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Your search keyword '"Alexander JF"' showing total 2 results
Start Over Author "Alexander JF" Journal cancer letters
2 results on '"Alexander JF"'

1. Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma.

Author

Borsoi C, Leonard F, Lee Y, Zaid M, Elganainy D, Alexander JF, Kai M, Liu YT, Kang Y, Liu X, Koay EJ, Ferrari M, Godin B, and Yokoi K

Subjects
Albumin-Bound Paclitaxel chemistry, Animals, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic metabolism, Apoptosis drug effects, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Caveolin 1 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Deoxycytidine pharmacology, Drug Compounding, Humans, Male, Mice, Nude, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Time Factors, Tumor Burden drug effects, Up-Regulation, Xenograft Model Antitumor Assays, Gemcitabine, Albumin-Bound Paclitaxel metabolism, Antimetabolites, Antineoplastic pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Carcinoma, Pancreatic Ductal drug therapy, Deoxycytidine analogs & derivatives, Drug Carriers, Drug Resistance, Neoplasm, Nanoparticles, Pancreatic Neoplasms drug therapy
Abstract

The mechanism for improved therapeutic efficacy of the combination therapy with nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb-PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also caused a substantial increase in tumor PTX accumulation, significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up-regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX in the tumor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2017
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2. Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers.

Author

Yokoi K, Godin B, Oborn CJ, Alexander JF, Liu X, Fidler IJ, and Ferrari M

Subjects
Animals, Antigens, Ly biosynthesis, Antigens, Ly metabolism, Antineoplastic Agents pharmacokinetics, Apoptosis drug effects, CD59 Antigens biosynthesis, CD59 Antigens metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Drug Delivery Systems methods, Endothelial Cells drug effects, Endothelial Cells pathology, Female, Humans, Macrophages drug effects, Macrophages pathology, Male, Mice, Mice, Nude, Pancreatic Neoplasms pathology, Silicon pharmacokinetics, Antineoplastic Agents administration & dosage, Endothelial Cells metabolism, Macrophages metabolism, Nanostructures administration & dosage, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms metabolism, Silicon administration & dosage
Abstract

Pancreatic cancer is a highly fatal disease characterized by a dominant stroma formation. Exploring new biological targets, specifically those overexpressed in stroma cells, holds significant potential for the design of specific nanocarriers to attain homing of therapeutic and imaging agents to the tumor. In clinical specimens of pancreatic cancer, we found increased expression of CD59 in tumor associated endothelial cells as well as infiltrating cells in the stroma as compared to uninvolved pancreas. We explored this dual targeting effect using orthotopic human pancreatic cancer in nude mice. By immunofluorescence analysis, we confirmed the increased expression of Ly6C, mouse homolog of CD59, in tumor associated endothelial cells as well as in macrophages within the stroma. We decorated the surface of porous silicon nanocarriers with Ly6C antibody. Targeted nanocarriers injected intravenously accumulated to tumor associated endothelial cells within 15min. At 4h after administration, 9.8±2.3% of injected dose/g tumor of the Ly6C targeting nanocarriers accumulated in the pancreatic tumors as opposed to 0.5±1.8% with non-targeted nanocarriers. These results suggest that Ly6C (or CD59) can serve as a novel dual target to deliver therapeutic agents to the stroma of pancreatic tumors., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Published
2013
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