Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attempts have been made by conventional gene therapy to suppress hepatic fibrogenesis, but potential oncogenic activity may prevent its clinical use. Recently, a novel major approach has been developed for resolution of liver fibrosis and cirrhosis: inactivation of hepatic stellate cells (HSC) using the endogenous expressing gene, which could mediate the homeostatic adaptation of liver. Cytoglobin (Cygb), originally identified in cultured rat HSC, is in a new class of heme containing proteins known as the hexacoordinate globin superfamily. These proteins exhibit peroxidase activity against hydrogen peroxides and lipid hydroperoxides. Considerable attention has been focused on the potential benefits of use of Cygb in fibrosis therapy, as up-regulation of Cygb expression could reduce oxidant stress, suppress HSC differentiation to a myofibroblast-like phenotype and eventually prevent the progress of liver fibrosis. Cygb has also been found to be a candidate tumor suppressor gene that might provide a new option for cancer gene therapy. In this review we systematically analyze the potential of Cygb as a prospective gene medicine for curing fibrosis, cancer, and other diseases such as diabetes. The molecular structure, regulation and subcellular location of Cygb are reviewed as well.
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PMID:Cytoglobin: a novel potential gene medicine for fibrosis and cancer therapy. 1869 Oct 24

Huanglian is a commonly used Chinese medicinal herb in the ancient and the present. It has a history of 2000 years in clinical application, having the efficacy of "Clear away heat and remove dampness, purge the sthenic fire and eliminate toxic materials", therefore can be used for various diseases or syndromes in types of dampness-heat and fire-toxin by internal or external use. Compound prescriptions mainly based on Huanglian or prescribed by Huanglian, such as Puji Xiaodu Yin, Huanglian Jiedu Tang, Zhusha Anshen Wan, Qingying Tang, Angong Niuhuang Wan, Niuhuang Qingxin Wan, Jiaotai Wan, Huanglian Ejiao Tang, Zuojin Wan, Danggui Longhui Wan, Huanglian Yanggan Wan, Wu Xiexin Tang, Lianpu Yin, Gegen Huangqin Huanglian Tang, Baitouweng Tang, Xianglian Wan etc. All of these are well-known formulas for clearing away toxin of heat-fire of heart and liver, as well as dampness-heat of stomach and intestines. Nowadays, Huanglian is generally considered as a kind of antibiotic and antivirus herb and is widely used for many infective diseases. In fact, it is also used to cure cardiovascular and cerebrovascular diseases, diabetes and cancer based on pharmacological studies. Having been using Huanglian in treating the above diseases and having conducted clinical and experimental research on cancer and liver diseases, the author observed that Huanglian and its compound prescriptions have obvious effects on liver diseases such as acute or chronic hepatitis, liver fibrosis, liver cirrhosis and liver cancer due to types of dampness-heat and fire-toxin. Part of the effects has been proved by experimental research and it is worth carrying out more research in this area for development and clinical application.
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PMID:[Explore new clinical application of Huanglian and corresponding compound prescriptions from their traditional use]. 1872 Aug 77

Changes in N-linked glycosylation are known to occur during the development of various diseases. For example, increased branching of oligosaccharides has been associated with cancer metastasis and has been correlated to tumor progression in human cancers of the breast, colon and melanomas. Increases in core fucosylation have also been associated with the development of hepatocellular carcinoma (HCC). Recently, changes in both the total serum glycome and the glycosylation of specific IgG molecules have been observed in people with liver fibrosis and cirrhosis. The mechanisms by which changes in glycosylation are observed and their use as biomarkers of disease will be discussed.
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PMID:Fucosylated glycoproteins as markers of liver disease. 1912 69

Cellular senescence is characterized by an irreversible cell cycle arrest that, when bypassed by mutation, contributes to cellular immortalization. Activated oncogenes induce a hyperproliferative response, which might be one of the senescence cues. We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro. Additionally, AKT-driven tumors undergo senescence in vivo following p53 reactivation and show signs of differentiation. In another in vivo system, i.e., liver fibrosis, hyperproliferative signaling through AKT might be a driving force of the senescence in activated hepatic stellate cells. Senescent cells up-regulate and secrete molecules that, on the one hand, can reinforce the arrest and, on the other hand, can signal to an innate immune system to clear the senescent cells. The mechanisms governing senescence and immortalization are overlapping with those regulating self-renewal and differentiation. These respective control mechanisms, or their disregulation, are involved in multiple pathological conditions including fibrosis, wound healing, and cancer. Understanding extracellular cues that regulate these processes may enable new therapies for these conditions.
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PMID:Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. 1915 Sep 58

The extraordinary developments made in the past decade in proteomic technologies, in particular in mass spectrometry, have enabled investigators to consider designing studies to search for diagnostic and therapeutic biomarkers by scanning complex proteome samples. We developed a method based on extensive fractionation of intact proteins, to comprehensively and quantitatively profile the liver and plasma proteomes in health and disease. We have applied this method to samples collected from patients with early hepatocellular carcinoma (HCC) and from patients with liver cirrhosis as well as to samples collected from three mouse models of HCC. This method allowed for the identification of proteins that differ in expression levels in liver tissue or in plasma with disease progression from liver fibrosis, cirrhosis or steatohepatitis to HCC. The comparative analysis of the liver and plasma proteomes generated from human and mouse specimens, constitutes a novel and powerful strategy for HCC biomarker discovery.
Cancer Lett 2009 Dec 01
PMID:Comparative analysis of the liver and plasma proteomes as a novel and powerful strategy for hepatocellular carcinoma biomarker discovery. 1923 62

Bioactive sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) have been implicated in many critical cellular events, including inflammation, cancer, and angiogenesis. However, the role of S1P/S1PR signaling in the pathogenesis of liver fibrosis has not been well documented. In this study, we found that S1P levels and S1P(3) receptor expression in liver tissue were markedly up-regulated in a mouse model of cholestasis-induced liver fibrosis. In addition, the S1P(3) receptor was also expressed in green fluorescent protein transgenic bone marrow (BM)-derived cells found in the damaged liver of transplanted chimeric mice that underwent bile duct ligation. Silencing of S1P(3) expression significantly inhibited S1P-induced BM cell migration in vitro. Furthermore, a selective S1P(3) receptor antagonist, suramin, markedly reduced the number of BM-derived cells during cholestasis. Interestingly, suramin administration clearly ameliorated bile duct ligation-induced hepatic fibrosis, as demonstrated by attenuated deposition of collagen type I and III, reduced smooth muscle alpha-actin expression, and decreased total hydroxyproline content. In conclusion, our data suggest that S1P/S1P(3) signaling plays an important role in cholestasis-induced liver fibrosis through mediating the homing of BM cells. Modulation of S1PR activity may therefore represent a new antifibrotic strategy.
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PMID:Involvement of sphingosine 1-phosphate (SIP)/S1P3 signaling in cholestasis-induced liver fibrosis. 1972 75

Choledochal cyst disease is uncommon. The presentation of the disease is being seen more commonly in the adult population than in the pediatric population, particularly in the West, making this a diagnosis a general surgeon should consider when evaluating a patient with biliary disease. The diagnosis of this disease has been greatly facilitated by improving technologies, particularly MRCP and interventional techniques of PTC. The consequences of not treating choledochal cysts can result in malignant transformation. When possible, complete surgical excision of the cyst is recommended and should be performed as early as possible to prevent complications and the progression of liver fibrosis. Long-term follow-up is required for surveillance for late complications and for cancer, particularly in type IV and V choledochal cysts where complete excision is not possible.
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PMID:The current management of choledochal cysts. 1984 81

Caloric restriction (CR), reduced protein, methionine, or tryptophan diets; and reduced insulin and/or IGFI intracellular signaling can extend mean and/or maximum lifespan and delay deleterious age-related physiological changes in animals. Mice and flies can shift readily between the control and CR physiological states, even at older ages. Many health benefits are induced by even brief periods of CR in flies, rodents, monkeys, and humans. In humans and nonhuman primates, CR produces most of the physiologic, hematologic, hormonal, and biochemical changes it produces in other animals. In primates, CR provides protection from type 2 diabetes, cardiovascular and cerebral vascular diseases, immunological decline, malignancy, hepatotoxicity, liver fibrosis and failure, sarcopenia, inflammation, and DNA damage. It also enhances muscle mitochondrial biogenesis, affords neuroprotection; and extends mean and maximum lifespan. CR rapidly induces antineoplastic effects in mice. Most claims of lifespan extension in rodents by drugs or nutrients are confounded by CR effects. Transcription factors and co-activators involved in the regulation of mitochondrial biogenesis and energy metabolism, including SirT1, PGC-1alpha, AMPK and TOR may be involved in the lifespan effects of CR. Paradoxically, low body weight in middle aged and elderly humans is associated with increased mortality. Thus, enhancement of human longevity may require pharmaceutical interventions.
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PMID:Caloric restriction: from soup to nuts. 1985 62

The early diagnosis of hepatocellular carcinoma (HCC) is of great clinical desirable due to lack of specific and sensitive markers. Alterations in the sugar chains of glycoprotein synthesized by the liver contribute to the molecular basis of abnormalities in carcinogenesis. This study aims to construct and assess the diagnostic value of N-glycan based diagnostic model in HCC identification and follow-up. A total of 393 subjects including HBV-related HCC, liver fibrosis and healthy controls were recruited. Follow-up was carried out before and after surgical treatment in HCC. N-glycome of serum glycoprotein was profiled by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Multiparameters diagnostic models were constructed based on N-glycan markers. The result found that 2 N-glycan structure abundances (NG1A2F, Peak 4; NA3Fb, Peak 9) were useful as N-glycan markers. The diagnostic efficacy of the log ratio [log(p9/4)] was similar to that of AFP in differentiating HCC from fibrosis. The accuracy and sensitivity of the diagnostic model combining AFP and N-glycan markers (Cscore B) were increased 7-10% compared with that of AFP. Log(p9/4) was more efficient in monitoring the progression of HCC with regarding to vascular invasion at improved specificity (16%) and accuracy (8%) compared with that of AFP. The N-glycan markers were found to be changed significantly after surgical resection in HCC follow-up. We conclude that the branching alpha (1,3)-fucosylated triantennary glycan and a biantennary glycan are promising as N-glycan markers. The diagnostic models based on the N-glycan markers and AFP improve the efficacy in HCC diagnosis and progression monitoring.
Int J Cancer 2010 Jul 01
PMID:N-glycan based models improve diagnostic efficacies in hepatitis B virus-related hepatocellular carcinoma. 1990 44

During the past years, we have explored the cellular delivery of kinase inhibitors. Kinase inhibitors have selectivity for specific kinases but they lack cellular selectivity. This is exemplified by recent reports on cardiotoxicity of kinase inhibitors used in cancer treatment. We postulate that targeted cellular delivery of kinase inhibitors can improve their safety/toxicity profiles, as will be exemplified by recent published studies. Cell specific delivery of therapeutics is a quickly growing area of investigation. This innovative strategy employs carrier molecules that bind to receptors exposed on the surface of cell types involved in disease processes. Binding and receptor mediated internalization of the carrier facilitates local accumulation of the product in target cells. Upon systemic administration, this may create local drug depots in specific organs, while other tissues are avoided, thus favoring enhanced localized drug efficacy and reduced side-effects. Synthesis of targeted kinase inhibitor-carrier conjugates was achieved using a new approach, in which kinase inhibitors were bound to a platinum(II) atom, the so-called Universal Linkage System (ULS). We review this novel linkage chemistry and demonstrate the applicability of ULS for drug targeting approaches aiming at angiogenic endothelial cells, hepatic stellate cells, and kidney tubular cells. We will review important issues like drug release mechanism, safety of the linker, and pharmacokinetics of the products in animals. Finally, we review the pharmacological efficacy of the cellular targeted drug conjugates in experimental animal models, especially in renal and liver fibrosis models.
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PMID:Organ- and cell-type specific delivery of kinase inhibitors: a novel approach in the development of targeted drugs. 2002 19


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