from its ability to activate RAW 264.7 macrophages, which play a major role in innate immunity.

생약 추출물의 RAW 264.7 세포를 이용한 면역증강 효과

유아름(A-Reum Yu),박호영(Ho-Young Park),최인욱(In-Wook Choi),박용곤(Yong-Kon Park),홍희도(Hee-Do Hong),최희돈(Hee-Don Choi) 한국식품영양과학회 2012 한국식품영양과학회지 Vol.41 No.11

본 연구에서 12종류의 생약재 중 대식세포를 활성화시켜 NO 생성능이 높은 감초, 건지황, 당귀, 도라지, 목천료 5종의 생약재를 선별하였다. 선별된 5종의 생약추출물의 성분을 실험한 결과 단백질, 다당 물질의 함유량이 감초(58.1%), 건지황(90.4%), 당귀(87.4%), 도라지(41.3%), 목천료(85.7%)로 대부분 고분자 물질이 함유되어 있는 것으로 나타났다. 생약추출물이 대식세포를 활성화시켜 면역을 증진시키는 효과를 알아보기 위해 RAW 264.7세포와 T세포를 이용하여 면역활성능 관련 지표를 측정한 결과 5종의 생약재를 RAW 264.7 세포에 처리하였을 때 면역 활성의 지표가 되는 NO, cytokine(TNF-α, IL-1β, IL-6, IL-10)의 생성이 추출물을 처리하지 않은 대조군에 비해 증가되었고, Molt-4 세포에 처리하였을 때 대조군에 비해 세포가 증식되었다. 이와 같은 결과는 고분자 물질인 단백질과 다당으로 이루어진 생약추출물을 섭취 시 외부로부터 침입한 항원이 들어오기 이전에 면역세포를 자극하여 활성을 증가시켜 면역매개물질을 생성하여 인체의 비특이적 면역반응을 증가시킴으로써 항원을 공격, 제거하는 등의 작용을 통해 자연 면역반응에 있어 중요한 역할을 할 수 있을 것으로 보인다. Medicinal herbs have long been used as a remedy for diverse diseases in Asia owing to their various pharmacological effect. In this study, the immuno-enhancing activity of medicinal herbs was investigated using macrophage cell lines. Specifically, we examined the effects of extracts of twelve medicinal herbs on nitric oxide (NO) production in RAW 264.7 cells, and selected five that were highly effective (Glycyrrhiza glabra, Rehmannia glutinosa, Angelica gigas, Platycodon grandflorum, and Actinidia polygama) for further immune related studies. The effects of extracts from five theses medicinal herbs, which were mainly composed of polysaccharides and proteins on the production of immune-related cytokines in the RAW 264.7 macrophage cell line and the Molt-4 T cell line were investigated. The extracts of all investigated medicinal herbs increased the production of NO and cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10). Additionally, they slightly increased the proliferation of T-cells when compared to the control. Overall, the result of this study suggests that the five medicinal herb extracts investigated herein are useful natural immune enhancing agents.