• Asian Pacific Journal of Cancer Prevention
• /
• 제14권2호
• /
• pp.915-921
• /
• 2013

Background: Hepatocellular carcinoma is one of the leading causes of mortalities worldwide. The search for new therapeutic targets is of utmost importance for improved treatment. Altered expression of HDAC1 in hepatocellular carcinoma (HCC) and its requirement for liver formation in zebrafish, suggest that it may regulate key events in liver carcinogenesis and organogenesis. However, molecular mechanisms of HDAC1 action in liver carcinogenesis are largely unknown. The present study was conducted to identify HDAC1 interacting proteins in HepG2 cells using modified SH-double-affinity purification coupled with liquid mass spectrophotemetery. Materials and Methods: HepG2 cells were transfected with a construct containing HDAC1 with a C-terminal strepIII-HA tag as bait. Bait proteins were confirmed to be expressed in HepG2 cells by western blotting and purified by double affinity columns and protein complexes for analysis on a Thermo LTQ Orbitrap XL using a C18 nano flow ESI liquid chromatography system. Results: There were 27 proteins which showed novel interactions with HDAC1 identified only in this study, while 14 were among the established interactors. Various subunits of T complex proteins (TCP1) and prefoldin proteins (PFDN) were identified as interacting partners that showed high affinity with HDAC1 in HepG2 cells. Conclusions: The double affinity purification method adopted in this study was very successful in terms of specificity and reproducibility. The novel HDAC1 complex identified in this study could be better therapeutic target for treatment of hepatocellular carcinoma.

• Journal of Yeungnam Medical Science
• /
• 제16권1호
• /
• pp.119-124
• /
• 1999

저자들은 우상복부 동통을 주소로 영남대학교 의과대학 부속병원 내과에 내원한 49세 여자 환자가 전산화 단총 촬영과 간동맥 조영술로 간세포암을 진단받은 후 간동맥 색전술로 치료받고 추적 관찰하던 중심초음파로 확인된 우심방 종괴를 진단받은 임상 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Journal of Ginseng Research
• /
• 제46권1호
• /
• pp.167-174
• /
• 2022

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.

• Journal of Hospice and Palliative Care
• /
• 제1권1호
• /
• pp.30-38
• /
• 1998

배경: 간암은 우리나라에 흔한 암으로 암등록 자료($1991{\sim}1992$)에 의하면 암발생율 3위, 암에 의한 사망 원인 중 2위를 차지한다. 암환자에서 환자의 생존기간을 예측하는 것은 환자의 진료에서 환자 자신이나 가족, 의료진에게 매우 중요하다고 생각된다. 본 연구는 간암 환자에서 환자의 생존 기간을 예측할 수 있는 예후 인자를 찾아 간암 환자의 진료에 도움이 되고자 하였다. 방법: 1995년 1월부터 6월 사이에 연세대학교 의과대학 부속 영동세브란스 병원에 간암으로 입원한 환자 91명(남자 73명, 여자 18명)을 대상으로 의무기록을 통해 입원 당시 임상적인 특성 28가지를 조사하였으며, 의무기록과 동사무소 기록을 가지고 1996년 7월 31일까지 추적하여 생존 여부를 확인하였다. Cox proportional hazard model을 이용하여 임상적 특성 중 사망위험도를 높이는 유의한 변수를 얻은 후 이를 예후 인자로 삼았다. 이것을 life regression analysis을 통해 예후 인자 각각이 존재할 때의 생존 기간 및 동반된 예후 인자 갯수에 따른 생존 기간을 예측하였다. 결과: 1) 원발성 간암 91명 중 남자가 73명(80.2%), 여자가 18명(19.8%)이며, 평균 연령은 $56.7{\pm}10.6$세이었고, 추적 불가능한 사람 16명을 제외한 75%명중 그 기간 사이에 사망한 사람이 57명(76%), 생존한 사람이 18명(24%)이었다. 2) 임상적인 특성 중 프로트롬빈 시간(prothrombin time) 40% 미만(RR: relative risk. 10.8), 체중감소(RR. 4.4), 고혈압의 과거력(RR. 3.2), 복수(RR. 2.8), 저칼슘혈증(RR. 2.5)인 경우가 환자의 사망위험도의 유의한 예후 인자였다(P<0.01). 3) 사망위험도 예후 인자 5가지가 모두 있는 경우는 생존 기간이 1.7일, 4가지만 있는 경우는 $4.2{\sim}10.0$일, 3가지만 있는 경우는 $10.4{\sim}41.9$일, 2가지만 있는 경우는 $29.5{\sim}118.1$일, 1가지만 있는 경우는 $124.0{\sim}296.6$일, 모두 없는 경우는 724.0일이었다. 결론: 간암 환자에서 프로트롬빈 시간의 연장(<40%), 체중감소 고혈압의 과거력, 복수, 저칼슘혈증(<8.7mg/dl) 등의 순으로 높은 사망위험도를 예측하게 하는 유의한 인자임을 알 수 있었고, 동반된 예후인자의 갯수로써 생존 기간을 예측할 수 있을 것으로 생각된다.

• 대한암한의학회지
• /
• 제20권1호
• /
• pp.55-79
• /
• 2015

Hepatocellular carcinoma(HCC) is the fifth most common cancer worldwide (fifth in male, seventh in female) and the third most common cause of cancer mortality. Since 2001, the various research group in the United States, Europe and Asia have published clinical practice guidelines for HCC. In Korea, a clinical practice guideline for HCC have been published by The Korean Liver Cancer Study Group in 2003, revised in 2009 and 2014. In China, oriental medicine clinical practice guideline have been published for the first time in 2014, and in the oriental medical profession of Korea, there is growing need for the guideline. This study will introduce the methods of diagnosis and the medical therapeutics which is commonly utilized for HCC in Korea, and existing korean medicine clinical practice guideline for Disease Analysis and Treatment(辨證論治) and herbal therapy of HCC. Further clinical research about various herbal medicines are needed to develop more advanced guideline of HCC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권16호
• /
• pp.7201-7204
• /
• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of Trans-arterial Chemo-Embolization (TACE) in treating Elderly patients with Hepatocellular Carcinoma (EHPC). Methods: Clinical studies evaluating the efficacy and safety of TACE on response and safety for patients with EHPC were identified by using a predefined search strategy. Pooled response rate of treatment were calculated. Results: In TACE based regimen, clinical studies which including patients with EHPC were considered eligible for the evaluation of response. And, in these TACE based treatments, pooled analysis suggested that, in all 288 patients whose response could be assessed, the pooled reponse rate was 29.5%(85/288) in TACE based treatment. The most commonly encountered TACE-related morbidity was liver function impairment. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in EHPC patients with TACE based treatments. Conclusion: This evidence based analysis suggests that TACE based treatments are associated with mild response rate and accepted toxicities for treating patients with EHPC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권16호
• /
• pp.6929-6934
• /
• 2015

Background: Real life management of hepatocellular carcinoma occasionally deviates from guidelines for recommended therapy. Aims: To evaluate how frequent this deviation happens in our center and assess its impact on outcome. Materials and Methods: The treatment of 770 patients (87% males, mean age 57.8 years) was analyzed and the effect of deviation on outcome over 36 months was examined. Results: Of Barcelona Clinic liver cancer stages 0 and A patients, 65.8% received resection, ablation, liver transplantation or transarterial chemoembolisation for unresectable tumors more than 5 cm in diameter, and 34.2% received treatment recommended for later stages. Of stage B patients, 62.2% received recommended therapy, 34.3% of patients received supportive therapy or sorafenib and 3.5% received upward treatment stage migration. Among stage C patients, 7.6% received sorafenib, and most (79.2%) were given supportive care. Deviation from recommended therapy occurred in 34.2%, 37.7%, and 92.4% in stages 0-A, B and C. Survival of stage 0-A patients who received downwards treatment stage migration was lower than those who received recommended treatment (p <0.001). Upward treatment stage migration in stages B, C and D did not improve survival compared to those who received recommended treatment. Conclusions: Deviation from recommended therapy had a negative impact on survival in Barcelona Clinic liver cancer stage A patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권9호
• /
• pp.4417-4421
• /
• 2012

Objective: The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta-analysis was performed to evaluate the relationship in detail. Methods: Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). Conclusion: The GSTT1 null genotype is associated with HCC susceptibility in Chinese.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3831-3836
• /
• 2013

Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

• Genomics & Informatics
• /
• 제2권3호
• /
• pp.134-141
• /
• 2004

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and a typical hypervascular tumor. Therefore, it is important to find factors related to angiogenesis in the process of HCC malignancy. In order to find angiogenesis-related factors in HCC, we used combined methods of in silico prediction and an experimental assay. We analyzed 1457 genes extracted from cDNA microarray of HCC patients by text-mining, sequence similarity search and domain analysis. As a result, we predicted that 16 genes were likely to be involved in angiogenesis and then the effects of these genes were confirmed by hypoxia response element(HRE)-luciferase assay. For instant, we classified osteopontin into a potent angiogenic factor and coagulation factor XII into a significant anti­angiogenic factor. Collectively, we suggest that using a combination of in silico prediction and experimental approaches, we can identify HCC-specific angiogenesis­related factors effectively and rapidly.