Kisseleva Ekaterina - personal page

Ekaterina P. Kisseleva (Kiseleva)
Head scientist, Ph.D., Doct.med.sci.

Ph.7(812)234-16-69
Fax.7(812)234-94-89
e-mail: ekissele@yandex.ru

Address: acad.Pavlov str.,12
St.Petersburg, 197376, Russia

Main direction of studies: antitumor immunity

Investigation of the mechanisms of thymic involution in tumor growth. The fact of thymic atrophy that followed the development of human and experimental tumors in animals in known for a long time, but the mechanisms remain unclear. The increase of apoptosis in thymi of tumor-bearers was first registered in our laboratory. We hypothesized that enhancement of intrathymic cells death by apoptosis was tone of the mechanism for thymic involution in cancer. In the joint project with group of Prof. D. Gabrilovich from USA, we identified the potent factor that induces thymic involution in experimental tumors. This factor was shown to be an angiogenic factor VEGF. We were the first to study the influence of this factor in thymocytes and showed the expression of VEGF receptors on these cells. Results obtained are important not only for tumor growth but for other processes with the excess pf angiogenesis like wound healing, pregnancy, rheumatoid arthritis.

Other direction is to investigate angiogenic functions of macrophages and variants of their alternative activation in pathology. It is known that macrophages play a dualistic role in tumor growth being both at the sites of defence and support for tumor growth. We study the role of macrophages in stimulation of tumor neoangiogenesis and describe their angiogenic phenotype. Immunomodulatory effects of VEGF on macrophages were studied and the expression of VEGF receptors.

Based on our results a conclusion was formulated that anti-angiogenic therapy and anti-VEGF drugs especially, are perspective not only for the inhibition of vessel growth but has immunomodulatory properties that could abolish undesirable effects of VEGF in the organism when the excess of angiogenic factors is produced.

Main publications:

1. Kisseleva E., Becker M., Lemm M., Fichtner I. Involvement of macrophages and cytokines into rejection mechanisms of the drug-resistant and immunogenic murinе lymphoma P399/adria. //Anticancer Research. 1996, 16, 1971-1978.

2. The role of apoptosis in thymic involution during growth of a syngeneic transplantable murine tumor. Kisseleva E.P., Suvorov A.N., Ogurtsov R.P. //Biology Bulletin, 1998, N.2, p.172-179 (Russian).

3. The influence of hyperlipidemia on susceptibility of thymocytes to apoptosis in mice of CBA and C57BL/6 strains. Kiseleva E.P., Puzyreva V.P., Ogurtsov R.P., Kovaleva I.G. //Byulleten Experimentalnoi Biologii i Meditsini, 2000, v.130, N.8, p.200-202 (Russian).

4. Early macrophage and cytokine response during the growth of immunogenic and non-immunogenic murine tumors. Kisseleva E., Fichtner I., Becker M., Lemm M.// Anticancer Res., 2001, v.21, p.3477-3484.

5. The influence of hyperlipidemia on functional activity of peritoneal macrophages in CBA and C57BL/6 mice. Kiseleva E.P., Puzyreva V.P., Ogurtsov R.P., Kovaleva I.G. //Byulletin Experimentalnoi Biologii i Meditsini, 2002, v.134, N.9, p.334-337 (Russian).

6. The influence of metabolic factors at the apoptosis of thymocytes in tumor growth. Kiseleva E.P., Ogurtsov R.P., Dotsenko E.K. //Byulletin Experimentalnoi Biologii i Meditsini, 2003, v.135, N.5, p.558-561 (Russian).

7. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Ohm J.E., Gabrilovich D.I., Sempowski G.D., Kisseleva E., Parman K.S., Nadaf S., Carbone D.P. //Blood, 2003, v.101, N.12, p.4878-4886.(full text .pdf 255 KB)

8. The mechanisms of thymic involution in tumor growth. Kiseleva E.P.// Uspechi sovremennoi biologii, 2004, 124(6), 102-114 (Russian). (full text .pdf 1355 KB)

9. The influence of VEGF on proliferation and apoptosis of murine thymocytes in vitro. Kiseleva E.P., Krylov A.V., Lioudyno V.I., Suvorov A.N. //Byulletin Experimentalnoi Biologii i Meditsini, 2005, 139 (5), 533-537 (Russian). (full text .pdf 459 KB)

10. Stepanova O.I., Krylov A.V., Lioudyno V.I., Kisseleva E.P. Gene expression for VEGF-A, VEGF-C, and their receptors in murine lymphocytes and macrophages //Biochemistry (Moscow)/ - 2007. – Vol.72(11). – 1194-1198. (full text .pdf 1799 KB)

Methods:

1. VEGF and VEGFR mRNA expression by semiquantitative RT-PCR.
2. Angiogenesis in vitro: adhesion, proliferation, chemotaxis of endothelial cells.
3. Apoptotsis: DNA fragmentation, immunofluorescent test, Annexin V, propidium iodide staining.
4. Functional activity of peritoneal macrophages: phagocytosis, pinocytosis, nitroxide and superoxide anion production, 5?-nucleotidase activity, cytokine production by ELISA.

Grants

1994 "Expression of immunogenicity in different experimental tumors: possible implication for cytokine modulation of host anti-tumor response", - supported by a DFG grant 436 RUS 17/184/93 S (Dr.Iduna Fichtner, Max-Delbruck-Center for Molecular Medicine, Berlin-Buch - principal investigator from Germany; Kisseleva E. - principal investigator from Russia)

1995-1996 ERSS grant 93-6: "Influence of air pollution on the host defense against infection", supported by CEU, Department of Environmental Sciences, Budapest, Soros Foundation (Kisseleva E. - principal investigator)

1997 - RSS grant No 1355/1997 "Ten years after Chernobyl accident: long-term immunological consequences; prognosis of autoimmune disorders", supported by OSI/HESP, Soros Foundation (Kisseleva E. - principal investigator)

1999 - NATO Collaboration Linkage grant SA(LST.CLG 975197) "Effects of Vascular Endothelial Growth Factor on Lymphocyte Differentiation. New Mechanism of Immunodeficiency" (Prof. D.Gabrilovich, Loyola University, Chicago - principal investigator from USA; Kisseleva E. - principal investigator form Russia)

2000-2002 Russian Federation for Basic Research N. 00-04-49430. "The role of macrophages in the regulation of angiogenesis in tumor growth." (Kisseleva E.P. - principal investigator)

2003-2005 Russian Federation for Basic Research N. 03-04-49186. "The mechanisms of thymic involution in tumor growth." (Kisseleva E.P. - principal investigator)

2003-2005 Russian Scientific Schools -540.2003.4 (Kisseleva E.P. -collaborator)