Experimental and Molecular Pathology

Our medical research library holds 9 studies published in Experimental and Molecular Pathology (1970–2014). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 3 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Elsevier
• Published: 1962 to the present, Netherlands
• Language: English
• ISSN: 0014-4800 (print), 1096-0945 (electronic)
• Its record in the NLM Catalog

2010s

• Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets. E.G. Ramírez-Salazar, L.C. Salinas-Silva, M.E. Vázquez-Manríquez, et al. 2014;97(3):375-85. PubMed · Publisher

  Abstract

  Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.

  Copyright © 2014 Elsevier Inc. All rights reserved.

• Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients. A.A. Bahnassy, A.R. Zekri, A.A. Abou-Bakr, et al. 2012;93(1):154-61. PubMed · Publisher

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM.

  Patients And Methods: Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS).

  Results: Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01).

  Conclusions: MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.

  Copyright © 2012 Elsevier Inc. All rights reserved.

• MT1-MMP plays an important role in an invasive activity of malignant pleural mesothelioma cell. T. Doi, Y. Maniwa, Y. Tanaka, et al. 2011;90(1):91-6. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) has a poor prognosis and is a treatment resistant tumor, which is increasing in frequency throughout the world. The poor prognosis is due to the aggressive local invasiveness rather than distant metastasis. In this study, we established a cell line of malignant mesothelioma from a clinical specimen and assessed the relationship between the expression of MT1-MMP and the invasion ability of that line, as well as the cultured cells of several other lines, using the simple method that we created previously. We established a cell line from a clinical specimen from a patient with malignant mesothelioma. We assessed the invasive activities of MPM cells in an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enabled us to visualize cell movements during invasion. To assess the role of MT1-MMP in the invasive activity of MPM cells, we knocked down its expression by RNA interference (RNAi). The invasion assay with DL-CGH revealed that a high expression of MT1-MMP in MPM cells was associated with aggressive invasive activity. The RNAi of MT1-MMP indicated that the expression of MT1-MMP might have a crucial role in the invasiveness of MPM cells. The MT1-MMP expression in MPM cells is related to their capacity for locally aggressive spreading into the pleura and the surrounding tissues, and MT1-MMP should be a suitable molecular target for the suppression of the invasiveness of MPM.

  Copyright © 2010 Elsevier Inc. All rights reserved.

2000s

• Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers. G. Cardinali, D. Kovacs, V. Maresca, et al. 2006;81(1):31-41. PubMed · Publisher

  Abstract

  In this study, we analyzed the effects of synthetic vitreous fibers (SVFs) on a mesothelial (MeT5A) and a fibroblast cell line (NIH3T3), compared to those exerted by crocidolite asbestos fibers. SVFs (glass wool, rock wools) do not induce significant changes in cell mortality, whereas crocidolite asbestos fibers caused a dose-dependent cytotoxicity. We investigated the correlation between the fiber-induced cytotoxicity and the extent and type of interaction of the fibers with the cell surface, and we observed that SVFs, unlike crocidolite asbestos fibers, establish few and weak interactions. Moreover, after internalization, crocidolite asbestos fibers are often found free in the cytoplasm, whereas glass wool fibers are mainly localized inside cytoplasmic vacuoles. After treatments, we also detected signs of oxidative stress, revealed by an increased reactive oxygen species (ROS) production and by an induction of superoxide dismutase (SOD) activity. The lipoperoxidative damage was characterized by a decrease in polyunsaturated fatty acids (PUFA), an increase in the content of thiobarbituric reactive species (TBARS) and a consumption of vitamin E, as a lipophilic antioxidant. Furthermore, we investigated the effect of fiber exposure on cell proliferation. and it was found that, unlike crocidolite asbestos fibers, SVFs did not induce a significant increase in DNA synthesis.

1990s

• Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from macrophages. N. Cheng, X. Shi, J. Ye, et al. 1999;66(3):201-10. PubMed · Publisher

  Abstract

  Asbestos exposure in humans is associated with inflammatory, fibrotic, and malignant diseases in the lung. Increasing evidence supports the hypothesis that the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha) is an important mediator of the pathologic responses of asbestosis. In this study, we examine the role of nuclear transcription factor-kappaB (NF-kappaB) and free oxygen radicals in asbestos-induced TNFalpha gene and protein expression in lung macrophages. Exposure of the cells to crocidolite asbestos caused a parallel increase in TNFalpha production and NF-kappaB activation, as analyzed by enzyme-linked immunosorbent assay and electrophoretic mobility shift assay. Inhibition of NF-kappaB by SN50, an inhibitor of NF-kappaB nuclear translocation, or by sequence-specific oligonucleotides directed against the NF-kappaB binding site of TNFalpha promoter attenuated the asbestos effect on TNFalpha production. Gene transfection assays using an expression plasmid containing a luciferase reporter gene and a TNFalpha-derived NF-kappaB gene promoter further indicated the dependence of NF-kappaB activation on asbestos-induced gene expression. The effects of asbestos on NF-kappaB and TNFalpha activation were inhibited by oxygen radical scavengers and were enhanced by antioxidant enzyme inhibitors. These results indicate that asbestos-induced TNFalpha gene expression is mediated through a process that involves NF-kappaB activation and free radical reactions.

  Copyright 1999 Academic Press.

1980s

• Experimental lesions in rats corresponding to advanced human asbestosis. J.M. Davis, R.E. Bolton, D. Brown, et al. 1986;44(2):207-21. PubMed · Publisher

  Abstract

  Rats inhaling chrysotile asbestos developed a progressive interstitial fibrosis similar in most respects to human asbestosis. The earliest lesions were focal deposits of fibrous tissue in the walls of respiratory bronchioles and alveolar ducts. Later alveolar septa between adjacent bronchioles became progressively thickened to produce lesions with similarities to human honeycombing. The thickened septa between alveoli or "micro-honeycomb" spaces were mainly surfaced with cuboidal epithelial cells although some spaces lined by ciliated columnar epithelium were also found. Transmission electron microscopy of these advanced lesions showed that the cuboidal epithelial cells retained most of the characteristics of type 2 pneumocytes but that they frequently exhibited apical cytoplasmic blebs normally associated with the apocrine secretion of Clara cells. Columnar cells exhibited all stages from fully cilitated to cells with only an occasional cilium among the normal cell surface microvilli. Alveolar or micro-honeycomb spaces frequently contained clusters of pulmonary macrophages with their surface processes interdigitated but with no signs of fusion to giant cells. At more than 18 months after the end of dust inhalation these macrophages contained no chrysotile asbestos. The basement membranes beneath the epithelial layers of thickened septa were irregular and often convoluted as well as being much thicker than normal. Microscopic deposits of calcification were frequently found within the basement membrane material. Some thickened septa were relatively acellular, consisting mainly of masses of collagen fibrils but others were cellular and contained many macrophages, fibroblasts, plasma cells and mast cells. In these advanced lesions extremely little chrysotile asbestos was found and this was present in two sites only. Some chrysotile, always as individual fibrils and usually of short length, was present among collagen fibrils in areas of fibrosis and some was present within the thickened basement membranes.

1970s

• Experimental studies on the effects of heated chrysotile asbestos and automobile brake lining dust injected into the body cavities of mice. J.M. Davis, S.W. Coniam. 1973;19(3):339-53. PubMed · Publisher

  Abstract

  A series of experiments with mice involving the intrapleural injection of chrysotile asbestos dust heated to varying temperatures up to 1000°C suggests that the physical shape of the dust particles is more important than the altered chemistry of the dust. Chrysotile heated to no more than 400°C produced dust samples containing many long fibers, and these samples resulted in large pleural granulomas. Chrysotile heated to more than 400°C produced dust containing mainly particles of low aspect ratio, and these produced very small granulomas. The initial size of the granulomas was very closely related to the final degree of fibrosis found in the animals and, therefore, chrysotile heated to 400°C or less was much more fibrogenic than when it was heated to higher temperatures. A sample of automobile brake lining dust was found to contain very little recognizable chrysotile, and consisted mainly of particles with a low aspect ratio. When this dust was injected into the pleural cavities of mice it produced very small granulomas and little fibrosis.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Asbestos dust as a nucleation center in the calcification of old fibrous tissue lesions, and the possible association of this process to the formation of asbestos bodies. J.M. Davis. 1970;12(2):133-47. PubMed · Publisher

  Abstract

  The intrapleural injection of chrysotile asbestos dust into the pleural cavity of guinea pigs results in the formation of fibrous lesions which eventually calcify to produce calcified plaques very similar to those found in human cases of asbestosis. The first stage in the process of calcification involves the coating of all the asbestos dust that remains among the collagen fibrils of the lesion with a thick coating of material that appears to be some form of acid mucopolysaccharide. Later, calcium, in the form of apatite crystals, is laid down. The initial deposition of apatite is on the surface of the mucopolysaccharide, but gradually all the spaces between the coated dust particles are filled with apatite crystals, and the lesion becomes completely calcified.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Further observations on the ultrastructure and chemistry of the formation of asbestos bodies. J.M. Davis. 1970;13(3):346-58. PubMed · Publisher

  Abstract

  The examination of pleural granulomas during the first 14 days after the injection of chrysotile asbestos dust in experimental animals produced new evidence on the formation of asbestos bodies. In those species which produced bodies readily, the longer dust fibers were seldom phagocytosed by a single macrophage, but were surrounded by macrophages which eventually fused to form giant cells. It is while dust fibers were surrounded by partially fused macrophages that the earliest signs of body coating were seen. It is therefore suggested that only those fibers that are retained in a site of partial fusion for some time ever become coated. The coating process probably ceases when fusion is complete and the body is completely enclosed in a fully formed giant cell. The first coating material of the asbestos bodies seems to be some form of acid mucopolysaccharide, but this coating soon becomes impregnated with ferritin or hemosiderin to form the well-known Perls-positive bodies.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

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