Induction of Endothelial Cell Apoptosis by Solid Tumor Cells

The mechanisms by which tumor cells extravasate to form metastasis remain controversial. Previous studies performed in vivo and in vitro demonstrate that the contact between tumor cells and the vascular wall impairs endothelium integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was significantly enhanced. Neither normal cells tested (mammary epithelial cells, fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60, Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell contact, since it could not be reproduced by media conditioned by MCF-7 cells cultured alone or cocultured with HUVEC. Our results suggest that cells derived from solid tumors may alter the endothelium integrity by inducing endothelial cell apoptosis. On the contrary, normal or malignant leukocytes appear to extravasate by distinct mechanisms and do not damage the endothelium. Our data may lead to a better understanding of the steps involved in tumor cell extravasation

What Is the Interest of Klinefelter's Syndrome for (Child) Psychiatrists?

peer reviewedÀ partir de la prise en charge psychiatrique et endocrinologique à l'âge de 22 ans d'un patient atteint d'un trouble schizoaffectif et d'un syndrome de Klinefelter (SK), nous présentons les aspects psychopathologiques de ce syndrome qui est fréquent (près d'un garçon sur 500 à la naissance) et dont, le plus souvent, le diagnostic n'est pas posé. Les garçons atteints de ce syndrome ont généralement un retard d'acquisition du langage, un QI verbal inférieur à la moyenne et un QI global dans les limites de la normale. Sans suivi spécifique, le risque de troubles psychiatriques (de tous types) est plus élevé que celui de la population générale, comme le prouvent des études réalisées en milieu psychiatrique. En cas d'hypotestostéronémie (très fréquente), un traitement substitutif par undécanoate de testostérone devrait être instauré (idéalement entre 11 et 15 ans, mais le diagnostic est souvent posé à l'âge adulte) pour ses effets bénéfiques somatiques et psychiques. Jusqu'à présent, aucune donnée fiable dans la littérature ne contre-indique formellement un traitement par androgènes en cas de trouble psychiatrique grave. Cependant, chaque situation devra être évaluée attentivement ; l'éventuelle androgénothérapie doit être intro­ duite progressivement et sera associée à une évaluation psychiatrique très régulière

Knockdown of Moesin Expression Accelerates Cellular Senescence of Human Dermal Microvascular Endothelial Cells

PURPOSE: Endothelial cells maintain the homeostasis of blood, which consists of plasma and cellular components, and regulate the interaction between blood and the surrounding tissues. They also have essential roles in vascular permeability, the circulation, coagulation, inflammation, wound healing, and tissue growth. The senescence of endothelial cells is closely related to the aging of the adjacent tissues and to age-related vascular disease. Recently, the expression of moesin was found to be decreased in elderly human dermal microvascular endothelial cells (HDMECs), and an association between moesin and senescence has been suggested. This study examined the functional role of moesin in cellular senescence. MATERIALS AND METHODS: To study the effects of decreased moesin expression on cellular senescence and metabolism, HDMECs were transfected with short hairpin-RNA (shRNA) lentivirus to silence moesin gene expression. In addition, specimens from young and old human skin were stained with antimoesin and anti-p16 antibodies as an in vivo study. RESULTS: Using shRNAlentivirus, moesin knock-down HDMECs developed characteristics associated with aging and expressed senescence associated-beta-galactosidase during early passages. They also showed increased p16 expression, decreased metabolic activity, and cell growth retardation. Human skin tissue from elderly persons showed decreased moesin expression and increased p16 expression. CONCLUSION: These findings suggest that there is a functional association between moesin expression and cellular senescence. Further study of the functional mechanism of moesin in the cytoskeleton and cellular senescence is needed. In addition, this study provides a useful model for developing anti-aging treatments.ope

A Heterogeneous In Vitro Three Dimensional Model of Tumour-Stroma Interactions Regulating Sprouting Angiogenesis

Angiogenesis, the formation of new blood vessels, is an essential process for tumour progression and is an area of significant therapeutic interest. Different in vitro systems and more complex in vivo systems have been described for the study of tumour angiogenesis. However, there are few human 3D in vitro systems described to date which mimic the cellular heterogeneity and complexity of angiogenesis within the tumour microenvironment. In this study we describe the Minitumour model – a 3 dimensional human spheroid-based system consisting of endothelial cells and fibroblasts in co-culture with the breast cancer cell line MDA-MB-231, for the study of tumour angiogenesis in vitro. After implantation in collagen-I gels, Minitumour spheroids form quantifiable endothelial capillary-like structures. The endothelial cell pre-capillary sprouts are supported by the fibroblasts, which act as mural cells, and their growth is increased by the presence of cancer cells. Characterisation of the Minitumour model using small molecule inhibitors and inhibitory antibodies show that endothelial sprout formation is dependent on growth factors and cytokines known to be important for tumour angiogenesis. The model also shows a response to anti-angiogenic agents similar to previously described in vivo data. We demonstrate that independent manipulation of the different cell types is possible, using common molecular techniques, before incorporation into the model. This aspect of Minitumour spheroid analysis makes this model ideal for high content studies of gene function in individual cell types, allowing for the dissection of their roles in cell-cell interactions. Finally, using this technique, we were able to show the requirement of the metalloproteinase MT1-MMP in endothelial cells and fibroblasts, but not cancer cells, for sprouting angiogenesis

Development of Bankruptcy Prediction Model for Latvian Companies

This article addresses the financial performance prediction for Latvian companies. It is of critical importance to be able to provide timely warnings to management, investors, employees, stakeholders and other interested parties who wish to reduce their losses. There are literature review structures that previously made research into company performance prediction. Estimating the risk of bankruptcy of Latvian companies has been carried out by applying two commonly used approaches: Altman’s Z-score estimation and an experience-based machine learning approach using C4.5 Decision Tree. The results show that Altman’s Z-score method predicts bankruptcy for a massive number of companies, while the ML method predicts bankruptcy for only a few. Each of these approaches has its drawbacks. We propose an extended company performance prediction model that considers other factors that influence distress risk, e.g., changes in regulation and other environmental factors. Expert opinion is of great value in estimating a company’s future performance; therefore, an automated solution supporting experts in their decision-making is presented

Demonstration in Vivo That Stromelysin-3 Functions through Its Proteolytic Activity

Stromelysin-3 (ST3), a matrix metalloproteinase (MMP) expressed in aggressive carcinomas, has been shown to promote tumor development in different in vivo experimental models. However, the inability of its mature form to degrade extracellular matrix components casts doubt on whether ST3 functions in vivo as a protease. In this study, we evaluated whether the ST3 tumor-promoting effect could be ascribed to its proteolytic activity and whether this putative protease could be targeted with MMP inhibitors. Catalytically inactive mutant cDNA of human (h) ST3 or mouse (m) ST3 were generated and transfected into MCF7 cells. When injected into nude mice in the presence of matrigel, the mutant-bearing cells did not exhibit the enhanced tumorigenicity elicited by MCF7 cells transfected with wild-type ST3 cDNA. In a second approach, TIMP2 overproduction in MCF7 cells expressing hST3 was induced by retroviral infection. The co-expression of ST3 and TIMP2 failed to enhance the tumorigenicity of MCF7 cells. Notably, matrigel depleted of low-molecular-weight proteins and growth factors failed to promote the tumorigenicity of ST3-expressing MCF7 cells. These findings provide the first in vivo evidence that ST3 is indeed a protease that can modulate cancer progression by remodeling extracellular matrix and probably by inducing it to release the necessary microenvironmental factors. Thus, ST3 represents an interesting target for specific MMP inhibition

Fitting lactation data with two mathematical models and extension factors for milk, fat and protein of Belgian dairy goats

peer reviewedData for 18 155 test day milk yields and fat and protein percentages recorded from 15 February 1988 to 1 September 1993 were obtained from the Office de promotion des petits élevages en Wallonie. Due to irregular test intervals and a variable number of tests per lactation, production was estimated at 25 day intervals (25, 50, ..., 250 days). A total of 13 773 test day records for Anglo-Nubian, Chamoisee, Saanen and crossbreds were available for analysis. Parities were classified into 1 and ≥ 2. The inverse polynomial and the incomplete gamma functions were fitted to test day milk yields in order to define the shape of the lactation curves for the various breeds and parities. Two data subsets were created by random selection of entire lactation data from the original data set, and both functions were fitted to test day milk yields within breed-parity classes. Parameters of equations estimated on a subset of the data were validated on the other subset. Estimates of peak yields were higher and times of peak yield later by the inverse polynomial method than by the incomplete gamma but remained within ranges found in the literature. Based on the coefficient of multiple determination (R2), both equations were equally accurate in fitting lactation data of a subset. Though average residual deviations were slightly higher with the inverse polynomial than with the incomplete gamma, the crossvalidation did not reveal any particular trend of residuals for any equation. For practical reasons, extension factors for milk, fat and protein yields were derived using the inverse polynomial and are presented

L’apoptose mammaire dans le sein normal et en pathologie

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