scholarly journals Macrophage Colony-stimulating Factor Mediates the Recruitment of Macrophages in Triple negative Breast Cancer

2019 ◽  
Vol 15 (13) ◽  
pp. 2859-2871
Author(s):  
Xiaoqing Lu ◽  
Rui Yang ◽  
Lichao Zhang ◽  
Yanfeng Xi ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Doxorubicin resistance mediated by cytoplasmic macrophage colony-stimulating factor is associated with switch from apoptosis to autophagic cell death in MCF-7 breast cancer cells

2016 ◽  
Vol 241 (18) ◽  
pp. 2086-2093 ◽  
Author(s):  
Mengxia Zhang ◽  
Hailiang Zhang ◽  
Fan Tang ◽  
Yuhua Wang ◽  
Zhongcheng Mo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Colony Stimulating Factor ◽  
Doxorubicin Resistance ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Mcf 7

Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte–macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.

A Quantitative Systems Pharmacology Framework for Optimal Doxorubicin Granulocyte Colony-Stimulating Factor Regimens in Triple-Negative Breast Cancer

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Rosalba Vivian Paredes Bonilla ◽  
Fahima Nekka ◽  
Morgan Craig
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumour Growth ◽  
Triple Negative ◽  
Effective Control ◽  
Systems Pharmacology ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Quantitative Systems Pharmacology ◽  
Stimulating Factor

<b><i>Introduction:</i></b> To mitigate the risk of neutropenia during chemotherapy treatment of triple-negative breast cancer, prophylactic and supportive therapy with granulocyte colony-stimulating factor (G-CSF) is administered concomitant to chemotherapy. The proper timing of combined chemotherapy and G-CSF is crucial for treatment outcomes. <b><i>Methods:</i></b> Leveraging our established mathematical model of neutrophil production by G-CSF, we developed quantitative systems pharmacology (QSP) framework to investigate how modulating chemotherapy dose frequency and intensity can maximize antitumour effects. To establish schedules that best control tumour size while minimizing neutropenia, we combined Gompertzian tumour growth with pharmacokinetic/pharmacodynamic models of doxorubicin and G-CSF, and our QSP model of neutrophil production. <b><i>Results:</i></b> We optimized a range of chemotherapeutic cycle lengths and dose sizes to establish regimens that simultaneously reduced tumour burden while minimizing neutropenia. Our results suggest that cytotoxic chemotherapy with doxorubicin 45 mg/m<sup>2</sup> every 14 days provides effective control of tumour growth while mitigating neutropenic risks. <b><i>Conclusion:</i></b> This work suggests future avenues for optimal regimens of chemotherapy with prophylactic G-CSF support. Importantly, the algorithmic approach that we developed can aid in balancing the anticancer and the neutropenic effects of both drugs, and therefore contributes to rational considerations in clinical decision-making in triple-negative breast cancer.

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