Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA base excision repair pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial step in the BER pathway involves the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not only as an AP endonuclease but also as a redox-modifying factor for a variety of transcription factors including Fos, Jun, paired box containing genes (PAX), nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels, scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and 67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1 nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and 36%, respectively) compared with BPH (5%). There was no correlation with prostate-specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer, the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm of PIN and cancer compared with BPH. Given these results, we conclude that Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role, through its repair, redox, or both functions, in the physiology of the early development of prostate cancer.
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PMID:Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. 1130 29

Vitamin D plays an important role in cell growth and differentiation and is proposed to protect against cancer initiation and/or progression. The vitamin D receptor (VDR) has a thymine/cytosine (T/C) polymorphism located in the first of two potential start (ATG) codons that can be detected by a RFLP using the endonuclease FokI. The C variant, which lacks the first ATG, results in a shorter VDR and is referred to as the F allele. The T variant (f allele) initiates at the first ATG. We examined the association of the VDR FokI genotype with histopathological characteristics and prognosis of prostate cancer among 191 mostly Caucasian subjects who had undergone radical prostatectomy between 1984 and 1992. The frequencies of the FF, Ff, and ff genotypes were 41%, 38%, and 21%, respectively. Subjects with the ff genotype had a lower mean percentage of Gleason grade 4/5 cancer (30.3%) than subjects with the FF or Ff genotypes (42.8% and 43.8%, respectively; P = 0.015 by t test for ff versus FF + Ff). The data suggest that the presence of an F allele increased the risk of being diagnosed with more aggressive cancer because higher percentage of Gleason grade 4/5 is associated with worse prognosis. The age-adjusted risk of prostate-specific antigen failure was lower for the ff genotype than for the FF genotype by Cox proportional hazards analysis but did not achieve statistical significance (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32). This risk reduction disappeared after further adjustment for percentage of Gleason grade 4/5, cancer volume, and preoperative serum prostate-specific antigen level (hazard ratio = 1.03; 95% confidence interval, 0.58-1.85). In conclusion, the ff genotype was associated with less aggressive histopathological findings than Ff or FF genotypes. Additional studies with a larger sample size and investigation of the functional significance of the FokI polymorphism in prostate cancer cells are warranted.
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PMID:Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression. 1254 Apr 99

We describe a strategy of utilizing specific target binding to trigger assembly of three DNA components that are otherwise unable to spontaneously assemble with one another. This binding-induced DNA assembly forms a three-arm DNA junction, subsequently initiating nicking endonuclease-assisted isothermal fluorescence signal amplification. Real-time monitoring of fluorescence enables amplified detection of specific protein targets. The implementation of the strategy necessitates the simultaneous binding of a single target molecule with two affinity ligands each conjugated to a DNA motif. Simple alternation of affinity ligands enables different protein targets to induce the formation of the DNA junction and subsequent isothermal amplification. The use of the strategy allowed us to develop a sensitive assay for proteins with three appealing features: homogeneous analysis without the need for separation, isothermal amplification, and high specificity. Streptavidin was chosen as an initial target to establish and optimize the assay. Sensitivity of protein detection was improved by 1000-fold upon the application of isothermal amplification. A limit of detection of 10 pM was achieved for detection of prostate-specific antigen in buffer and diluted serum. The combination of its three appealing features makes the assay attractive for potential applications in molecular diagnosis, point-of-care testing, and on-site analysis.
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PMID:Assembly of multiple DNA components through target binding toward homogeneous, isothermally amplified, and specific detection of proteins. 2497 52

Methods based on photoelectrochemistry have been developed for immunoassay, but most involve in a low sensitivity and a relatively narrow detectable range. Herein a new bio-bar-code-based split-type photoelectrochemical (PEC) immunoassay was designed for sensitive detection of prostate-specific antigen (PSA), coupling rolling circle amplification (RCA) with enzymatic biocatalytic precipitation. The bio-bar-code-based immunoreaction was carried out on monoclonal anti-PSA antibody (mAb1)-coated microplate using primer DNA and polyclonal anti-PSA antibody-conjugated gold nanoparticle (pDNA-AuNP-pAb2) with a sandwich-type assay format. Accompanying the immunocomplex, the labeled primer DNA on gold nanoparticle readily triggered RCA reaction in the presence of padlock probe/dNTPs/ligase/polymerase. The RCA product with a long single-stranded DNA could cause the formation of numerous hemin/G-quadruplex-based DNAzyme concatamers. With the assistance of nicking endonuclease, DNAzyme concatamers were dissociated from gold nanoparticle, which catalyzed the precipitation of 4-chloro-1-naphthol in the presence of H2O2 onto CdS nanorods-coated electrode (as the photoanode for the generated holes). The formed insoluble precipitate inhibited the electron transfer from the solution to CdS nanorods-modified electrode by using ascorbic acid as the electron donor. Under the optimum conditions, the photocurrent of the modified electrode decreased with the increasing of PSA concentration. A detectable concentration for target PSA with this system could be achieved as low as 1.8pgmL-1. In addition, our strategy also showed good reproducibility, high specificity and accuracy matched well with commercial PSA ELISA kits for real sample analysis. These remarkable properties revealed that the developed PEC immunoassay has great potential as a useful tool for the detection of PSA in practical application.
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PMID:Bio-bar-code-based photoelectrochemical immunoassay for sensitive detection of prostate-specific antigen using rolling circle amplification and enzymatic biocatalytic precipitation. 2906 41