The radiosensitivity of endothelial cells isolated from human breast cancer and normal tissue in vitro

2012 ◽  
Vol 84 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Moon-Taek Park ◽  
Eun-Taex Oh ◽  
Min-Jeong Song ◽  
Woo-Jean Kim ◽  
Young Up Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Human Breast Cancer ◽  
Normal Tissue ◽  
Human Breast

scholarly journals Damage to cardiac vasculature may be associated with breast cancer treatment-induced cardiotoxicity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rebecca K. Hoffman ◽  
Bang-Jin Kim ◽  
Payal D. Shah ◽  
Joseph Carver ◽  
Bonnie Ky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Ejection Fraction ◽  
Cancer Treatment ◽  
Human Breast Cancer ◽  
Breast Cancer Treatment ◽  
Human Breast ◽  
Lv Mass ◽  
Lv Ejection Fraction

Abstract Background Breast cancer is the most common female cancer worldwide. Effective therapies including doxorubicin and trastuzumab have improved survival, but are associated with a substantial risk of cardiovascular disease. Mechanisms underlying cancer treatment-induced cardiotoxicity (CTC) are poorly understood and have largely focused on cardiomyocyte damage, although other cellular populations in the heart such as the cardiac endothelium, may play an important role in cardiac damage. We treated a breast tumor-bearing mouse model with doxorubicin and trastuzumab to investigate the role of the cardiac endothelium in the development of CTC. Methods Immune compromised mice were inoculated in the 4th mammary fat pad with human breast cancer cells overexpressing HER2 (BT474). When tumors were palpable, mice were treated weekly with doxorubicin (5 mg/kg) and trastuzumab (4 mg/kg). The cardiac phenotype of mice was assessed by echocardiography and histological evaluation of the heart. Cardiac vascular damage was assayed by in vivo permeability assays and primary cultures of murine cardiac endothelial cells were used to assay doxorubicin toxicity in vitro. Results The growth of BT474 breast tumors in Balb/c Nude mice was suppressed upon treatment with doxorubicin and trastuzumab. Mice treated for 4 months with doxorubicin and trastuzumab maintained body weights, but demonstrated an echocardiographic phenotype consistent with preserved left ventricular (LV) ejection fraction, decreased LV mass and increased filling pressures (E/e’). Histological staining with Masson’s trichrome and Picrosirius red showed extensive fibrosis and increased collagen deposition in the ventricular myocardium surrounding blood vessels of treated mice compared to untreated mice. Evans blue permeability assays demonstrated increased cardiac vasculature permeability while primary cardiac endothelial cells exposed to doxorubicin in vitro showed increased cell death as compared to lung or liver endothelial cells. Conclusions An orthotopic mouse model of human breast cancer in Nude mice treated with doxorubicin and trastuzumab resulted in a cardiac vascular defect accompanied by preserved LV ejection fraction, decreased LV mass, suggesting mild diastolic dysfunction and cardiac remodeling consistent with subclinical cardiotoxicity. Our data suggest that cardiac endothelium is more sensitive to doxorubicin therapy as compared to other organ endothelium and cardiac endothelial damage may correlate with breast cancer treatment-induced cardiotoxicity.

scholarly journals Nucleocytoplasmic distribution of S6K1 depends on the density and motility of MCF-7 cells in vitro

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1332 ◽  
Author(s):  
Viktoriia Kosach ◽  
Kateryna Shkarina ◽  
Anastasiia Kravchenko ◽  
Yuliia Tereshchenko ◽  
Evelina Kovalchuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Subcellular Localization ◽  
Human Breast Cancer ◽  
Normal Tissue ◽  
Growth Surface ◽  
Human Breast ◽  
Multicellular Spheroids ◽  
Immunofluorescence Analysis ◽  
Mcf 7

Background: The ribosomal protein S6 kinase 1 (S6K1) is one of the main components of the mTOR/S6K signal transduction pathway, which controls cellular metabolism, autophagy, growth, and proliferation. Overexpression of S6K1 was detected in tumors of different origin including breast cancer, which was associated with a worse disease outcome. In addition, significant accumulation of S6K1 was found in the nuclei of breast carcinoma cells suggesting the implication of kinase nuclear substrates in tumor progression. However, this aspect of S6K1 functioning is poorly understood. The main aim of the present work was to study the subcellular localization of S6K1 in breast cancer cells with focus on cell migration. Methods: Multicellular spheroids of MCF-7 cells were generated using agarose-coated Petri dishes. Cell migration was initiated by spheroids seeding onto growth surface and subsequent cultivation for 24 and 72 hours. S6K1 subcellular localization was studied in human breast cancer and normal tissue, 2D and 3D MCF-7 cell culture using immunofluorescence analysis and confocal microscopy. Results: Analysis of histological sections of human breast cancer and normal tissue revealed predominantly nuclear localization of S6K1 in breast malignant cells and mainly cytoplasmic one in conditionally normal cells. In vitro studies of MCF-7 cells showed that the subcellular localization of S6K1 depends on the cell density in the monolayer culture. S6K1 relocalization from the cytoplasm into the nucleus was detected in MCF-7 cells migrating from multicellular spheroids onto growth surface. Immunofluorescence analysis of S6K1 and immunocoprecipitation assay revealed the colocalization and interaction between S6K1 and transcription factor TBR2 (T-box brain protein 2) in MCF-7 cells. Bioinformatical analysis revealed existence of several phosphorylation sites in TBR2 for S6K1 suggesting that TBR2 can be a target for phosphorylation and regulation by S6K1. Conclusions: Subcellular localization of S6K1 depends on the density and locomotor activity of the MCF-7 cells.

Clomiphene Analogs with Activity In Vitro and In Vivo against Human Breast Cancer Cells

1998 ◽  
Vol 55 (6) ◽  
pp. 841-851 ◽  
Author(s):  
R.Jeffrey Baumann ◽  
Tammy L. Bush ◽  
Doreen E. Cross-Doersen ◽  
Elizabeth A. Cashman ◽  
Paul S. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast
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