• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.172.2-173
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• 2003

3-Alkoxy-6-allylthiopyridazine derivatives showed the strongest protective effect against oxidative stress and their anticancer effect determined on the growth of SK-Hep-l hepatocellular carcinomar cells. The allythio group as a pharmacologically active group was introduced into pyridazine nucleus and a substituent such as halogen or alkoxy was also introduced into paraposition of allylthio group. Five kinds of 3-alkoxy-6-allylthiopyridazine derivatives were synthesized and their chemoprotective activities examined in rats exposed to aflatoxin $B_1$-toxicant. (omitted)

• Molecules and Cells
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• 제44권8호
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• pp.569-579
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• 2021

Cyclase-associated protein 2 (CAP2) has been addressed as a candidate biomarker in various cancer types. Previously, we have shown that CAP2 is expressed during multi-step hepatocarcinogenesis; however, its underlying mechanisms in liver cancer cells are not fully elucidated yet. Here, we demonstrated that endoplasmic reticulum (ER) stress induced CAP2 expression, and which promoted migration and invasion of liver cancer cells. We also found that the ER stress-induced CAP2 expression is mediated through activation of protein kinase C epsilon (PKCε) and the promotor binding of activating transcription factor 2 (ATF2). In addition, we further demonstrated that CAP2 expression promoted epithelial-mesenchymal transition (EMT) through activation of Rac1 and ERK. In conclusion, we suggest that ER stress induces CAP2 expression promoting EMT in liver cancer cells. Our results shed light on the novel functions of CAP2 in the metastatic process of liver cancer cells.

• Journal of Chest Surgery
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• 제55권2호
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• pp.171-173
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• 2022

A 65-year-old man underwent right trisectionectomy of the liver and reconstruction of the chest wall and diaphragm with a 2-mm Gore-Tex membrane due to recurrent hepatocellular carcinoma. After 3 years, the Gore-Tex membrane in the diaphragm migrated to the abdominal cavity and perforated the colon. We report a rare complication of a Gore-Tex membrane after diaphragm repair.

• Molecules and Cells
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• 제45권10호
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• pp.761-761
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• 2022

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.299-310
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• 2023

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

• Journal of Ginseng Research
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• 제48권2호
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• pp.122-128
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• 2024

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.

• 한국식품영양과학회지
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• 제44권2호
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• pp.200-207
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• 2015

본 연구에서 우리는 갈색거저리 유충 추출물의 암세포 선택적인 세포독성 활성을 암세포주를 대상으로 하는 in vitro 및 in vivo 실험으로 증명하였다. 먼저 갈색거저리 유충의 에탄올 추출물은 정상세포라 할 수 있는 primary hepatocyte에 대한 독성은 미미하였으나 암세포주들에 대한 세포독성과 함께 다른 정상세포인 primary cardiomyocyte에 대한 독성도 가지고 있었다. 에탄올 추출물을 hexane, butanol, ethyl acetate, 물을 이용하여 liquid-liquid partition으로 추가로 분획, 구성물질들을 분리하였고 이들 분획물 중에서 hexane 분획물은 다양한 암세포들(PC3, 22Rv1, HeLa, PLC/PRF5, HepG2, Hep3B, SK-HEP-1, HCT116, NCI-H460, MDA-MB231, SKOV3)에 대한 독성을 유지하면서 cardiomyocyte에 대한 독성이 상당히 줄어들었다. 0.4 mg/mL 에탄올 추출물이 cardiomyocyte를 대부분 죽이는 독성을 보였으나 동일조건에서 hexane 분획물은 약 20% 정도의 세포독성만을 보여주어 독성이 상당히 감소된 것을 확인하였다. 이렇게 비특이적인 세포독성이 물질분리 및 분획을 함으로써 줄어들 수 있다는 것을 확인하였다. 두 번째로 hexane과 ethyl acetate 분획물들이 아포토시스, 세포괴사, 오토파지와 같은 대표적인 세포죽음 기전들을 활성화시킬 수 있는 것으로 확인하였다. 더불어 hexane 분획물의 세포죽음 유도활성은 현재 임상에서 널리 처방되고 있는 항암물질들과 함께 간암세포주에 처리되었을 때 항암활성을 증대시킬 수 있는 것으로 확인하였다. 이와 같은 실험 결과를 바탕으로 갈색거저리 유충 추출물들이 단독으로 혹은 다른 세포독성 약물들과 함께 항암활성을 가질 수 있음을 확인하였다. 마지막으로 hexane 분획물의 항암활성을 in vivo xenograft 실험쥐 모델에서 확인하였는데, 간암세포주인 SK-HEP-1을 이식한 실험쥐에서 hexane 분획물을 15일간 복강주사 하였을 때 종양의 성장을 뚜렷하게 억제하는 것을 확인하였고, 앞선 정상세포에 대한 제한적인 영향과 일치하게 몸무게의 감소 등 부작용이라 할 수 있는 증상은 확인되지 않았다. 이상의 결과들을 종합하면 갈색거저리 유충 추출물의 항암활성을 in vitro와 in vivo에서 확인할 수 있었으며, 새로운 항암활성을 가지는 물질 발굴을 위해 추가적인 분획과 물질 분석이 필요하다고 사료된다.

• 핵의학기술
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• 제14권2호
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• pp.155-158
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• 2010

$^{99m}Tc$-macroaggregated albumin (MAA) 를 이용한 간동맥 관류스캔(hepatic arterial perfusion scintigraphy, HAPS)은 간종양의 경동맥 화학요법을 위해 종양의 관류 등을 평가하는데 매우 유용한 방법으로 알려져 있다. 본 연구는 간암환자(hepatocellular carcinoma, HCC)에서의 정상 간 조직에 대한 간세포암의 상대적인 혈류량을 평가하여 종양의 형태, 크기와 lung shunting, tumor to normal ratio (T/N ratio)를 측정하여 HAPS 의 유용성을 알아보고자 하였다. 2009년 6월부터 2009년 9월까지 본원에서 HCC 진단을 받은 환자 7명(평균 64세, 남자 6명, 여자 1명)을 대상으로 하였다. $^{99m}Tc$-MAA 5 mCi를 간 동맥 내에 위치된 카테타를 통하여 주입하고 20분경과 후 HAPS를 시행하였다. 환자의 흉부와 복부가 포함되게 시야를 잡고 anterior, posterior, both lateral 상을 얻고 SPECT를 시행하였다. liver, tumor, lung의 ROI를 그리고 각각의 count와 count/pixel (mean value) 를 구하여 lung shunting, T/N ratio를 구하였다. anterior, posterior 상에서 얻어진 ROI에서 얻어진 tumor size는 2.0~10.8 cm(평균 3.75 cm), liver size 는 8.8~18.5 cm(평균14.6 cm)였다. total tumor와 total normal의 mean value를 통해 얻은 T/N ratio의 범위는 2.41~5.76(평균 3.8)였다. total lung과 total liver의 counts를 통해 얻은 lung shunting의 범위는 3.14~13.92%(평균 6.77%)였다. $^{99m}Tc$-MAA를 이용한 HAPS 는 정상 간 조직에 비해 간세포암내에 강한 방사능 섭취를 보였으며 종양의 크기, 위치 및 T/N ratio를 통한 정량적 관류 평가를 할 수 있었다. 또한 폐 섭취 빈도는 종양 내 동정맥 단락을 추정할 수 있어 간동맥 동위원소 치료 전 단락 유무를 평가할 수 있다는 점이 유용하게 활용될 수 있을 것이다. 따라서 $^{99m}Tc$-MAA를 이용한 HAPS는 간암의 평가 및 치료를 결정 할 수 있는 유용한 검사법으로 이용될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7367-7369
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• 2013

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9487-9494
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• 2014

Background: The size of a hepatic neoplasm is critical for staging, prognosis and selection of appropriate treatment. Our study aimed to compare the radiological size of solid hepatocellular carcinoma (HCC) masses on magnetic resonance imaging (MRI) with the pathological size in a Chinese population, and to elucidate discrepancies. Materials and Methods: A total of 178 consecutive patients diagnosed with HCC who underwent curative hepatic resection after enhanced MRI between July 2010 and October 2013 were retrospectively identified and analyzed. Pathological data of the whole removed tumors wereassessed and differences between radiological and pathological tumor size were identified. All patients were restaged using a modified Tumor-Node-Metastasis (TNM) staging system postoperatively according to the maximum diameter alteration. The lesions were classified as hypo-staged, iso-staged or hyper-staged for qualitative assessment. In the quantitative analysis, the relative pre and postoperative tumor size contrast ratio ($%{\Delta}size$) was also computed according to size intervals. In addition, the relationship between radiological and pathological tumor diameter variation and histologic grade was analyzed. Results: Pathological examination showed 85 (47.8%) patients were overestimated, 82 (46.1%) patients underestimated, while accurate measurement by MRI was found in 11 (6.2%) patients. Among the total subjects, 14 (7.9%) patients were hypo-staged and 15 (8.4%) were hyper-staged post-operatively. Accuracy of MRI for calculation and characterized staging was related to the lesion size, ranging from 83.1% to 87.4% (<2cm to ${\geq}5cm$, p=0.328) and from 62.5% to 89.1% (cT1 to cT4, p=0.006), respectively. Overall, MRI misjudged pathological size by 6.0 mm (p=0.588 ), and the greatest difference was observed in tumors <2cm (3.6 mm, $%{\Delta}size=16.9%$, p=0.028). No statistically significant difference was observed for moderately differentiated HCC (5.5mm, p=0.781). However, for well differentiated and poorly differentiated cases, radiographic tumor maximum diameter was significantly larger than the pathological maximum diameter by 3.15 mm and underestimated by 4.51 mm, respectively (p=0.034 and 0.020). Conclusions: A preoperative HCC tumor size measurement using MRI can provide relatively acceptable accuracy but may give rise to discrepancy in tumors in a certain size range or histologic grade. In pathological well differentiated subjects, the pathological tumor size was significantly overestimated, but underestimated in poorly differentiated HCC. The difference between radiological and pathological tumor size was greatest for tumors <2 cm. For some HCC patients, the size difference may have implications for the decision of resection, transplantation, ablation, or arterially directed therapy, and should be considered in staging or selecting the appropriate treatment tactics.