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Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 91 records · Page 5Linked to original sources

[Comparative study of the efficacy and tolerability of 0.1 and 0.03 p.100 adapalene gel and 0.025 p.100 tretinoin gel in the treatment of acne].

INTRODUCTION: Adapalene is a new chemical entity with retinoid activity. PATIENTS AND METHODS: 0.1 p. 100 adapalene gel (Différine gel), 0.03 p. 100 adapalene gel and a commercially available 0.025 p. 100 tretinoin gel (Aberel gel) were compared in 89 male and female patients with acne. RESULTS: Inflammatory, non inflammatory, total lesion counts, and the global facial acne grade regularly decreased as a function of time in the three treatment groups. No statistically or clinicaly significant differences were observed for these parameters between 0.1 p. 100 adapalene gel and 0.025 p. 100 tretinoin gel following a 12-week treatment. Conversely, both of these gels were significantly more effective than 0.03 p. 100 adapalene gel with regards to inflammatory and total lesion counts, and the global facial acne grade. The differences of efficacy seen between both adapalene gels demonstrate a dose-dependent activity of the drug in the topical treatment of acne. The three products induced retinoid-like skin irritation with significant differences in intensity in favour of adapalene for erythema, dryness, scaling and burning after application and in favour of tretinoin for persistent burning. No treatment-related medical events were reported and adapalene plasma levels were lower than 0.15 ng/ml (limit of detection of the analytical method). CONCLUSIONS: The topical treatment of acne with adapalene gels was found to be safe and effective, with a dose-related response. The efficacy of 0.1 p. 100 adapalene gel and of 0.025 p. 100 tretinoin gel are not different but skin tolerance of 0.1 p. 100 adapalene gel is superior.

Acne Vulgaris↗

Childhood scleroderma and its peculiarities.

Based on a very large series of childhood scleroderma followed for more than ten years, the authors describe various subsets, which, in several aspects, differ significantly from the adult forms. Of special importance is a higher prevalence of linear scleroderma resulting in deformities and disabilities, as well as impairment of bone development in facial hemiatrophy. The immune abnormalities and vascular involvement leading to fibrosis are presented as the basic events in the pathogenesis. Critical discussion on a possible transitional form between localized and systemic disease and visceral involvement in cutaneous forms is followed by clinically applicable laboratory studies and management, including new therapeutic modalities.

Age of Onset↗

Vitamin D3 is a potent inhibitor of tumor cell-induced angiogenesis.

Vitamin D3 derivative 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) exerts various biological effects in cells that possess vitamin D3 receptor (VDR), including enhancement of cell differentiation and inhibition of cell proliferation. These activities of 1,25(OH)2D3 might be responsible for its anti-neoplastic effects, as shown in various experimental systems. The aim of this study was to compare the anti-angiogenic activity of 1,25(OH)2D3, retinoids, and interleukin-12 (IL-12) in an experimental tumor cell-induced angiogenesis assay in mice. Tumor cell-induced angiogenesis assay was performed in x-ray immunosuppressed BALB/c mice by intradermal injections of human tumor cell lines of different origin. The injections resulted within 3 d in a local formation of new blood vessels, and the intensity of angiogenesis correlated with the number of injected cells. Systemic treatment of the mouse recipients with 1,25(OH)2D3 significantly decreased angiogenesis, comparable to the effect of retinoids (all-trans retinoic acid [RA], 9-cis RA and 13-cis RA) and of IL-12. In vitro preincubation of the cells with all compounds (except IL-12) led to the inhibition of their angiogenic capability in vivo. Moreover, combination of 1,25(OH)2D3 and retinoids resulted in a synergistic inhibition of angiogenesis. The results strongly suggest that anti-angiogenic compounds with relatively low toxicity (e.g., 1,25(OH)2D3, retinoids, and IL-12) and their combinations could be beneficial in the treatment of some angiogenesis-associated malignancies.

Animals↗

Retinoids, interferon alpha, 1,25-dihydroxyvitamin D3 and their combination inhibit angiogenesis induced by non-HPV-harboring tumor cell lines. RAR alpha mediates the antiangiogenic effect of retinoids.

Retinoids combined with interferon alpha-2a (IFN alpha) or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] have shown marked synergistic inhibitory effects on angiogenesis induced by tumor cell lines harboring DNA of oncogenic human papillomaviruses (HPV) type 16 or 18. This report demonstrates comparable effects of these compounds on angiogenesis induced by non-HPV-bearing transformed cell lines, including breast carcinoma (T47D) and vulval carcinoma (A431) cell lines. Systemic treatment of mice with all-trans retinoic acid, 13-cis retinoic acid, 9-cis retinoic acid, IFN alpha or 1,25(OH)2D3 significantly decreased tumor cell-induced angiogenesis (TIA). In vitro pretreatment of T47D and A431 cells with these compounds also led to inhibition of their angiogenic capability when tested in the TIA assay. The inhibitory effects of retinoids could be counteracted by a selective antagonist of the nuclear retinoic acid receptor RAR alpha, suggesting a RAR alpha mediated mechanism of angiogenesis inhibition. The antiangiogenic effect of retinoids could be significantly enhanced by combination with IFN alpha or 1,25(OH)2D3. The results provide a further basis for the use of combinations of retinoids with IFN alpha or 1,25(OH)2D3 in the treatment of angiogenesis-dependent malignancies.

Animals↗

Ultrastructural localization of binding sites of sera from patients with linear IgA bullous dermatosis.

The localization of the antigen recognized by IgA basement membrane zone (BMZ) antibodies from patients with linear IgA bullous dermatosis (LABD) has not been established. The aim of our study was to find out the binding sites for IgA-BMZ antibodies in LABD in adults and children and, for comparison, the binding sites for IgA antibodies in IgA cicatricial pemphigoid (IgA-CP). Our series comprised 21 sera from adult LABD, 4 sera from childhood LABD, and 2 sera from IgA-CP. The studies were performed using the sodium chloride split-skin method and indirect immunoelectron microscopy (IEM) with the use of the pre-embedding immunoperoxidase technique on two substrates: monkey oesophagus and normal human skin. Of the 27 sera, 24 reacted with the epidermis (19 from adult, 4 from childhood LABD and 1 from IgA-CP) and at the electron microscopic level labelled the upper part of the lamina lucida (LL) and/or hemidesmosomes, and 2 reacted with the dermis (1 from typical adult LABD and 1 from IgA-CP) and labelled the sublamina densa (SLD) region. Two sera were negative in IEM. In conclusion, the study indicated that the localization of the antigens is similar in adult and childhood LABD, and in IgA-CP.

Adolescent↗

Butchers' warts.

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Food Handling↗

Synergistic effect of retinoids and interferon alpha on tumor-induced angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines.

Various retinoids and interferons exert anti-tumor effects both in experimental studies and in clinical trials. Recent reports indicate that they have a synergistic antineoplastic activity. Our study aimed to determine whether these synergistic anti-tumor effects are related to inhibition of tumor-cell-induced angiogenesis. A further aim was to compare the anti-angiogenic activity of various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic acid receptor RXR, given alone and in combination with interferon alpha-2a (IFN alpha-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse was used. Angiogenesis was induced by intradermal injection of HPV16- or HPV18 DNA-harboring tumor-cell lines. All-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as IFN alpha-2a applied to mice intraperitoneally for 5 consecutive days before induction of angiogenesis resulted in significant inhibition of angiogenesis. Combination of retinoids with IFN alpha-2a led to a synergistic inhibition of angiogenesis, as compared to the effects of the drugs given alone. Similar results were obtained when tumor cells were preincubated in vitro with the compounds, before injection into untreated mice. Our findings on synergistic anti-angiogenic effects of retinoids and IFN alpha-2a could explain, at least partially, the anti-tumor efficacy of combined therapy with these agents, and provide support for the role of angiogenesis in tumor growth.

Animals↗

A mouse model for studying epidermodysplasia-verruciformis-associated carcinogenesis.

Epidermodysplasia verruciformis (EV) is considered as a model of genetic cancer due to unusual susceptibility to EV-specific human papillomaviruses (HPVs). We established an in vivo experimental system for long-term propagation of EV tissue which should facilitate the study of tumor progression in EV. Skin fragments from benign and early pre-malignant lesions of 6 EV patients were grafted under the kidney capsule of athymic mice. After several months the grafted tissue formed epidermal cysts. These cysts showed typical EV cytopathic effect, in situ hybridization revealed the presence of HPV 5, 8, 9, 12 and 36 DNA, and immunoperoxidase staining detected papillomavirus-group-specific antigens in the permissive cells of the cysts. In some cysts, there were numerous mitoses and downward proliferation of the epidermis with slight dyskeratotic changes. The experimental system described constitutes a model for studies on the role of HPV and other co-factors in human cutaneous carcinogenesis.

Animals↗

Increased tumorigenicity of human keratinocytes harboring human papillomavirus type 16 is associated with resistance to endogenous tumor necrosis factor-alpha-mediated growth limitation.

The aim of this study was to evaluate the relationship between tumorigenicity of cell sublines derived from weakly tumorigenic SKv-e and SKv-l keratinocytes harboring human papillomavirus type 16 (HPV16) and their susceptibility to autocrine growth limitation mediated by tumor necrosis factor-alpha (TNF-alpha). These sublines displayed different in vitro proliferative potential which correlated with tumorigenicity in nu/nu mice. Recombinant TNF-alpha inhibited in vitro growth of weakly tumorigenic parental SKv cell lines while it did not affect proliferation of their respective highly tumorigenic sublines. Resistance to TNF-alpha correlated with both increased in vitro proliferation and tumorigenicity. Anti-TNF-alpha antibodies (Ab) significantly increased in vitro proliferation of weakly tumorigenic parental SKv cells up to the levels of their highly tumorigenic sublines. Growth of highly tumorigenic SKv cells was not affected. On the other hand, proliferation of SKv cells was affected neither by transforming growth factor-beta (TGF-beta) nor by anti-TGF-beta Ab. All SKv cell sublines tested spontaneously released TNF-alpha, as evaluated by a specific radioimmunoassay; however, the levels of the endogenous cytokine were not related to their proliferative potential and tumorigenicity. An increased resistance to the anti-proliferative effect of TNF-alpha may be associated with decreased expression of TNF-alpha receptors (TNF-alpha R) inasmuch as evaluation of 125I-TNF-alpha binding and Northern-blot analysis of TNF-alpha R-specific mRNA showed that highly tumorigenic SKv cell sublines expressed significantly lower numbers of TNF-alpha R than their respective parental cells. These results show that an increased tumorigenicity of HPV16-harboring SKv keratinocytes may be, at least partially, due to escape from autocrine TNF-alpha-mediated growth limitation.

Animals↗

Leukocyte-extracellular matrix interactions in psoriasis.

BACKGROUND: The basic phenomenon in psoriasis appears to be a directed leukocyte migration that in a great part, depends on the cell-extracellular matrix (ECM) interactions. METHODS: To evaluate the leukocyte-ECM interactions in psoriasis, we investigated the adherence of peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMNL) to ECM components (collagen type I, IV, laminin, and fibronectin), using crystal violet staining and measuring absorbance at 570 nm. RESULTS: In the most active cases of psoriasis (pin-point and guttate type) of short duration, we found a decreased adherence of PBMC to collagen type IV. In a majority of cases of actively spreading plaque psoriasis of large extent and longer duration, there was decreased adherence to all ECM components, especially to collagen type IV and laminin. The adhesion of PMNL to collagen type IV (but not to other ECM components) was increased only in cases of short duration. Preliminary data suggest that etretinate treatment may modulate leukocyte adherence to the ECM components in patients with psoriasis. CONCLUSIONS: The decreased in vitro adherence of PBMC to ECM components, especially those of the basement membrane, may reflect their in vivo activation and migration to the epidermis, which is a basic phenomenon in psoriasis that could be affected by etretinate therapy.

Cell Adhesion↗

Serum levels of interferons and TNF-alpha are not correlated to psoriasis activity and therapy.

Sera from 52 patients with psoriasis and 106 controls were tested for IFN-tau, IFN-alpha 2 and TNF-alpha in ELISA and for total IFN activity using an infectivity inhibition micromethod. Psoriasis patients had lower serum levels of IFN-tau than had the controls: median 0.10 ng/ml vs. 0.16 ng/ml (p = 0.01). The highest median serum IFN-tau levels were in patients with peripherally spreading psoriasis, 0.10 ng/ml, and acute guttate psoriasis, 0.09 ng/ml. Patients with stable plaque psoriasis had lower serum IFN-tau levels (median 0.0) than those with other forms of psoriasis, or blood donors. The serum levels of IFN-alpha 2, total IFN activity and TNF-alpha did not differ between the psoriasis and control group. Treatment with cyclosporin, acitretin and the Goeckerman regimen increased the total IFN activity, but did not affect the levels of IFNs nor TNF-alpha.

Acitretin↗

Cancer combination chemotherapy with retinoids: experimental rationale.

Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3 and its analogs are all classes of compounds with pleiotropic actions. They inhibit proliferation in human transformed epithelial cell lines and induce differentiation in human transformed hemopoietic cell lines. In a murine model of tumor cell-induced angiogenesis all three classes of compounds inhibit the formation of new blood vessels, necessary for supplying the growing tumor with oxygen and nutrients. Combinations of compounds from the three different classes lead to higher efficacy than the compounds administered as single agents. The effects of combinations vary depending on the individual representatives of the three classes and on the particular test models used. Additive, synergistic and potentiating effects have been observed. The results obtained in experimental systems raise hope that combination therapy might be useful in the treatment of certain human neoplastic diseases.

Animals↗