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Volume 9, Issue 11 (Suppl)

J Cancer Sci Ther

ISSN: 1948-5956 JCST, an open access journal

Asia Pacific Oncologists 2017

November 20-22, 2017

November 20-22, 2017 Melbourne, Australia

14

th

Asia Pacific

Oncologists Annual Meeting

Antineoplastic drug NSC631570 inhibits C6 glioma growth in rats through the re-education of tumor-

associated microglia

Larysa Skivka, Mariia Rudyk, Ievgenia Opeida, Vitalina Svyatetska, Kateryna Stepura, Niccola Funel, Ascold Nowicky and Wassil Nowick

1

Taras Sevchenko National University of Kyiv, Ukraine

2

University of Pisa, Italy

3

Ukrainian Anticancer Institute, Austria

G

lioblastoma (GB) is one of the most devastating and fatal tumors. Therapeutic approaches targeting tumor cells have failed.

GB is heavily infiltrated with myeloid cells that are collectively referred to as glioma-associated microglia/macrophages

or GAM. GAM acquires the alternative, pro-invasive phenotype and creates favorable conditions for disease progression.

GAM re-education seems to be an attractive therapeutic approach to GM treatment. NSC631570 is an anticancer agent that

influences phagocyte migration and functional polarization. This study was aimed to investigate the effect of NSC631570

on C6 glioma growth in rats and microglia metabolic profile

in vitro

and

in vivo

. For tumor-associated hypoxia induction

experiments, the rat microglial cells were treated under either normoxia (21% O2) or hypoxia (3% O2) for 48 hours

in vitro

.

Intracranial drug delivery device was developed for the local treatment of glioma-bearing rats with NSC631570. Tumor-

bearing animals received seven intracranial injections of the drug at 3 days interval starting from the second day after C6 cell

transplantation. NSC631570 re-polarized hypoxic microglia to pro-inflammatory metabolic profile

in vitro

. The treatment of

tumor-bearing rats with NSC631570 was associated with prolongation of their life by 18%. This effect was accompanied by

the increase in the number of phagocytizing CD14

+

cells in the microglia fraction without the alteration in their endocytosis

intensity. The frequency of CD206

+

cells was moderately increased in the fraction of both CD14

+

and CD14-microglial cells.

Oxidative metabolism of GAM was moderately down-regulated by the drug. Intracranial introduction of the preparation was

associated with the sharp increase of NO generation by microglial cells. Locally introduced NSC631570 can re-educate GAM.

This repolarizing effect is associated with moderate tumor growth inhibition and might be considered as an important part of

the mechanism of tumor-inhibiting action of the drug.

Biography

Larysa Skivka has completed her PhD from RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine and Postdoctoral

studies from Taras Shevchenko National University of Kyiv. Currently she is a Professor of the Educational and Scientific Centre, Institute of Biology and Medicine

of Taras Shevchenko National University of Kyiv, Ukraine, Head of the Department of Microbiology and Immunology. Her area of scientific activity includes

immunomodulation as a component of adjuvant cancer therapy, functional polarization of phagocytes in the pathogenesis of inflammatory diseases.

realmed@i.com.ua

Larysa Skivka et al., J Cancer Sci Ther 2017, 9:11 (Suppl)

DOI: 10.4172/1948-5956-C1-117