نمایش پرونده ساده آیتم

dc.contributor.advisorMolavi, Ommoleila
dc.contributor.authorRashid, Mohsen
dc.date.accessioned2024-08-18T06:20:45Z
dc.date.available2024-08-18T06:20:45Z
dc.date.issued2024en_US
dc.identifier.urihttps://dspace.tbzmed.ac.ir:443/xmlui/handle/123456789/70959
dc.description.abstractPurpose: The immunosuppressive context of the tumor microenvironment (TME) is a significant hurdle in breast cancer (BC) treatment. Combinational therapies targeting cancer core signaling pathways involved in the induction of TME immunosuppressive milieu have emerged as a potent strategy to overcome immunosuppression in TME and enhance patient therapeutic outcomes. This study presents compelling evidence that targeting hypoxia-inducible-factor-1 alpha (Hif-1α) alongside chemotherapy and immune-inducing factors leads to substantial anticancer effects through modulation of TME. Methods: Chitosan (Cs)/Hif-1alpha siRNA nano-complex was synthesized by siRNA adsorption methods. Nanoparticles were fully characterized using dynamic light scattering and scanning electron microscope. Cs/HIF-1α siRNA cytotoxicity was measured by MTT assay. The anticancer effects of the combinational therapy were assessed in BALB/c bearing 4T1 tumors. qPCR and western blotting were applied to assess the expression of some key genes and proteins involved in the induction of immunosuppression in TME. Results: Hif-1α siRNA was successfully loaded in chitosan nanoparticles. Hif-1α siRNA nanocomplexes significantly inhibited the expression of Hif-1α (P < 0.001). Triple combination therapy (Paclitaxel (Ptx)+Imiquimod (Imq)+Cs/HIF-1α siRNA) inhibited tumor growth and downregulated cancer progression genes while upregulating cellular-immune-related cytokines (P < 0.001). Mice without Cs/HIF-1α siRNA treatments revealed fewer cancer inhibitory effects and more TME immunosuppressive factors. These results suggest that the inhibition of Hif-1α effects synergize with Ptx and Imq to inhibit cancer progression more significantly than other combinational treatments. Conclusion: Combining Hif-1α siRNA with Ptx and Imq is promising as a multimodality treatment. It has the potential to attenuate TME inhibitory effects and significantly enhance the immune system's ability to combat tumor cell growth, offering an inspiration of hope in the fight against BC. Keywords: TME, Combinational therapy, HIF-1α, Imiquimod, Paclitaxelen_US
dc.language.isofaen_US
dc.publisherTabriz University of Medical Sciences Faculty Of Advanced Medical Sciencesen_US
dc.relation.isversionofhttps://dspace.tbzmed.ac.ir:443/xmlui/handle/123456789/70958en_US
dc.subjectTMEen_US
dc.subjectCombinational therapyen_US
dc.subjectHIF-1αlen_US
dc.subjectImiquimoden_US
dc.subjectPaclitaxeen_US
dc.titleThe Effect of Combined Immunotherapy Using Chemotherapy, TLR7 agonist and HIF-1α inhibitor in Breast Cancer Mice modelen_US
dc.typeThesisen_US
dc.contributor.supervisorRamezani, Fatemeh
dc.contributor.supervisorBaradaran, Behzad
dc.contributor.departmentMolecular Medicineen_US
dc.description.disciplineMolecular Medicineen_US
dc.description.degreePh.Den_US


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