Xeroderma pigmentosum patients

Reardon JT, Bessho T, Kung HC, Bolton PH, San car A (1997) In vitro repair of oxidative DNA damage by human nucleotide excision repair system possible explanation for neurodegeneration in Xeroderma Pigmentosum patients. Proc Natl Acad Sci USA 94 9463-8... 

Reardon, J. T., Bessho, T., Kung, H. G., Bolton, P. H., and Sancar, A. (1997b). In vitro repair of oxidative DNA dam e by human nucleotide excision repair system Possible explanation for neurodegeneration in xeroderma pigmentosum patients. Proc. Natl. Acad. Sci. USA 94, 9463-9468. 

H. Takebe, Y. Miki, T. Kozuka, J. Furuyama, K. Tanaka, M. Sasaki, Y. Fujiwara, and H. Akiba, DNA repair characteristics and skin cancers of xeroderma pigmentosum patients in Japan, Cancer Res, 37, 490-495 (1977). 

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

Defects have been found in these mechanisms that cause various human diseases. For example, patients with the genetic disease xeroderma pigmentosum are especially sensitive to ultraviolet light and develop skin cancer. Skin fibroblasts cultured from these patients have been shown to be defective in DNA repair. 

Theron T, Fousteri MI, Volker M, Harries LW, Botta E, Stefanini M, Fujimoto M, Andressoo JO, Mitchell J, Jaspers NG, McDaniel LD, Mullenders LH, Lehmann AR (2005) Transcription-associated breaks in xeroderma pigmentosum group D cells from patients with combined features of xeroderma pigmentosum and Cockayne syndrome. Mol Cell Biol 25(18) 8368-8378 Thiriet C, Hayes JJ (2005) Chromatin in need of a fix phosphorylation of H2AX connects chromatin to DNA repair. Mol Cell 18(6) 617-622... 

The deficiency of an excision endonuclease may produce an exquisite sensitivity to ultraviolet radiation in Xeroderma pigmentosum. Which of the following functions would be absent in a patient deficient in this endonuclease ... 

Investigations by Yarosh over almost two decades have proven that liposomal carriers allow uptake of a DNA repair enzyme into the skin [57], This uptake significantly reduces the number of new actinic keratoses and new lesions of basal cell carcinoma in patients with xeroderma pigmentosum who were treated for 12 months [58], Moreover, in a mice model, transdermal vaccination by antigen incorporation into liposomes has also been demonstrated [59,60],... 

Basal cell nevus syndrome or xeroderma pigmentosum The efficacy and safety of imiquimod cream have not been established for patients with basal cell nevus syndrome or xeroderma pigmentosum. 

Natarajan, A.T., Verdegaal-lmmerzeel, E.A.M., Ashwood-Smifh, M.J. and Poulton, G.A. (1981) Chromosomal damage induced hy furocoumarins and UVA in hamster and human cells including cells from patients with ataxia telangiectasia and xeroderma pigmentosum. Mutation Research, 84, 113-124. 

Patients with xeroderma pigmentosum are prone to develop skin cancer later in life. 

The answer is B. The patient has many of the features characteristic of xeroderma pigmentosum. The lesion, hyperpigmentation (freckles), and erythema are located over sun-exposed areas. His corneas have also suffered damage from exposure to ultraviolet irradiation from the sun. His photosensitivity is also manifested in easy sun-burning and aversion to sun exposure. This condition often leads to skin cancer. 

Park DJ, Stoehlmacher J, Zhang W et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001 61 8654-8658. 

The specific interaction of chemicals or radiation with DNA activate cdlular DNA repair processes which appear to play an important role in carcinogenesis. Eukaryotic cells show enhanced repair capacity for repair of viral nucleic add if the host cells are first damaged by chemicals or irradiation. The ihanced susceptibility to cancer of patients with defective repair systems, such as those with xeroderma pigmentosum, suggests that intact repair mechanisms are protective... 

It is also clear that apart from exposure to carcinogens, other factors such as the genetic predisposition of the organism exposed may also be important. Thus, patients with the genetic disease xeroderma pigmentosum are more susceptible to skin cancer. It has already been mentioned that the incidence of bladder cancer is significantly higher in those individuals who have the slow acetylator phenotype. 

Kim, N., Kage, K., Matsuda, F., Lefranc, M.-P., Storb, U. (1997). B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with inherited defects in nucleotide excision repair are fully capable of somatic hypermutation of immunoglobulin genes. J. Exp. Med. 186,413-419. 

E. coli bacteria4S) and in cultured human cells. In Fig. 21 the survival curves are given for human fibroblasts after treatment with various cispiatin concentrations50 The curves obtained for cells of patients suffering from inherited DNA repair deficiencies, such as xeroderma pigmentosum and Fanconi s anemia, clearly indicate that these cells are more susceptible to the cytotoxic activity of cispiatin than the same type of cells obtained from normal , healthy persons. 

Whilst cells are normally equipped with extensive DNA repair systems these can sometimes become overwhelmed, or they may be defective for genetic reasons. Patients with genetic defects in their DNA repair systems (e.g. Xeroderma pigmentosum, Fanconi s syndrome, Bloom s syndrome) are predisposed to the development of cancer [132]. 

Ultraviolet light produces pyrimidine dimers in human DNA, as it does in E. coli DNA. Furthermore, the repair mechanisms are similar. Studies of skin fibroblasts from patients with xeroderma pigmentosum have revealed a biochemical defect in one form of this disease. In normal fibro-blasts, half the pyrimidine dimers produced by ultraviolet radiation are excised in less than 24 hours. In contrast, almost no dimers are excised in this time interval in fibroblasts derived from patients with xeroderma pigmentosum. The results of these studies show that xeroderma pigmentosum can be produced by a defect in the excinuclease that hydrolyzes the DNA backbone near a pyrimidine dimer. The drastic clinical consequences of this enzymatic defect emphasize the critical importance of DNA-repair processes. The disease can also be caused by mutations in eight other genes for DNA repair, which attests to the complexity of repair processes. 

In 1990, etretinate (Tigason) was replaced by acitretin (Neo-Tigason), an aromatic retinoid, a carboxylic acid metabolite of etretinate (15). It is effective in pustular psoriasis and psoriatic palmoplantar keratoderma and in combination with PUVA or topical therapy (calci-potriol or glucocorticoids) in the treatment of other forms of psoriasis. It has also been used to treat disorders of keratinization (ichthyosis, palmoplantar keratoderma, Darier s disease) and severe cutaneous forms of lichen planus. It prevents new skin carcinomas in patients with xeroderma pigmentosum and those who are immunosuppressed. The main advantage of acitretin is its short half-life of 50 hours, compared with over 80 days for etretinate (16). 

Patients with xeroderma pigmentosum suffer DNA damage when they are exposed to UV light because UV light causes the formation of... 

Patients with xeroderma pigmentosum develop skin cancer when they are exposed to sunlight because they have a deficiency in... 

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