Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FK506-binding protein 51(FKBP51, coded by FKBP5) is a co-chaperone molecule that interacts with the chaperone HSP90 and the glucocorticoid receptor (GR) in an inactive GR complex. It is a negative regulator of glucocorticoid action and is replaced by the positive regulator, FK506-binding protein 52 (FKBP52, coded by FKBP4) when hormone binds to GR, which renders the GR complex active. In this study, we found that the expression of FKBP51 mRNA in 12 organs of Newcastle disease virus (NDV)-infected chickens was robustly induced. The level of corticosterone in NDV-infected chickens was also elevated, approximately 2- to 6.5-fold in the organs compared to non-infected control chickens. The induction of FKBP51 mRNA expression was reproduced by dexamethasone treatment, indicating a role for glucocorticoids in the systemic induction of FKBP51 mRNA expression. In chicken UMNSAH/DF-1 cells, nuclear factor kappaB (NF-kappaB) was activated in an FKBP51-dependent manner. Regulation of the three NF-kappaB-dependent, anti-apoptotic genes, bcl-2, bcl-x and bfl-1/A1 was investigated in UMNSAH/DF-1 cells. Dexamethasone treatment of UMNSAH/DF-1 cells resulted in up-regulation of bcl-2, and down-regulation of bcl-x and bfl-1/A1. Expression of FKBP51 also resulted in down-regulation of bfl-1/A1, but had no effect on bcl-2 and bcl-x, suggesting the involvement of glucocorticoid-FKBP51-NF-kappaB signaling in the regulation of expression of bfl-1/A1 in UMNSAH/DF-1 cells. We observed organ-specific up- or down-regulation of expression of, bcl-2, bcl-x and bfl-1/A1 in NDV-infected and dexamethasone-treated chickens. Differential regulation of bfl-1/A1, bcl-2 and bcl-x upon NDV-infection and dexamethasone treatment suggests that additional factors are involved in the regulation of these genes. These results suggest that systemic elevation of FKBP51 in NDV-infected chickens activates NF-kappaB, which cooperates with other factors to regulate the expression of NF-kappaB-dependent genes.
Mol Cell Endocrinol 2007 Nov 15
PMID:Glucocorticoids modulate NF-kappaB-dependent gene expression by up-regulating FKBP51 expression in Newcastle disease virus-infected chickens. 1787 Feb 33

E(rns) is an envelope glycoprotein of classical swine fever virus (CSFV) and has an unusual feature of RNase activity. In the present study, we demonstrate that E(rns) counteracts Newcastle disease virus (NDV)-mediated induction of IFN-beta. For this purpose, E(rns) fused to the enhanced green fluorescent protein (EGFP) was transiently expressed in porcine kidney 15 (PK15) cells. In luciferase activity assay, E(rns)-EGFP was found to prevent IFN-beta promoter-driven luciferase expression and block the induction of IFN-beta promoter mediated by NDV in a dosedependent manner. Through IFN-specific semi-quantitative RT-PCR detection, obvious decrease of IFN-beta mRNA in NDV-infected PK15 cells was observed in the presence of E(rns)-EGFP. In contrast, EGFP alone showed none of this block capacity. In addition, E(rns)-EGFP mutations with RNase inactivation were also found to block NDV-mediated induction of IFN-beta. These evidences establish a novel function for CSFV E(rns) glycoprotein in counteraction of the IFN-beta induction pathway.
J Biochem Mol Biol 2007 Sep 30
PMID:A novel role of classical swine fever virus E(rns) glycoprotein in counteracting the newcastle disease virus (NDV)-mediated IFN-beta Induction. 1792 91

Emerging and re-emerging infectious diseases pose a threat to individuals worldwide and necessitate the development of new vaccines and vaccine platforms. Newcastle disease virus (NDV) is an enveloped cytoplasmic RNA virus of avian origin that is highly attenuated in humans and other primates because of a strong host-range restriction. NDV infects the respiratory tract of non-human primates and appears to remain restricted to that site. As a vaccine vector, NDV induced substantial local and systemic responses against a protein expressed by a foreign gene insert and was protective against pathogen challenge. NDV is antigenically distinct from common human viruses, accommodates foreign sequences with a good degree of stability, can be readily produced in a cell line acceptable for human product development, and exhibits a low incidence of recombination. Because of its natural tropism for the respiratory tract, NDV may be particularly effective for the development of vectored vaccines against respiratory infections as well as infections that can be transmitted through the respiratory tract.
Curr Opin Mol Ther 2008 Feb
PMID:Newcastle disease virus as a vaccine vector for humans. 1822 81

Oncolytic viruses possess an inherent trophism for tumor cells or have been engineered in a variety of ways to selectively replicate in and destroy cancer cells. Because of the unique mode of tumor destruction, oncolytic virotherapy has the potential to augment the antineoplastic activity of chemotherapy and radiation therapy. Many oncolytic viruses, such as adenovirus, HSV, vaccinia, measles, reovirus, Newcastle disease virus and coxsackie virus, have entered into clinical trials and their efficacy and safety have been demonstrated with few, minor, side effects. Data obtained from several clinical trials of the oncolytic adenovirus, ONYX-015, in patients with cancer have been described in detail. Some preclinical studies of oncolytic viruses have demonstrated promising results, mainly when administered in combination with chemotherapeutic drugs. In this review, the clinical use of oncolytic viruses in combination with chemotherapy and radiation therapy, and future directions to enhance the efficacy of oncolytic virotherapy, are discussed.
Curr Opin Mol Ther 2008 Aug
PMID:Virus combinations and chemotherapy for the treatment of human cancers. 1868 2

The field of oncolytic viral therapy has undergone a major shift in focus in the last few years. Less research has been directed at making incremental improvements in original vectors based mainly on strains of adenovirus and HSV; instead a variety of different viral strains have been suggested as potential backbones for future oncolytic viruses (including Newcastle disease virus, reovirus, vesicular stomatitis virus, polio virus, retrovirus, Sindbis virus, picornavirus, mumps and measles virus), with many of these progressing to clinical trials. Of these, vaccinia virus represents a particularly promising candidate. It possesses a variety of intrinsic molecular properties suitable for an oncolytic virus (such as rapid life cycle and lysis of infected cells, and an ability to infect various cell types), in addition to undergoing extensive study both in the laboratory and in the clinic. Although not a natural human pathogen, there are extensive data on the effects of vaccinia infection in humans. Preclinical models incorporating new oncolytic vaccinia strains, as well as data from the first clinical trials that have utilized the next-generation oncolytic vaccinia strains for the potential treatment of cancer have been described.
Curr Opin Mol Ther 2008 Aug
PMID:Oncolytic vaccinia virus: from bedside to benchtop and back. 1868 4

Naturally occurring strains of Newcastle disease virus (NDV) are currently being investigated in multiple clinical trials for oncolytic cancer therapy in the United States and abroad. We have previously reported, for the first time, the development of recombinant NDVs designed for enhanced cancer therapeutic efficacy. Specifically, we have shown that NDV engineered to express interleukin-2 (IL-2) generates a robust therapeutic response associated with increased tumor-specific T-cell infiltration after intratumoral administration in mice. We have now demonstrated that this therapeutic response is dependent on T cells and we have investigated the potential to focus the NDV-induced immune response toward a tumor-associated antigen (TAA) to enhance the inherent therapeutic efficacy of NDV further. We found that intratumoral treatments of tumor-bearing mice with recombinant NDV expressing a model TAA elicited an enhanced tumor-specific response, resulting in a significant increase in the number of complete tumor regressions compared with control NDV. Additionally, coadministration of NDV expressing a model TAA with NDV expressing IL-2 enhanced the TAA-directed response and led to more complete tumor regressions. Our results show that TAA-directed immunotherapy by oncolytic recombinant NDV alone or in combination with IL-2 results in an enhanced therapeutic efficacy and warrant consideration in the development of cancer therapies based on the use of oncolytic NDV.
Mol Ther 2008 Nov
PMID:Recombinant Newcastle disease virus as a vaccine vector for cancer therapy. 1871 10

We establish a plasmid-driven minigenome system for Newcastle disease virus (NDV) V4 strain. Unlike the previously reported T7 polymerase based rescue system for Mononegavirales, the developed strategy does not necessitate the introduction of exogenous T7 polymerase by helper virus or stably expressing cell lines. This was achieved by transfection of plasmid pCAGGS-T7. The open reading frame (ORF) of enhanced green-fluorescent protein (EGFP) gene was inserted into constructed minigenome system pBRT7-mini and has been successfully expressed. Further packaging experiments indicate that 3' end leader and 5' end trailer regions are important for replication, transcription and packaging.
Mol Biol Rep 2009 Sep
PMID:Plasmids driven minigenome rescue system for Newcastle disease virus V4 strain. 1901 92

Newcastle disease virus (NDV) has been previously shown to possess oncolytic activity, causing specific lysis of cancerous but not normal cells. Here we show that despite these findings, the oncolytic efficiency of naturally occurring NDV strains can still be relatively low, as many tumors exhibit strong innate immune responses that suppress viral replication and spread. To overcome this problem, we generated a recombinant fusogenic NDV expressing influenza NS1 protein, a protein exhibiting interferon (IFN)-antagonist and antiapoptotic functions in human and mouse cells. Interestingly, the resultant virus was dramatically enhanced in its ability to form syncytia, lyse a variety of human and mouse tumor cell lines, and suppressed the induction of the cellular IFN responses. Using the aggressive syngeneic murine melanoma model, we show that the NDV-NS1 virus is more effective than virus not expressing NS1 in clearing the established footpad tumors and results in higher overall long-term animal survival. In addition, mice treated with NDV-NS1 exhibited no signs of toxicity to the virus and developed tumor-specific cytotoxic T lymphocyte (CTL) responses. These findings demonstrate that modulation of innate immune responses by NDV results in enhancement of its oncolytic properties and warrant further investigation of this strategy in design of oncolytic NDV vectors against human tumors.
Mol Ther 2009 Apr
PMID:Enhancement of oncolytic properties of recombinant newcastle disease virus through antagonism of cellular innate immune responses. 1920 45

This review deals with the avian paramyxovirus Newcastle disease virus (NDV) and describes properties that explain its oncolytic activity, its tumor-selective replication behavior, and its immune-stimulatory capacity with human cells. The strong interferon response of normal cells upon contact with NDV appears to be the basis for the good tolerability of the virus in cancer patients and for its immune stimulatory properties, whereas the weak interferon response of tumor cells explains the tumor selectivity of replication and oncolysis. Various concepts for the use of this virus for cancer treatment are pointed out and results from clinical studies are summarized. Reverse genetics technology has made it possible recently to clone the genome and to introduce new foreign genes thus generating new recombinant viruses. These can, in the future, be used to transfer new therapeutic genes into tumors and also to immunize against new emerging pathogens. The modular nature of gene transcription, the undetectable rate of recombination, and the lack of a DNA phase in the replication cycle make NDV a suitable candidate for the rational design of a safe and stable vaccine and gene therapy vector.
Methods Mol Biol 2009
PMID:Newcastle disease virus: a promising vector for viral therapy, immune therapy, and gene therapy of cancer. 1956 23

Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, which is currently under investigation as a clinical oncolytic agent. Several clinical trials have reported NDV to be a safe and effective agent for cancer therapy; however, there remains a clear need for improvement in therapeutic outcome. The endogenous NDV fusion (F) protein directs membrane fusion, which is required for virus entry and cell-cell fusion. Here, we report a novel NDV vector harboring an L289A mutation within the F gene, which resulted in enhanced fusion and cytotoxicity of hepatocellular carcinoma (HCC) cells in vitro, as compared with the rNDV/F3aa control virus. In vivo administration of the recombinant vector, termed rNDV/F3aa(L289A), via hepatic arterial infusion in immune-competent Buffalo rats bearing multifocal, orthotopic liver tumors resulted in tumor-specific syncytia formation and necrosis, with no evidence of toxicity to the neighboring hepatic parenchyma. Furthermore, the improved oncolysis conferred by the L289A mutation translated to significantly prolonged survival compared with control NDV. Taken together, rNDV/F(L289A) represents a safe, yet more effective vector than wild-type NDV for the treatment of HCC, making it an ideal candidate for clinical application in HCC patients.
Mol Ther 2010 Feb
PMID:Engineered newcastle disease virus as an improved oncolytic agent against hepatocellular carcinoma. 1980 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>