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)

A recombinant nonreplicating human adenovirus type 5, Ad5HCMVsp1lacZ, expressing the lacZ gene under control of the human cytomegalovirus immediate early promoter, was used to assess the effect of heat-shock (HS) on DNA repair of a UV-damaged reporter gene. Host cell reactivation (HCR) of beta-galactosidase (beta-gal) activity for UV-irradiated Ad5HCMVsp1lacZ was used as an indicator of DNA repair in the transcribed strand of an active gene. Repair was examined in heat-shock (HS) pretreated and mock-treated normal fibroblasts, normal lung epithelial cells, xeroderma pigmentosum group A, C, D and G fibroblasts (XP-A, XP-C, XP-D and XP-G), Cockayne's syndrome group A fibroblasts (CS-A), SV40-transformed normal fibroblasts (GM637f) and 5 tumour cell lines (SKOV-3, HeLa, HT29, SCC-25 and U20S). HS enhanced reactivation (HSER) of the reporter gene was detected in normal cells, HT29 tumour cells and XP-C fibroblasts. HSER was reduced or absent in all other XP, CS and tumour cell lines tested. HSER in normal and XP-C cell lines, but not CS-A, XP-A, XP-D or XP-G cells, suggests that HS treatment can enhance the repair of UV-damaged DNA through an enhancement of transcription coupled repair (TCR) or a mechanism which involves the TCR pathway. Since this response was absent in the SV40-transformed fibroblast cell line and 4 of 5 tumour cell lines examined, HSER of beta-gal activity for UV-irradiated Ad5HCMVsp1lacZ also requires some cellular function(s) affected by transformation.
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PMID:Heat-shock enhanced reactivation of a UV-damaged reporter gene in human cells involves the transcription coupled DNA repair pathway. 867 26

Nonmelanoma skin cancers (NMSC) has been evidenced with an impaired function in nucleotide excision repair (NER). However, malfunction of NER elements in NMSC has not been identified. Xeroderma pigmentosum F (XPF) is an essential subunit in NER and functions as a 5'-incision enzyme when repairing damaged DNA. So far, neither XPF's protein nor antibody is commercially available. To explore the expression of XPF in NMSC, the gene was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR). All the designed primers specifically amplified XPF cDNA as demonstrated by nested PCR, and one set of the primers was mimic constructed to form a controlled cDNA for the semiquantification of XPF gene in NMSC. The results indicated that the quantities of XPF expression of BCC and SCC specimens were approximately 57.0 and 76.4% less than that of normal skins, respectively. This paper indicates that the decrease expression of XPF gene may be one of mechanisms for impaired NER in NMSC, and the feasible and quantitative primers used in the experiments may explore the study of XPF in etiology of carcinogenesis.
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PMID:Quantitative determination of the expression of xeroderma pigmentosum F gene in human nonmelanoma skin cancers. 1087 27

Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.
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PMID:Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms. 1196 27

Multiple oculo-cutaneous malignancies are a common manifestation on sun-exposed facial areas in patients with Xeroderma pigmentosum (XP). Commonly seen are the basal cell carcinoma and the squamous cell carcinomas which manifest in the early first decade in contrast to fifth and sixth decade in the general population. XP manifests as photosensitivity, hyperpigmentation, premature skin aging and malignant changes like squamous cell carcinoma, basal cell carcinoma, fibrosarcoma and rarely malignant melanoma as well as internal malignancies. We report 11 cases of Xeroderma pigmentosa managed in our institute which included sex males and five females. All had photosensitivity, hyperpigmentation and consanguinity with facial malignant lesions like SCC and BCC. Ocular signs of photophobia and excessive lacrimation was seen in all the cases while blurring of vision due to corneal clouding, corneal injection, pterygium and limbal SCC were seen in 5 cases. SCC of the lids were seen in 7 cases while BCC seen in 8 cases and limbal and conjunctival SCC seen in one case. All were managed with excision while one case of melanoma with neck secondaries needed radical neck dissection while the other orbital exenteration. Oculo-cutaneous malignancies occur in the sun exposed areas so patients are advised regular follow up with speciality care. Awareness about the rare condition and importance of early detection and prevention of UV rays induced skin damage should be propagated. The disease is ultimately fatal, life can be prolonged by simple preventive measures to minimize sun exposure and early detection of the skin lesions and management.
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PMID:Xeroderma pigmentosum: clinicopathological review of the multiple oculocutaneous malignancies and complications. 2511 64