Emerging Strategies for the Management of Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000367981

Cited by 4 publications

(4 citation statements)

References 27 publications

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“… 1 More than 80% of cases of hepatocellular carcinoma (HCC) occur in Asia and are linked to the hepatitis B virus (HBV) epidemic. 2 Notable differences exist between Asian and Western regions in guidelines on surveillance, diagnosis, and management of hepatobiliary tumors, which reflect differences in the epidemiological and etiological factors underlying the disease as well as socioeconomic factors due to the large disease burden in Asia. The most common adult malignant liver tumors are HCC, metastases to the liver, fibrolamellar HCC, epithelioid hemangioendothelioma (EHE), and angiosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Hepatobiliary Tumors: Update on Diagnosis and Management

Kabbach

Assi

Bolotin

et al. 2015

JCTH

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Tumors of the liver and biliary tree, mainly hepatocellular carcinoma and cholangiocarcinoma, are the second leading cause of cancer related death worldwide and the sixth leading cause of cancer related death among men in developed countries. Recent developments in biomarkers and imaging modalities have enhanced early detection and accurate diagnosis of these highly fatal malignancies. These advances include serological testing, micro-ribonucleic acids, fluorescence in situ hybridization, contrast-enhanced ultrasound, and hepatobiliary-phase magnetic resonance imaging. In addition, there have been major developments in the surgical and nonsurgical management of these tumors, including expansion of the liver transplantation criteria, new locoregional treatments, and molecularly targeted therapies. In this article, we review various types of hepatobiliary tumors and discuss new developments in their diagnosis and management.

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Section: Introductionmentioning

confidence: 99%

Hepatobiliary Tumors: Update on Diagnosis and Management

Kabbach

Assi

Bolotin

et al. 2015

JCTH

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“…Because HCC patients are usually diagnosed at an advanced stage, their survival rate is still very low [3] . Early diagnosis and treatment are the key to improving the survival time of patients with liver cancer [4] . Therefore, the identi cation of new liver cancer diagnostic markers is very important.…”

Section: Introductionmentioning

confidence: 99%

Tumor Cells Talk to Normal Cells Through Exosomes to Rebuild the Tumor Microenvironment

Wang

Sun

et al. 2021

Preprint

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BackgroundExosomes play a key role in the growth of normal cells and various diseases such as cancer. Tumor exosomes regulate the connection between normal cells and cancer cells in the tumor microenvironment, thereby promoting the growth and invasion of cancer cells.MethodsWe used HepG2 cells silenced by shRNA targeting GPC3, LO2 and HepG2 cells treated with different concentrations of GPC3. We determined the effects of GPC3 on cell proliferation, apoptosis and invasion using CCK8, flow cytometry and Transwell, and Western blotting Method to determine the expression of GPC3/WNT3A/β-catenin.HepG2 exosomes (Exo) and HepG2 exosomes treated with shRNA targeting GPC3 (sh-GPC3-Exo) were used to treat LO2 and HepG2 cells separately. Cell proliferation was measured by CCK8 experiment.The cell cycle and apoptosis were measured by flow cytometry. The cell invasion ability was analyzed by Transwell. The expression of GPC3/WNT3A/β-catenin signal protein was determined by Western blotting.ResultsThis is the first study to prove the bidirectional regulation of GPC3 between normal cells and liver cancer cells. After treatment of LO2 cells and HepG2 cells with GPC3, the LO2 cell cycle was blocked in the G0/G1 phase, while inhibiting cell proliferation, promoting cell apoptosis and invasion, but for HepG2 cells it appeared to promote proliferation.Silencing GPC3 can inhibit the proliferation and invasion, and promote cell apoptosis of HepG2. Subsequent experiments found that the expression of GPC3 was found in both LO2 and HepG2 exosomes, and the expression of GPC3 in HepG2 exosomes was significantly higher than that in LO2 exosomes. These suggest that GPC3 in exosomes has the potential to become a biomarker of HCC.In addition, HepG2 exosomes (Exo) can inhibit the proliferation of LO2 cells and promote apoptosis and invasion, which is consistent with the effect of GPC3 treatment. We also found that GPC3 is contained in HepG2 exosomes (shGPC3-Exo) that have silenced GPC3, which has the same effect on LO2 cells as HepG2 exosomes (Exo), but the degree of influence is reduced. shGPC3-Exo showed a promoting effect on the proliferation of HepG2 cells, but inhibited cell invasion. Therefore, GPC3 in Exo plays a role in the proliferation of LO2 cells and HepG2 cells. Further studies have shown that GPC3 in liver cancer exosomes regulates the proliferation, apoptosis and invasion of LO2 and HepG2 cells through the Wnt /β-catenin signaling pathway.ConclusionGPC3 in the exosomes of liver cancer cells inhibits the proliferation of normal liver cells and promotes apoptosis by activating the Wnt/β-catenin signaling pathway, promotes the proliferation of liver cancer cells, and assists the occurrence and development of HCC.

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“…HCC patients are usually diagnosed at an advanced stage and their survival rate is very low [3] . Early diagnosis and treatment are the key to improving the survival time of patients with liver cancer [4] . Thus, the identi cation of novel diagnostic markers for liver cancer is crucial.…”

Section: Introductionmentioning

confidence: 99%

Title: GPC3 in the Exosomes from Hepatocellular Carcinoma HepG2 Cells

Wang

Sun

et al. 2021

Preprint

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Background Exosomes play an important role in regulating the growth in normal and abnormal cells. Exosomes secreted from tumor cells are also involved in regulating the growth behaviors of normal cells and tumor cells. Methods HepG2 cells, LO2 and HepG2 cells with GPC3 knocked down using shRNA (HepG2-shGPC3), were treated with different concentrations of GPC3. The effects of different concentrations of GPC3 on cell growth and apoptosis were determined using CCK8 and flow cytometry. HepG2 exosomes (Exo) and exosomes of HepG2 cells with GPC3 knocked down using shRNA (shGPC3-Exo) were used to treat LO2 and HepG2 cells separately. Cell growth was measured by CCK8 kit. The cell cycle and apoptosis were measured by flow cytometry. The expression of GPC3/WNT3A/β-catenin signal protein was determined by Western blotting. Results We found GPC3 has a two-way regulation between normal cells and HCC cells, which is the innovation of this research. After treating LO2 cells and HepG2 cells with GPC3, the LO2 cell cycle was blocked in the G0/G1 phase, while cell growth was inhibited and apoptosis was promoted; however, it appeared to promote the growth of HepG2 cells. Knocking down GPC3 can inhibit the growth and promote cell apoptosis of HepG2. In subsequent experiments, we found that GPC3 was expressed in both LO2 and HepG2 exosomes, and the expression of GPC3 in HepG2 exosomes is significantly higher than that of LO2 exosomes. These results suggested that GPC3 in exosomes has the potential to become a biomarker of HCC. In addition, HepG2 exosomes (Exo) can inhibit the growth of LO2 cells and promote apoptosis, which is consistent with the effect of GPC3 treatment. Further, we found that GPC3 in shGPC3-Exo had the same effect on LO2 cells as HepG2 exosomes (Exo), but the degree of influence was reduced. shGPC3-Exo showed a promoting effect on the growth of HepG2 cells. Therefore, GPC3 in exosomes plays a role in the growth of LO2 cells and HepG2 cells. Further studies have shown that GPC3 in liver cancer exosomes regulates the proliferation, apoptosis of LO2 and HepG2 cells through the Wnt /β-catenin signaling pathway. Conclusion GPC3 in the exosomes of liver cancer cells inhibits the growth of normal liver cells and promotes apoptosis by activating the Wnt/β-catenin signaling pathway, and assists the occurrence and development of HCC.

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Emerging Strategies for the Management of Hepatocellular Carcinoma

Cited by 4 publications

References 27 publications

Hepatobiliary Tumors: Update on Diagnosis and Management

Hepatobiliary Tumors: Update on Diagnosis and Management

Tumor Cells Talk to Normal Cells Through Exosomes to Rebuild the Tumor Microenvironment

Title: GPC3 in the Exosomes from Hepatocellular Carcinoma HepG2 Cells

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