bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of apoptosis in modulation of the growth of human colorectal tubular and villous adenomas
Authors: Arai Tomio , Kino Isamu 
Published: June 2005

AbstractTo estimate the effect of cell proliferation and deletion on the growth of the human colorectal adenoma, 27 tubular adenomas and eight villous adenomas were examined. Tubular adenomas were categorized into three grades of cellular atypia: mild, moderate, and severe. Villous adenomas were give a single grade. Morphological characteristics of apoptosis (nuclear condensation and budding) were used to quantify an apoptotic index, AI (percentage of apoptotic cells in viable adenomatous cells). The apoptotic cells were found mainly among the basal site of the adenomatous tubules. The AIs of tubular adenomas with mild, moderate, and severe grades of atypia were 3·5, 5·7 and 8·8 per cent, respectively. The AI of villous adenomas was 1·8 per cent, which was significantly lower than that of tubular adenomas. The mitotic indices, MIs (percentage of mitotic cells in viable adenomatous cells) of tubular adenomas were 0·41 per cent (mild), 0·58 per cent (moderate), and 0·83 per cent (severe), and for villous adenomas the MI was 0·38 per cent. There was a close positive relationship between the AI and MI of tubular adenomas, which paralleled the grade of atypia. These results indicate that both cell proliferation and death were more frequent in adenomas with severe atypia than in adenomas with mild atypia. Moreover, the significantly lower AI of villous adenomas, known to develop into large tumours when compared with tubular adenomas, suggests that reduced apoptoses may lead to a shift in tissue kinetics towards expansive growth.
Immunohistochemical detection of p53 protein in archival tissues from squamous cell carcinomas of the oral cavity using wet autoclave antigen retrieval
Authors: Piffko J. , Bankfalvi A. , Öfner D. , Joos U. , Böcker W. , Schmid K. W. 
Published: June 2005

AbstractUsing a panel of four anti‐p53 antibodies (CM‐1, PAb 1801, DO7, and PAb 240), the phenotypic characteristics of p53 protein overexpression were investigated in 22 routinely formalin‐fixed and paraffin‐embedded squamous cell carcinomas of the oral cavity. Conventional immunohistochemical staining without pretreatment for antigen retrieval was compared with wet autoclaving (AC) and microwave irradiation (MW). Applying AC or MW, p53 immunoreactivity was demonstrated in 9/22 cases with PAb 1801 and DO7 antibodies and in 8/22 cases with the CM‐1 antibody. Immunostaining with the PAb 240 antibody after AC pretreatment showed p53 positivity in 8/22 tumours, but in only 4/22 following MW pretreatment. Immunostaining without pretreatment revealed only 2/22 p53‐positive cases using CM‐1, 4/22 with PAb 1801, and 3/22 with DO7. Without pretreatment, the PAb 240 antibody was consistently negative. Wet autoclave pretreatment was significantly superior for all the antibodies used in this study when compared with conventional immunohistochemistry without pretreatment (P<0·005). It yielded better results than microwave irradiation for antigen unmasking in relation to the PAB 240 antibody (P<0·05). Wet autoclave pretreatment is recommended as a reliable and highly reproducible method for p53 antigen retrieval in routinely processed archival material. The advantages over microwave pretreatment include simple handling and good preservation of morphology.
Numerical aberrations of chromosomes 1 and 7 in renal cell carcinomas as detected by interphase cytogenetics
Authors: Beck J. L. M. , Hopman A. H. N. , Feitz W. F. J. , Schalken J. , Schaafssma H. E. , Van De Kaa C. A. , Ramaekers F. C. S. , Hanselaar A. G. J. M. , De Wilde P. C. M. 
Published: June 2005

AbstractAlcohol‐fixed single cell suspensions of 37 renal cell carcinomas (RCCs) were assessed by both flow cytometry (FCM) and the fluorescence in situ hybridization (FISH) technique, using chromosome 1‐ and chromosome 7‐specific centromere DNA probes. DNA diploidy or near‐diploidy was observed in 30 of the 37 RCCs and only 12 of these (near‐)diploid tumours were disomic for both chromosomes 1 and 7. Numerical aberrations of chromosome 1 and/or chromosome 7 were present in 18 of the 30 (near‐)diploid RCCs and five of these cases showed monosomy for chromosome 1 in more than 50 per cent of the tumour cells. A double target FISH, with a centromeric and a telomeric specific probe for 1p36, excluded misinterpretation on the basis of clustering of 1q12, and suggested a complete loss of chromosome 1. All these five (near‐)diploid RCCs with monosomy for chromosome 1 were eosinophilic chromophilic cell carcinomas, according to the Thoenes classification of RCC. This observation is of special interest, because it was recently concluded from cytogenetic studies that the diagnosis of chromophilic renal cell carcinoma must be considered as obsolete. Monosomy for chromosome 1 seems to be a non‐random numerical aberration of (near‐)diploid eosinophilic chromophilic cell carcinomas, and a gain of one or more chromosomes 1 appeared to be a common phenomenon in RCCs, especially in the DNA aneuploid tumours. As these chromosomal abnormalities were not found in the earlier classical cytogenetic studies, we conclude that in situ hybridization techniques are required in addition to chromosome banding techniques to obtain a complete characterization of the chromosome imbalances in RCCs.
Diagnosis of Ewing's sarcoma and related tumours by detection of chromosome 22q12 translocations using fluorescence in situ hybridization on tumour touch imprints
Authors: McManus Aidan P. , Gusterson Barry A. , Pinkerton C. Ross , Shipley Janet M. 
Published: June 2005

AbstractIt is increasingly recognized that the identification of t(11;22)(q24;q12) is a useful aid in the accurate diagnosis of Ewing's sarcoma and related tumours. However, cytogenetic studies have a low success rate and adequate tumour is not always available. This study describes the use of fluorescence in situ hybridization (FISH) to detect translocations at 22q12, the site of the EWS gene involved in t(11;22)(q24;q12), on tumour touch imprints made from true cut core‐needle biopsy and frozen tumour. Of the seven tumours analysed, five diagnosed as Ewing's sarcoma or primitive neuroectodermal tumour demonstrated chromosome translocation at 22q12. This is a rapid and reliable method to detect a diagnostically relevant chromosome translocation using minimal amounts of fresh or frozen tumour.
Distribution of sialosyl Tn and Tn antigens within normal and malignant colorectal epithelium
Authors: Jass Jeremy R. , Allison Louise J. , Edgar Stephen G. 
Published: June 2005

AbstractExpression of the core blood group structures sialosyl Tn (STn) and Tn is regarded as a colorectal cancer‐specific change reflecting truncated synthesis of the oligosaccharide component of goblet cell mucin. The distribution of STn and Tn in normal and malignant epithelium has been studied in detail by a combination of mucin‐, lectin‐, and immunohistochemistry with and without pretreatment with potassium hydroxide (KOH), neuraminidase, and KOH–neuraminidase. When O‐acetylated sialic acid (neuraminidase‐resistant) is converted by saponification to non‐O‐acetylated sialic acid (neuraminidase‐sensitive), normal colorectal goblet cells (mainly of the lower two‐thirds of crypts) are immunoreactive with the monoclonal antibody TKH2 (specific for STn). This immunoreactivity is abolished by the interposition of neuraminidase, but goblet cells then become immunoreactive with Hb‐Tn1 (specific for Tn). While colorectal cancer mucin expresses STn, expression of Tn is not seen in either goblet cell mucin or extracellular material showing the morphological and histochemical characteristics of secretory mucin. Tn expression in cancers is mainly limited to the Golgi zone and in a proportion of cases to cytoplasm and apical membrane (glycocalyx) of columnar cells and inspissated material within lumina. The material reacting with Hb‐Tn1 may be upregulated, membrane‐associated MUC1 glycoprotein rather than MUC2 or MUC4 goblet cell mucin. The presence of STn and cryptic Tn within normal colorectal goblet cells and the absence of Tn expression within colorectal cancer secretory mucin contradicts the generally accepted concept of cancer‐specific incomplete glycoprotein synthesis within these neoplasms.
Altered expression and function of E‐cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma
Authors: Vessey Carina J. , Wilding Jonathan , Folarin Najeem , Hirano Shinji , Takeichi Masatoshi , Soutter Pat , Stamp Gordon W. H. , Pignatelli Massimo 
Published: June 2005

AbstractHECD‐1 monoclonal antibody has been used to localize E‐cadherin, a calcium‐dependent cell–cell adhesion molecule, in microwave‐treated, paraffin‐embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E‐cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E‐cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E‐cadherin expression was also detected in 4/7 metastatic deposits. E‐cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C41, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E‐cadherin‐negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG‐1 was the only E‐cadherin‐negative cell line which showed a significant degree of cell–cell aggregation. These data indicate that loss of membranous E‐cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer.
Platelet‐derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: An immunohistochemical study
Authors: Fox Stephen B. , Moghaddam Amir , Westwood Mark , Turley Helen , Bicknell Roy , Gatter Kevin C. , Harris Adrian L. 
Published: June 2005

AbstractAngiogenesis is the formation of new blood vessels from the existing vascular bed. It is a complex multi‐step process controlled by a number of angiogenic factors. One such factor is platelet‐derived endothelial cell growth factor (PD‐ECGF), recently shown to be thymidine phosphorylase (TP), which is angiogenic in several in vivo assays and tumour systems. PD‐ECGF/TP catalyes the reversible phosphorylation of thymidine to deoxyribose‐1‐ phosphate and thymine. Since PD‐ECGF/TP has an important role in cellular metabolism and in angiogenesis and its expression has been only partially characterized, we raised a monoclonal antibody against recombinant PD‐ECGF/TP and used an immunohistochemical approach to examine the expression of PD‐ECGF/TP in a comprehensive range of normal human tissues. The clone P‐GF44. C, which recognized recombinant PD‐ECGF‐TP and cell lysates transfected with a plasmid expressing PD‐ECGF/TP cDNA on Western blotting, was selected for its ability to stain routinely processed tissue. Staining was observed in both the cytoplasm and/or the nucleus. Immunoreactivity was strongly expressed by macrophages, stromal cells, glial cells, and some epithelia. Gastrointestinal epithelium, smooth muscle, adrenal, lung, and testis were negative. Although endothelial cell expression was observed, there was no correlation with sites of new vessel growth. This pattern of expression suggests tight PD‐ECGF/TP regulation and that cellular thymidine pools may serve to control its different functions. Thus, in the nucleus it might modulate the pool for DNA synthesis, whilst in the cytoplasm it could control other effects through different enzyme systems. The high expression present in macrophages and skin might be important for total body thymidine homeostasis.
Absence of in situ hybridization evidence for latent ‐ or lytic‐phase Epstein‐Barr virus infection of preinvasive squamous lesions of the cervix
Authors: Payne S. , Kernohan N. M. , Walker F. 
Published: June 2005

AbstractTo investigate whether Epstein‐Barr virus (EBV) infection of the uterine cervix plays a significant role in cervical carcinogenesis, 30 preinvasive squamous lesions were subjected to in situ hybridization for (EBER−1,−2, and BHLF1) EBV transcripts which are expressed in latent and lytic infection, respectively. Twenty cases were known to contain EBV sequences by previous polymerase chain reaction (PCR) analysis. Irrespective of EBV PCR status or histological grade, none of the 30 cases demonstrated EBV transcripts in squamous epithelial cells. Two cases showed very occasional EBER‐positive stromal cells, most probably representing resident cervical lymphocytes. These findings suggest that EBV plays no part in early cervical carcinogenesis.
p53 protein expression and nuclear DNA content in breast intraductal proliferations
Authors: Schmitt Fernando C. , Leal Conceição , Lopes Carlos 
Published: June 2005

AbstractImmunohistochemical analysis of the p53 gene protein and cytometric assessment of nuclear DNA were performed in a series of 51 cases of intraductal breast proliferation. The series included 22 cases of intraductal hyperplasia without atypia, 6 cases of intraductal hyperplasia with atypia, and 23 cases of pure intraductal carcinoma. Expression of p53 protein was detected in one case of intraductal hyperplasia without atypia (4·5 per cent), one case of intraductal hyperplasia with atypia (16·6 per cent) and six cases of intraductal carcinoma (26·0 per cent). No significant correlation was observed between p53 expression and histological subtype of intraductal carcinoma. Aneuploidy was demonstrated in two cases of intraductal hyperplasia with atypia (33·3 per cent) and in 18 cases of intraductal carcinoma (78·2 per cent). All cases of intraductal hyperplasia without atypia were euploid. No significant association was observed between p53 protein expression and ploidy in intraductal hyperplasia. The only case of intraductal hyperplasia without atypia positive for p53 was euploid, whereas the only p53‐positive case of intraductal hyperplasia with atypia was aneuploid. Among the intraductal carcinomas, only the aneuploid cases showed positivity for p53, regardless of histological subtype. The results suggest that some of the changes observed in invasive breast carcinoma, such as p53 expression and aneuploidy, are already present in breast intraductal proliferation, especially in areas with atypia and in intraductal carcinoma. The expression of p53 in breast intraductal proliferation may reflect the acquisition of p53 gene mutations in cells unable adequately to repair DNA damage, with genomic instability which would lead to clonal expansion and putative evolution to invasive disease.
CD44v6 expression in non‐Hodgkin's lymphoma: An association with low histological grade and poor prognosis
Authors: Ristamäki Raija , Joensuu Heikki , Söderström Karl‐Ove , Jalkanen Sirpa 
Published: June 2005

AbstractThe family of CD44 glycoproteins has diverse functions in cell–cell and cell–matrix interactions. The standard form of CD44 is of importance in the dissemination of lymphoma, whereas the clinical significance of the variant exon v6‐containing forms of CD44 (CD44v6) is not known. The expression of different forms of CD44 was investigated by using antibodies against the constant part of CD44 (CD44c) and CD44v6 in 56 primary and 17 recurrent non‐Hodgkin's lymphomas and correlated with several clinicopathological parameters and with prognosis. Fifty‐seven per cent of the primary non‐Hodgkin's lymphomas expressed CD44v6 and 73 per cent expressed the constant epitope. Expression of both CD44c and CD44v6 was associated with low histological grade of malignancy. CD44c expression was associated with a low cellular proliferation rate as assessed by DNA flow cytometry. Of several factors tested, high expression of the variant from v6 was the only factor that was associated with unfavourable recurrence‐free survival (P=0·04). We conclude that CD44v6 is associated with a low histological grade, but, on the other hand, with an unfavourable outcome, which suggests that the combination of CD44v6 and histological grading may form a particularly strong prognostic parameter in non‐Hodgkin's lymphoma.
VWF release and platelet aggregation in human melanoma after perfusion with TNFα
Authors: Renard Nathalie , Nooijen Peet T. G. A. , Schalkwijk Lia , De Waal Robert M. W. , Eggermont Alexander M. M. , Liénard Danielle , Kroon Bin B. R. , Lejeune Ferdy J. , Ruiter Dirk J. 
Published: June 2005

AbstractTwenty‐nine stage IIIA/B melanoma patients treated by isolated limb perfusion (ILP) with a high dose of recombinant human tumour necrosis factor alpha (rHuTNFα), interferon γ (IFNγ), and melphalan were histologically documented with emphasis on therapy‐induced changes of the tumour vasculature. Sequential biopsies were taken at various intervals before and after the treatment to compare the morphological changes. In order to visualize microvascular changes, immunostaining was performed for von Willebrand factor (VWF), type IV collagen, α‐smooth muscle actin, endothelial antigen PAL‐E, tissue factor, CD41 (thrombocyte marker), and fibrin. In biopsies prior to perfusion, necrosis, haemorrhage, and fibrin thrombi were not found. Within 3 h following triple combination therapy, a change in the distribution of VWF staining occurred, from a discrete endothelial pattern in the untreated lesions to a fuzzy perivascular and subepidermal pattern in the treated lesions. Within 24 h, this was accompanied by intravascular thrombocyte aggregation and erythrostasis, in the absence of tissue factor and fibrin deposits. These findings indicate that the thrombocyte aggregation observed is not caused by local procoagulant activity, but is rather the result of the therapy‐associated vascular damage or haemostasis. Although it is difficult to derive the dynamics of this process from static images, we assume that TNFα induced endothelial cell damage, leading to VWF release. Released VWF may play a role in the adhesion between thrombocytes and the damaged endothelium or the denuded subendothelium. As a consequence, the blood flow is impaired, leading to congestion and oedema, compatible with an early stage of haemorrhagic infarction.
TP53 mutations in prostatic cancer. Analysis of pre‐ and post‐treatment archival formalin‐fixed tumour tissue
Authors: Berner Aasmund , Geitvik Gry , Karlsen Frank , Fosså Sophie D. , Nesland Jahn M. , BØRresen Anne‐Lise 
Published: June 2005

AbstractThe TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin‐fixed pre‐and post‐treatment tumour specimens from 84 prostatic cancer patients. Thirty‐four had hormone‐sensitive tumours and 50 were hormone‐resistant. Six of the 34 (18 per cent) therapy‐responding tumours and 19 of the 50 (38 per cent) hormone‐resistant tumours showed p53 protein accumulation in the post‐treatment specimen. Both pre‐ and post‐treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post‐treatment samples, mutations were detected in three of the six patients with hormone‐responsive tumours and in 11 of the 19 patients with hormone‐resistant tumours. The three (100 per cent) patients with therapy‐responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy‐resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post‐treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease.
A novel model for human interstitial lung disease: Hapten‐driven lung fibrosis in rodents
Authors: Roberts S. N. , Howie S. E. M. , Wallace W. A. H. , Brown D. M. , Lamb D. , Ramage E. A. , Donaldson K. 
Published: June 2005

AbstractA novel model is described of chronic pulmonary fibrosis in rodents. The condition is induced by a single intratracheal instillation of a well‐characterized fluorescent haptenic antigen, fluorescein isothiocyanate (FITC), into non‐immune animals. This results in an acute inflammatory response involving a granulocytic infiltrate, which disappears over a week and is replaced by a chronic mononuclear infiltrate in which T lymphocytes predominate. Over several months, a chronic patchy fibrosis is accompanied by a sustained mononuclear interstitial infiltrate localized at sites of persistent FITC deposition. Where no FITC is present, the lung tissues are apparently normal. An immune response is mounted, as measured by the appearance of specific anti‐FITC serum antibodies. This model has relevance to the pathogenesis of some forms of human interstitial lung disease.
The prognostic value of oncogenic antigen 519 (OA‐519) expression and proliferative activity detected by antibody MIB‐I in node‐negative breast cancer
Authors: Jensen Vibeke , Ladekarl Morten , Holm‐Nielsen Peter , Melsen Flemming , Sœrensen Flemming Brandt 
Published: June 2005

AbstractThe prognostic value of oncogenic antigen 519 (OA‐519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low‐risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter ⩽50 mm, and no histological evidence of invasion of skin or deep fascia (=T1N0M0 and T2N0M0). The median follow‐up time was 104 months (range 5–143 months). Immunohistochemical analysis of OA‐519 expression was performed on formalin‐fixed, paraffin‐embedded tissue. The proliferative activity was estimated using a Ki‐67 equivalent monoclonal antibody (MIB‐1), which is applicable on formalin‐fixed, paraffin‐embedded tissue after microwave pretreatment. OA‐519 was expressed in about one‐third of the tumours and the percentage of proliferating cells (the MIB‐1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox analysis, both the MIB‐1 index and OA‐519 expression were of independent prognostic value (2p⩽0·01), and the combined immunohistological approach may therefore be useful in selecting patients with node‐negative breast cancer who might benefit from adjuvant therapy.