Biomedical subjects

C Decaestecker

Publications and source records attributed to C Decaestecker.

At least 73 records · Page 4Linked to original sources

PubMed1998

Setting up of an original computer-assisted methodology to characterize in vitro drug-induced anti-angiogenic effects.

The development of angiogenesis within a tumor brings on a sequence of extremely complex molecular events. We have developed a methodology which enables a wide set of biological parameters to be quantitatively determined in the field of anti-angiogenesis pharmacology. This methodology which includes a video cell tracking device, is unique because it offers the possibility of evaluating the specific influence of a given compound with potential anti-angiogenic properties on cell cycle kinetics, cell death, global cell line growth, and cell motility. We chose TNP-470, a synthetic analogue of fumagilin, to test our methodology on HUVEC cell lines taken from various human umbilical cord veins. The experiments carried out with TNP-470 did not confirm all the data reported in the literature. Our results show that i) TNP-470 could be considered as a cytotoxic agent; ii) this compound had an apparently marginal cytostatic effect; and iii) it did not increase the apoptosis level. Our methodology also revealed that the HUVEC cell lines are very heterogeneous in terms of different biological parameters. This highlights the problem of the reproductibility of the result.

Angiogenesis Inhibitors↗

PubMed1998

Direct relationship between hormone sensitivity level and growth pattern. Evidence in 18 gastrointestinal neoplastic cell lines.

OBJECTIVE: We investigated whether a relationship exists in terms of growth pattern and hormone sensitivity in 18 gastrointestinal neoplastic cell lines. Hormones studied included gastrin, epidermal growth factor, estradiol and luteinizing hormone-releasing hormone. STUDY DESIGN: The growth patterns were assessed by means of computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques. This methodology enabled four variables characterizing the cell colony patterns to be computed. The information contributed by these variables was analyzed by means of discriminant analysis and the decision tree technique. RESULTS: Each phenotype (sensitivity level) exhibited distinct growth pattern (or cell colony) characteristics in the case of each hormone and/or growth factor under study. Furthermore, the sensitivity of the gastrointestinal cell lines to a given hormone (or growth factor) appeared to be peculiar to the hormone (or growth factor). CONCLUSION: A direct relationship seems to exist between growth pattern and hormone sensitivity levels in gastrointestinal cancers, particularly colorectal.

Cell Count↗

PubMed1998

Prognostic value of stem cell line identification for renal cell carcinomas.

OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight variables were used to characterize DNA ploidy levels. They included DNA index and seven others characterizing the presence of specific stem cell lines in each of the 95 RCCs under study. All these variables were determined by means of computer-assisted microscopy applied to Feulgen-stained nuclei. The actual information contributed by each of the eight variables was determined by means of univariate statistical analyses. RESULTS: The results showed that in the DNA ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with > 5C DNA content was associated with the most significant prognostic value in RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study clearly showed that stem cell line characterization, and particularly the presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs with significant prognostic value. This kind of marker may help the identification of patients who will develop metastases after surgery and for whom adjuvant therapy might thus be indicated.

Adult↗

PubMed1998

Use of image cytometry to classify biliary and ampullary adenocarcinomas.

OBJECTIVE: To create an objective classification system to perform TNM classification of ampullary adenocarcinoma and cholangiocarcinoma using image cytometric data derived from Feulgen-stained tumor nuclei. STUDY DESIGN: Surgically resected cases of ampullary adenocarcinoma and cholangiocarcinoma with established TNM classifications were selected on the basis of available formalin-fixed, paraffin-embedded tissue. Fifteen numerical variables related to morphometric, densitometric and textural features of each tumor nucleus were recorded. We employed a methodology based on multivariate statistical tools to characterize the association of morphonuclear variables with TNM classification. The first step consisted of identifying and selecting representative nuclei of each T class. From this "purified" data set an objective classification system was created. The classification system was assessed using internal and external validation. RESULTS: Employing ANOVA, all 15 variables were significantly associated with T classification, 11 of 15 with N and 4 with M. Multivariate analysis was employed to distinguish between T1, T2 and T3 lesions. Our methodology correctly classified 76% of T1 nuclei, 47% of T2 nuclei and 84% of T3 nuclei. Heterogeneity within an individual tumor was defined in 61% of cases included in the training set. Complete concordance between pathologic classification and the classification system was observed in 71% of an independent validation.

Adenocarcinoma↗

PubMed1997

Dynamic characterization of glioblastoma cell motility.

The cell motility dynamic of two glioblastoma cell lines (U373 and U87) was studied by means of an automatic video-cell-tracking-system enabling each cell in a colony to be tracked for several hours. Twenty-five experiments were performed on both models growing on three different supports (glass, plastic and Matrigel). Cell motility was significantly different in each cell line and also for different growth support in a given cell line. We observed that U87 cells are significantly (p < 0.00001) less motile than U373 cells. The most favorable growth supports for cell motility studies were Matrigel and glass. A significant (p < 0.001) correlation between cell colony density and cell motility was highlighted, with isolated cells exhibiting a motility level distinct from the one observed for colonies. The present methodology, which enabled cell motility to be quantified in human glioblastoma cells, represents an original tool for identifying new classes of compounds able to reduce glioblastoma cell motility and cell migration potential into the brain.

Cell Count↗

PubMed1997

Classification strategies for the grading of renal cell carcinomas, based on nuclear morphometry and densitometry.

The various grading systems proposed for renal cell carcinomas all suffer from problems related to inter-observer variability. Some of these grading systems are based, either partially or wholly, on morphonuclear criteria, such as nuclear size and shape, anisonucleosis, and chromatin pattern. These criteria can be quantitatively (and thus objectively) evaluated by means of the computer-assisted microscopic analysis of Feulgen-stained nuclei. In the present work, 39 quantitative variables, including two morphometric, 28 chromatin pattern-related, and nine DNA ploidy level-related, were computed for 65 renal cell carcinomas. The actual diagnostic information contributed by each variable was determined by means of multifactorial statistical analysis (discriminant analysis) and two artificial intelligence-related methods of data classification (the decision tree and production rule methods). The results show that quantitative information, as provided by the computer-assisted microscopy of Feulgen-stained nuclei and analysed by means of artificial intelligence-related methods of data classification, contributes significant diagnostic information for the grading of renal cell carcinoma, thus reducing the problem of inter-observer reproducibility.

Adult↗

PubMed1997

Ploidy level determination and quantitative chromatin pattern description in pregnancy-associated breast cancers.

The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation.

Breast Neoplasms↗

PubMed1997

The combined determination of proliferative activity and cell density in the prognosis of adult patients with supratentorial high-grade astrocytic tumors.

Tumor growth represents the ratio between cell gain (number of mitoses per unit of time, i.e., proliferative activity) and cell loss (number of cell deaths during the same unit of time). While in adults, proliferative activity parallels the level of malignancy in astrocytic tumors and therefore represents a useful diagnostic marker, cell loss has never been concomitantly assessed in tumors of this type. We hypothesize that cell density assessable on histologic slides represents the ratio between cell gain and cell loss. This hypothesis concerns only the diffuse type of astrocytic tumors. Proliferative activity (assessed by MIB1 antigen immunostain) and cell density were thus quantitatively assessed by means of a cell image processor in a series of 54 supratentorial astrocytic tumors of adult patients, which included 15 astrocytomas (ASTs), 18 anaplastic astrocytomas (ANAs), and 21 glioblastomas (GBMs). The results show that proliferative activity and cell density were highly correlated (P = .003) and that both correlated with histopathologic grade. The patients with a high-grade astrocytic tumor (i.e., ANA or GBM) that exhibited a low level of proliferative activity but high cell density survived for significantly shorter periods than did patients with a tumor that exhibited low proliferative activity and low cell density (P = .002). The patients with a high-grade astrocytic tumor that exhibited high proliferative activity and high cell density survived for significantly less time than did the patients with a tumor that exhibited high proliferative activity but low cell density (P < .05). A marked difference in survival periods was observed between the patients with a high-grade astrocytic tumor that exhibited a low level of proliferative activity and low cell density and the patients with a tumor that exhibited a high level of proliferative activity and high cell density (P < .001). The concomitant determination of proliferative activity and cell density seems likely to enable determination of the few adult patients who have high-grade astrocytic tumors and who will survive for a considerable period (several years).

Adolescent↗

PubMed1997

Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligo-astrocytomas.

The oligoastrocytoma, as a mixed glioma, represents a nosologic dilemma with respect to precisely defining the oligodendroglial and astroglial phenotypes that constitute the neoplastic cell lineages of these tumors. In this study, cell image analysis with Feulgen-stained nuclei was used to distinguish between oligodendroglial and astrocytic phenotypes in oligodendrogliomas and astrocytomas and then applied to mixed oligoastrocytomas. Quantitative features with respect to chromatin pattern (30 variables) and DNA ploidy (8 variables) were evaluated on Feulgen-stained nuclei in a series of 71 gliomas using computer-assisted microscopy. These included 32 oligodendrogliomas (OLG group: 24 grade II and 8 grade III tumors according to the WHO classification), 32 astrocytomas (AST group: 13 grade II and 19 grade III tumors), and 7 oligoastrocytomas (OLGAST group). Initially, image analysis with multivariate statistical analyses (Discriminant Analysis) could identify each glial tumor group. Highly significant statistical differences were obtained distinguishing the morphonuclear features of oligodendrogliomas from those of astrocytomas, regardless of their histological grade. When compared with the 7 mixed oligoastrocytomas under study, 5 exhibited DNA ploidy and chromatin pattern characteristics similar to grade II oligodendrogliomas, I to grade III oligodendrogliomas, and I to grade II astrocytomas. Using multifactorial statistical analyses (Discriminant Analysis combined with Principal Component Analysis). It was possible to quantify the proportion of "typical" glial cell phenotypes that compose grade II and III oligodendrogliomas and grade II and III astrocytomas in each mixed glioma. Cytometric image analysis may be an important adjunct to routine histopathology for the reproducible identification of neoplasms containing a mixture of oligodendroglial and astrocytic phenotypes.

Adult↗

PubMed1997

Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.

The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.

Adult↗

PubMed1997

Determination of proliferative activity in nasal polyps.

AIMS: To determine the level of proliferative activity in 39 nasal polyps with clear cut distinct clinical behaviour patterns. METHODS: The 39 nasal polyps included 11 polyps labelled as "single" and taken from the lateral nasal wall and the middle turbinate; 12 polyps labelled as "massive" and relating to diffuse polyposis involving the entire nasal cavity; six polyps labelled as "ASA" and relating to nasal polyps from patients with acetylsalicylic acid intolerance and asthma; and 10 polyps from cystic fibrosis related polyposis. Cell proliferation was determined by two independent methods: first, the computer assisted microscope analysis of isolated Feulgen stained nuclei for the measurement of the percentage of cells in the S phase of the cell cycle; and second, the immunohistochemical evaluation of a proliferation associated protein by means of the MIB 1 monoclonal antibody. RESULTS: The cystic fibrosis related polyposis exhibited the highest proliferative activity of all the clinically identified nasal polyp groups. Acute inflammatory nasal polyps exhibited a higher cell proliferation than chronic ones. The results also show that while the immunohistochemical determination of cell proliferation by means of the MIB 1 monoclonal antibody is a valuable tool in determining cell proliferation in nasal polyps, the cytometrical image analysis of Feulgen stained nuclei is not useful for this purpose. CONCLUSION: Cell proliferation activity identifies cystic fibrosis as being distinct from the other nasal polyp groups.

Acute Disease↗

PubMed1997

Characterization of the nuclear deoxyribonucleic acid content and nuclear morphometry in 71 primary cutaneous melanomas.

BACKGROUND: While the determination of nuclear deoxyribonucleic acid (DNA) content (DNA ploidy level) and nuclear morphometry characterization has proved to be of prognostic value in melanocytic lesions, there are several ways of performing these determinations. OBJECTIVE: To identify which of 9 DNA ploidy- and 2 nuclear morphometry-related variables are of prognostic and/or diagnostic value in 71 primary melanomas. METHODS: Histological typing, Breslow depth determination, the evaluation of Clark's level of invasion and the 11 quantitative variables (calculated in Feulgen-stained nuclei using computer-assisted microscope analysis) determined for each melanoma were submitted to discriminant analysis. RESULTS: The discriminant analysis of image cytometric variables enabled specific cell subpopulations to be identified in histological and the Breslow-related groups, but not in the Clark-related ones. CONCLUSION: The characterization of melanoma heterogeneity by means of the identification of specific DNA ploidy level-related cell subpopulations in specific Breslow-related groups enables the problem of intra- and interobserver variability in Breslow depth determination to be reduced and therefore can help dermatologists in their daily routine.

Adult↗

PubMed1997

Algorithm analysis of lectin glycohistochemistry and Feulgen cytometry for a new classification of nasal polyposis.

The aim of this study is to present a new classification of nasal polyps. This classification is based both on morphologic criteria relating to morphonuclear features from isolated Feulgen-stained nuclei and on glycohistochemical characteristics from histologic slides submitted to three lectins (peanut, wheat germ, and gorse seed agglutinins) and one neoglycoconjugate glycohistochemical stain. While the morphonuclear features (including 30 variables) relate essentially to chromatin pattern, the glycohistochemical stains (including 16 variables) are linked to the presence of specific carbohydrate moieties in cell membranes and cytoplasm. Forty-nine nasal polyps, including single polyps, diffuse polyposis, cystic fibrosis-related polyposis, and aspirin idiosyncracy-related polyposis associated with asthma, were thus characterized. All the variables were obtained quantitatively by means of computer-assisted microscopy. Two complementary methods of data classification were used to determine the actual diagnostic value contributed by each quantitative variable, namely, discriminant analysis, which forms part of multifactorial statistical analysis, and the decision tree technique, which is an artificial intelligence-related algorithm. The data so obtained show that our morphologic classification of nasal polyps fits in with the classification of nasal polyps defined on the basis of clinical criteria.

Algorithms↗

PubMed1997

Nearest-neighbor classification for identification of aggressive versus nonaggressive low-grade astrocytic tumors by means of image cytometry-generated variables.

The authors investigated whether cytometry-related variables generated by means of computer-assisted microscopic analysis of Feulgen-stained nuclei can contribute significant information toward the characterization of low-grade astrocytic tumor aggressiveness. This investigation was conducted using the nearest-neighbor rule (a traditional classification method used in pattern recognition) to analyze a series of 250 supratentorial astrocytic tumors from adult patients. This series included 39 low-grade astrocytomas and 211 high-grade astrocytic tumors (including 47 anaplastic astrocytomas and 164 glioblastomas multiforme [GBMs]). The results show that the 3-nearest-neighbors rule enabled a subgroup of "atypical" astrocytomas to be distinguished from the "typical" tumors. The atypical astrocytoma species exhibited a DNA content (DNA ploidy level) and morphonuclear characteristics that were statistically more similar to the characteristics of GBMs than to those exhibited by the typical astrocytomas. An analysis of survival data revealed that patients with atypical astrocytomas survived for a significantly shorter period (p < 0.001) than patients with typical lesions of this kind. In fact, patients with atypical astrocytomas had a survival period similar to that of patients with anaplastic astrocytomas, whereas patients with typical astrocytomas had a survival period significantly longer (p < 0.0001) than those associated with anaplastic astrocytomas and GBMs.

Adolescent↗

PubMed1997

Decision tree induction: a useful tool for assisted diagnosis and prognosis in tumor pathology.

The aim of the present work is to show that decision tree induction algorithms are a useful tool for extracting reliable information from data series, with the objective of assisting pathologists in identifying specific diagnostic and prognostic markers in various types of tumor pathologies. In terms of accuracy, we show that the decision tree technique exceeds other more sophisticated techniques, such as multilayer neural networks. Furthermore, because of the case with which decision tree results can be interpreted (logical classification rules), new methodologies can be readily developed to further assist in analyzing complex data that mix heterogeneous features. In this paper, we illustrate such capabilities in the context of different complex diagnostic and/or prognostic problems in tumor pathology relating to bladder, astrocytomas, and adipose tissues.

Adult↗

PubMed1997

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Adult↗

PubMed1996

Methodological aspects of using decision trees to characterise leiomyomatous tumors.

The aim of the present work is to present the potential uses of a classification technique labeled the "decision tree" for tumor characterisation when faced with a large number of features. The decision tree technique enables multifeature logical classification rules to be produced by determining discriminatory values for each feature selected. In this report, we propose a methodology that used decision trees to compare and evaluate the information contributed by different types of features for tumor characterisation. This methodology is able to produce a set of hypotheses related to a diagnosis and or prognosis problem. For example, hypotheses can be producted (on the basis of a set of descriptive features) to explain why tumor cases belong to a given histopathological group. To illustrate our purpose, this methodology was applied to the difficult problem of leiomyomatous tumour diagnosis. The aim was to illustrate what kind of diagnostic information can be extracted from a sample data set including 23 smooth muscle tumors (14 benign leiomyomas and 9 malignant leiomyosarcomas) described by a large set of computer-assisted, microscope-generated features. Three groups of features were used relating to: (1) ploidy level determination (10 features), (2) quantitative chromatin pattern description (15 features), and (3) immunohistochemically related antigen specificities (6 features). All these features were quantified by digital cell image analysis. The results suggest that an objective distinction between leiomyomas and leiomyosarcomas can be established by means of simple logical rules depending on only a few features among which the immunohistochemically revealed antigen expression of desmin plays a preponderant part. One of the combinations of features proposed by the methodology is interesting for pathologists, because it includes two features describing the appearance of a nucleus in terms of chromatin distribution homogeneity and density, two features widely used by pathologists in tumor-grading systems.

Adolescent↗

PubMed1996

The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.

The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.

Adult↗