Magdalena Jarosz

Publications of Magdalena Jarosz

• [Tumor blood vessels].

  Authors: Stanisław Szala, Magdalena Jarosz

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:437-46.

  Growth of tumors usually depends on the development of the tumor’s own vasculature. Small avascular tumors (1–2 mm3) cannot continue growth provided an equilibrium between pro-angiogenic andGrowth of tumors usually depends on the development of the tumor’s own vasculature. Small avascular tumors (1–2 mm3) cannot continue growth provided an equilibrium between pro-angiogenic and anti-angiogenic factors is maintained within the tumor environment. Angiogenesis is not the only factor responsible for tumor blood vessels forming, as vasculogenic mimicry plays an equally substantial role in this process. Vessel-like structures formed during this process are made up from cancer cells, macrophages and mast cells. Certain neoplasms are capable of growing without developing their own vasculature; instead they secure growth via normal blood vessels of the host. Slowed-down blood flow through an abnormally built tumor vascular network is the main reason for cancer cells’ underoxygenation (hypoxia). Defective blood vessels, with hypoxia resulting, play a major role in tumor progression. Underoxygenation induces formation of novel vessels and these new defective vessels are in turn the principal reason for hypoxia. The latter increases cancer cells’ malignancy and invasiveness. A particular process, called transdifferentiation, takes place in tumor vasculature when hypoxia is present and involves neoplastic cells transforming into endothelial cells. Since growth of a tumor is dependent on its own blood supply, inhibition of such vascular network growth and/or damage to this network should exert a strong impact on tumor growth. Long-term administration of anti-angiogenic drugs, however, encounters unexpected problems. Anti-angiogenic drug resistance, together with paradoxical stimulation of invasiveness and metastasis by these drugs, has lately become a dominant issue in anticancer therapy.

• Combination of vasostatin and cyclophosphamide in the therapy of murine melanoma tumors.

  Authors: Joanna Jazowiecka-Rakus, Magdalena Jarosz, Dorota Kozłowska, Aleksander Sochanik, Stanisław Szala

  Acta biochimica Polonica. 02/2007; 54(1):125-33.

  Growth of tumors is strongly dependent upon supply of nutrients and oxygen by de novo formed blood vessels. Inhibiting angiogenesis suppresses growth of primary tumors as well and affects developmentGrowth of tumors is strongly dependent upon supply of nutrients and oxygen by de novo formed blood vessels. Inhibiting angiogenesis suppresses growth of primary tumors as well and affects development of metastases. We demonstrate that recombinant MBP/vasostatin fusion protein inhibits proliferation of endothelial cells in vitro. The therapeutic usefulness of such intratumorally delivered recombinant protein was then assessed by investigating its ability to inhibit growth of experimental murine melanomas. In the model of B16-F10 melanoma the MBP/vasostatin construct significantly delayed tumor growth and prolonged survival of treated mice. A combination therapy involving MBP/vasostatin construct and cyclophosphamide was even more effective and led to further inhibition of the tumor growth and extended survival. We show that such combination might be useful in the clinical setting, especially to treat tumors which have already formed microvessel networks.

• Combination of vasostatin gene therapy with cyclophosphamide inhibits growth of B16(F10) melanoma tumours.

  Authors: Joanna Jazowiecka-Rakus, Magdalena Jarosz, Stanisław Szala

  Acta biochimica Polonica. 02/2006; 53(1):199-202.

  Angiogenesis, i.e. formation of new blood vessels out of pre-existing capillaries, is essential to the development of tumour vasculature. The discovery of specific antiangiogenic inhibitors hasAngiogenesis, i.e. formation of new blood vessels out of pre-existing capillaries, is essential to the development of tumour vasculature. The discovery of specific antiangiogenic inhibitors has important therapeutic implications for the development of novel cancer treatments. Vasostatin, the N-terminal domain of calreticulin, is a potent endogenous inhibitor of angiogenesis and tumour growth. In our study, using B16(F10) murine melanoma model and electroporation we attempted intramuscular transfer of human vasostatin gene. The gene therapy was combined with antiangiogenic drug dosing schedule of a known chemotherapeutic (cyclophosphamide). The combination of vasostatin gene therapy and cyclophosphamide administration improved therapeutic effects in melanoma tumours. We observed both significant inhibition of tumour growth and extended survival of treated mice. To our knowledge, this is one of the first reports showing antitumour efficacy of electroporation-mediated vasostatin gene therapy combined with antiangiogenic chemotherapy.