Tumor-targeted gene therapy with lipid nanoparticles inhibits tumor-associated adipocytes and remodels the immunosuppressive tumor microenvironment in triple-negative breast cancer

2021 ◽  
Vol 6 (4) ◽  
pp. 319-329
Author(s):  
Yun Liu ◽  
Karthik Tiruthani ◽  
Menglin Wang ◽  
Xuefei Zhou ◽  
Nasha Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative ◽  
Lipid Nanoparticles ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Chemokine Ligand ◽  
Immunosuppressive Tumor Microenvironment ◽  
Targeted Gene Therapy ◽  
Chemokine Ligand 2

In breast cancer model, we identified C–C Motif Chemokine Ligand 2 (CCL2) as the key mediator which is secreted by tumor associated adipocytes, and developed targeted lipid-protamine-DNA (LPD) nanoparticles to locally “trap” CCL2 to ameliorate the immunosuppressive tumor microenvironment.

scholarly journals Combined targeting of Raf and Mek synergistically inhibits tumorigenesis in triple negative breast cancer model systems

Oncotarget ◽  
2017 ◽  
Vol 8 (46) ◽  
pp. 80804-80819 ◽  
Author(s):  
Teddy S. Nagaria ◽  
Changnian Shi ◽  
Charles Leduc ◽  
Victoria Hoskin ◽  
Soma Sikdar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Model Systems ◽  
Cancer Model ◽  
Breast Cancer Model

scholarly journals Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model

2020 ◽  
Vol 21 (10) ◽  
pp. 3479 ◽  
Author(s):  
Elisa Roda ◽  
Fabrizio De Luca ◽  
Carmine Di Iorio ◽  
Daniela Ratto ◽  
Stella Siciliani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Lentinula Edodes ◽  
Metastatic Breast ◽  
Medicinal Mushroom ◽  
Cancer Model ◽  
Pulmonary Tissue ◽  
Markers Of Inflammation ◽  
Breast Cancer Model ◽  
Mouse Breast Cancer

Although medicinal mushroom extracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the effect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care, consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes. The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in both supplemented and non-supplemented mice. After sacrifice 35 days later, specific endpoints and pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2, SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1 results were also discussed. These findings support the valuable potential of Micotherapy U-care as adjuvant therapy in the critical management of triple-negative breast cancer.

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