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  • Blackwell Publishing Ltd  (3)
  • International Union of Crystallography (IUCr)
  • Wiley-Blackwell
  • Munksgaard International Publishers
  • 2000-2004  (3)
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  • 1
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. This has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. However, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. Because of this, organ transplant recipients are predisposed to epithelial malignancies and infections. The majority of transplant recipients will develop warts induced by human papillomavirus (HPV). Some of these viral warts may present with atypical histological features and may progress into squamous cell carcinomas. The risk for cutaneous cancers after transplantation is much higher than in the immunocompetent population. Current therapies for HPV-associated skin tumours mainly depend on the destruction of affected skin areas. These treatment modalities are of limited efficacy and are usually painful for the patients. A promising novel therapeutic agent is imiquimod, an immune response modifier. Clinical efficacy of imiquimod has been observed for different skin lesions, including viral warts in both immunocompetent and immunosuppressed patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Premaligant and malignant epithelial lesions are acknowledged as being the most frequent neoplasia in long-term immunosuppressed patients such as organ-transplant recipients. Paralleling the constant improvement in modern transplant techniques, their incidence increases together with the growing survival time post-transplantation, reaching 40% to 60% after 20 years. Against the background of lifelong immunosuppression, the impact of accepted cancer inducers and promoters such as ultraviolet radiation, oncogenic viruses and individual susceptibility has to be closely scrutinized. Precancerous lesions such as actinic keratoses in transplant patients progress more rapidly into squamous cell carcinomas, showing an increased tendency to metastasize. As it remains impossible to identify and consequently treat those lesions that may progress into invasive carcinoma, the best prophylaxis for nonmelanoma skin cancer in organ-transplant recipients may be the treatment of all existing precancerous lesions. As reduction of the immunosuppressive therapy is rarely practicable, other terms of prophylaxis and treatment, such as immune response modifiers, have to be considered.
    Type of Medium: Electronic Resource
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