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Improved anti-tumor efficacy of paclitaxel in combination with MicroRNA-125b-based tumor-associated macrophage repolarization in epithelial ovarian cancer.


ABSTRACT: In epithelial ovarian cancers, the presence of tumor-associated macrophages (TAMs) is well correlated with the poor disease outcomes. TAMs are know to suppress the immune system, induce pro-tumoral functions and inhibit anti-tumor responses associated with chemotherapy. In this study, we have evaluated the synergistic efficacy of TAM repolarization and intraperitoneal paclitaxel in epithelial ovarian cancers. We demonstrate that hyaluronic acid-based nanoparticles encapsulating miR-125b (HA-PEI-miR-125b) can specifically target TAMs in the peritoneal cavity of a syngeneic ID8-VEGF ovarian cancer mouse model and can repolarize macrophages to an immune-activating phenotype. These HA-PEI-miR-125b nanoparticles in combination with intraperitoneal paclitaxel can enhance the anti-tumor efficacy of paclitaxel during the later stages of disease progression as seen by the significant reduction in the ascitic fluid and peritoneal VEGF levels. Furthermore, these HA-PEI-miR-125b nanoparticles do not induce systemic toxicity and thus warrant a further evaluation in the clinical setting.

SUBMITTER: Parayath NN 

PROVIDER: S-EPMC6682447 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Improved anti-tumor efficacy of paclitaxel in combination with MicroRNA-125b-based tumor-associated macrophage repolarization in epithelial ovarian cancer.

Parayath Neha N NN   Gandham Srujan Kumar SK   Leslie Fraser F   Amiji Mansoor M MM  

Cancer letters 20190706


In epithelial ovarian cancers, the presence of tumor-associated macrophages (TAMs) is well correlated with the poor disease outcomes. TAMs are know to suppress the immune system, induce pro-tumoral functions and inhibit anti-tumor responses associated with chemotherapy. In this study, we have evaluated the synergistic efficacy of TAM repolarization and intraperitoneal paclitaxel in epithelial ovarian cancers. We demonstrate that hyaluronic acid-based nanoparticles encapsulating miR-125b (HA-PEI-  ...[more]

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