



@article {3299,
	title = {Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells},
	journal = {Journal of Biomedical Nanotechnology},
	volume = {10},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {1416 - 1428},
	abstract = {Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer. Copyright {\textcopyright} 2014 American Scientific Publishers All rights reserved.},
	keywords = {Cetuximab, colon cancer, Docetaxel, Epidermal growth factor receptor, Poly(γ-glutamic acid) nanoparticles, Targeted nanomedicines},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899683740\&partnerID=40\&md5=39d65057952b3e192590262631867971},
	author = {Maya, S. and Sarmento, B. and Lakshmanan, V.-K. and Menon, D. and Jayakumar, R.}
}
@article {3270,
	title = {Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y 1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity},
	journal = {Oncogene},
	volume = {33},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {2123 - 2133},
	abstract = {The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration, proteolysis and activated intracellular signaling pathways. We demonstrated that macrophages stimulate cancer cell invasion, motility and migration, and that these effects depend on matrix metalloproteinase (MMP) activity and on the activation of epidermal growth factor receptor (EGFR) (at the residue Y 1086), PLC-γ (phospholipase C-gamma) and Gab1 (GRB2-associated binding protein-1), as evidenced by siRNA (small interference RNA) experiments. Epidermal growth factor (EGF)-immunodepletion impaired macrophage-mediated cancer cell invasion and motility, suggesting that EGF is the pro-invasive and pro-motile factor produced by macrophages. Macrophages also induced gastric and colorectal cancer cell phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity. Interestingly, whereas macrophage-mediated cancer cell c-Src and ERK1/2 phosphorylation occurred downstream EGFR activation, Akt phosphorylation seems to be a parallel event, taking place in an EGFR-independent manner. The involvement of EGF, EGFR-downstream signaling partners and MMPs in macrophage-mediated invasion provides novel insights into the molecular crosstalk established between cancer cells and macrophages, opening new perspectives for the design of new and more efficient therapeutic strategies to counteract cancer cell invasion. {\textcopyright} 2014 Macmillan Publishers Limited.},
	keywords = {cancer cell invasion, colon cancer, Gastric cancer, invasion-related signaling pathways, Macrophages, tumor microenvironment},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899425243\&partnerID=40\&md5=beff5192ff42940c75fef8b48ebd3ae7},
	author = {Cardoso, A.P. and Pinto, M.L. and Pinto, A.T. and Oliveira, M.I. and Pinto, M.T. and Gon{\c c}alves, R. and Relvas, J.B. and Figueiredo, C. and Seruca, R. and Mantovani, A. and Mareel, M. and Barbosa, M.A. and Oliveira, M.J.}
}
