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51.
Hepatocyte growth factor (HGF), a stimulator of angiogenesis and cell migration, regulates the growth of a wide variety of
cells by binding to its high-affinity receptor met and is involved in the growth and aggressiveness of several tumors. In
this study we investigated the expression of HGF and met in normal endocrine cells and related neoplasms of the gut and pancreas
to verify their possible role in tumor pathogenesis, growth, and aggressiveness. Normal tissues and 60 different endocrine
tumors were immunostained using specific antibodies directed against HGF, met, and various hormones. HGF immunoreactivity
(IR) was found in antroduodenal G cells, rectal enterochromaffin (EC) cells, and pancreatic A and B cells, whereas met IR
was detected in antral EC and G cells, and in pancreatic B cells; 46 of 60 tumors examined were positive for HGF, and they
were mainly represented by ECL-, EC-, and L-cell neoplasms. met IR was identified in 50/60 tumors of various phenotypes. HGF
and met coexpression was found in 42/60 cases, most of which were represented by EC-cell tumors. HGF/met coexpression was
significantly more frequent in ileolonic EC-cell tumors, which in the majority of cases were malignant, than in appendiceal
EC-cell tumors, which were all benign. Our results demonstrated, for the first time, that HGF and met are specifically distributed
in normal gut and pancreatic endocrine cells and, in addition, suggest that HGF and met may be implicated as autocrine/paracrine
factors regulating the growth of gastroenteropancreatic endocrine tumors, mainly of ileocolonic EC-cell carcinoids. 相似文献
52.
Mutagenicity of drinking water is due not only to industrial,agricultural and urban pollution but also to chlorine disinfectionby-products. Furthermore, residual disinfection is used to providea partial safeguard against low level contamination and bacterialre-growth within the distribution system. The aims of this studywere to further evaluate the genotoxic potential of the worldwide used disinfectants sodium hypochlorite and chlorine dioxidein human leukocytes by the Comet assay and in Saccharomycescerevisiae strain D7 (mitotic gene conversion, point mutationand mitochondrial DNA mutability, with and without endogenousmetabolic activation) and to compare their effects with thoseof peracetic acid, proposed as an alternative disinfectant.All three disinfectants are weakly genotoxic in human leukocytes(lowest effective dose 0.2 p.p.m. for chlorine dioxide, 0.5p.p.m. for sodium hypochlorite and peracetic acid). The resultsin S.cerevisiae show a genotoxic response on the end-pointsconsidered with an effect only at doses higher (5- to 10-fold)than the concentration normally used for water disinfection;sodium hypochlorite and peracetic acid are able to induce genotoxiceffects without endogenous metabolic activation (in stationaryphase cells) whereas chlorine dioxide is effective in growingcells. The Comet assay was more sensitive than the yeast tests,with effective doses in the range normally used for water disinfectionprocesses. The biological effectiveness of the three disinfectantson S.cerevisiae proved to be strictly dependent on cell-specificphysiological/biochemical conditions. All the compounds appearto act on the DNA and peracetic acid shows effectiveness similarto sodium hypochlorite and chlorine dioxide.
1Author to whom correspondence should be addressed. Tel: +39 0521 905608; Fax: +39 0521 905604; Email: mutgen{at}unipr.it
Received on September 22, 2003; revised and accepted on November 27, 2003 相似文献
53.
Saccharomyces cerevisiae as an eukaryotic cell model to assess cytotoxicity and genotoxicity of three anticancer anthraquinones 总被引:1,自引:0,他引:1
The toxicity of most drugs is associated with their enzymatic conversion to toxic metabolites. Bioactivation reactions occur in a range of cellular organs and organelles, including mitochondria. We have investigated different effects (i.e. growth inhibition, mortality and genotoxicity) of doxorubicin, epirubicin and mitoxantrone on the D7 strain of Saccharomyces cerevisiae and on its petite (rho degrees ) respiratory-deficient mutant at various cellular concentrations of cytochrome P450 and glutathione (GSH). The data confirmed the importance of oxygen production for doxorubicin toxicity. The complete absence, or a very low level, of cytochrome oxidase subunit IV conferred some resistance to doxorubicin. Low GSH levels decreased resistance to doxorubicin in both strains, suggesting that thiol depletion could potentiate membrane lipid peroxidation. Doxorubicin induction of petite colonies suggests that the drug is able to select rather than induce respiratory-deficient mutants. Epirubicin induced levels of cytotoxicity similar to those of doxorubicin. The effects did not appear to be significantly dependent on mitochondrial function or GSH levels, whereas cells were strongly protected by cytochrome P450. GSH did not induce an evident alteration. Neither were genotoxic effects induced. Mitoxantrone had reduced levels of both growth inhibition and cytotoxicity in comparison to anthracyclines and induced convertants, revertants and aberrants. All the effects considered were amplified at high cytochrome P450 cellular concentrations, although the drug was also shown to act without previous metabolism via cytochrome P450. Anthracenedione effectiveness was increased by metabolism via cytochrome P450 and partially reduced by GSH. However, further mechanisms were suggested, which might implicate mitochondrial function and/or production of electrophilic cytotoxic and/or genotoxic intermediates by means of GSH conjugation. The biological effectiveness of doxorubicin, epirubicin and mitoxantrone on S.cerevisiae was shown to be strictly dependent on cell-specific physiological/biochemical conditions, such as a functional respiratory chain and levels of cytochrome P450 and GSH. 相似文献
54.
Evaluation of the BDProbeTec ET system for direct detection of Mycobacterium tuberculosis in pulmonary and extrapulmonary samples: a multicenter study 下载免费PDF全文
Mazzarelli G Rindi L Piccoli P Scarparo C Garzelli C Tortoli E 《Journal of clinical microbiology》2003,41(4):1779-1782
We evaluated the BDProbeTec ET system (Becton Dickinson, Sparks, Md.), a strand displacement amplification-based technique, for direct detection of Mycobacterium tuberculosis in 867 clinical samples. Of 294 extrapulmonary specimens, 52 had positive results by both BDProbeTec ET and culture and 209 had negative results by both methods; sensitivity and specificity were 76.5 and 95.9%, respectively. After resolution of discrepancies, the sensitivity rose to 77.8%. 相似文献
55.
Fausto Sessa Daniela Furlan Anna Genasetti Paola Billo Maddalena Feltri Carlo Capella 《Diagnostic molecular pathology》2003,12(2):96-102
We studied the MSI (microsatellite instability) status and p53 expression in a series of 71 gallbladder cancers (GCs) of different histologic type. All neoplasms were examined combining a microsatellite analysis at mononucleotide locus BAT-26 and an immunohistochemical study for hMSH2, hMLH1, and p53 proteins and markers of gastric and intestinal differentiation. All the 71 GCs were MSS (microsatellite stable). The p53 protein was found in 100% of undifferentiated GCs, 67% of conventional gallbladder adenocarcinomas, 50% of mucinous adenocarcinomas, and 20% GCs with squamous differentiation. All 71 MSS tumors showed presence of immunohistochemical expression of both hMLH1 and hMSH2 gene products. We concluded that microsatellite instability does not play a role in the developing of GC while p53 seems to be the most important alteration found in a large proportion of these cancers, with the only exception of mucinous and squamous gallbladder carcinomas. 相似文献
56.
57.
Sclerosteosis: report of a case in a black African man 总被引:3,自引:0,他引:3
Paolo Tacconi Paola Ferrigno Luigi Cocco Antonino Carinas Giorgio Tamburini Paolo Bergonzi Marcello Giagheddu 《Clinical genetics》1998,53(6):497-501
Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA.
Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry. 相似文献
Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry. 相似文献
58.
Ghiorzo P Villaggio B Sementa AR Hansson J Platz A Nicoló G Spina B Canepa M Palmer JM Hayward NK Bianchi-Scarrà G 《Human pathology》2004,35(1):25-33
Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16. 相似文献
59.
Paola Origone Carlo Bellini Debora Sambarino Barbara Banelli Guido Morcaldi Carmen La Rosa Franco Stanzial Claudio Castellan Domenico A. Coviello Cecilia Garrè Eugenio Bonioli 《Human mutation》2003,22(4):341-341
In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180 相似文献
60.
Malignant granular cell tumor of the lateral femoral cutaneous nerve: report of a case with cytogenetic analysis 总被引:5,自引:0,他引:5
Di Tommaso L Magrini E Consales A Poppi M Pasquinelli G Dorji T Benedetti G Baccarini P 《Human pathology》2002,33(12):1237-1240
Malignant granular cell tumors (MGCTs) are rare neoplasms of uncertain histogenesis. We report a case of MGCT involving a peripheral nerve with peritoneal and omental dissemination in which cytogenetic findings are available. Our results show that MGCTs share some cytogenetic abnormalities with malignant peripheral nerve sheath tumors (MPNSTs), supporting the hypothesis that they may represent histogenetically related lesions. 相似文献