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Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging

Subramanian, Nithya, Srimany, Amitava, Kanwar, Jagat R., Kanwar, Rupinder K., Akilandeswari, Balachandran, Rishi, Pukraj, Khetan, Vikas, Vasudevan, Madavan, Pradeep, Thalappil and Krishnakumar, Subramanian 2016, Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging, Molecular therapy : nucleic acids, vol. 5, no. 8, Article number : e358, pp. 1-11, doi: 10.1038/mtna.2016.70.

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Title Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging
Author(s) Subramanian, Nithya
Srimany, Amitava
Kanwar, Jagat R.
Kanwar, Rupinder K.
Akilandeswari, Balachandran
Rishi, Pukraj
Khetan, Vikas
Vasudevan, Madavan
Pradeep, Thalappil
Krishnakumar, Subramanian
Journal name Molecular therapy : nucleic acids
Volume number 5
Issue number 8
Season Article number : e358
Start page 1
End page 11
Total pages 11
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-08-30
Summary Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB.
Language eng
DOI 10.1038/mtna.2016.70
Field of Research 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy)
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution Non-Commercial No-Derivatives licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30087412

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.