Advances in Management of Hepatocellular Carcinoma

Abstract

Background & aims: Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Here we describe a low-density lipoprotein based nanoparticle that acts as a transporter for unesterified DHA (LDL-DHA) and demonstrates selective cytotoxicity toward HCC cells. We investigated the ability of LDL-DHA to reduce growth of orthotopic hepatomas in rats.Methods: AxC-Irish (ACI) rats were given intrahepatic injections of rat hepatoma cells (H4IIE); 24 tumor-bearing rats (mean tumor diameter, 1 cm) were subject to a single hepatic artery injection of LDL nanoparticles (2 mg/kg) loaded with DHA (LDL-DHA), triolein (LDL-TO), or sham surgery controls. Tumor growth was measured by magnetic resonance imaging and other methods; tumor, liver, and serum samples were collected and assessed by histochemical, immunofluorescence, biochemical, and immunoblot analyses.Results: Three days after administration of LDL-TO or sham surgery, the control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL-DHA had smaller, pale tumors that were devoid of vascular supply and >80% of the tumor tissue was necrotic. Four to 6 days after injection of LDL-DHA, the tumors were 3-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury. Injection of LDL-DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly down-regulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in the surrounding liver was not disrupted.Conclusion: LDL-DHA nanoparticle selectively kills hepatoma cells and reduces growth of orthotopic liver tumors in rats. It induces tumor-specific necrosis by selectively disrupting redox balance within the cancer cell.ABSTRACT 2

The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis

“…So far, there is an absence of high-quality evidence to prove the optimal interval between two TACE treatments. Shortening the interval between two TACE treatments may result in hepatic dysfunction or liver failure (Intaraprasong et al, 2016). Meanwhile, there is a greater chance of liver failure after repeating TACE treatments (Raoul et al, 2011).…”

Interferon alpha antagonizes the anti-hepatoma activity of the oncolytic virus M1 by stimulating anti-viral immunity

“…The 12 commonly used combination treatments were: LAM+ADV, ETV+ADV, ETV+TDF, SOF+TEL+DCV, ETV+IFN, TDF+IFN, RBV+IFN, SOF+RBV+IFN, DCV+RBV+IFN, TEL+ RBV+IFN and DCV+TEL+RBV+IFN [14, 15]. The data show that all regimens with IFN-α abrogated the oncolytic effect of M1 in Huh-7 and sk-hep-1 cells, but not in Hep-3B cells (Figure 2E).…”

“…IFN-α is often used in conjunction with other anti-viral drugs, so we also examined the possible effects of multi-drug combinations, with or without IFN-α, on the oncolytic activity of M1. The 12 commonly used combination treatments were: LAM+ADV, ETV+ADV, ETV+TDF, SOF+TEL+DCV, ETV+IFN, TDF+IFN, RBV+IFN, SOF+RBV+IFN, DCV+RBV+IFN, TEL+ RBV+IFN and DCV+TEL+RBV+IFN [ 14 , 15 ]. The data show that all regimens with IFN-α abrogated the oncolytic effect of M1 in Huh-7 and sk-hep-1 cells, but not in Hep-3B cells (Figure 2E ).…”

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“…So far, there is an absence of high-quality evidence to prove the optimal interval between two TACE treatments. Shortening the interval between two TACE treatments may result in hepatic dysfunction or liver failure (Intaraprasong et al, 2016). Meanwhile, there is a greater chance of liver failure after repeating TACE treatments (Raoul et al, 2011).…”