Novel<i>mfgl2</i>Antisense Plasmid Inhibits Murine<i>fgl2</i>Expression and Ameliorates Murine Hepatitis Virus Type 3-Induced Fulminant Hepatitis in BALB/cJ Mice

Zhu, Chuanlong; Sun, Yongming; Luo, Xiaoping; Yan, Weiming; Xi, Dong; Ning, Qin

doi:10.1089/hum.2006.17.589

Cited by 41 publications

(28 citation statements)

References 43 publications

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“…The observations that neutralizing Abs to mfgl2 prevent both fibrin deposition and death from MHV-3 infection support its role as a coagulant [17] . Recent studies have shown that inhibition of reticuloendothelial cell mfgl2 expression through the use of gene-targeted fgl2-deficient (fgl2-/-) mice or targeted fgl2 gene with antisense mfgl2 results in the prevention of MHV-3-induced fibrin deposition, liver injury, and death [2,18] . Our study shows that fgl2 prothrombinase was expressed in malignant tumor tissues including colon, breast, lung, gastric, esophageal, and cervical tissues from patients and in HCC nude mouse models.…”

Section: Discussionmentioning

confidence: 99%

Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ

Chen²,

Yan³

et al. 2008

WJG

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AIM:To examine the role of Fibrinogen-like protein 2 (fgl2)/fibroleukin in tumor development. Fgl2 has been reported to play a vital role in the pathogenesis in MHV-3 (mouse hepatitis virus) induced fulminant and severe hepatitis, spontaneous abortion, allo-and xenograft rejection by mediating "immune coagulation". METHODS: Tumor tissues from 133 patients with six types of distinct cancers and the animal tumor tissues from human hepatocellular carcinoma (HCC) model on nude mice (established from high metastasis HCC cell line MHCC97LM6) were obtained. RESULTS: Hfgl2 was detected in tumor tissues from 127 out of 133 patients as well as tumor tissues collected from human HCC nude mice.

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Section: Discussionmentioning

confidence: 99%

Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ

Chen²,

Yan³

et al. 2008

WJG

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“…Several studies have shown the importance of Fgl2/fibroleukin prothrombinase in both patients with HBV-ACLF and a fulminant hepatitis mouse model with murine hepatitis virus strain 3 (MHV-3) infection [12][13][14]. The mouse-fgl2 antisense administration remarkably increased the survival rate of mice with MHV-3-induced fulminant hepatitis [15,16]. A positive correlation was observed between human-fgl2 expression and the degree of liver injury, as indicated by the bilirubin levels.…”

Section: Pathophysiology Of Aclfmentioning

confidence: 99%

Definition of ACLF and inclusion criteria for extra-hepatic organ failure

2015

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A prominent characteristic of ACLF is rapid hepatic disease progression with subsequent extra-hepatic organ failure, manifesting as either hepatic coma or hepatorenal syndrome, which is associated with a high mortality rate in a short time. The APASL definition mainly emphasizes recognizing patients with hepatic failure. These patients may subsequently develop extra-hepatic multisystem organ failure leading to high mortality. It is therefore worthwhile to identify the short interim period between the development of liver failure and the onset of extra-hepatic organ failure, the potential therapeutic 'golden window.' Interventions during this period may prevent the development of complications and eventually change the course of the illness. Organ failure is suggested to be a central component of ACLF and may behave differently from chronic decompensated liver disease. Clear and practical criteria for the inclusion of organ failure are urgently needed so that patients with these life-threatening complications can be treated in a timely and appropriate manner. Recent studies suggested that the scoring systems evaluating organ failure [acute physiology, age and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores] work better than those addressing the severity of liver disease [Child-Pugh and model of end-stage liver disease (MELD) scores] in ACLF. However, a key problem remains that the former scoring systems are reflective of organ failure and not predictive, thus limiting their value as an early indication for intervention.

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“…Therefore, gene therapy for treating ALF is still in its infancy. Several studies report successful development of gene therapy for ALF in animals, mostly mice [257][258][259][260][261][262][263][264][265][266][267]. The main non viral vectors used in theses references are siRNA antisense oligonucleotides and Zinc-finger nucleases (ZFNs).…”

Section: Acute Liver Failurementioning

confidence: 99%

Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives

Domvri¹,

Porpodis²,

Koffa³

et al. 2012

CGT

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Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

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Novelmfgl2Antisense Plasmid Inhibits Murinefgl2Expression and Ameliorates Murine Hepatitis Virus Type 3-Induced Fulminant Hepatitis in BALB/cJ Mice

Cited by 41 publications

References 43 publications

Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ

Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ

Definition of ACLF and inclusion criteria for extra-hepatic organ failure

Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives

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