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Protein-Programmed Accumulation of Yeast Cytosine Deaminase in Cancer Cells in Response to Mock-Hypoxia.

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One limitation of gene-directed enzyme prodrug therapy (GDEPT) is the difficulty in selectively and efficiently transducing cancer cells with the gene encoding a prodrug-converting enzyme. To circumvent this issue, we sought to move the selectivity from the gene delivery level to the protein level.

Hypoxia imaging predicts success of hypoxia-induced cytosine deaminase/5-fluorocytosine gene therapy in a murine lung tumor model.

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Tc-99m-HL91 is a hypoxia imaging biomarker. The aim of this study was to investigate the value of Tc-99m-HL91 imaging for hypoxia-induced cytosine deaminase (CD)/5-fluorocytosine (5-FC) gene therapy in a murine lung tumor model. C57BL/6 mice were implanted with Lewis lung carcinoma cells transduced

Hypoxia-induced cytosine deaminase gene expression for cancer therapy.

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Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. It activates a signal cascade that culminates in the stabilization of hypoxia-inducible factor-1 (HIF-1) transcription factor and activation of genes that possess hypoxia response elements. The loss of

Development of a hypoxia-inducible cytosine deaminase expression vector for gene-directed prodrug cancer therapy.

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One important feature of human solid tumors is the presence of a hypoxic microenvironment. Under hypoxia, genes that contain a hypoxia-response element (HRE) can be activated by the binding of hypoxia-inducible factor-1. To reach the goal of selectively killing tumor cells in a hypoxic

Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system: a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro.

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BACKGROUND We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a

Adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts.

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Hypoxia is closely associated with the radioresistance of tumours; therefore, targeting hypoxic areas is very important for cancer therapy. The aim of this study is to establish such a targeting strategy by applying a bacterial cytosine deaminase (BCD)/5-fluorocytosine (5-FC) gene therapy system and

[Cerebellar toxicity of cytosine-arabinoside in a young man following cerebral anoxia].

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Global cytosine methylation in Daphnia magna depends on genotype, environment, and their interaction.

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The authors characterized global cytosine methylation levels in 2 different genotypes of the ecotoxicological model organism Daphnia magna after exposure to a wide array of biotic and abiotic environmental stressors. The present study aimed to improve the authors' understanding of the role of

Astrocytes protect cultured neurons from degeneration induced by anoxia.

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Neurons grown in cultures of dissociated brain cells degenerate when exposed to anoxia and deprived of glucose. We have developed culture systems in which neurons can be grown in the presence or absence of astrocytes and have used them to study the influence of astrocytes on the neuronal

Protein Kinase C Binding Protein 1(PRKCBP1) Inhibits Hypoxia Inducible Factor 1 (HIF-1) in the Heart.

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UNASSIGNED Hypoxia-inducible factor 1 alpha (HIF-1α) is a key transcription factor responsible for the induction of genes that facilitate adaptation to hypoxia. To study HIF-1 signaling in the heart, we developed a mouse model in which an oxygen-stable form of HIF-1α can be inducibly expressed in

The effects of hypoxia and cysteamine on X-ray mutagenesis in human cells. II. hprt mRNA expression and cDNA sequence analysis of induced mutants.

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Mutants at the hprt locus isolated after treatment of cells of the human lymphoblastoid cell line TK6 with X rays were examined by Northern blot and cDNA sequence analysis. In previous work, Southern blot analysis showed that approximately 25% of the mutants isolated from cultures treated with X

Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation-free hypoxia-inducible factor-1 DNA-binding site.

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The hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in the expression of oxygen-regulated genes such as that for erythropoietin. Following exposure to low oxygen partial pressure (hypoxia), HIF-1 binds to an hypoxia-response element located 3' to the erythropoietin gene

Cytosine deaminase/5-fluorocytosine exposure induces bystander and radiosensitization effects in hypoxic glioblastoma cells in vitro.

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OBJECTIVE Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study,

Photodynamic therapy-driven induction of suicide cytosine deaminase gene.

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Photodynamic therapy (PDT) of tumors is associated with induction of hypoxia that results in activation of hypoxia-inducible factors (HIFs). Several observations indicate that increased HIFs transcriptional activity in tumor cells is associated with cytoprotective responses that limit cytotoxic

[Individual characteristics of human adaptation to intermittent hypoxia: possible role of genetic mechanisms].

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The majority of the adaptation processes to hypoxia is based on transcriptional regulation by hypoxia-inducible factors--HIFs. Recently the allele polymorphism of oxygen-dependent degradation domain of HIF-lalpha has been described. It consists in the replacement of cytosine for thymine in 1772

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