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Biomedical subjects

M Marczak

Publications and source records attributed to M Marczak.

At least 37 records · Page 2Linked to original sources
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↗
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↗
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↗
PubMed1992

Antitumor action of retinoids: inhibition of tumor cell line-induced angiogenesis and prevention of tumors in mice.

Acitretin was shown to inhibit angiogenic response to the tumorigenic SKV cell line bearing HPV16 genome and to sarcoma L-1 cell line, both in vitro and in vivo systems. The lowered angiogenic response to tumor cells was independent of duration and timing of the application of acitretin to animals. Acitretin, but not etretinate, was also found to be effective in the prevention of sarcoma tumors in mice.

Acitretin↗
PubMed1991

Acitretin decreases tumor cell-induced angiogenesis.

The effects of acitretin and etretinate on angiogenesis induced in Balb/c mice by intradermal injection of keratinocyte tumor cell lines were evaluated. It was shown that both retinoids are capable of inhibiting angiogenesis evoked by a human epidermoid carcinoma cell line (A431). Acitretin, but not etretinate, inhibited also angiogenesis induced by the spontaneously transformed murine keratinocyte cell line Pam 212 and by the established tumorigenic SKv cell line harboring the HPV16 genome. We suggest that inhibition of blood vessel formation may be one of the mechanisms responsible for the anticancerogenic effect of retinoids.

Acitretin↗
PubMed1991

Beta-carotene in prevention of cutaneous carcinogenesis.

Beta-carotene, administered orally to mice, caused a decrease in angiogenesis evoked by HPV-transformed tumorigenic cell lines (SKv-t, HeLa). It did not affect angiogenesis induced by the non-tumorigenic SKv (not-t) cell line, and increased lymphocyte-induced immune angiogenesis. We suggest that the anti-cancerogenic effect of beta-carotene may be due, at least in part, to its inhibitory effect on formation of new blood vessels within the tumour mass.

Animals↗
PubMed1989

Immunological cellular response in denture stomatitis mycotic.

Antibody-dependent cellular cytotoxicity (ADCC) and lymphocyte-induced angiogenesis (LIA) of mononuclear leucocytes (MNC) isolated from the peripheral blood of patients with denture stomatitis mycotic were examined. The obtained results have shown a decrease in ADCC in patients with mycotic infection of oral cavity. Similarly, the ability to induce angiogenesis by MNC isolated from these patients was decreased in comparison with angiogenesis induced by control MNC. After the anti-mycotic treatment, an increase in ADCC and LIA was noted.

Animals↗
PubMed1986

Enhanced angiogenic capability of monocyte-enriched mononuclear cell suspensions from patients with systemic scleroderma.

Different subsets of peripheral blood mononuclear cells (MNC) from 15 patients with systemic scleroderma were tested for their ability to evoke angiogenesis in a xenogenic system. The angiogenic capability of total MNC from patients with systemic scleroderma was lower than that of normal human cells, irrespective of the form of the disease. However, the capability of a monocyte-enriched subset of MNC from patients with scleroderma was found to be increased, as compared with their total MNC and with that of the corresponding subset from healthy individuals. This might be due to the activation of monocytes in the disease.

Adult↗
PubMed1985

Modulatory effect of sera from scleroderma patients on lymphocyte-induced angiogenesis.

Sera from 22 patients with progressive systemic sclerosis were tested for the ability to modify the angiogenic capability of normal human mononuclear cells. The sera from patients with acrosclerosis, including the abortive form (CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), markedly enhanced this capability compared with sera from both healthy donors and patients with severe acrosclerosis and diffuse scleroderma. The enhancing effect of sera from patients with acrosclerosis decreased and/or disappeared in cases where the patient's acrosclerosis was chronic and severe. Thus, this test may be of diagnostic value in distinguishing various subgroups of systemic sclerosis.

Adult↗
PubMed1981

Decreased antibody-dependent cellular cytotoxicity in various types of leukaemia in man.

Antibody-dependent cellular cytotoxicity (ADCC) by cells from peripheral blood was studied in patients with; chronic lymphocytic leukaemia (CLL), chronic granulocytic leukaemia (CGL), acute lymphoblastic leukaemia (ALL), acute non-lymphoid leukaemia (ANLL) and compared with that of healthy donors. The ADCC activity in all the types of leukaemia was on the average lower as compared with the control values, being especially low in both CLL and CGL. Further, it has also been shown that the ADCC activity of non-leukaemic blood cells in ANLL was lower as compared with control values. The latter observation indicates that, at least in ANLL, the reduced ADCC potential of peripheral blood cells is not due to dilution of effector cells by poorly- or non-active leukaemic cells.

Acute Disease↗
PubMed1980

[High titre of antibodies to ds-DNA in a case of visceral lupus erythematosus with remission during many years].

In a 21-year-old female patient with lupus erythematosus exacerbation of the disease developed during pregnancy leading to eclampsia and birth of a stillborn fetus. After 10 years of immunosupressive treatment the patient continuing treatment with prednisone had another sucessful pregnancy with birth of a healthy child. Serious organ changes observed in the first years of the disease regressed completelt during 12 years of immunosupressive treatment. Throughout the whole observation period antinuclear antibodies were found in the serum, and in the last year their titre of antobodies to native DNA was high. The necessity of many years of immunosupressive treatment of patients with visceral lupus erythematosus is stressed.

Adult↗
PubMedDate not supplied

Ventilatory response to hypoxia in elderly women.

BACKGROUND: The respiratory system is subject to the ageing process, which could limit its responsiveness to stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane to the pathogenesis of hypoxic respiratory disorders developing more often in elderly subjects. AIM: The study seeks to determine the potential adverse effects of age on the hypoxic ventilatory response by comparing this response in groups of elderly and young female subjects. SUBJECTS AND METHODS: Nineteen healthy women of the mean age of 71+/-1.3 (SE) years and 16 women in their twenties were required to perform a progressive isocapnic hypoxic test, based on the rebreathing technique. The ventilatory response was evaluated from the slopes of minute ventilation and mouth occlusion pressure, an index of inspiratory neuromuscular drive, against arterial oxygen saturation. The breathing pattern components also were measured with the breath-by-breath routine. RESULTS: Ventilatory response to hypoxia averaged 0.65+/-0.10 L/min/% SaO(2) and neuromuscular output was 0.012+/-0.002 kPa/% SaO(2) in the elderly women and these slopes were not reduced compared with those in the young. Nor did the ventilatory slopes relate to age in the older subjects. Baseline breathing pattern was modified in the elderly in that the mean inspiratory flow was significantly higher, but it reached the same stimulated level as that in the young. CONCLUSIONS: Ventilatory response to hypoxia is independent of age in healthy women. Thus, functional sensitivity of the respiratory control mechanisms does not attenuate with age.

Adult↗