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Biomedical subjects

R Fink-Puches

Publications and source records attributed to R Fink-Puches.

At least 37 records · Page 2Linked to original sources

Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light.

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.

Administration, Topical↗

Cytoplasmic microtubules in two different mouse melanoma cell lines: a qualitative and quantitative analysis using confocal laser scanning microscopy and computer-assisted image analysis.

The microtubular system as one part of the cellular cytoskeleton is not only necessary for mitotic activity of malignant cells but also for invading neighboring tissues and for the formation of distant metastases. In the present study, the amount and distribution of tubulin in two murine melanoma cell lines (K1735-M2: high metastatic clone; K1735-c116: low metastatic clone) were determined quantitatively using an indirect immunofluorescence technique, confocal laser scanning microscopy (CLSM) and computer-assisted image analysis. Additionally, qualitative and quantitative changes after application of the microtubule-inhibitor nocodazole were investigated. Quantitative analysis showed a significant difference between the high and low metastatic cell line for the parameter TEXTURE, indicating a finer structured network within the high metastatic cells. After treatment with nocodazole the parameters TEXTURE and DENSITY were reduced, suggesting a decrease of assembled tubulin and a less delicate structure of the remaining microtubules. Our study shows that CLSM combined with computer-assisted image analysis provides a new method to examine quantitative variations of the cytoskeleton possibly related to cell function.

Animals↗

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↗

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↗

Different treatment modalities for the management of a patient with the nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma (BCC) syndrome is a genetically linked disorder characterized by multiple BCCs associated with various skeletal abnormalities and sometimes with mental retardation. Because of the large number of lesions, treatment of BCCs in these patients may be extremely difficult. The value of different therapeutic options was assessed in a patient with multiple, disfiguring nevoid BCC syndrome. Surgical excision and split-skin grafting was used to remove three larger tumors. Photodynamic therapy led to healing of flat lesions; small papules within the treated areas, however, did not respond to this type of management. Three nodular BCCs treated with intralesional application of interferon alfa-2b were markedly reduced in size. Still, complete healing could not be achieved. Nodular lesions vaporized with the CO2 laser disappeared and showed no recurrence after 2 years of follow up. Our experience indicates that CO2 laser vaporization of BCCs allows the treatment of a large number of lesions in a single session, and is indicated when surgical treatment is not feasible for all lesions. Photodynamic therapy with 5-amino-levulinic acid may be a valid therapeutic option for flat lesions only. Intralesional application of interferon alfa-2b removes papular lesions of small size.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

[Wissler's allergic subsepsis].

A 20-year-old female patient with the typical signs of Wissler's subsepsis allergica (Wissler-Fanconi syndrome) is described. This rare disease is characterized by four typical symptoms: polymorphous exanthemas, recurrent high fever, leucocytosis and arthralgia. In the early stages it is difficult to differentiate from septicaemia. This syndrome has sometimes been considered equivalent to or an initial stage of Still's disease (juvenile rheumatoid arthritis) progressing to degenerative arthritis in many patients, whereas other authors have classified it as a separate entity with good prognosis. The present case demonstrates that Wissler's subsepsis allergica should be considered when ever transient polymorphous exanthema is accompanied by high recurrent fever, leucocytosis and arthralgia.

Adult↗

[Retinoids in chemoprevention of tumors of the skin and mucous membranes. Theoretical principles and practical applications].

Chemoprevention, the use of drugs to prevent invasive neoplasia, has gained increasing significance in recent years. Especially for the skin, chemoprevention will become of importance, because large areas of the skin are exposed to environmental carcinogenic factors. Furthermore, many skin diseases predispose to the development of multiple skin tumors. One group of chemopreventive agents are the retinoids, which are effective modulators of cell proliferation and differentiation in normal as well as in transformed tissues. Though the mechanism of action of retinoids is not yet fully understood at the molecular level, chemoprevention studies have demonstrated the ability of retinoids to prevent the development of skin cancer, particularly in patients with xeroderma pigmentosum, multiple basal cell carcinoma and oral leukoplakia. A better understanding of the carcinogenic process should improve our ability to develop effective chemoprevention strategies.

Animals↗