• 대한의생명과학회지
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• 제28권4호
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• pp.260-275
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• 2022

Sterile alpha motif (SAM) domains bind to various proteins, lipids, and RNAs. However, these domains have not yet been analyzed as prognostic biomarkers. In this study, SAM domain containing 13 (SAMD13), a member of the SAM domain, was evaluated to identify a novel prognostic biomarker in various human cancers, including hepatocellular carcinoma (HCC). Moreover, we identified a correlation between SAMD13 expression and immune cell infiltration in HCC. We performed bioinformatics analysis using online databases, such as Tumor Immune Estimation Resource, UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis2. SAMD13 expression in HCC samples was significantly higher than that in normal liver tissue; additionally, SAMD13 was higher in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher SAMD13 expression was also associated with poorer prognosis. SAMD13 expression positively correlated with CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. In the analysis of SAMD13 co-expression networks, positively related genes of SAMD13 were associated with a high hazard ratio in different types of cancer, including HCC. In biological function of SAMD13, SAMD13 mainly include spliceosome, ribosome biogenesis in eukaryote, ribosome, etc. These results suggest that SAMD13 may serve as a novel prognostic biomarker for HCC diagnosis and provide novel insights into tumor immunology in HCC.

• Fisheries and Aquatic Sciences
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• 제26권2호
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• pp.133-144
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• 2023

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC₅₀) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

• 한국자원식물학회지
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• 제36권3호
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• pp.207-218
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• 2023

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

• Genomics & Informatics
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• 제21권2호
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• pp.19.1-19.13
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• 2023

Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.333-344
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• 2023

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high fatality. It has yet to be reported whether circ-SNX27 can affect the progression of HCC. This study attempted to analyze circ-SNX27's precise role and underlying mechanisms in HCC. HCC cell lines and tumor specimens from HCC patients were analyzed using quantitative real-time PCR and Western blotting to quantify the expressions of circ-SNX27, miR-375, and ribophorin I (RPN1). Cell invasion and cell counting kit 8 experiments were conducted for the evaluation of HCC cell invasion and proliferation. Caspase-3 Activity Assay Kit was utilized to gauge the caspase-3 activity. Luciferase reporter and RNA immunoprecipitation assays were executed to ascertain the relationships among miR-375, circ-SNX27, and RPN1. To determine how circ-SNX27 knockdown affects the growth of HCC xenografts in vivo, tumor-bearing mouse models were constructed. Elevated expressions of circ-SNX27 and RPN1 as well as a reduced miR-375 expression were observed among HCC cells and HCC patient tumor specimens. Knocking-down circ-SNX27 in HCC cells abated their proliferative and invasive abilities but raised their caspase-3 activity. Moreover, the poor levels of circ-SNX27 inhibited HCC tumor growth among the mice. Circ-SNX27 enhanced RPN1 by competitively binding with miR-375. Silencing miR-375 in HCC cells promoted their malignant phenotypes. Nonetheless, the promotive effect of miR375 silencing was reversible via the knockdown of circ-SNX27 or RPN1. This research demonstrated that circ-SNX27 accelerated the progression of HCC by modulating the miR-375/RPN1 axis. This is indicative of circ-SNX27's potential as a target for the treatment of HCC.

• Journal of Digestive Cancer Research
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• 제4권1호
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• pp.21-28
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• 2016

간세포암종은 만성 간질환과 간경변증을 동반하는 경우가 많고, 예후에 종양 인자 이외에도 잔존 간 기능이 주요한 영향을 미친다. 또한, 간세포암종에 대한 고위험인자를 가진 경우 특정한 영상 소견(예: 고혈관성)을 보이면, 조직검사 없이도 비침습적인 진단이 가능하다. 다른 고형암에서와 마찬가지로 수술적 절제, 방사선치료, 항암치료 등의 치료가 시행되기도 하지만, 간세포암종에서만 이루어진다고도 할 수 있는 간이식, 경동맥화학색전술, 고주파열치료술과 같은 치료 방법들이 시행되기도 한다. 종양의 다양성, 치료 방법의 다양성, 사회적 여건(의료 보건 체계, 의료 자원의 가용성 등) 등을 반영하며 여러 간세포암종 가이드라인들이 발표되어 왔으며, 각 가이드라인들은 여러 측면에서 유사하면서도 서로 상이하기도 하다. 본고에서는 다음의 간세포암종 진료 가이드라인들을 살펴보고, 가이드라인들의 특징과 앞으로 가이드라인에서 다루어야 할 부분 등에 대하여 논하고자 한다.

• 대한영상의학회지
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• 제83권4호
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• pp.808-829
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• 2022

간세포암종은 역동적 조영증강 컴퓨터단층촬영이나 자기공명영상에서의 동맥기 조영증강 및 문맥기 또는 지연기 씻김현상과 같은 전형적 영상 소견을 기반으로 비침습적으로 진단할 수 있다. 그러나 일부 간세포암종은 비전형적인 영상 소견을 나타내기 때문에 영상의학과 의사는 진단에 있어 어려움에 직면하게 된다. 더욱이 동맥 문맥 단락, 혼합 간세포-담관암, 간내 담관암, 혈관종과 같이 많은 간세포암 유사 병변들이 다수 존재하여 영상을 통한 감별 진단에 난항을 겪는다. 초기 영상 검사에서 간세포암종과 이러한 유사 종양을 구별하는 능력은 적절한 관리 및 치료 결정에 중요하다. 따라서 본 임상화보에서는 간세포암종의 비전형적 영상 소견과 간세포암종을 모방하는 악성 및 양성 병변들의 영상 소견을 제시하고 감별 진단을 좁히는 데 도움이 될 수 있는 중요한 단서들에 대해 알아보고자 한다.

• Korean Journal of Radiology
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• 제23권7호
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• pp.697-719
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• 2022

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

• Korean Journal of Radiology
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• 제24권7호
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• pp.606-625
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• 2023

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

• BMB Reports
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• 제57권2호
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• pp.98-103
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• 2024

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.