ISSN:0022-3417    

DOI:10.1002/path.1711750102

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractDespite advances in the design and use of chemotherapeutic drugs, the majority of human cancers are resistant to therapy at presentation or become resistant after an initial partial response. This suggests that resistance may be inherent in a tumour cell or may evolve under the selection pressure of drug administration. A number of possible molecular explanations for drug resistance exist. There may be exclusion of drug from the cell, failure to activate the prodrug to its active form, increased detoxification, alteration in the drug target, enahanced repair capability of the cell after injury, or failure to engage an appropriate response, leading to apoptosis in the damaged cell. Many of these factors may co‐existin vivoin human tumours; some are a feature of cell lineage whilst others appearde novoduring disease progression. Modulation of these mechanisms has been of some value in laboratory studies but widespread clinical application and benefit remain some way of

ISSN:0022-3417    

DOI:10.1002/path.1711750103

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractOverexpression of the multidrug resistance gene,mdr1, and its product, P‐glycoprotein (Pgp), has been associated with cross‐resistance to structurally unrelated compounds in cell lines and tumours. Recently, a non‐Pgp‐mediated form of drug resistance has been described, due to the overexpression of p110, a transport protein. Thirty formalin‐fixed, paraffin‐embedded neuroblastoma samples from 21 cases were examined for overexpression ofmdr1and Pgp using newly established non‐radioactivein situhybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease and from primary and metastatic sites. Paired tumour samples (pre‐chemotherapy and post‐chemotherapy) were available from cases with stage 2 (n=1) and stage 4 disease (n=8). Immunoreactivity to p110 was also tested on all the samples.Mdr1mRNA was expressed in 16/21 cases and in all the stages. Pgp immunoreactivity was detected in all the cases. Weak cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression ofmdr1, Pgp, and p110 showed a statistically significant (two‐sided Fisher exact test,P=0.04, 0.03, 0.04, respectively) correlation with differentiation (Beckwith and Martin grading) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variables: age less than 1 year at diagnosis and stages 1, 2, and 4 s (two‐sided Fisher exact test,P=0.01

ISSN:0022-3417    

DOI:10.1002/path.1711750104

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe feasibility of treating solid tumours with differentiation therapy using antineoplastic drugs is currently being investigated, but the emergence of multidrug resistance remains the major limitation to this therapeutic approach. A rhabdomyosarcoma cell line resistant to actinomycin D (RD‐DAC) has been used as anin vitromodel to investigate, with light and electron microscopy, the degree of differentiation in multidrug‐resistant cells. The parental cell line (RD), derived from a human embryonic‐type rhabdomyosarcoma, is undifferentiated, with no evidence of specific ultrastructural markers. Examination of resistant cells by transmission electron microscopy revealed myofilaments arranged parallel to the long axis of the cell, which was considered clear evidence of myogenic differentiation. These observations suggest that actinomycin D, the drug of choice in the treatment of rhabdomyosarcoma, induces differentiation in the cell line RD. It is postulated that multidrug resistance can interfere with cellular differenti

ISSN:0022-3417    

DOI:10.1002/path.1711750105

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study investigates themdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico‐pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bearmdm2 gene amplification (four‐ to ten‐fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three‐fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty‐seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P<0.0001). No association was observed betweenmdm2 gene amplification and any of the considered clinico‐pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P=0.009). p53 expression was associated neither withmdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 pr

ISSN:0022-3417    

DOI:10.1002/path.1711750106

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractSeven early gastric cancers obtained from patients also demonstrating Epstein‐Barr virus (EBV)‐positive gastric medullary carcinoma with lymphoid infiltration were investigated using a combined polymerase chain reaction (PCR) andin situhybridization (ISH) approach. Sharing the same background mucosa as gastric medullary cancers, they comprised four intramucosal carcinomas, predominantly well‐differentiated adenocarcinomas, and three submucosal carcinomas, histologically showing mixtures of well and poorly differentiated adenocarcinoma. In the three cases of submucosal carcinoma, the presence of EBV was proven by means of both PCR and ISH. However, not all cancer cells were positive for EBV on the basis of ISH examination, in contrast to the large series of gastric carcinoma with lymphoid infiltration previously investigated. All four mucosal carcinomas were EBV‐negative. Lymphocyte‐determined membrane antigen (LYDMA) monoclonality, performed by PCR, and latent membrane protein‐1 (LMP‐1) and Epstein‐Barr virus (EBNA2) expression, assessed immunohistochemically, were negative in all seven cases. The results suggest that EBV becomes associated with gastric medullary carcinoma with lymphoid infiltration (GMCL) at a relatively early stage of the disease, shortly after the tumour has initially progressed to an invasive form, and plays some role in the manife

ISSN:0022-3417    

DOI:10.1002/path.1711750107

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of cell adhesion is a critical event in the development of tumour invasiveness and metastases. Although loss of cadherin expression has been demonstrated to be associated with increased invasiveness and metastatic potential in some tumours, others, including renal carcinoma, show no such correlation. The aim of this study was to demonstrate that cell adhesion could be lost in phorbol ester‐treated renal epithelial cells and renal tumour cells without loss of A‐CAM expression. The model used has been shown previously to mimic changes that occur in the progression of renal carcinoma. We found that A‐CAM expression persists on the lateral surfaces of phorbol ester‐treated cells even though these cells lose cell‐cell adhesion. Similar findings were seen in renal carcinoma cells in culture. We conclude that loss of cell adhesion between tumour cells may occur either by loss of cadherins or as a result of loss cadherin function occurring as a consequence of cell trans

ISSN:0022-3417    

DOI:10.1002/path.1711750108

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractHaemangiomas are vascular tumours characterized by rapid growth and increased endothelial turnover. VE‐cadherin is a recently discovered endothelial cell‐specific cadherin located at intercellular junctions. In different types of epithelial tumours, cadherin expression is inversely correlated with invasiveness and metastatic dissemination. In this immunohistochemical study, VE‐cadherin expression has been analysed in different types of haemangioma. VE‐cadherin is highly expressed in endothelial cells of haemangiomas and is decreased, but still detectable, in some cases of haemangionendothelioma and angionsarcoma. The antigenic profile of most haemangioma cells was similar to that of normal endothelium. CD31, CD34, ICAM‐1, von Willebrand factor, and VLA integrins were expressed in haemangioma endothelium; in addition, the major components of vascular basement membrane, namely fibronectin, collagen type IV, and laminin, were correctly expressed and organized. Surprisingly, a marked reactivity for the M form of laminin (merosin) was detected in the basement membranes of two juvenile capillary haemangiomas. Overall, this study shows that, with the exception of angiosarcoma and haemangionendothelioma, vascular tumours maintain most of the differentiation characteristics of normal endothelium. This encourages speculation that in these pathologies, abnormal endothelial proliferation is more related to the release of local factors than to an altered endothelial

ISSN:0022-3417    

DOI:10.1002/path.1711750109

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn tumour development, proteases such as plasminogen activators (PAs) play a role in degradation of the extracellular matrix and other tissue barriers. Recently, we demonstrated that plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of cutaneous melanocytic tumour progression. In this study we investigated the expression and distribution of the various components of the PA system and the presence of PA enzyme activity in 45 freshly frozen primary uveal melanomas with known follow‐up (14 spindle and 31 non‐spindle type) and in metastases (n=5). Tissue‐type PA (t‐PA) was found in endothelium of blood vessels and in tumour cells in almost all leisons, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour‐related death could be established. Urokinase PA (u‐PA) was expressed focally, by only five non‐spindle cell melanomas but in all metastases. u‐PA expression correlated with occurence of metastasis. u‐PA receptor (u‐PAR) was present in one‐third of all the tumours examined. Plasminogen activator inhibitors (PAI‐1 and PAI‐2) were found only focally in approximately 10 per cent of the lesions. Staining of t‐PA, u‐PA, and PAI was observed in all the metastases. We conclude that in uveal melanoma, u‐PA expression may be associated with metastatic disease and accordingly with a poor prognosis. Further research on a larger group of tumours with known follow‐up is needed to establish whether u‐PA positivity is of additional

ISSN:0022-3417    

DOI:10.1002/path.1711750110

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe development of ductular structures in acute hepatitis with panacinar necrosis was studied in 15 cases of fulminant hepatitis with variable clinical duration, using immunohistochemical markers. The immunophenotype of ductular structures was assessed by the expression of two bile duct epithelium determinants, wide spectrum cytokeratin and epithelial membrane antigen (EMA), and by their glycoconjugate expression using the specific binding lectinsDolichos biflorusagglutinin (DBA) and soybean agglutinin (SBA). Ductular structures showed a predilective, but not a strictly selective location in acinar zone 1 and at the periphery of newly formed parenchymal nodules. All were positive for keratin, while EMA and the lectins were identified less frequently. Cytokeratin expression was additionally observed in hepatic cells with no other phenotypic alteration: this occurred along isolated hepatic cords, within parenchymal remnants, in the spared parenchyma in acinar zone 1 and occasionally at the periphery of parenchymal nodules. The presence of cytokeratin expression in liver cell plates in association with intermediate morphological stages of tubular remodelling speaks in favour of biliary metaplasia of hepatocytes. This process may represent a phenotypic‐functional accommodation of hepatocytes to an altered microenvironment, due to loss of parenchymal integrity. During the phenotypic shift, altered cytokeratin expression appears as one of the earliest biliary features, while EMA and the expression of glycoconjugates represent maturation marker

ISSN:0022-3417    

DOI:10.1002/path.1711750111

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY