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  • CANCER  (2)
  • 1
    Keywords: CANCER ; EXPRESSION ; TUMORS ; p53 ; HPV ; SQUAMOUS-CELL CARCINOMA ; INDIVIDUALS ; p16(INK4A) ; TRANSPLANT RECIPIENTS ; STAPHYLOCOCCUS-AUREUS
    Abstract: BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P〈0.001) and basal cell cancers (P = 0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P = 0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P = 0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions
    Type of Publication: Journal article published
    PubMed ID: 21427726
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  • 2
    Keywords: ANGIOGENESIS ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; GROWTH ; IN-VITRO ; proliferation ; tumor ; CELL ; Germany ; human ; IN-VIVO ; INHIBITION ; tumor growth ; VITRO ; VIVO ; DENSITY ; RISK ; GENE ; PROTEIN ; TUMORS ; MICE ; PATIENT ; MECHANISM ; TRANSCRIPTION FACTOR ; TRANSPLANTATION ; mechanisms ; fibroblasts ; ACID ; MALIGNANCIES ; ASSAY ; NUDE-MICE ; MODULATION ; RELATIVE RISK ; signaling ; AGENT ; molecular ; ONCOLOGY ; MOLECULAR-BASIS ; fibroblast ; TUMOR-GROWTH ; DEHYDROGENASE ; mycophenolic acid ; MOLECULAR-MECHANISMS ; analysis ; ASSAYS ; USA ; cancer research ; PROTEIN-KINASE-A ; GLIOBLASTOMA ; microvascular density ; quantitative ; MOFETIL
    Abstract: The relative risk for the development of malignancies following solid organ transplantation seems to be decreased in patients treated with the immunosuppressive agent mycophenolic acid (MPA). However, the molecular mechanisms of the antineoplastic effects of MPA are not completely understood. Here, we report that human endothelial cells and fibroblasts are highly sensitive to MPA treatment. We found that U87 glioblastoma cells were resistant to MPA treatment in vitro. However U87 tumor growth was markedly inhibited in vivo in BALB/c nude mice, suggesting that MPA exerted its antitumor effects via modulation of the tumor microenvironment. Accordingly, microvascular density and pericyte coverage were markedly reduced in MPA-treated tumors in vivo. Using functional in vitro assays, we showed that MPA potently inhibited endothelial cell and fibroblast proliferation, invasion/migration, and endothelial cell tube formation. To identify the genetic participants governing the antiangiogenic and antifibrotic effects of MPA, we performed genome-wide transcriptional analysis in U87, endothelial and fibroblast cells at 6 and 12 h after MPA treatment. Network analysis revealed a critical role for MYC signaling in endothelial cells treated with MPA. Moreover, we found that the antiangiogenic effects of MPA were organized by coordinated communications between MYC and NDRG1, YY1, HIF1A, HDAC2, CDC2, GSK3B, and PRKACB signaling. The regulation of these "hub nodes" was confirmed by real-time quantitative reverse transcription-PCR and protein analysis. The critical involvement of MYC in the antiangiogenic signaling of MPA was further shown by gene knockdown experiments. Together, these data provide a molecular basis for the antiangiogenic and antifibrotic effects of MPA, which warrants further clinical investigations
    Type of Publication: Journal article published
    PubMed ID: 18566237
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