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Biomedical subjects

J Smolle

Publications and source records attributed to J Smolle.

At least 109 records · Page 6Linked to original sources
PubMed1994

Evaluating intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.

A pilot study on intraoperative radiation therapy (IORT) combined with external beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC) was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11 adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the tumor. Unilateral continuous positive airway pressure ventilation of the diseased lung was used to reduce the amount of healthy lung tissue in the IORT port and to minimize the ventilatory movement. Secondary collimation and direct shielding of radio-sensitive structures within the IORT port by aluminium sheets were used to further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5 times a week; 8-23 MeV photons) were administered to the mediastinum and to the tumor-bearing area on an outpatient basis. In nodal positive cases the mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In 13 complete, in 8 partial (50-97% regression) and in 2 minor response has been achieved. Five patients experienced a recurrence (local only: 2; local and distant: 1; distant only: 2). Twelve patients died of underlying cardio-respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The overall 5-year survival rate including the incidental deaths is 14.7%. The recurrence-free survival rate is 53.2%.

Adenocarcinoma↗
PubMed1994

Quantitative assessment of melanoma single-cell motility in vitro.

Cell motility is a crucial property of tumor cells during invasion and metastasis. In this study we developed a computer assisted system to measure translocation and stationary motility of single cells and used this procedure to evaluate the influence of cytochalasin A (CA) on single-cell motility parameters of K1735-M2 mouse melanoma cells. The cells were seeded at low density into a microincubator. Time lapse microcinematography was performed every 20 seconds from a high power field to assess stationary motility and every 10 minutes with a screening objective to measure translocation. 1 muMol CA was added to the medium 48 hours before measurement. Calculation of stationary motility was performed by subtraction of subsequent images and the resulting image difference was used for quantitative evaluation. Three different measuring windows were drawn to discriminate between membrane ruffling, intracellular organelle transport and overall stationary motility. For each cell we measured change of density (CD), area of change (AC), perimeter of area of change (PC), area of ruffling (AR), number of ruffling sites (NR), change of intracellular organelles (CIO) and number of changing intracellular organelles (NIO). In order to quantify translocation, the center of gravity of each cell was assessed subsequently and the velocity was calculated by connecting the centers of gravity. CA-treated cells showed a significantly lower stationary motility and membrane ruffling compared to the untreated cells (U-test: p < = 0.01), but there was not significant difference concerning the intracellular organelle transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Spitz's nevus arising on a nevus spilus.

The first case of a solitary dermal Spitz's nevus arising on a nevus spilus is described. The special variant of a combined Spitz's nevus may cause difficulties in differential diagnosis from malignant melanoma in association with a nevus spilus.

Adolescent↗
PubMed1994

Pattern interpretation by cellular automata (PICA)--evaluation of tumour cell adhesion in human melanomas.

In routine pathology, the evaluation of the pattern of a tumour at scanning magnification often reveals diagnostic and prognostic features indicating that the biological properties of the tumour cells are related to the morphological pattern. For further evaluation of the relationship between functional properties of the cells on the one hand and the pattern on the other, we propose the pattern interpretation by cellular automata (PICA) procedure. The PICA system consists of an import module transferring real histological images into the data structure of a cellular automaton, a measurement module generating a comparable quantitative description of real and simulated images, a cellular automation designed to simulate tumour growth and invasion at the histological level, a database consisting of the morphological results obtained in simulated patterns, an interpretation module linking real histological images to the knowledge stored in the database and an image synthesis and display module. By comparing real images to computer-simulated patterns, PICA facilitates an estimation of functional properties based on the static histological pattern of a given tumour. Using the example of tumour cell adhesion, it is demonstrated that the degrees of tumour-tumour and tumour-stroma adhesion significantly affect the resulting simulated patterns, that, in turn, the morphological evaluation of the patterns enables a reproducible estimation of adhesion and that estimates of adhesion in real images of malignant melanoma of the skin are of prognostic significance. PICA may serve as an additional in situ evaluation technique linking morphological features to functional properties.

Cell Adhesion↗
PubMed1994

Histologic tumour image synthesis based on a cellular automaton.

Cellular automata are suitable models for simulating tumour growth and invasion at the microscopic level. The results of the stimulation, however, is usually represented by a pattern of grid points, which is difficult to relate to real histological patterns by visual inspection. In this paper a 2-dimensional image synthesis module is presented, which provides a more realistic visualisation by texture mapping to tumour cell nuclei, cytoplasm and stromal elements, simulating a melanocytic tumour invading the reticular dermis. The enhancement by image synthesis facilitates a visual comparison of simulated images of real histological specimens.

Computer Simulation↗
PubMed1993

Computer simulation of tumour cell invasion by a stochastic growth model.

The structure and function of biological systems are considered to be closely related. The present study addresses the question of how histological patterns of tumours are related to specific functional properties of the tumour cells. A mathematical model was developed, which facilitates the simulation of tumour growth and invasion by computer. The degree of cell division, migration and death can be interactively set and the simulation results can be observed on the screen. Additionally, these basic functional properties of a particular cell can be influenced by autocrine and paracrine factors. The study shows that the resulting morphological patterns closely depend on the preset functional properties of the tumour cells. Furthermore, each autocrine or paracrine factor, or combinations of these factors, induce peculiar modifications of the tumour pattern. These results provide evidence that histological tumour patterns reflect functional properties of the tumour cells and their interaction with the micro-environment. Qualitative and quantitative comparison of real tumour specimens with patterns simulated by computer may thus provide a logical base for a functional interpretation of static histological images.

Cell Death↗
PubMed1993

Specific skin manifestations in acute leukemia with monocytic differentiation. A morphologic and immunohistochemical study of 11 cases.

BACKGROUND: Monocytic differentiation is present in the myelomonocytic (M4) and monocytic (M5) type of acute myeloblastic leukemia. Infiltration of the skin in acute myelomonocytic leukemia occurs in 10-20% of patients, the skin lesions occasionally being the first symptom, even preceding monocytosis. METHODS: Eleven patients with myelomonocytic (n = 2) and monocytic leukemia (n = 9) were studied who had skin manifestations. RESULTS AND CONCLUSIONS: Clinically, all patients showed disseminated papules or nodules that corresponded histologically to nodular or diffuse infiltrates of monocytoid cells, occasionally displaying a whorled pattern. The currently available antibodies for paraffin-embedded sections (lysozyme, elastase, leukocyte common antigen (CD45), MT1 (CD43), Leu-M1 (CD15), LN2 (CD74), MB2, MB1 (CD45RA), LN1 (w75), Mac387, L26 (CD20), UCHL1 (CDR0), MT2 (CD45RA), and KP-1 (CD68)) and chloracetate-esterase are not more helpful in diagnosis than are the histologic findings. By contrast, the antibodies used on frozen sections (Leu-4 (CD3), Leu-3a (CD4), BA1 (CD24), B4 (CD19), Leu-M5 (CD11c), Vim12 (CD11b), VimD5 (CD15), KiM6 (CD68), KIM7 (CD68), My7 (CD13), and My9 (CD33) allow the definition of a reaction pattern that is diagnostic for acute myeloid leukemia with monocytic differentiation.

Adult↗
PubMed1993

Inhibition of K1735-M2 melanoma cell invasion in vitro by retinoic acid.

Melanoma cell invasion in vitro was tested by means of confrontation cultures of melanoma multicellular spheroids with rounded fragments of embryonic chick heart tissue. Quantitative determination of invasion was performed using a computerized image analysis program, facilitating the evaluation of the efficacy of potentially anti-invasive compounds. Retinoic acid (RA; 1 microM) [corrected] considerably impaired K1735-M2 melanoma cell invasion, as demonstrated by various measuring parameters. Parameter TUMAREA, expressing the amount of tumor tissue, indicates a growth inhibitory effect and the invasion parameter STRCSTR shows that after treatment with RA the stromal component was better preserved than in untreated controls. Besides the inhibitory effect of RA on melanoma cell invasion in confrontation cultures, RA increased the dynamics of adhesion of melanoma cells to the extracellular matrix components type I collagen and laminin, and slightly impaired melanoma cell directional migration. Fluorescence microscopy using rhodamine-labeled phalloidin showed that RA also modulated the organization of the actin cytoskeleton by inducing the formation of actin-containing stress fibers. Our data show that 1 microM RA exhibited a pronounced anti-invasive effect on highly metastatic melanoma cells in vitro. Impairment of host tissue degradation, altered adhesion abilities, changes in the actin cytoskeleton, as well as the antiproliferative effect may all account for inhibition of melanoma cell invasion.

Actin Cytoskeleton↗
PubMed1993

Analytic morphology in clinical and experimental dermatology.

During the past several years, quantitative morphology has gained increasing attention in diagnostic pathology and in certain research applications. In the field of dermatopathology, quantitative morphology has been applied to numerous problems, ranging from the interactive measurement of nuclear contours to fully automated, high-resolution image analysis of ultrastructural micrographs. Dermatologic applications are reviewed, and potential developments in the future are briefly outlined.

Animals↗
PubMed1993

Clinical features and therapy of "typical" and "atypical" bronchial carcinoid tumors (grade 1 and grade 2 neuroendocrine carcinoma).

Between 1971 and 1992, 55 patients with grade 1 (G1) (n = 32) or grade 2 (G2) (n = 23) neuroendocrine bronchial carcinomas (males: 26, females: 29; mean age: 47.7 years, range: 13-77 years) were treated. The sexes were evenly distributed in the two groups. Patients with G1 were significantly younger than those with G2 tumors (43.3 vs 53.7 years; P < 0.05). There were no statistically significant differences between G1 and G2 concerning peripheral or central localization, laterality or maximum tumor diameters. Patients with G1 had a higher incidence of tumor-related symptoms and a longer mean duration of these symptoms (21.8 months) than G2 cases (14 months) but the differences were not statistically significant either. No case displayed any symptoms of hormonal activity. Fifty-two patients underwent resection, one was non-resectable for anatomical, and one for functional, reasons; a third refused an operation. We performed 8 pneumonectomies, 36 lobectomies (8 by using bronchoplasty), 2 bronchotomies and 6 segmental resections. Twelve G2 cases had N1 or N2 lymph node metastases, two intrapulmonary metastases were removed. After a median observation time of 55.7 months the 10-year survival rate for the total collective is 90.6%. For G1 it is 100%, compared with 76.4% for G2 patients, 3 of whom died of the tumor (P < 0.05; significant). In univariate analysis: age over 48 years, lymphatic invasion, and lymph node metastasis were also significantly correlated with a poor survival rate. Multivariate analysis proved lymphatic permeation to be the only independent prognostic factor (the survival rate was 100% where there was no invasion, but only 74% where this had occurred).

Adolescent↗
PubMed1993

Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions.

Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.

Antigens, Neoplasm↗
PubMed1993

Cytoskeleton and motility: an immunohistological and computer simulation analysis of melanocytic skin tumors.

Tumor cell motility and tumor cell proliferation are supposed to be essential for tumor invasion. The cytoskeleton, which consists of different components, is considered to be important for maintaining cell shape and facilitating cell movement. Numerous data are available about tumor cell motility in vitro, but the behavior of tumor cells in vivo is as yet poorly understood. In the present study, estimates of tumor cell motility and proliferation were statistically derived from morphological tumor patterns in human melanocytic skin tumors, and their relationship to expression of certain cytoskeletal components was evaluated. Overexpression of vimentin within tumor cells correlated with low actual tumor cell motility and proliferation, indicating a structurally stabilizing function of these filaments. An overexpression of actin was found within tumor cells of high motility and proliferation, suggesting the contribution of cytocontractile elements to active tumor cell locomotion in situ. Concerning the cytoskeleton of the stromal cells, expression of actin, myosin and tubulin correlated with a high number of motile tumor cells and high mitotic counts. Thus increased tumor cell motility seems to be associated with cytoskeletal changes not only of the tumor cells themselves but also of the surrounding stromal cells.

Cell Division↗
PubMed1993

Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.

Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p << 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 +/- 28.4 [mean +/- standard deviation], PMM: 48.1 +/- 41.0, MMM: 117.0 +/- 64.6; Ki-67: BMN: 6.4 +/- 3.3, PMM 25.0 +/- 31.1, MMM: 95.2 +/- 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p << 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA-Breslow index: r = 0.42, p < 0.01; Ki-67-Breslow index: r = 0.60, p << 0.001; PCNA-mitotic rate: r = 0.40, p < 0.01; Ki-67-mitotic rate: r = 0.50, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Inhibition of melanoma cell directional migration in vitro via different cellular targets.

In malignant melanoma active movement of cancer cells is considered to be essential for tissue invasion. Various mechanisms, such as the Ca(2+)-calmodulin-proteinkinase C cascade or G-protein-dependent processes are considered to play a role in tumor cell functions. The assay of directional migration, combined with computer-assisted image analysis, was used to evaluate the antimigratory efficacy of drugs interfering with different steps of signal transduction pathways. Treatment with different compounds showed a more or less concentration-dependent reduction of migration rates: The Ca(2+)-channel blockers verapamil and devapamil showed a slight reduction of motility. The effect was more pronounced when the calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors dequalinium, tamoxifen and H-7 were applied. A marked inhibition of motility was found with the G-protein antagonist L 651582. Thus, our results indicate that different signal transduction pathways are involved in the regulation of directional migration of K1735-M2 melanoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Quantitative effects of intercellular signals on computer-simulated tumor patterns.

The behavior of tumor cells within a particular in vivo microenvironment is considered to be regulated by intercellular signals. Previous studies of computer simulations of tumor growth demonstrated a qualitative effect of autocrine and paracrine signaling factors on the resulting morphologic patterns. We investigated the quantitative effect of these intercellular signals when the evolving patterns were evaluated by a set of pattern analysis procedures, yielding 18 quantitative morphologic features. The results show that both autocrine and paracrine factors regulating either tumor cell proliferation, motility or death influenced at least 10 of the 18 features significantly (linear regression analysis; n = 50 for each experiment; P = < .01). Furthermore, multivariate analysis of 600 simulated patterns also demonstrated highly significant relationships between intercellular signals and quantitative features of the evolving pattern (P = < .001). The study showed that various pattern measurement features indicate a direct influence of intercellular signals on tumor patterns in computer simulations.

Cell Communication↗
PubMed1993

Tumor cell proliferation and motility estimates are prognostic factors in malignant melanoma.

Metastatic spread of solid tumors depends on a complex metastatic cascade. Metastatic tumor cells must therefore express a variety of biological properties including the ability to proliferate and the ability to migrate. In the present study, the prognostic significance of both parameters was investigated in 184 cases of malignant melanoma of the skin. Proliferative activity was assessed by mitotic counts, the degree of cell motility was estimated by comparing the histological pattern of the tumor with patterns obtained by computer simulations with predefined values of cell motility. Follow up of surviving patients was at least 5 years. Statistical analysis was done using classification and regression tree (CART) analysis combining mitotic counts and motility estimates. As far as overall survival was concerned, mitotic counts were the most significant variable separating one group of patients with mitotic counts < 17/mm2 and a 5-year survival rate of 82% and a group with mitotic counts > or = 17/mm2 and a 5-year survival rate of 52%. Within the group with low mitotic counts, motility estimates found a subgroup of patients with a coefficient of motility > or = 126, which had a 5-year survival rate of 55% similar to those patients with high mitotic counts. Corresponding results were obtained in the assessment of metastasis-free interval. The data show that not only proliferation as assessed by mitotic counts, but also estimates of tumor cell motility based on image analysis and computer simulations provide prognostic information in primary malignant melanoma of the skin.

Cell Division↗
PubMed1992

Tumor-cell motility and invasion within tumors determined by applying computer simulation to histologic patterns.

Proliferation and motility are crucial prerequisites for tumor-cell invasion in vivo. While proliferation can be assessed in situ by a variety of methods, the measurement of motility is largely restricted to in vitro models. In previous studies, computer simulations of tumor growth strongly indicated that a close relationship exists between tumor-cell motility on the one hand and the resulting morphological pattern on the other. Moreover, estimates of motility parameters can be based on image analysis of the particular pattern. The objective of the present study was to examine whether tumor-cell populations differing in their in vitro motility produce particular patterns in vivo similar to those predicted by the computer simulations, and whether the motility estimates derived from these patterns are consistent with the in vitro motility results. This was done using murine fibrosarcomas grown in syngeneic animals from various cell lines which had been selected for and confirmed to show greatly increased speeds of motility in vitro relative to the unselected parent cell population. Computer simulations coupled with image analysis of the various variant tumors showed that the calculated motility of tumor cells within the different tumors agreed well with the relative levels of tumor-cell motility observed in vitro. Our results thus show that the computer simulation method, along with histological analysis, produced reliable estimates of tumor-cell motility within tumors.

Animals↗