49 research outputs found

    MDM2 overexpression is rare in Ovarian Carcinoma irrespective of TP53 mutation status

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    Somatic mutations in TP53 are seen in many human cancers. In addition, the protein product of the wild-type TP53 can be sequestered by the protein MDM2 (murine double minute 2). This protein is commonly overexpressed in human sarcomas and gliomas, usually as a result of gene amplification. In this study, 43 ovarian carcinomas (OCs) were analysed for aberrations in the TP53 gene by immunohistochemistry (IHC), loss of heterozygosity (LOH) or mutation analysis. The MDM2 gene and its product was studied by Southern blotting and IHC. Over 50% of the OCs studied showed mutations in TP53 by either direct sequencing (19/36, 53%), positive IHC (23,43, 53%) or both, whereas 0/32 had amplification of MDM2 and only 1/37 tumours had positive IHC using the anti-MDM2 antibody IF-2. The solitary example of positive IHC in this series was seen in a mixed müllerian tumour with sarcomatous differentiation and was not accompanied by MDM2 DNA amplification. These results support previous data showing that around 50% of OCs have mutations in TP53 and in addition, suggest that MDM2 is not amplified in OC, but the presence of sarcomatous features in mixed müllerian tumours may result in positive immunohistochemistry with IF-2

    Exploding electron bubbles.

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    Electron bubbles, used in laboratories throughout the world for probing the unusual properties of liquid helium, can be made to explode by the application of negative pressure, according to investigations by Classen et al. published last month

    PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

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    Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients

    Lysozyme gene expression in inflammatory bowel disease.

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    Riboprobe in situ hybridization (rISH) demonstrates active lysozyme synthesis in ulcerative colitis and Crohn's disease. Maximal labeling was seen in Paneth cells, macrophages, and granulomas. Diffuse infiltration of the mucosa by lysozyme-rich polymorphs characterizes ulcerative colitis but obscures reactivity in other cell lineages in immunohistochemical studies; lysozyme mRNA is not detected in polymorphs, rISH giving a clearer picture than immunohistochemical studies of the active synthesis of lysozyme within the gut in inflammatory bowel disease. In ulcerative colitis, strong signals localized to Paneth cell metaplasia were found in 11 of 20 cases and to a lesser degree in non-Paneth cell lineages in regenerative mucosa in 13 of 20 cases. In Crohn's disease, abundant labeling was seen in tuberculoid granulomas (5 of 20) and over macrophage aggregates in the lamina propria in another 7, characteristic patterns not encountered in ulcerative colitis. Low levels of lysozyme messenger RNA were found in the ulceration-associated cell lineage ("pseudopyloric metaplasia"). These results support the view that neutrophils are largely responsible for elevated fecal lysozyme levels in ulcerative colitis and macrophages for elevated serum lysozyme levels in Crohn's disease

    Effect of packaging on the spoilage of king scallop (Pecten maximus) during chilled storage

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    Biochemical and sensory measures of quality for frozen king scallops which had been thawed and stored in melting ice were compared with those for samples wrapped in aluminium foil and cling film and then stored in a refrigerator at 4°C.Significant differences (P≤0.05) were apparent between the iced and packaged samples with respect to flesh concentrations of trimethylamine oxide nitrogen, trimethylamine nitrogen (TMA-N) and total volatile basic nitrogen (TVB-N) and the sensory aspects of appearance and smell after 7 days of storage. TMA-N and TVB-N levels were substantially higher in the packaged samples, exceeding the limits for fitness by days 9 and 7 respectively in both packaged samples, whilst in the iced sample the limit was not exceeded even after 16 days of storage. The latter sample, however, was judged unfit for consumption by sensory analysis after day 9. The levels of the biochemical indices of spoilage, TMA-N and TVB-N, would appear, therefore, to be misleadingly depressed through the leaching effect of the ice meltwater. © Springer-Verlag 2001.This work was funded by the Project QUALPOISS 2: FAIR PL. 97.3253. The fellowship awarded by the Ministry of Education and Science of Spain is gratefully acknowledged.Peer Reviewe
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