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)

Among various strains of skin fibroblasts tested, two strains derived from xeroderma pigmentosum (XP) patients (ages 19 and 25) with neurological complications and two strains obtained from heterozygotes (ages 54 and 18) showed relatively higher susceptibility than normal age-matched controls to transformation by feline sarcoma virus (FSV). Only one strain from a normal individual also showed a high susceptibility. Generally, there was a parallelism in susceptibilities to FSV and Kirsten murine sarcoma virus (KiMsv). However, cells from normal individuals of 46 years or older exhibited high ratios of FSV:KiMSV titers which were due to their lower susceptibility to KiMSV. Cells from two XP patients (ages 25 and 22) and a heterozygote (age 18), who were in a younger age group, manifested such a differential susceptibility to FSV and KiMSV. There was a correlation between the relative sensitivity of XP cells to the cytotoxic effect of 4-nitroquinoline 1-oxide and killing effect of UV light. Pretreatment of fibroblasts from three XP patients by a subtoxic dose of 4-nitroquinoline 1-oxide 24 hr before viral infection facilitated transformation by KiMSV and FSV, whereas no such effect was observed with three normal cells strains similarly treated.
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PMID:Susceptibility of xeroderma pigmentosum cells to transformation by murine and feline sarcoma viruses. 18 47

The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum.
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PMID:Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation. 19 37

Xeroderma pigmentosum (XP) is a DNA repair defect syndrome associated with an increased risk to developing skin neoplasms on sun-exposed cutaneous surfaces. This report describes the case of a 15-year-old boy with XP who developed cutaneous angiosarcoma. The patient was cured with surgery alone, despite incomplete resection, and he is alive without evidence of disease 40 months after diagnosis. It is the fourth reported case--and the third in pediatric age--of the association of XP with this soft part sarcoma.
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PMID:Cutaneous angiosarcoma in a patient with xeroderma pigmentosum. 1466 Mar 3

Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C (XPC) are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog (Kras) or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, Kras(LA1), as a driver for lung cancer development in mice, we showed for the first time that mice with Kras(LA1) and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured cells, we demonstrated that induced expression of oncogenic KRAS(G12V) led to increased levels of reactive oxygen species (ROS) as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS.
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PMID:Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development. 2655 12

"Mutational signatures" are patterns of mutations that report DNA damage and subsequent repair processes that have occurred. Whole-genome sequencing (WGS) can provide additional information to standard diagnostic techniques and can identify therapeutic targets. A 32-yr-old male with xeroderma pigmentosum developed metastatic angiosarcoma that was unresponsive to three lines of conventional sarcoma therapies. WGS was performed on his primary cancer revealing a hypermutated tumor, including clonal ultraviolet radiation-induced mutational patterns (Signature 7) and subclonal signatures of mutated DNA polymerase epsilon (POLE) (Signature 10). These signatures are associated with response to immune checkpoint blockade. Immunohistochemistry confirmed high PD-L1 expression in metastatic deposits. The anti-PD-1 monoclonal antibody pembrolizumab was commenced off-label given the POLE mutation and high mutational load. After four cycles, there was a significant reduction in his disease with almost complete resolution of the metastatic deposits. This case highlights the importance of WGS in the analysis, interpretation, and treatment of cancers. We anticipate that as WGS becomes integral to the cancer diagnostic pathway, treatments will be stratified to the individual based on their unique genomic and/or transcriptomic profile, enhancing classical approaches of histologically driven treatment decisions.
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PMID:Dramatic response of metastatic cutaneous angiosarcoma to an immune checkpoint inhibitor in a patient with xeroderma pigmentosum: whole-genome sequencing aids treatment decision in end-stage disease. 3164 45