Current Trends and Recent Advances in Diagnosis, Therapy, and Prevention of Hepatocellular Carcinoma

Wang, Chun‐Hsiang; Wey, Keh-Cherng; Mo, Lein-Ray; Chang, Kuo‐Kwan; Lin, Ruey‐Chang; Kuo, Jen-Juan

doi:10.7314/apjcp.2015.16.9.3595

Cited by 88 publications

(68 citation statements)

References 102 publications

(85 reference statements)

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“…Jia et al (2011) showed that UA was a PPAR-a agonist which regulated hepatic lipid metabolism and, therefore, significantly reduced intracellular triglyceride concentrations in hepatocytes. In addition, Wang et al (2015) and Sundaresan et al (2014) found that the combination of UA with artesunate or rosiglitazone exhibited the same pharmacological effect and free of toxic side effects. indicated that UA reversed high-fat diet-induced hepatic steatosis.…”

Section: Introductionmentioning

confidence: 97%

“…HCC is the fifth most common cancer in men and the seventh in women (El-Serag 2012), and the third leading cause of cancer-related death, only behind the lung and the stomach cancer (Ferlay et al 2010). Liver cancer is caused by many factors (Figure 1), including infection with HBV and HCV (Honda et al 2001;Goossens & Hoshida 2015;Wang et al 2015), nonalcoholic liver disease (Ekstedt et al 2006), exposure to aflatoxin B 1 and cadmium (Liu & Wu 2010;Satarug 2012), hemochromatosis, alpha-antitrypsin deficiency, autoimmune hepatitis, some porphyrias, and Wilson 0 s disease (ElSerag 2011). Moreover, alcohol, tobacco and obesity are also independent risk factors for HCC in patients, and they interact synergistically to increase the risk of HCC (Marrero et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

Huang

Chen

Ren

et al. 2016

Pharmaceutical Biology

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Context: Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists' attention. Objective: This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs. Methods: All of the data resources were derived from PubMed. By comparing the IC 50 values and analyzing the structure-activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism. Results: From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed. Conclusion: UA's anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds 45 and 53, can be used as potential drugs for the treatment of liver cancer. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

Huang

Chen

Ren

et al. 2016

Pharmaceutical Biology

View full text Add to dashboard Cite

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“…However, confounding variables have been not been well controlled. Because 23% of patients with NASH progress to liver cirrhosis with the possibility of HCC development [68] it is difficult to discern the single effect of obesity in the increased risk for HCC. Based on the associations between HCC, obesity, and NALFD, clinical studies evaluating the role of bariatric surgery in the prevention of HCC development are required.…”

Section: Effects On Hepatocellular Carcinomamentioning

confidence: 99%

The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome

et al. 2016

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“…Partial hepatectomy has been one of the most reliable methods of treatment and offers the hope of cure to those with early HCC 3. Unfortunately, the number of patients who can benefit is limited because of the advanced disease caused by intrahepatic metastasis at the time of diagnosis, and the associated viral hepatitis-induced cirrhosis 4.…”

Section: Introductionmentioning

confidence: 99%

Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability

Hsu¹,

Chen²,

Su³

et al. 2017

J. Cancer

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Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy. Therefore, we consider the targeting TPX2 could provide novel therapeutic strategies for cancer. In this study, increased TPX2 protein expression was present in 16 (42%) of 38 primary HCCs and was associated with advanced stage, distant metastatic HCCs and poor prognosis. Knockdown of TPX2 inhibited cancer cell growth and downregulation of cyclin A, cyclin E and CDK2 proteins. However, over-expressed EGFP-TPX2 protein enhanced the in vitro tumor spheroid formation and rescued the TPX2 depleted cell growth. Targeting TPX2 caused a rising impaired chromosomal instability resulting in multinuclearity, cell cycle progression arrest, apotosis, senescence and an increased polyploidy in cells. An image-cytometry analysis revealed cell cycle progression arrest after TPX2 inhibition. A correlation was observed between the downregulation of the protein levels of genes related to chromosomal segregation and spindle assembly checkpoint (securin, seprase, Aurora A, Aurora B, Cyclin B1, Cyclin B2, MPS1, BUB1, BUB3, MAD1 and MAD2) and increased cell ploidy, indicating mitotic progression failure and the loss of the balance of genomic instability. In vitro tumor spheroid assay and in vivo xenografts mouse model showed a therapeutic opportunity. Our findings indicate that targeting TPX2 lead to suppress tumorigenicity in liver cancer cells, suggesting that TPX2 is a potential target for anticancer therapy in HCC.

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Current Trends and Recent Advances in Diagnosis, Therapy, and Prevention of Hepatocellular Carcinoma

Cited by 88 publications

References 102 publications

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome

Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability

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