Quantitative immunohistochemistry for evaluating the distribution of Ki67 and other biomarkers in tumor sections and use of the method to study repopulation in xenografts after treatment with paclitaxel.

Neoplasia : an International Journal for Oncology Research
Andrea S FungIan F Tannock

Abstract

Surviving cells may repopulate tumors between courses of chemotherapy, thereby reducing the effectiveness of treatment. Using a novel quantitative method, we characterize the influence of the tumor microenvironment on repopulation of surviving cells in human tumor xenografts after paclitaxel treatment and evaluate the potential of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, to inhibit repopulation. High-EGFR-expressing A431 xenografts and low-EGFR-expressing MCF-7 xenografts were treated with paclitaxel or gefitinib. Time-dependent changes in cell proliferation (Ki67) and apoptosis (cleaved caspase 3) in relation to total and functional tumor blood vessels (recognized by CD31 and a flow marker), and regions of hypoxia (recognized by EF5) were quantified using fluorescence microscopy. Decrease in functional tumor vasculature and in cell proliferation and increase in apoptosis were observed in A431 xenografts after treatment with either paclitaxel or gefitinib. There was a rebound in functional vasculature and cell proliferation ≈ 12 days after treatment with paclitaxel, and repopulation was observed from tumor cells close to regions of hypoxia. Cell proliferation increased ≈ 5 days after the last dose of gef...Continue Reading

Citations

Feb 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paz de la TorreAna I Flores
May 28, 2019·Cancer Biology & Therapy·Xinjian MaoKevin O Hicks
Dec 18, 2013·International Journal of Cancer. Journal International Du Cancer·Jasdeep K Saggar, Ian F Tannock
May 30, 2013·PloS One·Nilasha BanerjeeChristine Allen
Jan 26, 2013·Molecular Cancer Therapeutics·Jasdeep K SaggarIan F Tannock
Feb 14, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jasdeep K Saggar, Ian F Tannock

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