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Biomedical subjects

S Majewski

Publications and source records attributed to S Majewski.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Prognostic factors in radiotherapy of supraglottic cancer].

In 971 patients with squamous cell carcinoma of supraglottic larynx several clinical and physical prognostic factors were evaluated. There were 55% of patients with advanced primary tumours and 71% of patients with no regional neck metastases. All patients were irradiated radically using external megavoltage beam. The total dose was in range 60-70 Gy for 95% of patients. The 3-year local control rate and 3-year overall in whole group were 41% and 50% respectively. Clinical stage, haemoglobin level at the end of treatment, overall treatment time, sex and total dose were estimated as an independent and important prognostic factors for the outcome in radiotherapy of supraglottic larynx cancer.

Adult↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

Excessive costimulation of CD3-dependent lymphocyte response by extracellular matrix proteins in severe widespread psoriasis.

Costimulation of anti-CD3-triggered proliferative T-cell responses by type I and type IV collagen and fibronectin was studied in 25 patients with psoriasis and 12 healthy subjects. The stimulation index of anti-CD3-mediated responses in the presence of type I collagen was about half that in the controls. Although the CD3-dependent proliferative response of psoriatic lymphocytes in patients with active widespread plaque psoriasis was reduced by about 50%, costimulatory responses induced by type IV collagen and fibronectin were found to be enhanced in relation to the controls. The degree of costimulation by type IV collagen and fibronectin was related to disease severity. The highest values of the stimulation index were found in patients with a PASI greater than 24, skin involvement of more than 40% of body surface area, and a duration of psoriatic lesions of more than 3 months. The results indicated that in active widespread plaque psoriasis subpopulations of T cells bearing receptors for some extracellular matrix proteins were increased in the peripheral blood. A factor responsible for this phenomenon may be trafficking of T cells through the basement membrane zone of psoriatic lesions, which presumably causes modification of T cell immunological responsiveness after recirculation.

Adult↗
PubMed1995

Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin.

BACKGROUND: Epidermodysplasia verruciformis is a rare lifelong disease that has raised an enormous interest since it is a model of cutaneous genetic cancer induced by specific human papillomaviruses. OBSERVATIONS: The interacting immunogenetic and environmental factors, especially UV irradiation, result in the inability of the patients' immune system to respond to epidermodysplasia verruciformis-specific human papillomaviruses. The local immunosuppression is an effect, at least in part, of the overproduction of tumor necrosis factor alpha and transforming growth factor beta1 and of the excessive formation of cis-urocanic acid. CONCLUSIONS: Epidermodysplasia verruciformis is a model not only of cutaneous viral oncogenesis but also of local defense mechanisms in the progression of human papillomavirus-associated cancers.

Epidermodysplasia Verruciformis↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Modulation of lymphocyte-fibroblast interactions by 2-chloro-2'-deoxyadenosine (2-CdA) in subarachnoid hemorrhage.

The adherence to monolayers of human fibroblasts of chromium-51 labelled peripheral blood mononuclear cells (PBMC) from normal subjects, and from patients after single or multiple subarachnoid hemorrhage (SAH), and the effect of 2-CdA on cell adhesion have been quantified. The fraction of cells adhering to fibroblasts were the lowest for multiple SAH patients and the highest for normal subjects, which can be explained by depletion of activated lymphocytes from peripheral blood of SAH patients. 2-CdA decreased the fraction of adhering cells isolated from normal subjects, did not change the adherence of cells from single SAH patients and increased the fraction of adhering cells isolated from multiple SAH patients. We conclude that the influence of 2-CdA on the adherence of PBMC to fibroblasts is inversely related to the degree of immune system activation.

Autoimmunity↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

[Relationship between decreased activity of NK cells in umbilical cord blood and infection incidence in children].

In our study the natural cytotoxic activity of the umbilical blood of healthy newborns born in 1987 was examined. All mothers of the examined children were healthy and pregnancy was normal. Blood was drawn from the umbilical vein immediately after the delivery to the heparinized tubes. Mononuclear cells of the blood were isolated using the modified Boyums method. The mean activity of the NK cells was 8.6 +/- 1.5 (SE), and was lower than in the studies by other authors. Three years after the delivery all mothers of the examined children got the questionnaire about the health of their babies. After the analysis of the results, the correlation between lowered NK cells activity in the umbilical blood and the morbidity of the children was shown.

Adult↗
PubMed1993

Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination.

Tumor-induced angiogenesis (TIA), i.e., the ability of transformed cells to stimulate new blood vessel formation is an important factor contributing to tumor growth and invasiveness. The antiangiogenic effect of the retinoids, all-trans retinoic acid, 13-cis retinoic and 9-cis retinoic acid, of 1,25-dihydroxyvitamin D3, and of their combinations were studied using an experimental system in vivo. TIA was induced in immunosuppressed mice by intradermal injection of the two human transformed keratinocyte lines, Skv-e2, harboring DNA of human papillomavirus (HPV) type 16, and HeLa, harboring HPV18 DNA. The three retinoids and 1,25-dihydroxyvitamin D3, when administered systemically to mice, before the angiogenesis assay significantly decreased TIA. Their combination led to a synergistic inhibition of TIA. These results provide the basis for the use of combination of retinoids and 1,25-dihydroxyvitamin D3 in treatment of neoplastic diseases.

Animals↗