Journal of Pathology
1096-9896
0022-3417
Anh Quốc
Cơ quản chủ quản: John Wiley and Sons Ltd , WILEY
Lĩnh vực:
Pathology and Forensic Medicine
Phân tích ảnh hưởng
Thông tin về tạp chí
The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. In general, hypothesis driven studies that appropriately employ multiple investigative techniques are preferred over those that rely on a single methodology. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited. Purely descriptive papers on diagnostic pathology (including case reports and prognostic papers without mechanistic and experimental insights) are not considered central to the Journal’s purpose. Correspondence relating to papers published in the Journal will be considered, but only if of general interest. Such correspondance may be published in online versions only, at the Editor's discretion. In determining content, the primary considerations are excellence, relevance and novelty. As the journal of The Pathological Society, it seeks to reflect the broad scientific interests of the Society’s membership but its ethos, authorship, content and purpose are those expected of a leading publication in the international scientific literature.
Các bài báo tiêu biểu
KIT (CD117) is frequently overexpressed in thymic carcinomas but is absent in thymomas Abstract KIT (CD117), a tyrosine kinase receptor, has not been widely studied in epithelial tumours. In a systematic immunohistochemical survey of KIT expression on tissue arrays incorporating 671 cases, it was found that thymic carcinomas frequently express KIT. Twenty‐two thymic carcinomas, 110 thymomas, and 16 non‐neoplastic thymus glands were retrieved for further analyses. Immunohistochemically, 19 (86%) thymic carcinomas revealed heterogeneous to diffuse membranous positivity, whereas no thymomas or normal thymus glands contained positive epithelial cells. Using reverse transcriptase‐polymerase chain reaction (RT‐PCR), c‐kit transcripts could be demonstrated in all immunohistochemically positive cases. PCR amplification and direct sequencing of the c‐kit juxtamembrane domains (exons 9 and 11) and tyrosine kinase domain (exons 13 and 17) were also performed on the thymic carcinomas but mutations were not found. Some non‐thymic epithelial tumours showed frequent KIT expression including adenoid cystic carcinomas of the salivary gland (100% positive), chromophobe renal cell carcinomas (94%), renal oncocytomas (67%), and neuroendocrine tumours (34%). Other carcinomas were infrequently immunoreactive for KIT. The findings of this study suggest that KIT is involved in the pathogenesis of thymic carcinomas. The overexpression of KIT in thymic carcinomas has potential diagnostic utility in differentiating these tumours from thymomas and carcinomas arising from other sites, which express KIT infrequently. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tập 202 Số 3 - Trang 375-381 - 2004
Expression of luminal and basal cytokeratins in human breast carcinoma Abstract We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of α‐smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease. Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tập 203 Số 2 - Trang 661-671 - 2004
Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease Abstract Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well‐characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.
Tập 155 Số 1 - Trang 9-15 - 1988
Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann–Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease Abstract Niemann–Pick type C (NPC) disease is a fatal hereditary neurovisceral disorder with diagnostically relevant intracellular accumulation of cholesterol in non‐brain tissue, for example the spleen and fibroblasts. In the brain, many ballooned neurons are seen. Using filipin microfluorodensitometry, significant accumulations of free cholesterol in specified neurons have been described in NPC patients. The present study demonstrates spatial and temporal accumulation of free cholesterol in the brains of homozygous NPC (−npc /−npc ) mice, a widely acknowledged mouse model, and in primarily cultured neurons therefrom. Intraneuronal storage of free cholesterol was already prominent at a pre‐clinical stage in various grey matter areas of the murine cerebral cortex. Hippocampal areas showed differential development of the pathological distribution of free cholesterol. The pyramidal cells in the CA3 sector of Ammon's horn were affected much earlier than in CA1. Some of the deeper cerebral nuclei were affected only slightly, even at the final stage. Neurons (E15–E17) cultured in a cholesterol‐free medium also showed massive accumulation of intracellular free cholesterol. In addition, brains from the murine NPC model for Alzheimer's disease (AD)‐like changes in the microtubule‐associated protein tau were tested using the Gallyas silver technique and AT8‐immunolabelling, since both human diseases are accompanied by intraneuronal tangles made up of tau protein aggregations. Although the analysis failed to show classical silver‐stainable tangles of the AD type in the NPC mice, tau protein phosphorylated at epitopes considered to represent early stages of AD was found. This further strengthens the concept that an alteration in cholesterol metabolism may play an important role in AD. The NPC mouse model may thus serve as a tool to analyse the role of cholesterol in initial changes of tau that eventually lead to the formation of tangles in both NPC and AD. Copyright © 2003 John Wiley & Sons, Ltd.
Tập 200 Số 1 - Trang 95-103 - 2003
The origin of vimentin expression in invasive breast cancer: epithelial–mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential?
Tập 206 Số 4 - Trang 451-457 - 2005
<scp>MicroRNA</scp>‐542‐3p inhibits tumour angiogenesis by targeting Angiopoietin‐2 Abstract Angiopoietin‐2 (Angpt2) plays a critical role in angiogenesis and tumour progression. Therapeutic targeting of Angpt2 has been implicated as a promising strategy for cancer treatment. Whereas miRNAs are emerging as important modulators of angiogenesis, regulation of Angpt2 by miRNAs has not been established. Here we firstly report that Ang2 is targeted by a microRNA , miRNA ‐542‐3p, which inhibits tumour progression by impairing Ang2's pro‐angiogenic activity. In cultured endothelial cells, miR ‐542‐3p inhibited translation of Angpt2 mRNA by binding to its 3′ UTR , and addition of miR ‐542‐3p to cultured endothelial cells attenuated angiogenesis. Administration of miR ‐542‐3p to tumour‐bearing mice reduced tumour growth, angiogenesis and metastasis. Furthermore, the level of miR ‐542‐3p in primary breast carcinomas correlated inversely with clinical progression in primary tumour samples from stage III and IV patients. Together, these findings uncover a novel regulatory pathway whereby an anti‐angiogenic miR ‐542‐3p directly targets the key angiogenesis‐promoting protein Angpt2, suggesting that miR ‐542‐3p may represent a promising target for anti‐angiogenic therapy and a potential marker for monitoring disease progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Tập 232 Số 5 - Trang 499-508 - 2014
Genome‐wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target Abstract Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of kidney cancer. Here, we integrated an unbiased genome‐wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease. One of the most potent survival regulators, the monocarboxylate transporter MCT4 (SLC16A3), impaired ccRCC viability in all eight ccRCC lines tested and was the seventh most overexpressed gene in a meta‐analysis of five ccRCC expression datasets. MCT4 silencing impaired secretion of lactate generated through glycolysis and induced cell cycle arrest and apoptosis. Silencing MCT4 resulted in intracellular acidosis, and reduction in intracellular ATP production together with partial reversion of the Warburg effect in ccRCC cell lines. Intra‐tumoural heterogeneity in the intensity of MCT4 protein expression was observed in primary ccRCCs. MCT4 protein expression analysis based on the highest intensity of expression in primary ccRCCs was associated with poorer relapse‐free survival, whereas modal intensity correlated with Fuhrman nuclear grade. Consistent with the potential selection of subclones enriched for MCT4 expression during disease progression, MCT4 expression was greater at sites of metastatic disease. These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tập 227 Số 2 - Trang 146-156 - 2012
The Human Protein Atlas—a tool for pathology Abstract Tissue‐based diagnostics and research is incessantly evolving with the development of new molecular tools. It has long been realized that immunohistochemistry can add an important new level of information on top of morphology and that protein expression patterns in a cancer may yield crucial diagnostic and prognostic information. We have generated an immunohistochemistry‐based map of protein expression profiles in normal tissues, cancer and cell lines. For each antibody, altogether 708 spots of tissues and cells are analysed and the resulting images and data are presented as freely available in the Human Protein Atlas (www.proteinatlas.org ). The new version 4 of the atlas, including more than 5 million images of immunohistochemically stained tissues and cells, is based on 6122 antibodies, representing 5011 human proteins encoded by approximately 25% of the human genome. The gene‐centric database includes a putative classification of proteins in various protein classes, both functional classes, such as kinases or transcription factors and project‐related classes, such as candidate genes for cancer or cardiovascular diseases. For each of the internally generated antibodies, the exact antigen sequence is presented, together with a visualization of application‐specific validation data, including a protein array assay, western blot analysis, immunohistochemistry and, in most cases, immunofluorescent‐based confocal microscopy. The updated version also includes new search algorithms to allow complex queries regarding expression profiles, protein classes and chromosome location. Thus, the presented Human Protein Atlas provides a resource for pathology‐based biomedical research, including protein science and biomarker discovery. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tập 216 Số 4 - Trang 387-393 - 2008
MAP kinase activation and apoptosis in lung tissues from patients with idiopathic pulmonary fibrosis Abstract Three major MAP kinases (MAPKs), including extracellular signal‐regulated kinase (ERK), c‐jun N‐terminal kinase (JNK), and p38 kinase (p38 MAPK), are involved in the regulation of lung inflammation and injury. This study investigated whether MAPKs are activated and associated with lung injury in lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The expression of the active ERK, JNK, and p38 MAPK was examined using western blot analysis and immunohistochemistry and apoptosis was also examined by the TUNEL method, in lung tissues from ten patients with IPF obtained by thoracoscopic biopsy and in eight normal lung parenchyma specimens obtained by lobectomy for lung cancer. Activated MAPKs are significantly increased in lung homogenates from patients with IPF compared with controls. Activated ERK in epithelial and endothelial cells, but not in fibroblasts or smooth muscle cells, was decreased, accompanied by the progression of fibrosis. Activated JNK in epithelial and endothelial cells, but not in fibroblasts, was increased, accompanied by the progression of fibrosis. Activated p38 MAPK in epithelial, endothelial, smooth muscle cells, and fibroblasts was increased at the intermediate stage of fibrosis, in which the TUNEL‐positive cells were predominantly detected. This is the first study to suggest that MAPKs may be associated with the regulation of inflammation and lung injury in IPF. Copyright © 2002 John Wiley & Sons, Ltd.
Tập 198 Số 3 - Trang 388-396 - 2002
Chemical carcinogenesis: A view at the end of the first half‐century
Tập 130 Số 2 - Trang 117-146 - 1980