• Journal of Korean Neurosurgical Society
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• 제48권2호
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• pp.166-169
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• 2010

Spontaneous intracranial epidural hematoma (EDH) due to dural metastasis of hepatocellular carcinoma is very rare. A 53-year-old male patient with hepatocellular carcinoma, who was admitted to the department of oncology, was referred to department of neurosurgery because of sudden mental deterioration to semicoma with papillary anisocoria and decerebrate rigidity after transarterial chemoembolization for hepatoma. Brain computed tomography (CT) revealed large amount of acute EDH with severe midline shifting. An emergent craniotomy and evacuation of EDH was performed. Active bleeding from middle cranial fossa floor was identified. There showed osteolytic change on the middle fossa floor with friable mass-like lesion spreading on the overlying dura suggesting metastasis. Pathological examination revealed anaplastic cells with sinusoidal arrangement which probably led to spontaneous hemorrhage and formation of EDH. As a rare cause of spontaneous EDH, dural metastasis from malignancy should be considered.

• 대한한방내과학회지
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• 제34권4호
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• pp.478-483
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• 2013

Objectives : To observe the therapeutic effects of an oriental herbal prescription in a hepatocellular carcinoma patient with splenomegaly and pancytopenia. Methods : Modified Sipjeondaebo-tang was prescribed three times a day to a hepatocellular carcinoma patient with splenomegaly and pancytopenia. Laboratory tests were carried out regularly to observe the therapeutic effects of the oriental herbal prescription for pancytopenia. Results : When treated with modified Sipjeondaebo-tang including Cinnamomi Cortex, the levels of white blood cells, red blood cells, hemoglobin, and hematocrit increased. However, aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamic transpeptidase, total bilirubin, direct bilirubin levels also increased. Conclusions : Administering modified Sipjeondaebo-tang with Cinnamomi Cortex showed effect in improving pancytopenia but an increase in liver enzyme levels was also observed.

• 대한핵의학회지
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• 제17권1호
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• pp.85-87
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• 1983

$^{99m}Tc-Sulfur$ Colloid is concentrated in Kupffer cells of the liver, whereas the new biliary agents such as $^{99m}Tc-HIDA$ are processed by hepatic parenchymal cells. The distant metastatic lesiors in skull and lung of the primary hepatocellular carcinoma in 38-year old Korean male were detected with $^{99m}Tc-HIDA$ scintigraphy. The chest PA, skull bone X-ray and radionuclide scintigraphic studies are illustrated. This observation suggests that $^{99m}Tc-HIDA$ scintigraphy is useful for detection of distant metastases of primary hepatocellular carcinoma.

• Natural Product Sciences
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• 제19권2호
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• pp.155-159
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• 2013

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.

• Journal of Microbiology and Biotechnology
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• 제20권4호
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• pp.821-827
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• 2010

Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase the transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested, including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.

• 한국동물위생학회지
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• 제44권4호
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• pp.299-303
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• 2021

A captive male polar bear (Ursus maritimus) was found dead after a long-term anorexia at a Park Zoo in Republic of Korea. At necropsy, the liver lesion was prominent with hepatomegaly carrying a big mass and numerous small nodules in various sizes. The cut surface of the nodules was creamy white, firm, and solid with umbilicated appearance. Histologically, there was proliferation of hepatocellular neoplastic cells arranged in glandular-like (pseudoglandular) pattern and complete loss of hepatocellular arrangement. The immunoreactivity for neoplastic hepatocyte antigens was positive for hepatocyte paraffin 1, and negative for vimentin, cytokeratin 7 and 19, and carcinoembryonic antigen. Based on those diagnostic features, the neoplasia was diagnosed as hepatocellular carcinoma. To the author's knowledge, this is the first case report of hepatocellular carcinoma in the captive polar bear in Republic of Korea.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10085-10089
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• 2015

Background: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. Materials and Methods: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. Results: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. Conclusions: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3289-3294
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• 2016

Naringin, a bioflavonoid found in Citrus seeds, inhibits proliferation of cancer cells. The objectives of this study were to investigate the mode and mechanism(s) of hepatocellular carcinoma HepG2 cell death induced by naringin. The cytotoxicity of naringin towards HepG2 cells proved dose-dependent, measured by MTT assay. Naringin-treated HepG2 cells underwent apoptosis also in a concentration related manner, determined by annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) employing flow cytometry. Mitochondrial transmembrane potential (MTP) measured using 3,3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and flow cytometer was reduced concentration-dependently, which indicated influence on the mitochondrial signaling pathway. Caspase-3, -8 and -9 activities were enhanced as evidenced by colorimetric detection of para-nitroaniline tagged with a substrate for each caspase. Thus, the extrinsic and intrinsic pathways were linked in human naringin-treated HepG2 cell apoptosis. The expression levels of pro-apoptotic Bax and Bak proteins were increased whereas that of the anti-apoptotic Bcl-xL protein was decreased, confirming the involvement of the mitochondrial pathway by immunoblotting. There was an increased expression of truncated Bid (tBid), which indicated caspase-8 proteolysis activity in Bid cleavage as its substrate in the extrinsic pathway. In conclusion, naringin induces human hepatocellular carcinoma HepG2 cell apoptosis via mitochondria-mediated activation of caspase-9 and caspase-8-mediated proteolysis of Bid. Naringin anticancer activity warrants further investigation for application in medical treatment.

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

• BMB Reports
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• 제52권5호
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• pp.330-335
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• 2019

Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.