Wyniki wyszukiwania - Biblioteka Nauki

1

Mathematical modelling of tumour angiogenesis

100%

Poleszczuk J.

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2013

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tom Vol. 41, No. 1

1--12

EN

Mathematical models are valuable tools for studying the underlying mechanisms of tumour progression. They enable us to explore possible radio-, chemo- and other various therapy combinations that until now have been only a promising hypotheses because of the huge costs of their clinical studies. Here we present a family of mathematical models of tumour angiogenesis, which give an accurate fit to biological data. In addition, after modifications they can describe the effect of anti-angiogenic treatment using various vessel targeting agents, as well as the impact of cytotoxic agents on proliferating cancer cells. We present two ways in which anti-angiogenic treatment can be incorporated into the model. In the first one, the agents directly target tumour vessels, whereas in the second one, they interfere with angiogenic signalling. We illustrate differences between these two approaches by presenting the results of fitting the corresponding models to the biological data.

PL

Modele matematyczne okazały się być cennym narzędziem do badania podstawowych mechanizmów progresji nowotworu. Modele pozwalają nam na badanie możliwości łączenia radioterapii, chemioterapii i innych metod leczenia, co do tej pory, z powodu bardzo wysokich kosztów badań klinicznych, było nieosiągalne. W pracy prezentujemy rodzinę matematycznych modeli angiogenezy nowotworowej, które okazały się dobrze odpowiadać wynikom przeprowadzonych eksperymentów biologicznych. Ponadto, po wprowadzeniu pewnych modyfikacji, modele te skutecznie opisują wpływ terapii antyangiogennej wykorzystującej leki o różnorakim sposobie działania. W pracy przedstawiamy dwa sposoby na uwzględnienie w modelu wpływu leków działających na naczynia krwionośne dostarczające w rejony nowotworu tlen i substancje odżywcze. Pierwszy sposób odnosi się do środków działających bezpośrednio na naczynia guza. Drugi opisuje środki wpływające na proangiogenna sygnalizacje. Różnice miedzy tymi dwoma podejściami ilustrujemy poprzez przedstawienie wyników dopasowywania modeli do danych eksperymentalnych.

2

Microvessel density assessment in benign and malignant endometrial changes

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Czekierdowski A. , Czekierdowska S. , Czuba B. , Cnota W. , Sodowski K. , Kotarski J. , Zwirska-Korczala K.

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nr 4

45-51

3

Recombinant angioarrestin secreted from mouse melanoma cells inhibits growth of primary tumours

84%

Smagur A. , Szary J. , Szala S.

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2005

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tom 52

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nr 4

EN

Angioarrestin is a recently described anti-angiogenic protein whose expression is down-regulated in solid tumours of various origins. It has a sequence identical to angiopoietin related protein-1. In this study we investigated anti-tumour properties of angioarrestin in B16 (F10) melanoma tumour model. We constructed an expression vector encoding human angioarrestin under the control of EF-1α promoter. This vector was transferred to B16 (F10) cells and recombinant angioarrestin secreted from the transfected cells was tested for anti-angiogenic activity using endothelial cell proliferation assay. Finally, mice were injected subcutaneously with cells that had been transfected with either angioarrestin-encoding vector or empty vector and tumor growth was compared. The obtained recombinant angioarrestin inhibited proliferation of bovine aortic endothelial cells. Tumours derived from an angioarrestin-secreting B16 (F10) cell clone grew in vivo more slowly than tumours derived from a cell clone transfected with empty vector. These data show, to our knowledge for the first time, that angioarrestin can inhibit primary melanoma tumour growth.

4

Effect of Immunostim plus - a standardized fixed combination of Schizandra chinensis with Eleutherococcus senticosus extracts on granulocyte activity and tumour angiogenesis in mice

84%

Siwicki A. K. , Skopinska-Rozewska E. , Nartowska J. , Malaczewska J. , Wojcik R. , Sommer E. , Trapkowska S. , Filewska M. , Skurzak H.

Bulletin of the Veterinary Institute in Puławy

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2004

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tom 48

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nr 4

5

Chimeric protein ABRaA-VEGF121 is cytotoxic towards VEGFR-2-expressing PAE cells and inhibits B16-F10 melanoma growth

67%

Smagur A. , Boyko M. M. , Biront N. V. , Cichon T. , Szala S.

Acta Biochimica Polonica

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2009

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tom 56

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nr 1

115-124

EN

It has been known that VEGF121 isoform can serve as a carrier of therapeutic agents targeting tumor endothelial cells. We designed and constructed synthetic cDNA that encodes a chimeric protein comprising abrin-a (ABRaA) toxin A-chain and human VEGF121. Expression of the ABRaA-VEGF121 chimeric protein was carried out in E. coli strain BL21(DE3). ABRaA-VEGF121 preparations were isolated from inclusion bodies, solubilized and purified by affinity and ion-exchanged chromatography (Ni-agarose and Q-Sepharose). Finaly, bacterial endotoxin was removed from the recombinant protein. Under non-reducing conditions, the recombinant protein migrates in polyacrylamide gel as two bands (about 84 kDa homodimer and about 42 kDa monomer). ABRaA-VEGF121 is strongly cytotoxic towards PAE cells expressing VEGFR-2, as opposed to VEGFR-1 expressing or parental PAE cells. The latter are about 400 times less sensitive to the action of this fusion protein. The biological activity of the ABRaA domain forming part of the chimeric protein was assessed in vitro: ABRaA-VEGF121 inhibited protein biosynthesis in a cell-free translation system. Preincubation of ABRaA-VEGF121 with antibody neutralizing the biological activity of human VEGF abolished the cytotoxic effect of the chimeric protein in PAE/KDR cells. Experiments in vivo demonstrated that ABRaA-VEGF121 inhibits growth of B16-F10 murine melanoma tumors.