Garkavtsev, Igor, MD, PhD

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Cancer Metastasis

Our research focuses on mechanisms governing the development of brain tumors, with primary emphasis on the identification and character-ization of novel tumor sup-pressor genes. We are particularly interested in understanding how these genes are involved in the regulation of brain tumor angiogenesis and invasion. A detailed understanding of this regulation may lead to the rational selection of molecular targets for anti-cancer drug development.

Gliomas are the most common primary tumors of the central nervous system, with nearly 15,000 diagnosed annually in the U.S. and a mortality approaching 80% within the first year after diagnosis. Malignant gliomas are very aggressive, highly invasive, and one of the deadliest of human cancers. Glioblastomas have been linked to the inactivation of the

ING4 tumor suppressor gene

The predicted amino acid sequence revealed that ING4 encodes a protein containing 249 amino acids with a molecular mass of 29 kDa. ING4 expression is significantly diminished in gliomas compared to normal human brain tissue, and the extent of reduction correlates with tumor progression from lower to higher grades of tumors. We have shown that ING4 is a component of the NF-kB signaling pathway and that ING4 regulates brain tumor angiogenesis through transcriptional repression of the NF- kB target genes. The molecular mechanisms underlying upstream regulation and interaction of this gene with other brain tumor suppressors are under investigation.

Selected Publications (from total of 25)

Gupta N, Badeaux M, Liu Y, Naxerova K, Sgroi D, Munn LL, Jain RK, Garkavtsev I
Stress granule-associated protein G3BP2 regulates breast tumor initiation.
Proc Natl Acad Sci U S A. 2017;114(5):1033-1038 - PMID: 28096337 - PMCID: PMC5293063
Han S, Ma X, Zhao Y, Zhao H, Batista A, Zhou S, Zhou X, Yang Y, Wang T, Bi J, Xia Z, Bai Z, Garkavtsev I, Zhang Z
Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer.
Oncotarget. 2016;7(28):44406-44416 - PMID: 27259271 - PMCID: PMC5190106
Wong HK, Shimizu A, Kirkpatrick ND, Garkavtsev I, Chan AW, di Tomaso E, Klagsbrun M, Jain RK
Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism.
Neoplasia. 2012;14(2):84-94 - PMID: 22431917 - PMCID: PMC3306254
Garkavtsev I, Chauhan VP, Wong HK, Mukhopadhyay A, Glicksman MA, Peterson RT, Jain RK
Dehydro-alpha-lapachone, a plant product with antivascular activity.
Proc Natl Acad Sci U S A. 2011;108(28):11596-601 - PMID: 21709229 - PMCID: PMC3136298
Perentes JY, Kirkpatrick ND, Nagano S, Smith EY, Shaver CM, Sgroi D, Garkavtsev I, Munn LL, Jain RK, Boucher Y
Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors.
Cancer Res. 2011;71(13):4527-38 - PMID: 21571860
Nelson GM, Padera TP, Garkavtsev I, Shioda T, Jain RK
Differential gene expression of primary cultured lymphatic and blood vascular endothelial cells.
Neoplasia. 2007;9(12):1038-45 - PMID: 18084611 - PMCID: PMC2137938
Kozin SV, Winkler F, Garkavtsev I, Hicklin DJ, Jain RK, Boucher Y
Human tumor xenografts recurring after radiotherapy are more sensitive to anti-vascular endothelial growth factor receptor-2 treatment than treatment-naive tumors.
Cancer Res. 2007;67(11):5076-82 - PMID: 17545583
Garkavtsev I, Boucher Y
An intact ING1-P53 pathway can potentiate the cytotoxic effects of taxol.
Cancer Biol Ther. 2005;4(1):48-9 - PMID: 15711122
Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK
Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.
Cancer Cell. 2004;6(6):553-63 - PMID: 15607960
Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK
The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis.
Nature. 2004;428(6980):328-32 - PMID: 15029197
Fukumura D, Ushiyama A, Duda DG, Xu L, Tam J, Krishna V, Chatterjee K, Garkavtsev I, Jain RK
Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis.
Circ Res. 2003;93(9):e88-97 - PMID: 14525808 - PMCID: PMC2755542
Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N
A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).
FEBS Lett. 2002;524(1-3):163-71 - PMID: 12135761
Garkavtsev I
Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation
Nat Genet. 1999;23(3):373 - PMID: 10545957
Toyama T, Iwase H, Watson P, Muzik H, Saettler E, Magliocco A, DiFrancesco L, Forsyth P, Garkavtsev I, Kobayashi S, Riabowol K
Suppression of ING1 expression in sporadic breast cancer.
Oncogene. 1999;18(37):5187-93 - PMID: 10498868
Garkavtsev I, Hull C, Riabowol K
Molecular aspects of the relationship between cancer and aging: tumor suppressor activity during cellular senescence.
Exp Gerontol. 1998;33(1-2):81-94 - PMID: 9467719
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