• BMB Reports
• /
• 제56권4호
• /
• pp.225-233
• /
• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• BMB Reports
• /
• 제55권10호
• /
• pp.506-511
• /
• 2022

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

• 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.

• Radiation Oncology Journal
• /
• 제35권2호
• /
• pp.185-188
• /
• 2017

Primary liver tumor, especially hepatocellular carcinoma (HCC), is a common cause of cancer death worldwide. The incidence is generally higher in Asian countries than in western countries. Carcinogenesis of HCC is often associated with hepatitis viral infections. Current standard treatment of HCC is surgical resection or transplantation in patients with early stage disease. However, the patient with advanced stage disease, surgical resection is often limited. Sorafenib or other treatment modalities are not so effective as well. We report a case of unusual radiation super-sensitivity in advanced stage HCC, and review the literature.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권2호
• /
• pp.1063-1063
• /
• 2014

• Molecules and Cells
• /
• 제45권8호
• /
• pp.550-563
• /
• 2022

Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.

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

• Advances in Traditional Medicine
• /
• 제7권4호
• /
• pp.436-440
• /
• 2007

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and a leading cause for death in Asia, where the major risk factors are chronic hepatitis B virus and hepatitis C virus infection. Because most HCC patients die within 3 to 6 months from the time of diagnosis, searching for a new treatment has become more urgent for HCC than other cancers because there is no existing effective systematic therapy. In Korea and Asia, traditional herbal medicine is frequently administered to patients with advanced HCC. We present a HCC case where complete regression was observed after taking herbal medicine. Since the specific mechanism is unknown, we cannot determine whether the herbal preparation had a direct effect on the regression of HCC. Nevertheless, this case provides us a reason and hope for further research.

• Journal of Yeungnam Medical Science
• /
• 제32권1호
• /
• pp.47-49
• /
• 2015

Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient's clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.

• Journal of Yeungnam Medical Science
• /
• 제29권1호
• /
• pp.48-53
• /
• 2012

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in South Korea. To decrease its mortality rate, its early detection is very important. Screening for HCC detection has been accepted as the management modality for patients with chronic liver disease. Reported herein is a case involving the marked rapid growth of HCC detected at an advanced stage in a screening test with a 3 months interval. A 49-year-old male patient with chronic hepatitis B was admitted to the hospital due to a liver mass detected on CT scan. The patient underwent a first CT scan 3 months earlier, and no tumor was detected. Follow-up CT scan was performed and showed a 9.1 cm HCC with portal vein thrombosis. Percutaneous liver biopsy was performed, and the diagnosis of hepatocellular carcinoma was confirmed. In the pertinent guidelines, the recommended screening interval for HCC is 6-12 months, but the screening interval and additional diagnostic methods should be considered due to the variation in the HCC growth rate according to the patient's clinical characteristics.