We explored APC gene mutations and chromosome 5q21 allelic losses (5qLOH) in 18 neoplasms of the papilla of Vater, including 6 early-stage tumours (3 adenomas, 3 carcinomas) and I 2 advanced-stage cancers. Eleven PCR-amplified polymorphic sequences were used to analyse 5qLOH. AfK mutations were investigated both by an In vitro APC-protein truncation test and by single-strand conformation polymorphism analysis. Mutations in the Ki-ras, N-ras and p53 genes were also assessed. We found: 5qLOH in 8 of 16 cases (50%), including I adenoma. 3 early-and 4 advanced-stage cancers; APC mutations in 2 adenomas and I advanced-stage carcinoma; Ki-or N-ras mutations in 3 adenomas and 3 advanced-stage cancers; pS3 mutations in 2 early-stage and 7 advanced-stage adenocarcinomas. Our results suggest that SqLOH, APC mutations and ras mutations are present at early stages, whereas p53 inactivation is associated with progression of malignancy in a large proportion of cases. These data indicate that sporadic ampullary tumours differ from those occurring in familial adenomatous polyposis in the frequency (I 7% vs. 64Oh) as well as in the site of APC somatic mutations, suggesting a different molecular pathogenesis in the 2 conditions. cri 1906 Wilq-Liss, Inc.Ampullary epithelial neoplasms include benign (5%) and malignant tumours (95%) centered in the region of the papilla of Vater. They represent 5% of all sporadic gastrointestinal tumours, but account for up to 36% of the surgically operable pancreatoduodenal tumours, whereas sporadic duodenal neoplasms not originating from ampullary structures arc exccedingly rare. Ampullary and duodenal non-ampullary neoplasms occur at a high frequency in patients affected by familial adenomatous polyposis (FAP) (reviewed in Gallinger et a/.,
Cosmic rays, mostly composed of high energy muons, continuously hit the Earth's surface (at sea level the rate is about 10 000 m−2 min−1). Various technologies are adopted for their detection and are widespread in the field of particle and nuclear physics. In this paper, cosmic ray muon detection techniques are assessed for measurement applications in engineering, where these methods could be suitable for several applications, with specific reference to situations where environmental conditions are weakly controlled and/or where the parts to be measured are hardly accessible. Since cosmic ray showering phenomena show statistical nature, the Monte Carlo technique has been adopted to numerically simulate a particular application, where a set of muon detectors are employed for alignment measurements on an industrial press. An analysis has been performed to estimate the expected measurement uncertainty and system resolution, which result to be strongly dependent on the dimensions and geometry of the set-up, on the presence of materials interposed between detectors and, ultimately, on the elapsed time available for the data taking.
p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single- strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.
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