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Biomedical subjects

Hanna Ławnicka

Publications and source records attributed to Hanna Ławnicka.

5 recordsLinked to original sources

Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.

Angiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.

Angiogenesis Inhibitors↗

Stimulatory effect of GH3 cell line conditioned medium on the proliferation of the endothelial cell line (HECa10) in vitro.

OBJECTIVES: The process of neoangiogenesis plays a key role in development and progression of solid tumours. The formation of new blood vessels different from the portal network system is important for pituitary tumour formation. The pivotal role of activated endothelial cells in angiogenesis was well documented. The degree of endothelial cells stimulation depends on the angiogenic activity of the tumorous cells. The aim of the study was to elucidate the angiogenic properties of the lactosomatotrophic pituitary cell line. MATERIAL AND METHODS: The study was carried out on the mouse endothelial HECa10 cell line subjected to medium obtained from the culture of rat lactosomatotrophic pituitary GH3 cell line. The endothelial cell growth was measured using the modified colorimetric method EZ4Y detecting the viable cells. The secretion of vascular endothelial growth factor (VEGF) to GH3 cells conditioned medium was assessed by immunoenzymatic method. RESULTS: It was shown that the exposure of endothelial cells to pituitary tumorous conditioned medium significantly stimulated the cellular growth after 24 and 48 hours of incubation. Moreover, the concentration of VEGF in GH3 conditioned medium occurred to be 13 times higher than in the control medium. CONCLUSION: Our results indicate the angiogenic activity of lactosomatotrophic GH3 cell line and suggest the role of VEGF in pituitary tumorous angiogenesis.

Animals↗

Angiotensin II and its fragments (angiotensins III and IV) decrease the growth of DU-145 prostate cancer in vitro.

BACKGROUND: There is growing evidence that angiotensin II (AngII) and its smaller fragments 2-8 (AngIII) and 3-8 (AngIV) are involved in cell-growth control in the vascular smooth muscle and in some other tissues, including prostate. The aim of this paper was to investigate the effects of AngII and its fragments AngIII and AngIV on the growth of an androgen-independent human prostate cancer cell line in vitro. To see whether the conversion of Ang II into its shorter fragments plays a role in the action of the former, we used specific inhibitors of aminopeptidases: compound EC33 (inhibitor of aminopeptidase A), which blocks the conversion of AngII into AngIII, and compound PC 18 (inhibitor of aminopeptidase N), which blocks the conversion of AngIII into AngIV. MATERIAL/METHODS: Human prostate cancer DU-145 cells were exposed in culture to different concentrations of AngII, AngIII, and AngIV separately or jointly with the aminopeptidase inhibitors EC33 or PC18. To measure cell growth, the colorimetric method, based on the reduction of tetrazolium salt by viable cells, was applied. RESULTS: It was found that exposure of DU-145 cells in vitro to all the investigated angiotensins resulted in a moderate, concentration-dependent inhibition of cell growth. The joint exposure of DU-145 cells to AngII plus EC33, but not to AngII plus PC 18, abolished the effect of AngII. CONCLUSIONS: These findings suggest that angiotensin peptides (AngII as well as its smaller fragments) are involved in the negative control of prostate cancer cell growth.

Angiotensin II↗

[Evaluation of the effect of GHRH(1-44)NH2 on the secretion of interleukin-2 (IL-2) and soluble IL-2 receptor alpha (sIL-2Ralpha) from human peripheral blood mononuclear cells in vitro].

OBJECTIVE: The bidirectional communication between the neuroendocrine and the immune systems is now a subject of an intensive investigation. Somatoliberin (GHRH) is a hypothalamic hormone that enhances the synthesis and the release of growth hormone (GH) from the anterior pituitary cells. Few recent reports demonstrate also role of the neuropeptide in the regulation of the immune system function. AIM: The aim of the study was to examine the influence of GHRH on IL -2 as well as sIL -2Ralpha secretion from mitogen-stimulated peripheral blood mononuclear cells. MATERIAL AND METHOD: Mononuclear cells (PBMC) were isolated from the peripheral blood of healthy adults according to the technique described by Böyum. Cells, cultured 24 hours at 37 degrees C in humidified atmosphere of 95% air and 5% CO2, were stimulated with phytohemaglutinin (PHA; 10 microg/ml), and then GHRH(1-44)NH2 at the final concentrations 10(-12), 10(-10), 10(-8) and 10(-6) M was added to appropriate wells. ELISA kits were used to measure IL-2 and sIL-2Ralpha concentrations in the supernatants of cultured cells. Comparisons between tested groups were made by U Mann-Whitney test. The differences were considered significant if p < 0.05. RESULTS: GHRH stimulated the secretion of IL -2 into the supernatants acting significantly at the concentration of 10(-12) M (p < 0.001). Moreover, GHRH at concentrations 10(-10) M and 10(-8) M significantly increased the secretion of sIL-2Ralpha as well (p < 0.001). Strong positive correlation between tested GHRH concentrations and sIL-2Ralpha levels in the supernatants was demonstrated (r = 0.8664; p <0.001). CONCLUSIONS: The results demonstrate the potential involvement of GHRH in the regulation of T lymphocytes secretory function.

Adult↗

The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro.

The role of gastrins and their receptors in the pathogenesis of colon cancer has been discussed for many years but it still remains unresolved. Although fluorouracil (FU) remains to be reference chemotherapy for colon cancer, its efficacy is unsatisfactory. Recently, we have shown a synergistic effect of proglumide (a non-selective blocker of cholecystokinin-gastrin receptors) applied together with FU, on the proliferation and apoptosis of transplantable Colon 38 cancer cells in vivo. The aim of this study was to examine direct effects of proglumide (10(-5)-10(-10) M) applied either alone or together with FU (0.25, 2.5 and 25 microg/ml) on the proliferation of murine Colon 38 cancer cells in vitro. Cell proliferation was assessed by the modified colorimetric Mosmann method. Proglumide inhibited the proliferation of Colon 38 cells at the concentrations of 10(-6), 10(-8) and 10(-10) M. FU inhibited the proliferation of cancer cells in all studied concentrations, exerting the most profound antiproliferative effect at the concentrations of 2.5 and 25 microg/ml. Thus, the former concentration was chosen to study its interactions with proglumide. Proglumide applied together with FU exerted a synergistic effect on the inhibition of proliferation of Colon 38 cells at 10(-8), 10(-9), 10(-10) M concentrations. The most profound inhibitory effect was observed in the group incubated with FU and 10(-10) M of proglumide. The obtained results indicate a possibility of new therapeutic options for colon cancer, but further studies are needed to elucidate, if the synergistic effect of FU and proglumide occurs also in the colon cancer in humans.

Analysis of Variance↗