当前位置： SCI文献检索 > BMC CANCER期刊下所有文献 > Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer.

Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer.

Abstract：

BACKGROUND:Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. METHODS:Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes. RESULTS:The mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT. CONCLUSIONS:Our data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Mohammad AS,Adkins CE,Shah N,Aljammal R,Griffith JIG,Tallman RM,Jarrell KL,Lockman PR

doi

10.1186/s12885-018-5115-x

subject

Has Abstract

pub_date

2018-12-07 00:00:00

pages

1225

issue

issn

1471-2407

pii

10.1186/s12885-018-5115-x

journal_volume

pub_type

杂志文章

在线工具

Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer.