bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation and apoptosis of macrophages in cat scratch disease
Authors: Schweyer S , Fayyazi A 
Published: November 2002

AbstractCat scratch disease is an infectious disease usually caused by Bartonella henselae. Within 1–3 weeks after inoculation, patients typically develop regional self‐limited lymphadenopathy. Lymph nodes reveal granulomas consisting of central necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and non‐palisading macrophages. In animals, cat‐scratch disease leads to an interferon‐γ (IFNγ)‐mediated T‐helper 1 immune response, resulting in macrophage recruitment, stimulation, and thereby granuloma formation. The present study has sought to find in situ evidence for macrophage migration, activation, and cell death in human cat scratch disease. By non‐radioactive in situ hybridization and immunohistochemistry on serial sections, it was demonstrated that IFNγ+ T lymphocytes and S100A8+, S100A9+ macrophages embrace granulomas, which consisted of S100A8–, S100A9–, HLA‐DR+, CD40+, TNFα+ macrophages. Combination of in situ end‐labelling and immunofluorescence revealed large numbers of DNA‐fragmented CD68+ cells with intact plasma membranes corresponding to apoptotic macrophages. On the basis of these data, it was hypothesized that in human cat scratch disease, S100A8+, S100A9+ macrophages continuously migrate to the granulomas. During this process, they may be activated by IFNγ T‐helper 1 lymphocytes and be differentiated to S100A8–, S100A9–sessile, HLA‐DR+, CD40+ antigen‐presenting, TNFα+ pro‐inflammatory macrophages forming granulomas. In parallel, macrophages undergo apoptosis in the centre of granulomata, a phenomenon that may restrict the destructive potential of macrophages and contribute to self‐limitation of cat scratch disease. Copyright © 2002 John Wiley & Sons, Ltd.
Oestrogen receptors alpha and beta differ in normal human breast and breast carcinomas
Authors: Shaw Jacqueline A , Udokang Kufre , Mosquera Juan‐Miguel , Chauhan Hina , Jones J Louise , Walker Rosemary A 
Published: November 2002

AbstractThe identification of a second oestrogen receptor, oestrogen receptor (ER) β, has led to a need to assess the relative importance of the classical ERα and ERβ in human breast and breast carcinomas. ERα and ERβ mRNA was assessed in 61 carcinomas, 8 benign breast lesions, and 30 samples of normal breast using reverse transcriptase (RT)‐nested polymerase chain reaction (PCR). Immunohistochemical analysis of ERα and ERβ was performed in 62 carcinomas, the 38 non‐malignant breast tissues, and 32 normal breast samples with menstrual cycle data. ERα mRNA was detected in 92% of breast cancers, with ERβ mRNA (wild‐type and/or variant form) in 85%; 72% had ERα protein, 62% progesterone receptor (PgR), and 32% ERβ. ERα protein had a strong correlation with grade; ERβ did not, although it was present in three of four grade I carcinomas and in special types. There was no correlation between the presence of ERα and ERβ protein. In non‐malignant breast, similar expression of ERα and β was observed, apart from expression of ERβ in stromal cells and myoepithelium, the latter being confirmed by RT‐PCR and western blotting. There were differences in ERα in relation to the menstrual cycle but not PgR or ERβ. The findings indicate a need to understand the role and regulation of ERβ in normal breast and the reason for its down‐regulation in mammary carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Differential expression of p63 isoforms in normal tissues and neoplastic cells
Authors: Nylander Karin , Vojtesek Borek , Nenutil Rudolf , Lindgren Britta , Roos Göran , Zhanxiang Wang , Sjöström Björn , Dahlqvist Åke , Coates Philip J 
Published: November 2002

AbstractThe p63 gene encodes at least six different proteins with homology to the tumour suppressor protein p53 and the related p53 family member p73. So far, there have been limited data concerning the expression patterns of individual p63 proteins, due to a lack of reagents that distinguish between the different isoforms. Three antibodies have been produced specifically directed against the two N‐terminal isoforms (TAp63 and ΔNp63) and the C‐terminal region of the p63α proteins. TAp63 proteins are located suprabasally in stratified epithelia compared with the N‐terminal truncated forms, which are more abundantly expressed in the basal cell layer, indicating a switch in expression of p63 isoforms during normal cellular differentiation. Analysis of squamous cell carcinomas shows ΔNp63α to be the most widely expressed isoform, compatible with a role for this protein in promoting neoplastic cell growth in these tissues. ΔNp63 protein expression is also restricted to basal cells in breast and prostate, whilst TAp63 isoforms are more widely expressed in these tissues as well as in tumours at these sites. TAp63, but not ΔNp63 or p63α, is detected in normal colon and in colon carcinoma. TAp63 proteins are also expressed in the nuclei of a sub‐population of lymphoid cells and in most malignant lymphomas, whereas ΔNp63 proteins are not expressed. Taken together, a hitherto unrecognized regulation of p63 isoform expression in vivo has been uncovered, with different p63 proteins expressed during differentiation and in different cell types. The data indicate roles for specific p63 isoforms not only in maintaining epithelial stem cell populations, but also in cellular differentiation and neoplasia. Copyright © 2002 John Wiley & Sons, Ltd.
Human colorectal adenomas demonstrate a size‐dependent increase in epithelial cyclooxygenase‐2 expression
Authors: Elder Douglas JE , Baker Jenny A , Banu Nahida A , Moorghen Moganaden , Paraskeva Christos 
Published: November 2002

AbstractNon‐steroidal anti‐inflammatory drugs are chemopreventive for colorectal cancer. This effect is due in part to their ability to inhibit the inducible isoform of cyclooxygenase (COX‐2). However, the cellular expression and role of COX‐2 in the premalignant stages of colorectal tumourigenesis is unclear. COX‐2 expression was assessed in 35 human colorectal adenomas and 38 sporadic invasive colorectal adenocarcinomas. Adenomas were classified as small (<5 mm in diameter), medium (5–10 mm), and large (>10 mm). All tissues were paraffin‐embedded and formalin‐fixed. COX‐2 protein expression was determined using immunohistochemistry. COX‐2 was detected in the epithelial cells in 35 of 38 carcinomas (92%) and in 8 of 8 (100%) lymph node metastases. All of the epithelial cells expressed COX‐2 in 30 of 35 (86%) carcinomas and in 100% of the lymph node metastases. Twenty‐three of 35 (66%) adenomas expressed COX‐2 in the tumour epithelium. With an increase in the size of adenoma (<5 mm, 5–10 mm, >10 mm), there was an increase in (i) the proportion of adenomas with immunoreactive COX‐2 in the epithelium (p = 0.036)—this was 38% in small adenomas and 82% in large adenomas; (ii) the extent of epithelial COX‐2 staining within a given tumour (p = 0.003)—100% of epithelial cells were COX‐2‐positive in 15% of small adenomas and in 73% of large adenomas; and (iii) the intensity of epithelial COX‐2 staining (p = 0.009)—strong COX‐2 staining occurred in 8% of small adenomas and in 36% of large adenomas. COX‐2 immunoreactivity was not detected in adjacent normal epithelium but was apparent in fibroblasts and inflammatory mononuclear cells of adjacent normal, adenoma, and carcinoma tissue. These results suggest that epithelial COX‐2 activity is important for the growth and/or survival of adenomatous epithelial cells from an adenoma diameter of less than 5 mm and that there is a selective advantage for adenoma epithelial cells expressing higher levels of COX‐2. Copyright © 2002 John Wiley & Sons, Ltd.
Relative paucity of gross genetic alterations in myoepitheliomas and myoepithelial carcinomas of salivary glands
Authors: Hungermann Daniela , Roeser Kerstin , Buerger Horst , Jäkel Thorsten , Löning Thomas , Herbst Hermann 
Published: November 2002

AbstractThe diagnosis of salivary gland myoepithelioma, an entity with heterogeneous cytomorphology and inconsistent immunophenotype, rests on conventional histology. However, the clinical course cannot be predicted reliably from cytomorphological and immunophenotypic analysis. The present study determined the immunophenotype of a representative series of 12 myoepitheliomas and 21 malignant myoepitheliomas. Among the seven markers tested, antibodies against cytokeratins 5/6, S‐100 protein, and vimentin produced the most consistent reactivity profile. Comparative genomic hybridization (CGH) profiles of 12 myoepitheliomas showed chromosomal losses in three of 12 cases. In myoepithelial carcinomas, however, ten of 19 tissues investigated by CGH lacked detectable cytogenetic aberrations. In five cases, aberrations involved chromosome 8, in line with observations in salivary gland carcinomas of other differentiation. One case that was represented in three separately localized manifestations of the disease proved informative as to the relevance of gross aberration for tumour development, as these tumours differed in their CGH profiles. Staining for cytokeratins 5/6 is a useful addition to the established immunohistological marker panel in the work‐up of myoepitheliomas, because of its reliable expression in most cases and because it may underline the epithelial nature of the lesion. CGH proved to be of limited value as a diagnostic adjunct; the presence of numerous gross cytogenetic aberrations should raise the suspicion of malignancy. The low frequency of aberrations detectable by CGH in overtly malignant myoepithelial neoplasms suggests that gross cytogenetic alterations were acquired in the course of tumour progression and points to the relevance of genetic changes not resolved by CGH. Copyright © 2002 John Wiley & Sons, Ltd.
Increase in lymphoid follicles and leukocyte adhesion molecules emphasizes a role for the gut in spondyloarthropathy pathogenesis
Authors: Demetter P , Van Huysse JA , De Keyser F , Van Damme N , Verbruggen G , Mielants H , De Vos M , Veys EM , Cuvelier CA 
Published: November 2002

AbstractThe aim of this study was to investigate the expression of leukocyte adhesion molecules and the number of lymphoid follicles in gut mucosa of patients with spondyloarthropathy (SpA) in comparison with controls, in search for early immune alterations in the development of SpA‐related gut inflammation. Histological evaluation and immunohistochemistry were performed on the ileum and colon of 14 SpA patients without macroscopic or microscopic gut inflammation and those of 21 controls. Lymphoid follicles were counted and immunohistochemical staining for leukocyte adhesion molecules, lymphocyte subtypes, macrophages, and plasma cells was scored semi‐quantitatively. The number of lymphoid follicles was increased in both the ileum (p < 0.01) and the colon (p < 0.01) of SpA patients. SpA ileum showed an increase in leukocytes expressing CD11c (p < 0.01), whereas CD11a+ (p < 0.02) and VCAM‐1+ cells (p < 0.05) were increased in SpA colon. Macrophages, characterized by the expression of CD68, were more numerous in colonic mucosa from SpA patients (p < 0.05). The amount of lymphoid follicles and lamina propria mononuclear cells expressing CD11a, CD11c, and VCAM‐1 was increased in non‐inflamed gut mucosa from SpA patients. These findings might point to increased antigen handling and presentation and augmented maturation of naïve T cells towards memory T cells in the SpA gut, which supports the concept that the gut is involved in the pathogenesis of SpA. Copyright © 2002 John Wiley & Sons, Ltd.
High numbers of granzyme B/CD8‐positive tumour‐infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent
Authors: Oudejans Joost J , Harijadi Hari , Kummer J Alain , Tan I Bing , Bloemena Elizabeth , Middeldorp Jaap M , Bladergroen Belinda , Dukers Danny F , Vos Wim , Meijer Chris JLM 
Published: November 2002

AbstractThis study determined whether tumour‐infiltrating lymphocytes (TILs) in nasopharyngeal carcinomas (NPCs) include activated cytotoxic T lymphocytes (CTLs) and whether the numbers of activated CTLs in these biopsies are related to clinical outcome. Moreover, the study investigated whether the numbers of activated CTLs are associated with the expression of MHC class I proteins and the granzyme B antagonist PI‐9 in the tumour cells. Forty‐three Indonesian NPC patients (T1–3, N1–3, M0), who were treated with curative intent by radiotherapy only, were studied. Tumour‐infiltrating activated CTLs were detected using antibodies against granzyme B, CD8, and CD56. Expression of MHC class I proteins and PI‐9 was also determined by immunohistochemistry. Granzyme B‐positive TILs were detected in all NPC biopsies. The presence of a high percentage (>25%) of granzyme B‐positive TILs appeared to be a very strong predictor of a rapid fatal clinical outcome, independent of stage. Complete absence of MHC class I heavy chain expression in tumour cells was observed in 11 of 31 evaluable cases and low levels were observed in seven additional cases. No association between MHC class I expression and the numbers of granzyme B‐positive TILs was observed. Expression of the granzyme B antagonist PI‐9 in tumour cells was detected in three cases. It is concluded that the presence of many granzyme B‐positive TILs in a selected group of Indonesian NPC patients is a strong and stage‐independent marker for a rapid fatal clinical outcome. Copyright © 2002 John Wiley & Sons, Ltd.
Hypermethylation‐associated transcriptional silencing of E‐cadherin in primary sporadic colorectal carcinomas
Authors: Garinis George A , Menounos Panayiotis G , Spanakis Nick E , Papadopoulos Kostas , Karavitis George , Parassi Ismailou , Christeli Evangelia , Patrinos George P , Manolis Evangelos N , Peros George 
Published: November 2002

AbstractLoss of E (epithelial)‐cadherin expression has been previously documented in sporadic colorectal carcinomas (SCRCs), but not as a consequence of mutations or allelic loss. In this study, the methylation status of the E‐cadherin promoter was examined by utilizing the methylation‐specific polymerase chain reaction (MSP) assay in 63 primary SCRCs and paired adjacent normal tissues. This was correlated with E‐cadherin expression at both the RNA and the protein levels using multiplex reverse transcription (RT)‐PCR and immunohistochemistry (IHC), respectively. Data were associated with the patients' clinicopathological features. Methylated alleles were present in 34/61 (56%) of the samples examined. Decreased E‐cadherin mRNA expression was demonstrated in 29/61 carcinomas (47.5%) and was significantly associated with lymph node (LN) metastases (p = 0.03, Kruskal–Wallis) and tumour stages Astler‐Coller B1 and B2 (p = 0.01, chi2). E‐cadherin IHC expression was significantly associated with the absence of LN metastases (p = 0.01, chi2) and tumour stages Astler‐Coller B1 and B2 (p = 0.002, Kruskal–Wallis) in 28/63 (44.4%) of the samples examined. Twenty‐three out of 29 (79.3%) samples with decreased mRNA expression and 20/33 (60.6%) with detected protein expression revealed methylated (p = 0.03, Kruskal–Wallis) and unmethylated (p = 0.01, Kruskal–Wallis) alleles, respectively. In agreement with previous work demonstrating that somatic mutations and loss of heterozygosity of the E‐cadherin gene are rare or absent in the majority of SCRCs studied so far, this study reports a consistent and uniform decrease or absence of E‐cadherin expression, associated with aberrant methylation, in the majority of carcinomas examined, suggesting an epigenetically mediated loss of E‐cadherin function in these carcinomas. Copyright © 2002 John Wiley & Sons, Ltd.
The role of heregulin‐α as a motility factor and amphiregulin as a growth factor in wound healing
Authors: Schelfhout Vera RJ , Coene Elisabeth D , Delaey Bernard , Waeytens Anouk AT , De Rycke Leen , Deleu Mattias , De Potter Christian R 
Published: November 2002

AbstractWound healing is a complex process of which growth and motility are essential features. The aim of this study was to search for keratinocyte‐derived secreted factors that may play a role in these mechanisms, and their corresponding receptors. Growth and motility factors were purified from conditioned medium from cultured primary keratinocytes. Receptor and growth factor expression profiles were investigated by immunohistochemical, western blotting, and in situ hybridization analysis on cultured keratinocytes and tissue sections derived from chronic wounds. The most potent autocrine growth factor for keratinocytes, which it was possible to purify and sequence from keratinocyte‐conditioned medium, is amphiregulin. Its receptor HER‐1 is up‐regulated on the membranes of keratinocytes lining the edge of the wound. From the same keratinocyte‐conditioned medium, heregulin‐α was purified as a potent motility factor for keratinocytes. Its receptor is HER‐3, which is up‐regulated on the membranes of keratinocytes lining the edge of the wound and on keratinocytes that had migrated towards the centre of the wound. HER‐4 — another receptor for heregulin‐α — is weakly present in occasional cells near the edge of the wound. The co‐receptor for HER‐3 and HER‐4 is HER‐2/neu, which is also present in epidermal cells but not overexpressed. This study shows that heregulin‐α is a potent motility factor for normal epithelial cells and that it plays a central role in the process of wound healing of stratified epithelia. Heregulin‐α has already been shown to be the motility factor leading to migration of HER‐2/neu‐overexpressing breast cancer cells. The role of amphiregulin as a growth factor and of heregulin‐α as a motility factor for keratinocytes in epidermal and mucosal wound healing parallels their motility and growth induction in carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ
Authors: Boecker Werner , Moll Roland , Dervan Peter , Buerger Horst , Poremba Christopher , Diallo Raihanatou Ina , Herbst Hermann , Schmidt Ansgar , Lerch Markus M , Buchwalow Igor B 
Published: November 2002

AbstractCurrent classification systems in proliferative mammary gland pathology are based on a two‐cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by double‐immunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double‐labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ, all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5‐positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ, which display the differentiated glandular immunophenotype (Ck8/18/19‐positive, but Ck5‐negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development. Copyright © 2002 John Wiley & Sons, Ltd.
Mutated p53 as a molecular marker for the diagnosis of head and neck cancer
Authors: van Houten Viola MM , Tabor Maarten P , van den Brekel Michiel WM , Alain Kummer J , Denkers Fedor , Dijkstra Janny , Leemans René , van der Waal Isaäc , Snow Gordon B , Brakenhoff Ruud H 
Published: November 2002

AbstractIn total, 10–30% of patients with head and neck squamous cell carcinoma (HNSCC) develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC): small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies, p53 mutations have been considered as selective and sensitive DNA markers of cancer cells. There are two potential problems in using mutated‐p53 DNA as a marker. Firstly, p53 mutations occur early in progression and might therefore detect unresected precursor lesions besides tumour cells. Secondly, DNA is a very stable biomolecule that might lead to false‐positive results. These two potential problems have been evaluated in this study. Fifty patients with a radical tumour resection were included, of whom 30 showed a p53 mutation in the primary tumour. Histopathologically tumour‐free surgical margins were quantitatively analysed for mutated p53 by molecular diagnosis (plaque assay) and subsequent (immuno)histopathology. p53 mutated DNA was detected in the surgical margins of 19/30 patients. Immunohistochemistry confirmed the presence of small tumour foci in 2/19 mutated p53‐positive cases. In 7/19 cases, the tumour‐specific p53 mutation was found in unresected dysplastic mucosal precursor lesions. Moreover, in a number of cases small p53‐immunostained patches were detected, but the mutations found were never tumour‐related. By screening contralateral exfoliated cells and plaque assays on RNA it was shown that detection of mutated‐p53 DNA is prone to false‐positive results. In conclusion, using p53 mutations as a marker, both MRC and unresected mutated p53‐positive mucosal precursor lesions are detected within surgical margins. Molecular assessment of surgical margins using p53 mutations enables the selection of HNSCC patients at high risk for tumour recurrence, but tumour RNA seems at present to be a more specific biomolecule for analysis than tumour DNA. Copyright © 2002 John Wiley & Sons, Ltd.