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  • 1
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Epstein-Barr virus (EBV) initially enters the body through the oropharyngeal mucosa and subsequently infects B lymphocytes through their CD21 (CR2) complement receptor. Mechanisms of EBV entry into and release from epithelial cells are poorly understood. To study EBV infection in mucosal ...
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  • 2
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Proliferative verrucous leukoplakia (PVL) is a recently described clinical entity characterized by multifocal oral lesions that frequently progress to oral cancer despite abstinence from tobacco use by most patients. To determine if this condition is associated with human papillomavirus (HPV), a polymerase chain reaction (PCR) for HPV DNA was performed on 9 lesions from 7 patients with PVL, histologically diagnosed with focal keratosis (1), papilloma (1), epithelial dysplasia (5) and squamous cell cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For comparison, we studied 55 non-PVL-associated oral specimens, including 24 oral squamous cell cancers. Of the cancers, 8 (33%) were HPV positive, 4 for HPV 16. These data suggest that HPV 16 infection may play an important role in the pathogenesis of PVL-associated oral dysplasia and possibly cancer, but is found in only a small proportion of the more common, non-PVL associated-oral lesions.
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  • 3
    ISSN: 1530-0358
    Keywords: Anus ; High-grade squamous intraepithelial lesion ; Carcinoma ; Proliferation ; Apoptosis ; Microvessel density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
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  • 4
    ISSN: 1530-0358
    Keywords: Anus ; Squamous intraepithelial lesion ; Colposcopy ; Human immunodeficiency virus ; Anal cancer ; Anal intraepithelial neoplasia ; Anoscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The incidence of anal cancer is increased in men with a history of anal receptive intercourse. Analogous to cervical cancer, whose precursor is cervical high-grade squamous intraepithelial lesion (HSIL), anal cancer may be preceded by anal HSIL. Although not yet proven, detection, follow-up, and treatment of HSIL may prevent development of anal cancer. Cervical colposcopic methodology was used to describe anal lesions and to determine if HSIL could be distinguished from low-grade squamous intraepithelial lesion (LSIL). METHODS; The colposcopic characteristics of 385 biopsied anal lesions were described and correlated with results of histopathology in a cohort of 121 human immunodeficiency virus-positive and 31 human immunodeficiency-negative homosexual/bisexual men with anal lesions followed as part of a longitudinal study of anal squamous intraepithelial lesions. Color, contour, surface, and vascular patterns of anal lesions were analyzed and correlated with histologic diagnosis. RESULTS: Sixty-seven percent of biopsies showed LSIL and 26 percent showed HSIL. The positive predictive value for anal HSIL in lesions with characteristics typical of cervical LSIL was 7.7 percent (95 percent confidence interval, 1.8–14), whereas the positive predictive value for anal HSIL in lesions with characteristics typical of cervical HSIL was 49 percent (95 percent confidence interval, 40–58). CONCLUSIONS: The colposcopic appearance of different grades of anal squamous intraepithelial lesions was similar to those described for the cervix. Incorporation of colposcopy into assessment of anal disease could aid in distinguishing anal LSIL from HSIL.
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  • 5
    ISSN: 1573-7276
    Keywords: cervical cancer ; cervical intraepithelial neoplasia ; human papillomavirus ; urokinase-type plasminogen activator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The molecular events underlying progression of human papillomavirus (HPV) 16-associated intraepithelial neoplasia to invasive cancer have not been studied in detail. Penetration of the basement membrane is an early, but poorly understood step in this process and probably involves the action of one or more metallo- and serine proteinases. Urokinase-type plasminogen activator (uPA) is a serine proteinase that has been implicated in the pathogenesis of several epithelial tumors, but its role in HPV-associated tumors is not known. To examine uPA expression by HPV 16-transformed keratinocytes in vitro, primary foreskin keratinocyte cultures were transfected by HPV 16 DNA. The primary parental cells and the HPV 16-transformed keratinocytes were studied using substrate gel zymography, Western blot analysis and an in vitro assay measuring penetration of a Matrigel artificial basement membrane. Both uPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were overexpressed in the HPV 16-transformed cells relative to the parental cell line. The transformed cells, but not the parental cells, were able to degrade and penetrate the Matrigel membrane and penetration was blocked by both PAI-1 and by antibodies to uPA. Our data suggest that HPV 16-induced transformation of keratinocytes is associated with upregulation of uPA expression. In conjunction with other proteinases, uPA plays an important role in the ability of HPV 16-transformed keratinocytes to penetrate artificial basement membranes.
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