Molecular pathology : MP最新文献

{"title":"Molecular aspects of multiple myeloma.","authors":"G Pratt","doi":"10.1136/mp.55.5.273","DOIUrl":"https://doi.org/10.1136/mp.55.5.273","url":null,"abstract":"<p><p>Multiple myeloma is a malignant tumour of plasma cells with a median survival of two to three years. Karyotypic instability is seen at the earliest stage of the disease and increases with disease progression, leading to extreme genetic abnormalities similar to solid tumours. Translocations involving the immunoglobulin heavy chain region on chromosome 14q32 are clearly important in the pathogenesis of most myelomas. This review focuses on the different genetic abnormalities found in myeloma and discusses possible pathogenetic mechanisms and the implications for biologically based treatments.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"273-83"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori.","authors":"H Eguchi,&nbsp;S F Moss","doi":"10.1136/mp.55.5.284","DOIUrl":"https://doi.org/10.1136/mp.55.5.284","url":null,"abstract":"Purpose of review Helicobacter pylori is an important human pathogen, responsible for most peptic ulcer disease, gastritis and gastric malignancies. H. pylori has several unique features: it is highly adapted for gastric colonization, yet it produces clinical consequences in a small minority, its genome is known, and it is the only bacterium strongly associated with cancer. H. pylori is therefore of great interest to clinicians and researchers of many, often disparate, disciplines. We highlight recent advances in this fast changing field from many different areas. Recent findings The major contentious clinical issues relate to the synergistic gastrotoxic interactions of H. pylori with non-steroidal anti-inflammatory drugs, and a possible association of H. pylori with atherosclerotic events. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. Studies of pathogenesis have been aided by increasingly sophisticated murine models. The effects in gastric epithelial cells of two of the major virulence factors (genes within the cag pathogenicity island and the vacuolating cytotoxin, VacA) of H. pylori illustrate the complex network of cellular reactions activated by H. pylori. The metabolism of H. pylori is dependent on the availability of hydrogen. Summary Basic science research into H. pylori continues to elucidate the mechanisms by which H. pylori infection causes disease. These findings have implications for the design of novel therapies and for improving clinical strategies to identify at-risk individuals. Many are also worthy of consideration for other epithelial-microbial interactions.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"284-5"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of proteinases and inhibitors in human breast cancer progression and survival.","authors":"E A Baker,&nbsp;T J Stephenson,&nbsp;M W R Reed,&nbsp;N J Brown","doi":"10.1136/mp.55.5.300","DOIUrl":"https://doi.org/10.1136/mp.55.5.300","url":null,"abstract":"<p><strong>Aims: </strong>The expression of proteinases and their inhibitors determines the extracellular matrix (ECM) turnover in normal and pathological processes. In cancer, proteolysis is abnormally regulated, favouring ECM degradation, which aids tumour invasion and metastasis. Previous studies have determined the expression of proteinases and inhibitors in breast cancer using a variety of techniques, including immunohistochemistry; however, most have looked at the expression of individual proteinases and/or inhibitors. Therefore, the aim of the current study was to determine the simultaneous cellular expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and tissue inhibitors of metalloproteinases (TIMPs) in patients with breast cancer and correlate this with clinical pathological staging and survival.</p><p><strong>Methods: </strong>Immunohistochemistry was used to determine the expression of proteinases (MMP-1, MMP-2, MMP-3, MMP-9, urokinase-type PA, and tissue-type PA) and inhibitors (TIMP-1 and TIMP-2) in 44 patients with breast cancer.</p><p><strong>Results: </strong>The expression of all the factors studied was stronger or equivalent in tumour cells than in fibroblasts or inflammatory cells within the tumour section. Both positive and negative trends have emerged in the correlation between the cellular expression of proteinases and inhibitors and breast tumour pathology (tumour grade, lymphovascular invasion, and Nottingham prognostic index).</p><p><strong>Conclusions: </strong>The interactions between proteinases and their inhibitors in breast cancer progression are complex. Although there are differences in the expression of these factors that relate to differences in breast cancer pathology, there are no outstanding individual factors that consistently correlate with prognosis. Therefore, different factors are probably important at different stages of the process, and the balance in the relative concentrations of proteinases and inhibitors probably determines ECM degradation in breast tumour invasion and metastasis in vivo.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"300-4"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The production and characterisation of a chimaeric human IgE antibody, recognising the major mite allergen Der p 1, and its chimaeric human IgG1 anti-idiotype.","authors":"P B Furtado,&nbsp;J E McElveen,&nbsp;L Gough,&nbsp;K L Armour,&nbsp;M R Clark,&nbsp;H F Sewell,&nbsp;F Shakib","doi":"10.1136/mp.55.5.315","DOIUrl":"https://doi.org/10.1136/mp.55.5.315","url":null,"abstract":"<p><strong>Background: </strong>Two mouse monoclonal antibodies have been described, namely: mAb 2C7 (IgG2bkappa), which is directed against the major house dust mite allergen Der p 1, and mAb 2G10 (IgG1kappa), which is an anti-idiotypic antibody raised against mAb 2C7. Given its broad IgE specificity, anti-idiotype mAb 2G10 could potentially have immunomodulatory applications. For example, a chimaeric human IgG version of mAb 2G10 could prove to be a useful molecule for binding to mast cell and basophil FcepsilonRI bound IgE, and in doing so co-ligating FcepsilonRI with FcgammaRIIB, which has been reported to have downregulatory effects.</p><p><strong>Aims: </strong>To produce a chimaeric human IgE version of mAb 2C7 (mAb 2C7huE) and a chimaeric human IgG1 version of its anti-idiotype mAb 2G10 (mAb 2G10huG1).</p><p><strong>Methods: </strong>The Vkappa and VH regions of mAb 2C7 and its anti-idiotype mAb 2G10 were engineered into human constant regions of the IgE and IgG1 isotypes, respectively.</p><p><strong>Results: </strong>The production of chimaeric mAb 2C7huE and its anti-idiotype mAb 2G10huG1 confirmed that the respective mouse antibody V regions were successfully engineered into human constant regions and still retained the specificity of the original murine V regions.</p><p><strong>Conclusion: </strong>The newly constructed chimaeric antibodies will be useful to investigate the downregulation of IgE mediated hypersensitivity by the crosslinking of FcepsilonRI with FcgammaRIIB.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"315-24"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can electorporation make all the difference in gene therapy?","authors":"","doi":"10.1136/mp.55.5.285","DOIUrl":"https://doi.org/10.1136/mp.55.5.285","url":null,"abstract":"","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"285 - 285"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer.","authors":"A P M Jongsma,&nbsp;J M J Piek,&nbsp;R P Zweemer,&nbsp;R H M Verheijen,&nbsp;J W T Klein Gebbinck,&nbsp;G J van Kamp,&nbsp;I J Jacobs,&nbsp;P Shaw,&nbsp;P J van Diest,&nbsp;P Kenemans","doi":"10.1136/mp.55.5.305","DOIUrl":"https://doi.org/10.1136/mp.55.5.305","url":null,"abstract":"<p><strong>Background/aims: </strong>Loss of heterozygosity (LOH) on chromosome 13q has been reported to occur frequently in human ovarian cancer, and indications have been found that chromosome 13 may also play a specific role in the inherited form of ovarian cancer. The aim of this study was to define regions on chromosome 13 that may harbour additional tumour suppressor genes involved in the tumorigenesis of BRCA1 related ovarian and fallopian tube cancer.</p><p><strong>Materials/methods: </strong>DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q.</p><p><strong>Results: </strong>High LOH frequencies were found on loci 13q11, 13q14, 13q21, 13q22-31, 13q32, and 13q32-4, suggesting the presence of putative tumour suppressor genes on the long arm of chromosome 13 that may play a role in the pathogenesis of BRCA1 related ovarian and fallopian tube cancer. LOH patterns appeared to be independent of the type of BRCA1 mutation, stage, and grade. Although in some cases there were indications for loss of larger parts of chromosome 13, in most cases losses were fairly randomly distributed over chromosome 13 with retained parts in between lost parts. Microsatellite instability was found in six cases.</p><p><strong>Conclusion: </strong>Several loci on chromosome 13q show high frequencies of LOH in BRCA1 related ovarian and fallopian tube cancer, and may therefore harbour putative tumour suppressor genes involved in the carcinogenesis of this particular type of hereditary cancer.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"305-9"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of C-MYB DNA binding to cognate responsive elements in HL-60 variant cells.","authors":"C Gaillard, E Le Rouzic, C Créminon, B Perbal","doi":"10.1136/mp.55.5.325","DOIUrl":"10.1136/mp.55.5.325","url":null,"abstract":"<p><strong>Aims: </strong>To establish whether the MYB protein expressed in HL-60 variant cells, which are cells resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA) induced differentiation, is able to bind MYB recognition elements (MREs) involved in the transcriptional regulation of myb target genes. In addition, to determine whether alterations in the binding of the MYB protein to MREs affects HL-60 cell proliferation and differentiation.</p><p><strong>Methods: </strong>Nuclear extracts of HL-60 variant cells exhibiting different degrees of resistance to TPA induced monocytic differentiation were used in electrophoretic mobility shift experiments (EMSAs), bandshift experiments performed with labelled oliogonucleotides containing the MYB consensus binding sequences.</p><p><strong>Results: </strong>The MYB protein contained in nuclear extracts from HL-60 variant cells did not bind efficiently to the MYB recognition elements identified in the mim-1 and PR264 promoters. Molecular cloning of the myb gene and analysis of the MYB protein expressed in the HL-60 variant cells established that the lack of binding did not result from a structural alteration of MYB in these cells. The lack of MRE binding did not abrogate the ability of variant HL-60s to proliferate and to undergo differentiation. Furthermore, the expression of the PR264/SC35 splicing factor was not affected as a result of the altered MYB DNA binding activity.</p><p><strong>Conclusions: </strong>Because the MYB protein expressed in HL-60 variant cells did not appear to be structurally different from the MYB protein expressed in parental HL-60 cells, it is possible that the HL-60 variant cells contain a MYB binding inhibitory factor (MBIF) that interferes with MYB binding on MREs. The increased proliferation rate of HL-60 variant cells and their reduced serum requirement argues against the need for direct MYB binding in the regulation of cell growth.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"325-35"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187265/pdf/mp55000325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori.","authors":"S Maeda,&nbsp;H Yoshida,&nbsp;Y Mitsuno,&nbsp;Y Hirata,&nbsp;K Ogura,&nbsp;Y Shiratori,&nbsp;M Omata","doi":"10.1136/mp.55.5.286","DOIUrl":"https://doi.org/10.1136/mp.55.5.286","url":null,"abstract":"<p><strong>Background and aims: </strong>Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated.</p><p><strong>Methods: </strong>(1) H pylori strains (type 1 wild, TN2-deltacagE, TN2-deltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor IkappaBalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay.</p><p><strong>Results: </strong>(1) Wild-type and deltavacA mutant H pylori induced apoptosis more potently than the deltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor IkappaBalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains.</p><p><strong>Conclusion: </strong>cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"286-93"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Further evidence to support the melanocytic origin of MDA-MB-435.","authors":"G Ellison,&nbsp;T Klinowska,&nbsp;R F R Westwood,&nbsp;E Docter,&nbsp;T French,&nbsp;J C Fox","doi":"10.1136/mp.55.5.294","DOIUrl":"https://doi.org/10.1136/mp.55.5.294","url":null,"abstract":"<p><strong>Background/aims: </strong>Until recently, the cell line MDA-MB-435 was widely accepted as originating from a breast cancer. However, microarray derived data have suggested that this cell line may in fact originate from an occult melanoma. This study was designed to investigate this hypothesis further.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to investigate the tissue of origin of two sublines of MDA-MB-435 (MDA-MB-435 S and MDA-MB-435 HGF). The expression of a panel of genes typical of breast cells or melanocytes was analysed.</p><p><strong>Results: </strong>The MDA-MD-435 cell lines expressed none of the genes characteristic of breast cancer cells but did express several genes commonly expressed by melanocytes.</p><p><strong>Conclusions: </strong>These results strongly suggest that MDA-MB-435 is indeed of melanoma origin.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"294-9"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymidylate synthase protein expression and activity are related to the cell proliferation rate in human cancer cell lines.","authors":"M Derenzini,&nbsp;L Montanaro,&nbsp;D Treré,&nbsp;A Chillà,&nbsp;P L Tazzari,&nbsp;F Dall'Olio,&nbsp;D Ofner","doi":"10.1136/mp.55.5.310","DOIUrl":"https://doi.org/10.1136/mp.55.5.310","url":null,"abstract":"<p><strong>Aims: </strong>To ascertain whether the expression and enzyme activity of thymidylate synthase (TS) are related to the rapidity of cell proliferation in human cancer cell lines.</p><p><strong>Methods: </strong>Ten asynchronously growing human cancer cell lines of different origin were used, characterised by various doubling times. TS expression was evaluated by western blot analysis using the TS 106 monoclonal antibody. TS activity was determined by the enzyme catalytic assay. The quantitative variation of TS in different phases of the cell cycle was investigated using two parameter flow cytometry for the TS protein and DNA analysis. The number of proliferating cells was evaluated by Ki67 immunostaining.</p><p><strong>Results: </strong>TS expression and activity were significantly related to each other (r = 0.765; p = 0.01) and to the cell doubling time (r = -0.899; p < 0.001 and r = -0.919; p < 0.001, respectively). Ki67 immunolabelling showed no association between the number of cycling cells and TS protein expression and activity. Two parameter flow cytometry indicated that differences of TS expression in the cell lines were not related to the cell cycle phases or to the proportion of S phase cells.</p><p><strong>Conclusions: </strong>These results show that the expression and activity of the TS protein in asynchronously growing cancer cells are significantly related to the cell doubling time; the faster the cell proliferation, the greater the expression and activity of TS. These findings could explain why TS values are of prognostic value per se and why tumours with high TS expression benefit more from chemotherapy.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 5","pages":"310-4"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.5.310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22046303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}