Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three of the most plausible biological theories of arsenic carcinogenesis are protein binding, oxidative stress and altered DNA methylation. This review presents the role of trivalent arsenicals binding to proteins in arsenic carcinogenesis. Using vacuum filtration based receptor dissociation binding techniques, the lifetimes of unidentate (<1s), bidentate (1-2min) and tridentate (1-2h) arsenite containing peptide binding complexes were estimated. According to our experimental data some of the protein targets to which arsenite may bind in vivo include tubulin, poly(ADP-ribose)polymerase (PARP-1), thioredoxin reductase, estrogen receptor-alpha, arsenic(+3)methyltransferase and Keap-1. Arsenite binding to tubulin can lead to several of the genetic effects observed after arsenic exposures (aneuploidy, polyploidy and mitotic arrests). Among many other possible arsenite binding sites are rat hemoglobin, the DNA repair enzyme xeroderma pigmentosum protein A (XPA), and other C2H2, C3H and C4 zinc finger proteins including members of the steroid receptor superfamily (e.g. glucocorticoid receptor). Macromolecules to which arsenite does not bind to include calf thymus DNA, mixed Type II-A histones and bovine H3/H4 histone. Although all six tested arsenicals released iron from ferritin, radioactive arsenite did not bind to the protein horse ferritin.
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PMID:The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. 1816 70

The aim of the current study was to evaluate the relation between xeroderma pigmentosum complementation group C (XPC) polymorphisms and susceptibility to breast cancer (BC), the development and progression of disease, and response to different individualized drug treatments. We investigated two polymorphisms in XPC Ala499Val and Lys939Gln using PCR-RFLP assays including 618 cases and 622 controls. The frequency of the TT genotype of Ala499Val (adjusted odds ratio = 1.575; 95% confidence interval, 1.104-2.245; P = 0.012) and the AC genotype of Lys939Gln (adjusted odds ratio = 1.330; 95% confidence interval, 1.045-1.694; P = 0.020) were found to significantly increase the risk of developing BC. The CT+TT genotypes of Ala499Val were associated with estrogen receptor positive, and Her-2 and p53 negative status, and the AC+CC genotypes of Lys939Gln were associated with BRCA1 negative status. Moreover, a significantly increased chance of treatment with neoadjuvant anthracycline-based chemotherapy response was found in women carrying TT genotype of Ala499Val, or CC and AC genotypes of Lys939Gln. In addition, a significantly longer overall survival after chemotherapy was observed in patients who had XPC Lys939Gln AC+CC genotypes with estrogen receptor positive (log-rank test, P = 0.086) and p53 negative (log-rank test, P = 0.020). The current data suggested that XPC Ala499Val and Lys939Gln polymorphisms may contribute to the identification of patients with increased risk for BC. Moreover, the polymorphisms were associated with the prognosis of BC patients.
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PMID:Association of XPC polymorphisms with susceptibility and clinical outcome to chemotherapy in breast cancer patients. 2251 60