Biomedical subjects

J L Pasteels

Publications and source records attributed to J L Pasteels.

At least 37 records · Page 2Linked to original sources

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↗

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

Influence of gastrin on human astrocytic tumor cell proliferation.

BACKGROUND: Gastrin and cholecystokinin (CCK) mediate their effects through at least two types of receptors (CCK receptors A and B). While it has been hypothesized that gastrin, a stimulator of gastric acid secretion, is also a neurotransmitter and a stimulator of cell proliferation in various normal and neoplastic tissues, its effect on astrocytic brain tumors has not been actively investigated. PURPOSE: Our goal was to determine the effects of gastrin and gastin and/or CCK antagonists on the proliferation in vitro of astrocytic tumor cells by use of both established cell lines and primary cell cultures of tumor tissue. METHODS: Ten established astrocytic tumor cell lines, SW1088, SW1783, Hs683, H4, U87, U118, U138, U373, T98G, and A172, were studied. The effects of added gastrin (at 0.01, 0.1, and microM) and the gastrin/CCK antagonists L-365,260, CI-988, L-364,718, and JMV 234 (each at 0.01, 0.1, and 1 microM) on the cellular proliferation rates of the 10 cell lines were indirectly measured by use of the colorimetric tetrazolium assay. The influence of gastrin (at 0.01 microM) on the cellular proliferation of primary cultures from nine freshly explanted astrocytic tumors was assessed by means of tritiated thymidine uptake and autoradiography. RESULTS: At specific concentrations, added gastrin increased the cellular proliferation of three established astrocytic cell lines (A172, Hs683, and SW1088), decreased it in two (U373 and T98G), and was without effect on the remaining five. Gastrin decreased cellular proliferation in one primary astrocytic tumor cell culture, stimulated it in five, and had no apparent effect in the remaining three. L-365,260, a CCK receptor B antagonist used at 0.01 microM, increased cellular proliferation in seven cell lines (A172, H4, Hs683, SW1783, T98G, U118, and U138), decreased it in one (U87), and had no effect in the remaining two. CI-988, another CCK receptor B antagonist used at 0.01 microM, inhibited cellular proliferation in five cell lines (A172, H4, SW1783, U373, and U87), stimulated it in two (T98G and U138), and had no effect in three. The CCK receptor A antagonists L-364,718 and JMV 234, both used at 0.01 microM, affected the cellular proliferation of only three of the 10 cell lines. CONCLUSIONS: These results suggest that gastrin (and perhaps CCK that belongs to the same peptide family) may play a role in the growth of a substantial proportion of human astrocytic tumors.

Amino Acid Sequence↗

PubMed1996

In vitro characterization of prolactin-induced effects on proliferation in the neoplastic LNCaP, DU145, and PC3 models of the human prostate.

BACKGROUND: Proliferation of normal and tumoral prostate tissue is regulated by androgens and various growth factors. We characterized the in vitro proliferative influence of prolactin (PRL) in androgen-sensitive and androgen-insensitive human prostate cancers. METHODS: The biologic models employed included the androgen-sensitive LNCaP and the androgen-insensitive DU145 and PC3 cell lines. PRL-induced influences (0.1-10 mIU/ml of medium) on proliferation were assessed using the colorimetric methylthiotetrazole assay. Androgen sensitivity in the three cell lines was determined by assessing the proliferative influence of dihydrotestosterone (DHT) (0.1-10 nM). PRL-induced modifications in PC3 cell kinetics were assessed using Feulgen-stained nuclear image cytometry. RESULTS: Although DHT markedly stimulated LNCaP proliferation, it had no proliferative effect on the DU145 and PC3 cell lines. By contrast, PRL significantly modulated the proliferation of the DU145 and PC3 lines, but exerted weak, if any, effect on the proliferation of the LNCaP cell line. PRL increased the percentage of PC3 proliferating cells (i.e., cells in the S/G2 phases of the cell cycle) at low doses (0.1 mIU/mL) and decreased this percentage at high doses (10 mIU/ml). CONCLUSIONS: Proliferation of androgen-insensitive human prostate cell lines can be significantly modulated by prolactin.

Androgens↗

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↗

PubMed1996

Computer-assisted microscope characterization of BCNU-induced modifications in the collective behavior of 12 human brain cancer cell lines.

The aim of our study is to characterize the disturbance induced by repeated BCNU treatments in 12 human brain tumor cell lines in terms of their collective behavior. This collective behavior was characterized by means of the Delaunay triangulation and Voronoi mathematical paving techniques combined with the computer-assisted microscope analysis of Feulgen-stained nuclei. This methodology enabled growth to be characterized in terms of cell colony size and density. In addition to this colony pattern characterization, the DNA ploidy level was assessed by means of DNA histogram typing. The cell proliferation level was also determined. Ten astrocytic and two medulloblastoma cell lines treated weekly with BCNU were analyzed. Study of the cell colony architecture and cell proliferation revealed specific BCNU-induced modifications in connection with the origins of the cell lines, i.e. astrocytoma (AST), glioblastoma (GBM), or medulloblastoma (MED). The BCNU-induced effect on GBM (the more malignant of the cell lines) was very different in that proliferation was weakened, but the cell colony density increased after a latency phase. The decrease in cell colony density and cell proliferation of MED seems to indicate that they are more sensitive to BCNU than GBM, but relatively tolerant of this type of chemotherapy in comparison with AST.

Brain Neoplasms↗

PubMed1996

DNA ploidy level assessments in 83 human brain metastases. Relationship to the survival of 35 patients.

The nuclear DNA content (DNA ploidy) level was determined in a series of 83 human brain metastases, for which 35 complete clinical follow-ups were available. The DNA ploidy level determination was carried out by means of DNA histogram types. The results show that certain brain metastases were diploid, while others exhibited aneuploidy levels ranging from low to very high. The present study also shows that a significant proportion, i.e. 18%, of the 83 brain metastases, exhibited very high levels of aneuploidy, i.e. hypertetraploidy, hyperpentaploidy and octoploidy. We have previously observed that this feature appeared only rarely, i.e. in less than 2% of primary nervous tumours. Furthermore, the present study shows that DNA ploidy level in brain metastases is related significantly (P < 0.001) to patient survival. Indeed, while 9/13 (69%) patients with diploid brain metastases survived longer than 9 months, none (0%) of the 22 patients with aneuploid brain metastases survived longer than the 9 months following the diagnosis of their brain metastases.

Brain Neoplasms↗

PubMed1996

Cross resistance and collateral sensitivity between cytotoxic drugs and radiation in two human bladder cell lines.

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) test was employed as a means of studying the cross resistance and collateral sensitivities of two bladder cell lines able to grow in the presence of several antineoplastic drugs and/or despite the effects of radiotherapy. This cross resistance and collateral sensitivities were investigated in the context of two antineoplastic drugs (i.e. doxorubicin (an anthracycline) and vinorelbine (a Vinca alkaloid) and radiotherapy. The results show that cell lines able to grow in the presence of anticancer drugs develop a significant degree of resistance to antineoplastic compounds and may also develop resistance to radiotherapy. On the other hand, most cell lines treated first with radiotherapy develop a significant degree of resistance towards ionizing radiation and may also display increased sensitivity towards anticancer drugs. If these results obtained in vitro are clinically relevant, they may have important applications in the treatment of patients. Nevertheless, it will be necessary to validate the results on extensive series of chemo- and/or radioresistant cell lines exhibiting different mechanisms of resistance.

Antibiotics, Antineoplastic↗

PubMed1996

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma↗

PubMed1996

The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines.

We have investigated the potential role of gastrin in the regulation of cell growth in human astrocytic tumors. To this end we have used synthetic analogs of gastrin and cholecystokinin (CCK) which behave as gastrin and/or CCK antagonists, e.g. compounds JMV-97, JMV-209 and JMV-179. Their effects on astrocytic tumor cell proliferation was investigated by the use of the colorimetric MTT assay. The in vitro biological models used in the present study included the SW1088, U87 and U373 astrocytic tumor cell lines. The results demonstrated marked influence of gastrin and CCK antagonists in the regulation of astrocytic tumor growth. This suggests that gastrin and/or CCK antagonists might be tested in experimental glioblastoma.

Astrocytes↗

PubMed1996

Neurotensin-mediated effects on astrocytic tumor cell proliferation.

Neurotensin (NT) and neurotensin receptors (NTRs) are widely found in the brain, NT may be considered as a mitogen factor in some tissues. However, no NT-mediated effects on glioma cell proliferation have been reported so far. In our present study we investigated the influence of NT on the proliferation of astrocytic tumor cell lines. To this end we used a synthetic NT agonist (JMV-449), a protease inhibitor which blocks the natural degradation of NT (JMV-531), and NT. The in vitro biological models used in the present study included the low grade SW1088, and the high grade U87, U373 and A172 astrocytic tumor cell lines. The peptide-induced influence on astrocytic tumor cell proliferation was investigated by means of the colorimetric MTT assay. Our results show that the NT and the NT agonist significantly stimulated the proliferation in 2/4 and 3/4 of the astrocytic cell lines respectively. Similarly, compound JMV-531 also induced an increase in the proliferation of 2/4 of the astrocytic cell lines. This marked influence of the NT and NT agonists, or the enzyme-endogenous prevention of its degradation on the regulation of astrocytic tumor growth therefore suggests that NT antagonists might be used to treat certain patients with high grade astrocytic tumors that do not respond to chemotherapy and/or radiotherapy.

Astrocytoma↗

PubMed1996

Image cytometry analysis of Feulgen-stained nuclei in 72 lipomatous lesions including atypical lipomas and well-differentiated liposarcomas.

Well-differentiated lipomatous tumors constitute a histopathologic category whose nomenclature has been controversial, particularly with respect to the distinction between atypical lipomas of the extremities and well-differentiated liposarcomas of the retroperitoneum. To determine whether there were differences in image analytic parameters between these neoplasms, 72 lesions including 21 typical lipomas, 7 atypical lipomas, 16 retroperitoneal and 5 nonretroperitoneal well-differentiated, 9 dedifferentiated, and 14 pleomorphic liposarcomas were submitted to the computer-assisted microscopic analysis of Feulgen-stained nuclei. This methodology enabled four groups of variables to be calculated. These included: (1) quantitative chromatin pattern description (14 variables); (2) the measurement of proliferative activity (1 variable); (3) nuclear DNA content (DNA ploidy level, 5 variables); and (4) the measurement of cell density and topographical cell nuclei organization (2 variables). The results strongly suggest that atypical lipomas, whether superficial or deep, and well-differentiated liposarcomas, whether retroperitoneal or not, belong to the same category in terms of the variables analyzed.

Adult↗

PubMed1996

The additional predictive value contributed by quantitative chromatin pattern description as compared to DNA ploidy level measurement in 257 superficial bladder transitional cell carcinomas.

The results of quantitative chromatin pattern description were compared with the determination of the DNA ploidy level, and the histological grading and clinical staging of superficial transitional cell carcinomas (sTCCs) of the bladder. We investigated whether this quantitative description adds useful information to the one obtained by the other methods used for predicting the biological behavior of sTCCs. The quantitative chromatin pattern description was carried out by means of the digital cell image analysis of Feulgen-stained nuclei in a series of 257 sTCCs. The results show that according to the clinical sequence "remission (134 patients) --> stable recurrence (101 patients) --> progression (13 patients) --> death (9 patients)', quantitative chromatin pattern description shows that certain areas of the nucleus undergo a continual process of condensation and that the distribution and spread of the chromatin becomes more and more heterogeneous. This is accompanied by a more frequent appearance of pale areas in the nucleus and an increase in nuclear size. Of the 257 sTCC patients, 148 had pTa/PpT1 grade I or III tumors. Of these 148, histological grading and clinical staging made it possible to correctly predict the biological behavior of the tumors of 120/148 (81%). DNA ploidy level determination increased this correct prediction from 81 to 84%. When the information contributed by quantitative chromatin pattern description was added to that contributed by the combination of histological grading, clinical staging and DNA ploidy level determination, the prediction level was 93%.

Adult↗

PubMed1996

The value of nuclear DNA and texture analysis by digital image processing in the diagnosis of lipomatous and leiomyomatous tumours.

The present study investigates whether the quantitative chromatin pattern description carried out by means of the digital cell image analysis of Feulgen-stained nuclei can contribute valuable diagnostic information on sarcomas. A series of 77 soft tissue tumours was consequently studied. This series included 9 benign lipomas versus 26 malignant liposarcomas and 26 benign leiomyomas versus 16 malignant leiomyosarcomas. Of the 26 liposarcomas, 14 were primary and 12 recurrent tumours. Of the 16 leiomyosarcomas, 13 were primary and three recurrent tumours. The results show that the combined use of principal-components analysis and the discriminant analyses of digital data obtained by means of the computer-assisted microscope analysis of Feulgen-stained nuclei made it possible to obtain a clear-cut distinction between the three histopathological groups relating to the lipoma/liposarcoma group of soft tumours. In contrast, while a clear-cut distinction could be made between the recurrent leiomyosarcomas and the primary leiomyosarcomas, such a distinction was not possible between the benign leiomyomas and the malignant primary leiomyosarcomas. This feature, along with previous ones obtained through DNA ploidy level determination, suggests to us that leiomyomas, or at least some of them, are in the process of malignant transformation. In other words, leiomyomas might be the pre-malignant counterpart of leiomyosarcomas, a feature that the present results do not suggest for lipomas versus liposarcomas.

Adult↗

PubMed1996

The computer-assisted microscope analysis of Feulgen-stained nuclei linked to a supervised learning algorithm as an aid to prognosis assessment in invasive transitional bladder cell carcinomas.

The aim of the present work is to ascertain whether additional information to grading and staging can be obtained for the prognosis of invasive bladder tumours (T2, T3, T4) by means of two computer-assisted methodologies. The first methodology relates to the digital image analysis of Feulgen-stained nuclei and the second to a supervised learning algorithm named Decision Tree. The digital image analysis of Feulgen-stained nuclei generated 11 variables for nuclear DNA content and 15 for quantitatively describing chromatin pattern. These 26 variables were submitted to a Decision Tree technique which produces multi-attribute logical classification rules by selecting informative variables and determining discriminatory values for each of them. A series of 41 patients for which the majority of the T2 bladder tumours (68%) were associated with a 'good' prognosis (remission) while the majority of the T3-T4 ones (77%) were associated with a 'bad' one (clinical progression or death) were submitted to the proposed approach. The results show that the decision tree was able to characterise the tumours associated with a 'bad' prognosis in the T2 sub-group (32%) and the tumours associated with a 'good' prognosis in the T3-T4 one (23%), by using only few image-generated variables (added to the clinical stage).

Adult↗

PubMed1996

The contribution of image cytometry and artificial intelligence-related methods of numerical data analysis for adipose tumor histopathologic classification.

Thirty-five lipomatous tumors were quantitatively described using 47 variables generated by means of computer-assisted microscope analysis. Of these 47 quantitative variables, 27 were computed on Feulgen-stained specimens (25 on cytologic and 2 on histologic samples) and, of the remaining 20, 8 related to vimentin and S-100 protein immunostaining patterns and the other 12 to the glycohistochemical staining patterns of peanut agglutinin, succinylated wheat germ agglutinin, and concavalin A agglutinin. The 35 lipomatous tumors included 6 atypical lipomas and 8 well differentiated, 5 dedifferentiated, 6 myxoid, and 10 pleomorphic liposarcomas. The actual diagnostic value contributed by each of the 47 variables with respect to the 5 lipomatous tumor groups was determined by means of the decision tree technique, an artificial intelligence-related algorithm that forms part of the supervised learning algorithms. Of the 47 quantitative variables, the decision tree technique retained 8: i.e., 2 tissue architecture-, 2 DNA ploidy level-, 2 morphonuclear-, 1 lectin histochemical-, and 1 vimentin immunostain-related variables. The decision tree technique made use of these 8 variables to set up logical rules that make it possible to identify atypical lipomas from well differentiated liposarcomas, on the one hand, and dedifferentiated liposarcomas from those that are well differentiated and pleomorphic, on the other. Thus, the combination of an artificial intelligence algorithm analyzing quantitative variables generated by means of the computer-assisted microscope analysis of cytologic and histologic samples from lipomatous tumors can be considered an expert system contributing significant diagnostic information to conventional diagnosis.

Algorithms↗