Biomedical subjects

J L Pasteels

Publications and source records attributed to J L Pasteels.

At least 19 recordsLinked to original sources

PubMed1999

Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS: The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS: Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS: The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.

Computer Simulation↗

PubMed1999

Improving the prognostic value of histopathological grading and clinical staging in renal cell carcinomas by means of computer-assisted microscopy.

The present work aims to refine prognosis in cases of renal cell carcinoma (RCC) by integrating a variety of parameters with the prognostic information provided by histopathological grading and clinical staging, carried out on a series of 97 RCCs. To this end, Feulgen-stained RCC cell nuclei were characterized by means of 38 variables describing nuclear DNA ploidy levels and morphology. All of these data were subjected to a principal components analysis. On the basis of this multivariate analysis, Fuhrman grade II was subdivided into grades II- and II+, and Fuhrman grade III into grade III- and III+. The same kind of subcategorization was performed in the case of the T2 and T3 clinical stages. The results show that the classification into grade II- and III- RCCs correspond to a more favourable prognosis than grade II+ and III+, to which shorter survival periods were attributable. Similar results were obtained for the subcategorization of the T2 and T3 clinical stages. Very simple biological characterizations of these grade- or stage-related RCC groups were obtained by means of a decision tree approach applied to the cytometry-generated variables. The resulting classification rules were validated on a new series of 18 patients and enabled very accurate predictions of survival.

Adult↗

PubMed1998

Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines.

Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.

Amino Acid Sequence↗

PubMed1998

The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.

Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.

Cell Division↗

PubMed1998

Characterization of astroglial versus oligodendroglial phenotypes in glioblastomas by means of quantitative morphonuclear variables generated by computer-assisted microscopy.

The current WHO classification places glioblastomas in the astrocytoma category. However, whether or not glioblastomas also show oligodendroglial differentiation remains a matter of controversy. This study investigates, at the morphonuclear level, the hypothesis that some glioblastomas (GBMs) may also represent the ultimate level of malignancy in the oligodendroglial lineage. Using a series of 164 GBMs, we sought to ascertain whether any of these GBMs exhibited phenotypical characteristics that were more closely related to oligodendroglial lineages than astrocytic lineages. Phenotypical features were quantitatively determined by means of the computer-assisted microscope analysis of Feulgen-stained nuclei, a process that made it possible to quantitatively describe the patterns of the cell nuclei (and, more specifically, of their chromatin) through 16 variables, and the distribution of the nuclear DNA content (DNA ploidy) through 8 variables. The phenotypical characteristics typical of astrocytic and oligodendroglial tumors were analyzed by means of Discriminant Analysis, a statistical multivariate analysis, performed on a series of 65 astrocytic and oligodendroglial tumors. This series consisted of 14 WHO grade II and 19 grade III astrocytomas and 24 WHO grade II and 8 grade III oligodendrogliomas. This multivariate analysis enabled an accurate model to be produced that distinguished between astrocytomas and oligodendrogliomas on the basis of 5 cytometry-generated variables. This model was used to characterize the phenotype of each of the 164 glioblastomas. The results show that of these 164 glioblastomas, 6 (about 3.5%) displayed phenotypes that were very similar to oligodendrogliomas, and 141 displayed phenotypes that were very similar to astrocytomas. The phenotypes of the 17 remaining GBMs were too ambiguous to be categorized as having a pure astrocytic or oligodendroglial lineage.

Adolescent↗

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↗

PubMed1997

Coregulatory effects of epidermal growth factor, dihydrotestosterone, and prolactin on benign human prostatic hyperplasia tissue culture proliferation.

BACKGROUND: A variety of hormones have demonstrated effects on prostatic tissue growth dynamics. Our goal was to define the effect of dihydrotestosterone (DHT), epidermal growth factor (EGF), and prolactin (PRL) on prostate cellular proliferation. METHODS: Thirty benign human prostatic hyperplasias (BPH) were maintained 48 hr as in vitro cultures. Culture media were supplemented with EGF, DHT, and PRL alone and in combinations. Proliferation was assessed by labeling with tritiated thymidine. RESULTS: The proliferative response of individual BPH cultures was heterogeneous. DHT and EGF tended to have a greater proliferative effect than PRL, both in terms of the percent cultures responding and the magnitude of the response. PRL antagonized EGF-induced proliferative effects. EGF- and PRL-mediated effects correlated with each other, while DHT-mediated effects did not correlate with either those of PRL or EGF. CONCLUSIONS: The proliferative response of individual BPH to DHT, EGF, and PRL, alone or in combination, is too variable to define a predictable response to their influence. Our methodology represents a technique with the capacity to define therapeutic potential for individual cases.

Aged↗

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

Influence of epidermal growth factor and gastrin on the cell proliferation of human meningiomas versus astrocytic tumors maintained as ex vivo tissue cultures.

The hormone sensitivity of a tumor is traditionally based on the presence of steroid receptors. Other factors should be taken into consideration. Here, we studied the influence of 10 nM epidermal growth factor (EGF) or gastrin on the proliferation of human ex vivo tumor cultures by means of [3H]thymidine autoradiography. The immunohistochemical EGF-receptor expression was also quantified by means of computer-assisted microscopy. The results demonstrated that the proliferation of 6/11 astrocytic tumors and 3/16 meningiomas was sensitive to at least one factor tested, i.e. EGF or gastrin (P < 0.01), and 5 of these 9 'hormone-sensitive' tumors were sensitive to both factors. The immunohistochemical labeling index for the EGF receptor was higher than 80% in 15/16 meningiomas, but only in 6/11 gliomas (P < 0.01). These results suggest that EGF and gastrin are important for astrocytic tumor proliferation and significantly (P < 0.01) less important for meningiomas. Thus, astrocytic tumors may be steroid insensitive in term of cell growth, but are certainly not hormone insensitive.

Astrocytoma↗

PubMed1997

Lunatomalacia associated with congenital shortening of the ulna in Langer-Giedion syndrome: a case report.

A 22-year-old patient with type I trichorinophalangeal Langer-Giedion syndrome presented a stage 2 osteonecrosis of the lunate associated with congenital shortening of the ulna and carpal tunnel syndrome. The patient was treated by shortening osteotomy of the radius and median nerve neurolysis, with an excellent result. This case provides an additional piece of evidence associating ulnar-minus variance with lunatomalacia, and another argument in favor of the theory that Kienböck's disease results from microfractures sustained by the lunate under an abnormal stress distribution situation.

Abnormalities, Multiple↗

PubMed1997

Determination of the mechanism of action of anticancer drugs by means of the computer-assisted microscope image analysis of Feulgen-stained nuclei.

The antitumoral effects of 30 drugs was monitored in vitro on three neoplastic cell lines. These 30 drugs belonged to various pharmacological classes which included alkylating agents, antimetabolites, Vinca alkaloids, topoisomerase II inhibitors, and intercalating agents. The aim of the present work is to use the same methodology to characterize the drug-induced effects at several biological levels. The drug-induced modifications were, therefore, monitored by means of the digital cell image analysis of Feulgen-stained nuclei. This methodology enabled the cell cycle kinetics to be studied. Furthermore, the numerical data quantitatively describing chromatin patterns were submitted to multivariate (principal-components) analyses, with the canonical transformation of the data. Statistical analysis shows that each pharmacological class of anticancer drugs induces specific modifications to the chromatin patterns. The present study, therefore, shows that it is possible to identify distinct classes of antineoplastic drugs on the basis of their mechanisms of action by means of the quantitative chromatin pattern description of Feulgen-stained nuclei.

Animals↗

PubMed1997

Lectin histochemistry of astrocytic tumors and in vitro characterization of lectin-induced modifications on the proliferation of the SW1088, U373 and U87 human astrocytic cell lines.

The role of lectins as biosignalling molecules or as markers of human astrocytic tumors remains relatively unexplored. The aim of the present work is to investigate (1) whether or not human astrocytic tumors express specific glycans, evidenced experimentally by means of lectin histochemistry, and (2) whether, in turn, these lectins can significantly modulate astrocytic tumor cell proliferation. Using a cell image processor, we therefore began by quantitatively measuring the histochemical binding pattern of 5 lectins (WGA, PNA, PHA-L, GSA-IA4 and Con A) in 5 astrocytomas, 5 anaplastic astrocytomas and 5 glioblastomas. Secondly, we measured the influence of these 5 lectins on the proliferation of 3 astrocytic tumor cell lines (SW1088, U373 and U87) growing in vitro as monolayers. Cell proliferation was assessed by means of the colorimetric MTT assay. The histochemical lectin staining markedly varied intra- and inter-group. However, some constant results were obtained. Indeed, the staining increased markedly from GSA-IA4 and PHA-L through WGA and PNA to ConA in the three histopathological groups. The assessment of cell proliferation demonstrated that WGA, Con A and PHA-L very significantly decreased proliferation in the 3 astrocytic cell lines in a dose-dependent manner. Astrocytic tumor cells in the confluent growth phase were less sensitive to the WGA, Con A and PHA-L lectin-induced effects than cells in the log growth phase. The GSA-IA4 and PNA lectins had globally very weak effects on the proliferation of the astrocytic tumor cell lines. Increasing the fetal calf serum from 1% to 10% in the culture media significantly antagonized the WGA-, Con A- and PHA-L-induced cell proliferation decrease in the 3 astrocytic cell lines. In conclusion, the present data strongly suggest that some lectins (including WGA, Con A and PHA-L) significantly influence the proliferation of astrocytic tumor cells.

Analysis of Variance↗

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

In vitro influence of Phaseolus vulgaris, Griffonia simplicifolia, concanavalin A, wheat germ, and peanut agglutinins on HCT-15, LoVo, and SW837 human colorectal cancer cell growth.

BACKGROUND/AIMS: Compared with normal colonic mucosa, lectin receptor expression is increased in hyperplastic and neoplastic tissues; some lectins have been shown to influence human colonic epithelial cell proliferation. The aim was to assess further the influence of five lectins (Phaseolus vulgaris (PNA), Griffonia simplicifolia (GSA), concanavalin A (Con A), wheat germ (WGA), and peanut (PHA-L) agglutinins) on cellular growth in three human colorectal cancer cell lines (LoVo, HCT-15 and SW837). METHODS: Cells were cultured in four lectin concentrations (0.1, 1.0, 10, and 100 micrograms/ml) and growth assessed at days 2, 3, 5, and 7. The experiments were performed in media supplemented with either 1% or 10% fetal calf serum (FCS). Growth was assessed using the MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric assay. RESULTS: Growth in each cell line was greatly affected by at least two of the lectins tested. There was some variation in the effect of a given lectin on different cell lines. Lectin effects showed a dose-response and the greatest effects generally resulted from the highest concentrations at the longest culture time. WGA and Con A induced large effects in all cell lines; the effects of Con A were partly blocked by the higher concentration of FCS. PNA had modest and uniform stimulatory effects overall. The effects of GSA and PHA-L varied between cell lines. CONCLUSIONS: The lectins studied all have the potential to affect colonic cancer growth in vitro. Many dietary lectins are resistant to digestion and may have important effects in vitro but the definition of their role in human colonic cancer biology must take into account the variability in lectin response.

Cell Division↗

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↗