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Author John, Constance M. ♦ Leffler, Hakon ♦ Kahl-Knutsson, Barbro ♦ Svensson, Inga ♦ Jarvis, Gary A.
Source CiteSeerX
Content type Text
File Format PDF
Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Subject Keyword Orthotopic Nude Mouse Model ♦ Galectin-3 Inhibits Tumor Growth ♦ Nude Mouse ♦ Human Breast Cancer1 ♦ Organ Biodistribution Study ♦ Breast Cancer ♦ Primary Tumor ♦ Mean Tumor Volume ♦ Overt Adverse Effect ♦ Vehicle Control ♦ Collagenase Enzyme Digestion ♦ Recombinant Human Galectin-3 ♦ Cellular Fraction ♦ Experimental Design ♦ Treated Group ♦ Efficacy Study ♦ Potential Therapeutic Agent ♦ Breast Cancer Cell Line Mda-mb-435 ♦ Escherichia Coli ♦ Tumor Volume ♦ Mg Kg ♦ Elimination Half-life ♦ Control Mouse ♦ Lymph Node Metastasis ♦ Tumor Growth ♦ Human Breast Cancer ♦ Control Group
Abstract Purpose: The goal of this research was to evaluate a potential therapeutic agent for breast cancer based on ga-lectin-3 that has been implicated in tumorigenicity and me-tastasis of breast cancer. The hypothesis was that therapy with NH2-terminally truncated form of galectin-3 (galectin-3C) will be efficacious for reduction in tumor growth and for inhibition of metastases. Experimental Design: Recombinant human galectin-3 was produced in Escherichia coli from which galectin-3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and organ biodistribution studies were performed in nude mice. For efficacy studies, nude mice bearing orthotopically implanted tumors derived from breast cancer cell line MDA-MB-435 were treated with ga-lectin-3C or a vehicle control i.m. twice daily for 90 days. Results: The maximum tolerated dose of galectin-3C in nude mice was determined to be>125 mg/kg without overt adverse effects. The elimination half-life when administered i.m. was found to be 3.0 h in the serum and 4.3 h in the cellular fraction of the blood. Organ biodistribution studies revealed that galectin-3C localized in the liver, kidneys, and spleen but not in the heart or lungs. We found that the mean tumor volumes and weights were statistically significantly less in mice treated with galectin-3C compared with control mice, and that fewer numbers of mice exhibited lymph node metastases in the treated group compared with the control group. Conclusions: Galectin-3C is not overtly toxic, and is efficacious in reducing metastases and tumor volumes and weights in primary tumors in an orthotopic nude mouse model of human breast cancer.
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study