Search PubMed⌕ Search

Biomedical subjects

R Hofmann-Wellenhof

Publications and source records attributed to R Hofmann-Wellenhof.

At least 55 records · Page 3Linked to original sources
PubMed1997

Interrelation of motility, cytoskeletal organization and gap junctional communication with invasiveness of melanocytic cells in vitro.

Intercellular communication and the active movement of malignant cells into and through host tissue barriers play a critical role during the complex process of tumor invasion. Motile activity, cytoskeletal actin and vinculin organization as well as gap junctional communication of in vivo benign and malignant melanocytes were compared and related to in vitro invasiveness. Normal melanocytes, Melan-a, showed significantly less motile activity, a higher organization of the actin cytoskeleton and more vinculin-containing cell-substratum adhesion plaques than highly metastatic melanoma cells, K1735-M2. There was no pronounced difference in gap junctional communication under comparable culture conditions. However, cultivation of Melan-a cells in a conventional melanocyte growth medium containing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced intercellular communication. Melanocytes were less invasive than melanoma cells both in the embryonic chick heart model and in the Matrigel invasion assay. The least invasive activity was determined for melanocytes cultivated in TPA-deficient medium indicating that the medium supplement TPA stimulates invasion. The comparison of certain in vitro properties of both melanocytic cell lines revealed a positive correlation of motility with in vitro invasion, whereas an inverse correlation was found for the degree of actin filament organization as well as for the number of vinculin plaques. Gap junctional communication was not directly related to in vitro invasiveness.

Actins↗
PubMed1996

Pathological findings suggestive of interclonal stabilization in a case of cutaneous melanoma.

Metastatic spread is a complex process based on manyfold interactions of the tumor cells with each other and with the surrounding stroma. In experimental systems tumor cell heterogeneity and presence of various subpopulations which interact with one another to stabilize their relative proportions within the population has been shown. Here we report a patient with melanoma, showing morphological evidence of two distinct tumor cell populations in the primary tumor and in all subcutaneous metastases. By image analysis, both populations were clearly characterized by minimal nuclear diameter and by nuclear form factor and were demonstrable in each specimen. The fact that these peculiar cell populations were present in all melanoma lesions removed from the patient might indicate that the populations require the presence of each other and that none of them is metastatically competent on its own.

Cell Division↗
PubMed1996

Differential effects of synthetic sphingosine derivatives on melanoma cell motility, growth, adhesion and invasion in vitro.

Cancer cell surface glycosphingolipids are considered to play a critical role in tumor growth and metastasis. However, the implications of glycoconjugates in the control of cell motility, which is considered to be involved in tumor invasion, are not fully understood. In this study, the effects of a series of synthetic sphingosine derivatives, obtained by the chemical transformation of azidosphingosines, on directional migration of K1735-M2 melanoma cells grown on type I collagen-coated surfaces were investigated. Following the application of 60 microM (2R, 3S, 4E)-2, 3-epimino-4-octadecen-3-ol (S4) the migration rate was 94 +/- 10 microns/day, compared with 377 +/- 22 microns/day in the control experiment. Six other analogues were not as potent. S4 also considerably down-modulated melanoma single cell motility. Inhibition of motile activity was associated with changes in the actin filament organization as well as with changes in the number and distribution of vinculin plaques. Moreover, the compound reduced the attachment abilities of melanoma cells to basement membrane Matrigel. Tumor cell invasion, however, was less affected and proliferation remained unimpaired after treatment with S4. These data suggest at least one intracellular mode of action of this particular synthetic sphingosine derivative by modulation of cytoskeletal organization. Melanoma cell motility and growth may be controlled independently via glycosphingolipids.

Actins↗
PubMed1996

Melanoma and stroma: an interaction of biological and prognostic importance.

Stromal relationships are crucial to metastatic spread of solid malignancies. Some aspects of this stroma interaction are obviously associated with particular morphological features, which may carry prognostic significance. In cutaneous melanoma, level of invasion, arrangement of cells (horizontal or vertical growth phase), neovascularization, vessel invasion, architecture of the border, and inflammatory infiltrate have been examined. Expression of adhesion molecules, signalling factors, cytoskeletal components, extracellular matrix molecules and matrix-degrading enzymes have been assessed by immunohistology and in situ hybridization. Besides providing prognostic information, a thorough evaluation of stromal relationships may help to increase our knowledge about factors mediating the growth and metastatic spread of malignancies.

Disease Progression↗
PubMed1996

Quantitative morphology of collagen fibers in cutaneous malignant melanoma and melanocytic nevus.

Since tumor growth and metastastatic spread are considered to depend on tumor-stroma interaction, the present study describes the architecture of collagen fibers in 12 cases each of primary melanoma (vertical tumor thickness > 1 mm) and common melanocytic nevi in azan-stained sections by using automated image analysis. In each case, at least 100 high-power fields were consecutively sampled from the tumor center, the tumor periphery, and the surrounding normal-appearing reticular dermis. In both diagnostic groups, collagen density (amount of collagen per tissue volume) and mean collagen fiber bundle diameter was significantly lower in the tumor periphery than in the surrounding stroma and again lower in the tumor center than in the tumor periphery. When melanomas and nevi were compared with each other, melanomas had fewer, but thicker, collagen bundles than did nevi, particularly at the tumor periphery. Taking the mean values of each case as classifiers in multivariate logistic regression analysis, 21 of 24 cases were correctly classified (chi-squared test, p < 0.0001), indicating that the parameters of collagen architecture at least in part reflect biological differences between benign and malignant melanocytic skin lesions.

Adult↗
PubMed1996

Clinical and histological features of poor prognosis in cutaneous metastatic melanomas.

Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell-stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n = 59) and lesions from patients with a longer survival (n = 285). Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1 +/- 14.1 years versus 58.8 +/- 15.3 years), had developed earlier after the primary tumor (mean time of 21.7 +/- 19.9 months versus 43.3 +/- 27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p < 0.001) and PRECOLL (82.8% versus 57.6; p < 0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p < 0.01) and PREFAT (68.1% versus 46.8%; p < 0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen. In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.

Adult↗
PubMed1996

Zosteriform lichen planus.

A 42-year-old woman developed a papular eruption mainly localized on the right side of the body and with a zosteriform pattern within the nerve segments TH6-TH12, L1-L4 as well as S1 and S2. The skin lesions were characteristic of lichen ruber planus. The zosteriform arrangement of lichenoid papules is rare and is interpreted as a cutaneous reaction possibly triggered by some neural factor.

Adult↗
PubMed1996

Cellular invasion without cellular motility in a stochastic growth model.

Invasion of a tissue by distinct cell types is common to various biological processes including embryonic development and tumour growth. Active movement is usually considered to be a prerequisite for invasiveness. Using a computer simulation program based on a stochastic cellular automata model, we provide evidence that invasive patterns may evolve in the absence of active cellular motility. Cells characterized by low proliferation, a high rate of cell loss, pronounced tumour-stroma adhesion and an expansive instead of a destructive behaviour invade the surrounding matrix, despite a complete lack of active movement. The resulting morphological patterns are similar to those obtained with motile cells. Thus invasion does not necessarily indicate the presence of motility.

Cell Adhesion↗
PubMed1996

Assessment of tumor cell cohesion in vivo using pattern interpretation by cellular automata.

OBJECTIVE: There is abundant evidence that patterning in life sciences may be closely related to the functional properties of the constitutive elements. In order to estimate some of these functional properties by examining the static pattern evolved, pattern interpretation by cellular automata (PICA) was introduced and applied to the mechanisms of tumor growth. Previously it was shown that the estimates concerning tumor cell proliferation and motility were consistent with those obtained by other methods. STUDY DESIGN: Morphologic patterns obtained by growing two variants of the C4 cervical carcinoma cell lines with different in vitro adhesive properties in the hamster cheek pouch were evaluated by PICA. RESULTS: PICA estimates of tumor cell cohesion turned out to be significantly higher in tumors derived from the C4-I cell line (0.73 +/- 0.02 SD) with high in vitro cohesiveness than in tumors derived from the less adhesive C4-II cell line (0.32 +/- 0.04 SD; t test, P = .001). CONCLUSION: These results indicate that functional estimates concerning tumor cell cohesion obtained by PICA may be in good agreement with in vitro observations of the same cellular property and further underscore that PICA may be a useful tool for the functional interpretation of static histologic patterns.

Animals↗
PubMed1995

Pathology of tumor-stroma interaction in melanoma metastatic to the skin.

Tumor invasion and metastasis formation largely depend on tumor-stroma interaction. In the present study morphological correlates of tumor-stroma interaction were examined in 344 melanoma lesions metastatic to the skin. In particular, the presence of simple infiltration into the surrounding dermis or subcutis without evident stromal reaction, the incorporation of pre-existent dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our results showed that simple infiltration into the surrounding tissue as well as the incorporation of pre-existent stroma tissue without destruction is associated with poor outcome, whereas capsule and fibrous septa are favorable prognostic signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a prognostic indicator independent of the location of the metastasis (locoregional or distant), as shown by multivariate analysis. These data indicate that morphological aspects of tumor-stroma interaction in metastatic skin lesions of melanoma may reflect biological behavior of the tumor cells, may facilitate a pathological subclassification of metastatic melanoma in addition to clinical data, and are directly related to the patient's outcome.

Adult↗
PubMed1995

Quantitative assessment of fat cells in subcutaneous metastatic melanoma. Correlation with outcome.

The metastatic behavior of tumor cells largely depends on tumor-stroma interactions. In the present study, a particular morphological feature of tumor-stroma interaction was evaluated; hematoxylin-eosin-stained slides of 81 lesions of melanoma metastatic to the skin involving the subcutis were examined by automated image analysis for the presence of preexistent fat cells in the tumor. The area occupied by fat cells, expressed in micrometers squared per slide, was of prognostic significance; lesions with a fat cell area of < 41,000 microns 2 showed a 2-year survival rate of 42%, versus 10% in lesions with a fat cell area of > 41,000 microns 2 (log-rank test, z = 3.24; p < or = 0.01). The adverse effect of fat cell area on prognosis still was seen when age, sex, and site of metastatic spread were concomitantly taken into account in a Cox proportional-hazard model. These data indicate that melanoma deposits involving the subcutis with preservation of preexistent subcutaneous fat cells have high metastatic potential and a high risk for rapid internal dissemination.

Adipose Tissue↗
PubMed1995

Correlation of melanoma cell motility and invasion in vitro.

Cell motility and the ability to grow invasively are crucial properties within the metastatic cascade. The relation of cell motility in vitro and metastatic behaviour of tumour cells in animal experiments indicates that they are directly correlated. We undertook this study to see whether a quantitative correlation could be found in complex in vitro systems. Using the assay of directional migration and a newly developed image analysis system to measure cell motility of K1735-M2 mouse melanoma cells and the embryonic chick heart assay of Mareel to follow invasion, we examined the influence of eight compounds on cell motility seven compounds on invasion. For stationary motility we calculated the change of density, area of change, area of ruffling sites (representing only changes at the leading edge and tail of the cell), number of ruffling sites, area of changing intracellular particles and number of intracellular particles. Velocity of single tumour cells and directional migration were also measured. In the invasion assay the parameters STRCSTR and INVASLOG, expressing different forms of stromal (i.e. embryonic chick heart) disintegration and degradation, were calculated. Directional migration and all parameters of stationary motility except number of ruffling sites, changing intracellular particles and number of changing intracellular particles correlated significantly (p < 0.05) with STRCSTR and INVASLOG. For velocity, area of change and area of ruffling we found the most significant correlation with parameters of invasion indicating that both stationary and translocative motility contribute to invasion. Our systems also showed that the compounds tested exerted differential effects on various aspects of motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Computer simulations of histologic patterns in melanoma using a cellular automaton provide correlations with prognosis.

Computer simulations have been used frequently in the life sciences to investigate the mechanisms of morphologic pattern formation. The cellular automaton program SMN5 is designed to simulate tumor growth and to estimate biologic properties by comparing real tumor patterns with computer-simulated reference patterns. This method was applied to 195 cases of primary melanoma of the skin. S-100-stained sections were evaluated by image analysis and compared statistically to a reference set of 4000 simulated patterns. Estimates of tumor cell proliferation, motility, cell loss, cohesion, stroma destruction, and intercellular signals (autocrine and paracrine factors affecting growth, motility, and cell loss) were calculated. Twelve of 18 estimated parameters correlated significantly with tumor progression, as indicated by vertical tumor thickness (linear regression analysis: p < or = 0.05), and 13 of 18 parameters carried prognostic significance (log rank test: p < or = 0.05). Poor prognosis was associated particularly with a pronounced increase in the estimates of proliferation, tumor cell motility, and stromal degradation. Poor prognosis was also associated with a decrease in the estimates of cell loss, tumor cell cohesion, and paracrine growth factor dependence. In multivariate analysis using Cox's proportional hazard model, stromal degradation and motility showed prognostic information in addition to conventional prognostic parameters. The study shows that analytical comparison of real tumors with computer-simulated patterns of a cellular automaton facilitates a functional interpretation of tumor morphology, which carries prognostic significance in cutaneous melanoma.

Computer Simulation↗
PubMed1995

Confocal laser scanning microscopy: a new optical microscopic technique for applications in pathology and dermatology.

Confocal laser scanning microscopy (CLSM) is a new optical microscopic technique, which offers significant advantages over conventional microscopy. CLSM is microscopy of optical sections. Light, which is emitted from regions other than the focal plane, is cut off by introducing a diaphragm in the beam path. The result is an optical "slice", which shows more details because the blurring from out of focus haze disappears. It has been repeatedly used in experimental, but also in diagnostic dermatopathology. The "in vivo" confocal microscopy, applied directly to the intact skin provides details of living cells in the superficial layers comparable to that of fixed and stained tissue. While the extent of its future applications is hard to predict, its potential for applications in dermatology appears enormous, particularly for studies of fixed or living tissues, where it is desirable to obtain clear images many micrometers below the surface of the tissue under examination.

Animals↗
PubMed1995

Approach to diagnostic image analysis of melanocytic tumors.

Numerous attempts have been made to apply image analysis in dermatopathology. The technics used comprise measurement of nuclear size, shape, chromatin content, and texture, evaluation of immunohistological slides, assessment of proliferation, pattern analysis, and tumor volume estimation. For commonly accepted routine use, however, image analysis research has to be extended to large numbers of cases, using straightforward and reproducible measuring procedures, and to the development of ready-to-use equipment for specific tasks. In this way, image analysis in dermatopathology might supply useful diagnostic tools in addition to conventional microscopy, and may increase our understanding of morphology as a whole.

Diagnosis, Differential↗
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↗