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

The familial occurrence of head and neck cancers supports the role of heredity in this disease group. The roles of environmental and genetic factors are difficult to separate. There are several well-characterized entities, however, that are associated with risk and prognosis of head and neck cancer, including Lynch-II syndrome, Bloom syndrome, Fanconi's anemia, xeroderma pigmentosum, ataxia telangiectasia, and Li-Fraumeni syndrome. Mutagen-induced chromosomal damage is associated with an increased risk of multiple primary neoplasms and upper aerodigestive tract cancers. A possible reduction of genotoxicity, mediated by micronutrients, was demonstrated in vitro. Sister chromatid exchanges and micronuclei are useful exposure and disease markers. Metabolic changes (acetylation, DBQ phenotype, and the AH locus polymorphism) have been found to be associated with cancer of the upper aerodigestive tract. Most associations between histocompatibility antigens and solid tumors are relatively weak, probably because of the masking effects of environmental factors. Infections by HPV, EBV, and HSV have a causative or predisposing role in several types of head and neck cancer. Amplification and rearrangement of oncogenes may also play a role in carcinogenesis, and oncogene amplification may be associated with aggressive tumor behavior and unfavorable clinical prognosis. Ploidy of tumors seems to be an important determinant of survival and response to therapy.
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PMID:Hereditary and environmental factors associated with risk and progression of head and neck cancer. 140 93

The denV gene from bacteriophage T4 encodes a pyrimidine dimer-specific endonuclease that has the capacity to initiate excision repair of DNA. Cells from excision repair-deficient xeroderma pigmentosum (XP) patients are able to carry out excision repair initiated by the denV gene product and introduction of the denV gene into XP cells results in the partial restoration of colony-forming ability after irradiation with UV light. In this work we have constructed a helper-independent recombinant human adenovirus, Ad5denV, which contains the denV gene. A 1.9 kb cartridge consisting of the denV gene flanked by the long terminal repeat (LTR) promoter from Rous sarcoma virus (RSV) and the simian virus 40 (SV40) polyadenylation (poly A) splice signals, was inserted into the E3 region of an E3 deletion mutant (Ad5d1E3) of adenovirus type 5. Infection of human fibroblasts and other permissive human cells with Ad5denV resulted in lytic infection and expression of the denV gene was confirmed by primer extension of infected cell RNA. The ability of the denV gene to restore the DNA repair deficiency in XP fibroblasts was examined using host cell reactivation of viral structural antigen formation for UV-irradiated adenovirus. The control virus, Ad5VSV, was also a recombinant which contained the gene for vesicular stomatitis virus glycoprotein G inserted into the E3 region of Ad5d1E3. UV survival of Ad5denV was similar to that of Ad5VSV following infection of two normal fibroblast strains and a Cockayne syndrome fibroblast strain, CS7SE, from complementation group B. In contrast, UV survival of Ad5denV was significantly greater than that for Ad5VSV after infection of three unrelated XP fibroblast strains from complementation groups A, C and E. However, UV survival of Ad5denV in the XP fibroblasts did not reach levels obtained in normal fibroblasts, indicating that restoration of the XP defect was partial.
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PMID:Construction of a recombinant adenovirus containing the denV gene from bacteriophage T4 which can partially restore the DNA repair deficiency in xeroderma pigmentosum fibroblasts. 170 21

Infection with immunosuppressive lentiviruses is associated with increased cancer risk,but most studies have implicated indirect mechanisms as the tumor cells generally lack integrated viral sequences. An exception wasfound in a B-cell lymphoma (Q254) where the tumor cells contained a single integrated feline immunodeficiency virus genome. Additional analysis now indicates that feline immunodeficiency virus integration in lymphoma Q254 resulted in promoter insertion and truncation of a conserved gene on feline chromosome B3, whereas the unaffected allele of the gene appeared to be transcriptionally down-regulated. The orthologous human gene (FLJ12973), is expressed ubiquitously and encodes a WD-repeat protein with structural similarity to DDB2, the small subunit of the xeroderma pigmentosum XP-E complex. Moreover, the gene is located within a region of frequent tumor-specific deletions on chromosome 15q15. These observations demonstrate the direct mutagenic potential of the lentiviruses and identify a new candidate tumor suppressor gene.
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PMID:Feline immunodeficiency virus integration in B-cell lymphoma identifies a candidate tumor suppressor gene on human chromosome 15q15. 1249 53

The nucleotide excision repair (NER) is one of the major human DNA repair pathways. Defects in one of the proteins that act in this system result in three distinct autosomal recessive syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). TFIIH is a nine-protein complex essential for NER activity, initiation of RNA polymerase II transcription and with a possible role in cell cycle regulation. XPD is part of the TFIIH complex and has a helicase function, unwinding the DNA in the 5' --> 3' direction. Mutations in the XPD gene are found in XP, TTD and XP/CS patients, the latter exhibiting both XP and CS symptoms. Correction of DNA repair defects of these cells by transducing the complementing wild-type gene is one potential strategy for helping these patients. Over the last years, adenovirus vectors have been largely used in gene delivering because of their efficient transduction, high titer, and stability. In this work, we present the construction of a recombinant adenovirus carrying the XPD gene, which is coexpressed with the EGFP reporter gene by an IRES sequence, making it easier to follow cell infection. Infection by this recombinant adenovirus grants full correction of SV40-transformed and primary skin fibroblasts obtained from XP-D, TTD and XP/CS patients.
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PMID:Restoring DNA repair capacity of cells from three distinct diseases by XPD gene-recombinant adenovirus. 1565 Jul 64