Aim 1: Assessment of repair efficiency of single and clustered oxidatively-induced DNA lesions
(SSBs, AP sites and oxidized bases, OCDLs) in a panel of DSBR deficient human tumor cell
lines after a challenging ‘low’ dose of γ-rays.
MCF-7 (BRCA1 wild type) and HCC1937 (truncated BRCA1) human breast cancer cells, human
glioblastoma MO59K (DNA-PKcs+/+ proficient) and its isogenic MO59J (DNAPKcs -/- deficient) will
be exposed to different levels of oxidative stress i.e., ‘low’ doses of γ-rays (2-4 Gy) and repair of all
DNA lesions will be studied analytically. As positive controls, complementary experiments will be
also performed using cells with BRCA1 knockdown expression (MCF-7) and cells treated with the
specific DNA-PKcs kinase activity inhibitors IC86621/NU7026 (M059K). Through the proposed
experiments we will test directly our hypothesis that a DSBR deficiency can also lead to compromised
processing of single or clustered non-DSB oxidative DNA lesions not expected to be repaired by
DSBR pathways.
Aim 2: Investigation of the effects of DNA-PKcs/BRCA1 knockdown or inhibition of base
excision repair (BER) and other DNA repair pathways. The design of this aim is driven by the
need for more biochemical and mechanistic insights into the OCDL repair mechanisms and the
involvement of BRCA1/DNA-PK proteins.
Our hypothesis is that under a DNA-PKcs/BRCA1 deficiency we will detect a reduction in the
expression of several BER or nucleotide excision repair (NER) proteins (based also on our
preliminary studies).
Publications
Biography - Featuring the special issue editor: Professor Alexandros G. Georgakilas.
Georgakilas AG.
Cancer Lett. 2014 Apr 3. pii: S0304-3835(14)00196-7. doi: 10.1016/j.canlet.2014.03.027.
[Epub ahead of print]
PMID:
24705307
[PubMed - as supplied by publisher]
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Select item 24704295
2.
Bystander and non-targeted effects: A unifying model from ionizing radiation to cancer.
Georgakilas AG.
Cancer Lett. 2014 Apr 2. pii: S0304-3835(14)00201-8. doi: 10.1016/j.canlet.2014.03.032.
[Epub ahead of print] No abstract available.
PMID:
24704295
[PubMed - as supplied by publisher]
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Select item 24333869
3.
Non-targeted radiation effects in vivo: A critical glance of the future in radiobiology.
Hatzi VI, Laskaratou DA, Mavragani IV, Nikitaki Z, Mangelis A, Panayiotidis MI, Pantelias
GE, Terzoudi GI, Georgakilas AG.
Cancer Lett. 2013 Dec 13. pii: S0304-3835(13)00828-8. doi: 10.1016/j.canlet.2013.11.018.
[Epub ahead of print]
PMID:
24333869
[PubMed - as supplied by publisher]
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4.
Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs.
Yang G, Nowsheen S, Aziz K, Georgakilas AG.
Pharmacol Ther. 2013 Sep;139(3):392-404. doi: 10.1016/j.pharmthera.2013.05.005. Epub
2013 May 24. Review.
PMID:
23711794
[PubMed - indexed for MEDLINE]
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Select item 23682596
5.
Induction and repair of clustered DNA lesions: what do we know so far?
Georgakilas AG, O'Neill P, Stewart RD.
Radiat Res. 2013 Jul;180(1):100-9. doi: 10.1667/RR3041.1. Epub 2013 May 17. Review.
PMID:
23682596
[PubMed - indexed for MEDLINE]
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Select item 23523616
6.
Tetramethylpyrazine (TMP) protects cerebral neurocytes and inhibits glioma by down
regulating chemokine receptor CXCR4 expression.
Chen Z, Pan X, Georgakilas AG, Chen P, Hu H, Yang Y, Tian S, Xia L, Zhang J, Cai X, Ge
J, Yu K, Zhuang J.
Cancer Lett. 2013 Aug 19;336(2):281-9. doi: 10.1016/j.canlet.2013.03.015. Epub 2013 Mar
21.
PMID:
23523616
[PubMed - indexed for MEDLINE]
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Select item 22634493
7.
Epigenetic inactivation of DNA repair in breast cancer.
Nowsheen S, Aziz K, Tran PT, Gorgoulis VG, Yang ES, Georgakilas AG.
Cancer Lett. 2014 Jan 28;342(2):213-22. doi: 10.1016/j.canlet.2012.05.015. Epub 2012 May
23. Review.
PMID:
22634493
[PubMed - indexed for MEDLINE]
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Select item 22484468
8.
Oxidative stress, DNA damage and repair in carcinogenesis: have we established a
connection?
Georgakilas AG.
Cancer Lett. 2012 Dec 31;327(1-2):3-4. doi: 10.1016/j.canlet.2012.03.032. Epub 2012 Apr 3.
PMID:
22484468
[PubMed - indexed for MEDLINE]
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9.
Featuring the special issue editor: associate professor Alexandros G. Georgakilas.
Georgakilas AG.
Cancer Lett. 2012 Dec 31;327(1-2):1-2. doi: 10.1016/j.canlet.2012.03.012. Epub 2012 Mar
20.
PMID:
22445907
[PubMed - indexed for MEDLINE]
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10.
Pleiotrophic effects of natural products in ROS-induced carcinogenesis: the role of plantderived natural products in oral cancer chemoprevention.
Ziech D, Anestopoulos I, Hanafi R, Voulgaridou GP, Franco R, Georgakilas AG, Pappa A,
Panayiotidis MI.
Cancer Lett. 2012 Dec 31;327(1-2):16-25. doi: 10.1016/j.canlet.2012.02.025. Epub 2012 Feb
28. Review.
PMID:
22381695
[PubMed - indexed for MEDLINE]
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Select item 22303842
11.
Biomarkers of oxidative stress and cancer: from chemistry, biology to clinical applications
and personalized therapy.
Georgakilas AG, Panayiotidis MI.
Curr Mol Med. 2012 Jul 1;12(6):653-4. No abstract available.
PMID:
22303842
[PubMed - indexed for MEDLINE]
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12.
Oxidative stress based-biomarkers in oral carcinogenesis: how far have we gone?
Hanafi R, Anestopoulos I, Voulgaridou GP, Franco R, Georgakilas AG, Ziech D, MalamouMitsi V, Pappa A, Panayiotidis MI.
Curr Mol Med. 2012 Jul 1;12(6):698-703. Review.
PMID:
22292437
[PubMed - indexed for MEDLINE]
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13.
Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins.
Sideridou M, Zakopoulou R, Evangelou K, Liontos M, Kotsinas A, Rampakakis E, Gagos S,
Kahata K, Grabusic K, Gkouskou K, Trougakos IP, Kolettas E, Georgakilas AG, Volarevic
S, Eliopoulos AG, Zannis-Hadjopoulos M, Moustakas A, Gorgoulis VG.
J Cell Biol. 2011 Dec 26;195(7):1123-40. doi: 10.1083/jcb.201108121.
PMID:
22201124
[PubMed - indexed for MEDLINE]
Free PMC Article
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14.
Targeting DNA damage and repair: embracing the pharmacological era for successful cancer
therapy.
Aziz K, Nowsheen S, Pantelias G, Iliakis G, Gorgoulis VG, Georgakilas AG.
Pharmacol Ther. 2012 Mar;133(3):334-50. doi: 10.1016/j.pharmthera.2011.11.010. Epub
2011 Dec 14. Review.
PMID:
22197993
[PubMed - indexed for MEDLINE]
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15.
Molecular markers for cancer prognosis and treatment: have we struck gold?
Nowsheen S, Aziz K, Panayiotidis MI, Georgakilas AG.
Cancer Lett. 2012 Dec 31;327(1-2):142-52. doi: 10.1016/j.canlet.2011.11.022. Epub 2011
Nov 25. Review.
PMID:
22120674
[PubMed - indexed for MEDLINE]
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Results so far