PDGFR β-targeted TRAIL specifically induces apoptosis of activated hepatic stellate cells and ameliorates liver fibrosis

In this study, we found that platelet-derived growth factor receptor β (PDGFRβ) was co-expressed with DR5 in aHSCs. And the ZPDGFR β affibody with high affinity for PDGFR β could bind aHSCs and, thus, accumulate in the fibrotic liver. ZPDGFR β was fused to hTRAIL to produce the fusion protein Z-hTRAIL. Compared to hTRAIL, Z-hTRAIL showed greater in vitro cell binding and apoptosis-induction in aHSCs. In addition, Z-hTRAIL induced apoptosis of aHSCs but spared other normal liver cells. In vivo, Z-hTRAIL accumulated preferentially in fibrotic livers and exerted greater effects than hTRAIL in inducing aHSCs apoptosis and reducing extracellular matrix (ECM) deposition. These results demonstrated that the antihepatofibrotic effect of hTRAIL was improved by PDGFR β-targeted delivery. To enhance its pharmacokinetics, Z-hTRAIL was modified with 10 kDa polyethylene glycol (PEG), which significantly (30–40 times) prolonged its half-life. The PEGylated long-acting Z-hTRAIL was more potent than the native Z-hTRAIL in regressing liver fibrosis. These results su ggest that the aHSC-targeting and long-acting Z-hTRAIL might serve as a novel tool for antihepatofibrotic therapy.
Source: Apoptosis - Category: Molecular Biology Source Type: research

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An unexpected early increased incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported in HCV cirrhotic patients after treatment with direct-acting antivirals (DAA), but denied in other studies. To clarify this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients with or without history of HCC undergoing DAA therapy.
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
This article highlights key developments in antiviral/immunomodulatory therapy, the rationale for these approaches, and possible therapeutic regimens.
Source: Gastroenterology Clinics of North America - Category: Gastroenterology Authors: Source Type: research
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research
Authors: El-Daly UM, Saber MM, Abdellateif MS, Nassar HR, Namour AE, Ismail YM, Zekri AN Abstract BACKGROUND: Adipokines play an important role in the regulation of inflammation and tumor progression. AIM: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). METHODS: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
SummaryHepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers. The prognosis remains poor —the 5‑year overall-survival (OS) is 12–18%, all stages taken together. Systemic therapy has been limited to the use of tyrosine kinase inhibitors for more than a decade. Now immune therapy has also arrived in the field of systemic HCC treatment. Despite initial enthusiasm, the response rate to single agent immune checkpoint blockade (ICB) in HCC patients is approximately 15–20%. The immune tolerance of the liver and cirrhosis-associated immune dysfunction (CAID) may play a ...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
This study aims to investigate the effect of periodontal treatment for liver damage,P. gingivalis infection, and endotoxemia on patients with NAFLD.MethodsWe will include adult patients (20 –85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size,n = 40 patients; planned number of patients with outcome data,n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change...
Source: Trials - Category: Research Source Type: clinical trials
Abstract In spite of a decrease in the prevalence and incidence seen in recent years, chronic hepatitis B (CHB) still remains a major healthcare challenge, prevalent mostly in developing but also in developed regions. CHB is associated with significant morbidity and mortality, secondary to the complications of disease progression; cirrhosis and hepatocellular carcinoma (HCC). Historically, antiviral treatment has been restricted to patients with active hepatitis, established liver disease, fibrosis or cirrhosis and/or the risk of HCC development. As a result, patients with hepatitis B 'e' antigen (HBeAg) positive ...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
amvis Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geograph...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
CONCLUSION: Perisinusoidal macrophages appear to accumulate in NASH. It is possible that collections of macrophages are a response to chronic portal endotoxemia or lipotoxic activation of immuno-mediators. The persistent activation of these macrophages could lead to the chronic release of pro-inflammatory cytokines and contribute to chronic inflammation, fibrosis and cirrhosis leading to HCC. PMID: 32217109 [PubMed - as supplied by publisher]
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
AbstractThe optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are amenable to this option. Percutaneous radiofrequency interstitial thermal ablation (TA) proved to be effective in the treatment of unresectable HCC. Recent advances in laparoscopic ultrasound have improved the accuracy in detecting small intrahepatic HCC nodules missed by pre-operative imaging techniques. Our objective was to evaluate an operative combination of laparoscopic ultrasound with laparoscopic thermoablation (LTA) in the treatment of HCC not amenable to liver resection. The aim ...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
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