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Full-Text Articles in Medicine and Health Sciences

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu Nov 2015

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu

Doctoral Dissertations

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …


Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao Aug 2015

Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao

Dissertations & Theses (Open Access)

Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment …


Co-Targeting Of Cyclooxygenase-2 And Foxm1 Is A Viable Strategy In Inducing Anticancer Effects In Colorectal Cancer Cells, Maqbool Ahmed, Azhar Hussain, Abdul K. Siraj, Shahab Uddin, Nasser Al-Sanea, Fouad Al-Dayel, Mohammed Al-Assiri, Shaham Beg, Khawla S. Al-Kuraya Jan 2015

Co-Targeting Of Cyclooxygenase-2 And Foxm1 Is A Viable Strategy In Inducing Anticancer Effects In Colorectal Cancer Cells, Maqbool Ahmed, Azhar Hussain, Abdul K. Siraj, Shahab Uddin, Nasser Al-Sanea, Fouad Al-Dayel, Mohammed Al-Assiri, Shaham Beg, Khawla S. Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Background: Cross-talk between deregulated signaling pathways in cancer cells causes uncontrolled growth and proliferation. These cancers cells become more aggressive and quickly develop resistance to therapy. Therefore targeting of these deregulated pathways simultaneously can result in efficient cell death of cancer cells. In this study we investigated co-expression of Cox-2 and FoxM1 in a cohort of colorectal carcinoma (CRC) samples and also examined whether inhibition of Cox-2 and FoxM1 simultaneously can lead to inhibition of cell viability and induction of apoptosis in colorectal cancer cell lines and in vivo xenograf
Methods: Protein expression of Cox-2 and FoxM1 was determined …