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Full-Text Articles in Medicine and Health Sciences

Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way Aug 2013

Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way

Electronic Thesis and Dissertation Repository

RNAi (RNA interference) is emerging as a promising tool for cancer therapy. Small interfering RNA (siRNA) molecules are activated in that pathway to reduce specific tumour cell RNAs that mediate malignancy. SiRNA treatment has been primarily limited to in vitro studies: lack of efficient, preferential in vivo delivery to target cells remains a major obstacle. Many human tumours overexpress folate receptors (FR), and siRNA-mediated reduction of thymidylate synthase (TS) sensitizes tumour cells to anti-TS drugs. I developed a folate-containing cationic liposome to preferentially deliver anti-TS siRNA to FR-expressing human tumour cells. I show, in vitro, that liposome-encapsulated siRNA (but …


Β-Estradiol-Dependent Activation Of The Jak/Stat Pathway Requires P/Cip And Carm1, N. Coughlan, G. Thillainadesan, J. Andrews, M. Isovic, J. Torchia Jun 2013

Β-Estradiol-Dependent Activation Of The Jak/Stat Pathway Requires P/Cip And Carm1, N. Coughlan, G. Thillainadesan, J. Andrews, M. Isovic, J. Torchia

Paediatrics Publications

The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 (CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/CARM1 complex. Following E2-treatment, histone …