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J Smolle

Publications and source records attributed to J Smolle.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of dequalinium on K1735-M2 melanoma cell growth, directional migration and invasion in vitro.

Cationic lipophilic compounds have an antiproliferative effect on certain tumour systems in vitro and in vivo. We have investigated whether the cationic lipophilic compound dequalinium affects not only proliferation but also motility and invasion of the highly metastatic and highly invasive melanoma cell line K1735-M2. Proliferation was assessed in monolayer cultures and in multicellular spheroids, motility was estimated in the assay of directional migration, and invasiveness was tested through confrontation cultures of tumour multicellular spheroids with embryonic chick heart tissue evaluated by computerized image analysis. 2 mumol/l dequalinium impaired melanoma cell proliferation, reduced directional migration and significantly blocked invasion in vitro. On the ultrastructural level, dequalinium caused obvious changes in mitochondria of both melanoma and embryonic chick heart cells. The mechanisms of the antiproliferative, antimigrating and antiinvasive effects remain to be determined. Inhibition of protein kinase C, calmodulin antagonism, DNA intercalation and/or direct effects on mitochondrial functions may be considered.

Animals↗
PubMed1992

Relationship of tumor cell motility and morphologic patterns. Part 1. Melanocytic skin tumors.

In the diagnosis of melanocytic skin tumors, the assessment of the overall architectural pattern (silhouette) is often essential. We have previously shown by a computer simulation model that tumor patterns are likely to depend on the relative degrees of proliferation and motility of the tumor cells. In this study, we examined the morphological pattern of 12 cases each of nevocellular nevi, primary melanoma, and metastatic melanoma by image analysis. The patterns of the individual melanocytic skin tumors were compared statistically with patterns generated by computer simulation, which facilitates estimates of biological properties of the tumor cells. Additionally, mitotic counts were made to measure tumor cell proliferation. A comparison of the three diagnostic groups revealed that the cells of nevocellular nevi show a low degree of motility, which, however, still exceeds the very low degree of proliferation. Thus, an "invasive" pattern with numerous small nests and single cells at the base of the lesion is common. In primary malignant melanoma, tumor cell motility and tumor cell proliferation are significantly increased in various proportions, thus leading to varying morphological patterns. In metastatic melanoma, a strikingly elevated degree of proliferation exceeds the only slightly elevated degree of motility and leads to sharply demarcated, "expansive" lesions. To check the validity of the technical procedure, estimates of proliferation based on pattern analysis alone were compared with the results obtained by mitotic counts. There was a significant correlation, indicating that the assumptions of the computer model and the image analysis procedure are in fact applicable to real-life melanocytic skin tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1992

Relationship of tumor cell motility and morphologic patterns. Part 2. Analysis of tumor cell sublines with different motility in vitro.

We have previously demonstrated by computer simulation that the relationship of proliferation and motility is likely to influence the morphological pattern of a tumor. Our study of a set of melanocytic skin tumors provided evidence that the assumptions of the model were correct with respect to proliferation. In order to test the validity of the assumptions concerning motility, we injected a tumor cell line with low motility in vitro and a subline of the same tumor cell line with high motility in vitro into the thigh of syngeneic rats. When we evaluated the morphological patterns of the resulting tumors by image analysis and compared them with computer simulations, we found that the differences of the morphological patterns were the same as predicted by the computer model. This finding further supports the concept that estimates of tumor cell proliferation and motility can be derived from the analysis of static histological patterns.

Animals↗
PubMed1992

Prognostic significance of proliferation and motility in primary malignant melanoma of the skin.

The metastatic cascade depends on the presence of tumor cells which are capable of proliferation as well as of invasion with active motility. In the present study, it was examined whether the demonstration of both features in the primary lesion of malignant melanoma of the skin carries prognostic significance. Proliferation was assessed by mitotic counts and Ki 67 staining, and motility was estimated by image analysis and comparison of the image analysis results with computer simulations; 27 cases of primary malignant melanoma with a maximum vertical tumor thickness exceeding 1 mm were prospectively sampled. Mitotic counts were carried out on H & E stained sections, image analysis of the tumor pattern on S-100 immunostained paraffin slides, and Ki 67 labeling of actively cycling cells was evaluated on frozen sections. Neither proliferation nor pattern analysis alone provided a significant prognostic result with respect to overall survival and to metastasis free survival. The estimates of motility, derived from a combination of pattern analysis and proliferation values, however, proved to be significant predictors of overall survival and metastasis-free survival (log rank test: p less than or equal to 0.05). The motility features were superior to Clark level and Breslow index in this set of cases. The results demonstrate that the assessment of tumor cell proliferation and motility in histological sections may reflect the metastatic potential of primary malignant melanomas of the skin.

Cell Division↗
PubMed1992

Primitive neuroectodermal tumor arising in the skin. Differentiation from neuroendocrine carcinoma of the skin.

We report a 25-year-old male patient with primitive neuroectodermal tumor presenting as a subcutaneous tumor on the right buttock, which was initially diagnosed as neuroendocrine carcinoma of the skin. Subsequently, local recurrence and metastatic spread to the lung occurred. The tumor was resistant to highly aggressive chemotherapy. The patient died 6 months later with severe pulmonary and lymph node involvement.

Adult↗
PubMed1992

Morphometry in clinical dermatology.

Rapid and simple methods are presented which allow the estimation of areas, area fraction and contour lengths in clinical dermatology. They are based on point counting and intercept measurements using simple grids made on transparent film or on overhead foils. Because of their ease of use, these grids allow the determination of the size as well as the irregularity of skin lesions even during daily clinical work. The applications presented here include the area determination of naevi, leg ulcers, wheal and flare reactions and migration areas in lymphocyte and macrophage migration assays. Additionally, the determination of area fraction in psoriasis and sebutape evaluation is described. Other possible applications such as estimation or contour length, and determination of irregularity and estimation of the volume of tumours are discussed.

Dermatology↗
PubMed1992

Alcoholic liver disease. Parenchyma to stroma relationship in fibrosis and cirrhosis as revealed by three-dimensional reconstruction and immunohistochemistry.

Severe ethanol-induced liver damage is characterized by fibrous dissociation of liver cell plates leading to many apparently isolated hepatocytes. Three-dimensional reconstruction, however, revealed hepatocytes that were surrounded by connective tissue as endpoints of "parenchymal pillars" or in association with liver cell plates and bile ductules. Double immunofluorescence studies displayed the expression of cytokeratin (CK) 7 in bile ducts, including bile ductules, but also in some hepatocytes still organized in liver cell plates. The other bile duct, typical CK, namely CK 19, was only detectable in few hepatocytes. However, the expression of CK 7 and/or CK 19 was less frequent in hepatocytes that were closely associated with bile ductules. CK 7 and CK 19 were also found in some, but not all, Mallory bodies. These observations indicate that the expression of these two CKs is neither related to a transformation of hepatocytes to bile duct-like structures ("ductal metaplasia") nor to the formation of Mallory bodies. Furthermore, double immunofluorescence studies revealed small groups of hepatocytes and bile ductules that were encircled by basement membrane material, thus suggesting the formation of "secretory units."

Aged↗
PubMed1992

Surgical and non-surgical treatment of cancer of the oesophagus and the oesophagogastric junction: results of 200 consecutive cases.

200 consecutive, unselected patients with cancer of the oesophagus or the oesophagogastric junction (89 squamous, 110 adenocarcinoma or undifferentiated, 1 oat cell) between 1984 and 1987 were reviewed. Resection with postoperative adjuvant irradiation in the cases of squamous cell cancer, was carried out in 51 patients and non-surgical treatment [57 combined dilation and Nd-YAG-laser, 64 iridium 192 high-dose rate brachytherapy with or without 60 Gy external beam irradiation (EBR); 28 endoprostheses] was performed in the remaining 149 patients. The overall 5 year-survival rate was 9.2% (resections: 17.9%, non-resected: 5.2%). Resected nodal negative T1 or T2 patients had the best prognosis (45.8% 5-year survival). The median survival following dilation and laser was 3.4 months for all T-stages. Endoprostheses yielded a median survival of 1.7 months. Intracavitary brachytherapy gave the best palliative result with 6.5 months median survival, whereby only T1 and T2 patients benefitted from additional EBR. Histological subtype, age, sex or tumour localization did not influence survival. Multivariate analysis showed that in M0 patients the choice of treatment had a significant impact on prognosis.

Adenocarcinoma↗
PubMed1992

[Biological basis of metastasis formation].

Disseminated metastases are the most common cause of death in patients suffering from malignant disease. Tumor cell invasion and metastatic spread have often been considered to indicate an "undifferentiated" state of the tumor cells. In recent years, however, numerous studies point out, that invasiveness and the metastatic cascade are complex, highly differentiated processes based on manyfold interactions of the tumor cells and the surrounding stroma tissue. Changes of the cytoskeleton, adhesion molecules, motility, matrix-degrading enzyme activities, intercellular communication and intracellular signal transduction are considered to regulate the metastatic process. Thus basic research provides insight in pathogenetic mechanisms, which might represent targets for antimetastatic therapy in the future. This would be particularly mandatory in the case of malignant melanoma of the skin, where conventional cytotoxic chemotherapy has been rather disappointing.

Angiogenesis Inducing Agents↗
PubMed1992

An image analysis and statistical evaluation program for the assessment of tumour cell invasion in vitro.

Tumour cell invasion is a complex process, which is essential for the formation of metastasis and is therefore of critical clinical importance. For detailed investigations of the invasive process, quantifiable in vitro models of invasion are necessary. In this study we describe an image analysis procedure and a statistical program which facilitate an objective analysis of experiments carried out using the embryonic chick heart invasion model of Mareel. Tumour multicellular spheroids are confronted with embryonic chick heart fragments in culture and are sampled after different time intervals for up to 7 days. Immunohistological sections are then evaluated by an image analysis procedure which provides 9 parameters indicating invasion, proliferation and destruction taking place in the confrontation cultures. The data obtained by image analysis are further evaluated by a statistical program which describes the change with time of each parameter by means of linear regression analysis. Thus the data obtained at various time intervals serve as the source data for a single statistic, namely the slope of the regression line. Confidence intervals and statistical differences between various experiments can be calculated. In order to make the procedure more comprehensible in biological terms, the program provides a full text interpretation of the experimental results. The image analysis procedure in conjunction with statistical evaluation and text interpretation provides a comprehensive tool for the quantitative assessment of experimental invasion in vitro.

Animals↗
PubMed1991

PUVA-induced lymphomatoid papulosis in a patient with mycosis fungoides.

The occurrence of lymphomatoid papulosis in patients with cutaneous lymphoma, particularly mycosis fungoides, has been described in medical literature. A 68-year-old woman affected by mycosis fungoides in the plaque stage noticed that multiple papulonodular lesions of lymphomatoid papulosis developed suddenly after a few sessions of PUVA therapy. The PUVA induction of lymphomatoid papulosis was confirmed by the appearance of new lesions after a second cycle of PUVA exposure on a limited area of the body. Complete regression of all PUVA-induced lymphomatoid papulosis lesions was achieved within a few weeks with oral prednisone and topical steroids. During the entire treatment the patches and plaques of mycosis fungoides persisted unchanged.

Aged↗
PubMed1991

Computer simulation analysis of morphological patterns in human melanocytic skin tumours.

Tumour cell proliferation and particularly tumour cell motility are considered to be essential pre-requisites for invasive tumour growth. Despite abundant in vitro data on tumour cell motility, the behaviour of tumour cells in complex human tumour tissues is yet unknown. In this study, estimates of proliferation and motility are statistically derived from morphological tumour patterns in human melanocytic skin tumours. Two-dimensional, discrete, random computer simulations of tumour growth were carried out in order to determine the influence of tumour cell proliferation and motility on morphological patterns. A set of binary morphological criteria turned out to facilitate a significant estimate of the relative probabilities of motility and proliferation (CART analysis). When the same morphological criteria were applied to H & E stained slides of 45 melanocytic skin tumours, benign common nevi showed a predominance of motility, whereas primary and metastatic malignant melanoma revealed a predominance of proliferation. The direct assessment of the number of proliferating cells by Ki-67 staining shows a steep increase from benign nevi to primary and metastatic melanoma. These data provide first evidence that in benign common nevi the overall motility exceeds the very low degree of proliferation, whereas in malignant melanocytic tumours proliferation considerably exceeds tumour cell motility.

Cell Division↗
PubMed1991

Expression of cytoskeletal components in melanocytic skin lesions. An immunohistochemical study.

The cytoskeleton is considered to be important for maintaining cell shape and facilitating cell movement. In the present study, the expression of cytoskeletal components is examined in benign and malignant melanocytic skin tumors. Paraffin sections of 75 cases (25 each of nevocellular nevus, primary malignant melanoma, and cutaneous metastases of malignant melanoma) were stained with antibodies to tubulin, myosin, actin, and vimentin using a three-step immunoperoxidase method. The staining results were assessed independently for tumor cells and stroma cells in comparison to inbuilt reference structures. Vimentin is found in all melanocytic lesions in the tumor as well as in the stroma cells. In malignant lesions, the tumor cell staining intensity varies between neighboring regions; particularly in malignant melanoma the staining is pronounced in the tumor periphery (chi 2 test: p less than 0.05). Actin is only weakly positive in nevus cells and primary melanoma tumor cells, but strongly expressed in metastatic tumor cells (p less than 0.001). Nevus fibroblasts are only weakly positive, whereas the stroma fibroblasts in the malignant lesions are strongly positive (p less than 0.001). The same is true for myosin and tubulin expression in dermal fibroblasts (p less than 0.001), whereas the tumor cells are equally (weakly) positive in all melanocytic lesions. Our study shows that there are significant differences in the immunohistochemical expression of cytoskeletal components in various melanocytic tumors. There is an elevated expression of vimentin and actin in the tumor cells, particularly of metastatic lesions. However, the most pronounced differences are found in the dermal fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1991

Epidermal Langerhans cells in myelodysplastic syndromes are abnormal.

The myelodysplastic syndromes (MDS) represent clonal disorders of the hematopoietic stem cell that are associated with quantitative and qualitative disturbances of the peripheral blood cells and a high risk for the transition to overt leukemia. As epidermal Langerhans cells (LC) are bone-marrow-derived cells, we were interested to see whether they are altered in patients with MDS. Epidermal sheets were prepared from biopsies taken from the thighs of nine patients with MDS and five control persons and processed for immunoperoxidase staining of CD1a antigens. The density and morphology of CD1a+ cells (i.e., LC) was evaluated by visual assessment as well as automatic image analysis. The density of LC was reduced in seven of nine patients (range, 30-75% of normal), whereas the morphology of LC appeared to be altered in all MDS patients in that the LC displayed large and bizarre cell bodies with only a few and often abnormally long dendrites. The HLA-DR expression by LC was not altered, as shown by double immunofluorescence staining of CD1a and HLA-DR antigens. Ultrastructurally, LC again appeared enlarged and often presented with bizarre nuclei, yet displayed no other abnormalities. Our findings suggest that LC are abnormal in MDS and might even indicate a more wide-spread involvement of the dendritic cell lineage in this syndrome.

Humans↗
PubMed1991

[Clinical epidemiologic data of malignant melanoma based on 1,368 patients of the Graz University Dermatology Clinic (1970-1989)].

Epidemiological and histological data of 1368 patients with invasive malignant melanoma treated at the Department of Dermatology between 1970 and 1989 were analysed retrospectively. Frequency of melanoma increased from 103 cases between 1970 and 1974 to 593 between 1985 and 1989. The male/female ratio was 1/1.5 and did not change during the study period. Mean age of patients at the time of primary operation was 56.1 years and was approximately the same for males and females (males 55.8, females 56.3 years). The predominant site was the trunk in males (58.7 per cent) and the lower leg in females (41.6 per cent). There was a relative increase of melanomas of the back in males and the lower leg in females at the expense of melanomas of the face. The Breslow index was significantly higher in males than in females. In patients older than 69 years, the proportion of thick melanomas was above average. During the study period, the frequency of thick melanomas (greater than 1.5 mm) showed an encouraging decrease in both sexes. In 1989, 50 per cent of all melanomas were thinner than 1.01 mm. This can be interpreted as a successful outcome of efforts in preventive medicine.

Adult↗
PubMed1991

[Acquired naevus flammeus (Fegeler syndrome)].

In contrast to common port-wine stains, acquired port-wine stains are extremely rare. We report on an acquired port-wine stain that evolved on the thigh of a 69-year-old male patient and was accompanied by lumbalgia on the same side. Impairment of vegetative nerve fibres by spinal root compression may be considered a causative factor in our patient.

Aged↗