http://dspace.nbuv.gov.ua:80/handle/123456789/133118 2026-04-17T16:33:08Z 2026-04-17T16:33:08Z Roomi, M.W. Kalinovsky, T. Niedzwiecki, A. Rath, M. http://dspace.nbuv.gov.ua:80/handle/123456789/138207 2018-06-19T00:02:54Z 2009-01-01T00:00:00Z

Antiangiogenic properties of a nutrient mixture in a model of hemangioma Roomi, M.W.; Kalinovsky, T.; Niedzwiecki, A.; Rath, M. The pathogenesis of hemangiomas is still largely unknown and the current therapy, such as systemic corticosteroid, vincristine, and interferon-alpha, is toxic and remains unsatisfactory. A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract has shown significant anti-angiogenic and anti-tumor effect against a number of cancer cell lines. Aim: Using a mouse hemangioendothelioma model, we investigated the efficacy of NM. We also tested the effect of NM in vitro, evaluating cell viability, MMP secretion, invasion, morphology and apoptosis. Methods: Athymic nude mice, 5–6 weeks old, were inoculated with 3 x106 EOMA cells subcutaneously and randomly divided into two groups; group A was fed a regular diet and group B — a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histology. We also tested the effect of NM in vitro. Results: NM inhibited the growth of tumors by 50%. In vitro, NM exhibited dose response cytotoxicity with 10%, 30% and 55% at 10, 100 and 1000 μg/ml. Invasion through Matrigel was inhibited at 50, 100 and 500 μg/ml by 25%, 30% and 100% respectively. NM induced dose-dependent apoptosis of EOMA cells. Conclusions: These results suggest that NM may have therapeutic potential in treating infantile hemangioendotheliomas and, perhaps, other cutaneous vascular tumors.

2009-01-01T00:00:00Z Saczko, J. Skrzypek, W. Chwilkowska, A. Choromanska, A. Pola, A. Gamian, A. Kulbacka, J. http://dspace.nbuv.gov.ua:80/handle/123456789/138206 2018-06-19T00:03:49Z 2009-01-01T00:00:00Z

Photo-oxidative action in cervix carcinoma cells induced by HpD — mediated photodynamic therapy Saczko, J.; Skrzypek, W.; Chwilkowska, A.; Choromanska, A.; Pola, A.; Gamian, A.; Kulbacka, J. Photodynamic therapy leads to oxidative stress through the generation of free radicals. Oxidative stress causes damage to cellular macromolecules such as nucleic acids, proteins and lipids. Aim: To examine the hematoporphyrin derivative (HpD) — mediated photodynamic effect on cervical adenocarcinoma cell line HeLa. Methods: The HpD localization in HeLa cells was analyzed by confocal microscopy with epi-fluorescence system. Lipid peroxidation (LPO) was estimated by measurement of the concentration of malondialdehyde, protein degradation — by modified Ellman’s method, superoxide dysmutase (SOD) — using Ransod Kit. The expression of inducible nitric oxide synthase (iNOS) was detected by immunocytochemical staining. Results: The HpD was distributed all over the cytoplasm with preferential localization in the inner side of the plasma membrane and around the nuclear envelope. The process of photosensitizer distribution was time dependent. PDT-HpD increased the level of malonodialdehyde (MDA), SOD activity and the expression of iNOS in HeLa cells. However, PDT induced the decrease in the level of protein-associated thiol groups. Conclusions: Our study showed the important role of PDT-mediated oxidative stress in HeLa cells. HpD-PDT might be alternative and less invasive approach for treatment of patients with cervical cancer resistant for standard chemotherapy and radiotherapy.

2009-01-01T00:00:00Z Baldea, I. Mocan, T. Cosgarea, R. http://dspace.nbuv.gov.ua:80/handle/123456789/138205 2018-06-19T00:03:11Z 2009-01-01T00:00:00Z

The role of ultraviolet radiation and tyrosine stimulated melanogenesis in the induction of oxidative stress alterations in fair skin melanocytes Baldea, I.; Mocan, T.; Cosgarea, R. Melanocytes are producing melanin after UV irradiation as a defense mechanism. However, UV-induced damage is involved in melanoma initiation, depending on skin phototype. Melanocytes seem to be extremely susceptible to free radicals. Their main enzymatic antioxidants are superoxide dismutase and catalase. Aim: To study how melanin synthesis modulates the activity of the oxidative stress defense enzymes and cell proliferation after UV induced cell damage. Methods: Normal human melanocyte cultures from fair skin individuals were exposed to high levels of L-tyrosine and irradiated, with 20, 30, 40 mJ/cm2 UVA, and respective UVB. Proliferation was measured using a MTS assay; viability was assessed by trypan blue exclusion dye method. Spectrophotometrical methods were used to determine total melanin content, the enzymatic activity of tyrosinase, superoxide dismutase and catalase. Results: Tyrosine had a negative effect on proliferation, enhanced with time elapsed. Overall, UV irradiation decreased proliferation. UVA increased proliferation relative to UVB in the cultures exposed for a longer time to high (2 mM) tyrosine concentration. There were no proliferation differences between UVA and UVB irradiation in lower tyrosine concentration exposed melanocytes. Both, UV irradiation and tyrosine increased melanogenesis. Exposure of the melanocytes to increased levels of tyrosine in medium (0.5 mM and 1 mM) and UV irradiation enhanced the activity of superoxide dismutase and catalase. The enzymes showed a high activity rate in melanocytes while exposed for a short time to 2 mM tyrosine, but their activity was dramatically decreased with longer tyrosine exposure and UV irradiation. Conclusion: Our data indicate that in low phototype melanocytes, melanogenesis, either following UV irradiation, or tyrosine exposure, especially in high concentrations, was detrimental for the cells by reducing the activity of catalase and superoxidedismutase, the natural antioxidants. UVA was more efficient in stimulating the activity of superoxide dismutase and catalase but also in depleting the reserves of the enzymatic defense against oxidative stress, especially catalase, than UVB. This physiologic response to UV light can be considered as an adjunctive risk factor for people with low phototype for developing a melanoma, when exposed to UV irradiation.

2009-01-01T00:00:00Z Kojima, T. Hashimoto, Y. Inamura, Y. Koide, T. Nagata, H. Ito, N. Suzumura, K. http://dspace.nbuv.gov.ua:80/handle/123456789/138204 2018-06-19T00:03:56Z 2009-01-01T00:00:00Z

Serum factors that suppress cytotoxic effect of methotrexate Kojima, T.; Hashimoto, Y.; Inamura, Y.; Koide, T.; Nagata, H.; Ito, N.; Suzumura, K. To study the phenomenon that human erythroid leukemia K-562 cells are more sensitive to cytotoxic effect of antimetabolites when cultured in a serum-free medium than in a conventional medium containing fetal calf serum (FCS). Methods: Cytotoxic effects of methotrexate, azaserine and 5-fluorouracil were estimated by accessing the lactate dehydrogenase (LDH) activity of viable tumor cells. Proteins of FCS were separated using two-dimensional electrophoresis followed by mass spectrometry analysis. Results: Addition of 10% FCS attenuated anti-tumor activity of methotrexate and azaserine against K-562 cells compared with serum-free medium. Such an activity of FCS was different for each serum lot. Comparison of the proteins in active serum lot with those in not active one using two-dimensional electrophoresis showed that in the active serum there were proteins 150 kDa, which were absent in the not active serum lot. Mass spectrometry indicated that all those proteins had the amino acid sequence of albumin. Sera of one healthy volunteer and two patients with thyroid cancer also attenuated the activity of the agent. Conclusion: Several lots of FCS and human serum demonstrated the ability to attenuate the cytotoxic effect of methotrexate in vitro, possibly due to the formation of albumin dimers/MTX complexes.

2009-01-01T00:00:00Z