FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4229050525> ?p ?o ?g. }

• W4229050525 abstract "Abstract Background Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer. Methods We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models. Results Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model. Conclusions In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies." @default.
• W4229050525 created "2022-05-08" @default.
• W4229050525 creator A5003848046 @default.
• W4229050525 creator A5007076553 @default.
• W4229050525 creator A5008777409 @default.
• W4229050525 creator A5014078497 @default.
• W4229050525 creator A5014481026 @default.
• W4229050525 creator A5020763381 @default.
• W4229050525 creator A5021375905 @default.
• W4229050525 creator A5024034968 @default.
• W4229050525 creator A5028332129 @default.
• W4229050525 creator A5038806823 @default.
• W4229050525 creator A5045415904 @default.
• W4229050525 creator A5050957879 @default.
• W4229050525 creator A5056373193 @default.
• W4229050525 creator A5064761712 @default.
• W4229050525 creator A5075863856 @default.
• W4229050525 date "2022-05-06" @default.
• W4229050525 modified "2023-10-07" @default.
• W4229050525 title "Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer" @default.
• W4229050525 cites W1581220495 @default.
• W4229050525 cites W1596163114 @default.
• W4229050525 cites W1655307540 @default.
• W4229050525 cites W1781167248 @default.
• W4229050525 cites W1968002492 @default.
• W4229050525 cites W1981222418 @default.
• W4229050525 cites W1990675339 @default.
• W4229050525 cites W1992772472 @default.
• W4229050525 cites W1995770815 @default.
• W4229050525 cites W2007347651 @default.
• W4229050525 cites W2009211019 @default.
• W4229050525 cites W2013262011 @default.
• W4229050525 cites W2048455086 @default.
• W4229050525 cites W2049233124 @default.
• W4229050525 cites W2068232829 @default.
• W4229050525 cites W2077255241 @default.
• W4229050525 cites W2079707111 @default.
• W4229050525 cites W2081374651 @default.
• W4229050525 cites W2090968329 @default.
• W4229050525 cites W2102310375 @default.
• W4229050525 cites W2105724560 @default.
• W4229050525 cites W2112121482 @default.
• W4229050525 cites W2114039233 @default.
• W4229050525 cites W2122874141 @default.
• W4229050525 cites W2127387778 @default.
• W4229050525 cites W2147414006 @default.
• W4229050525 cites W2147622445 @default.
• W4229050525 cites W2157130910 @default.
• W4229050525 cites W2164823502 @default.
• W4229050525 cites W2167279371 @default.
• W4229050525 cites W2168310809 @default.
• W4229050525 cites W2168368163 @default.
• W4229050525 cites W2216262028 @default.
• W4229050525 cites W2222086386 @default.
• W4229050525 cites W2368001341 @default.
• W4229050525 cites W2407374726 @default.
• W4229050525 cites W2524516638 @default.
• W4229050525 cites W2549628327 @default.
• W4229050525 cites W2572174216 @default.
• W4229050525 cites W2588916311 @default.
• W4229050525 cites W2617012077 @default.
• W4229050525 cites W2735527928 @default.
• W4229050525 cites W2739132742 @default.
• W4229050525 cites W2760661635 @default.
• W4229050525 cites W2762122558 @default.
• W4229050525 cites W2794577178 @default.
• W4229050525 cites W2795125879 @default.
• W4229050525 cites W2890261294 @default.
• W4229050525 cites W2892058240 @default.
• W4229050525 cites W2893690806 @default.
• W4229050525 cites W2897422388 @default.
• W4229050525 cites W2901320017 @default.
• W4229050525 cites W2902023274 @default.
• W4229050525 cites W2910221008 @default.
• W4229050525 cites W2926691411 @default.
• W4229050525 cites W2942828674 @default.
• W4229050525 cites W2971468927 @default.
• W4229050525 cites W2977579415 @default.
• W4229050525 cites W2998882776 @default.
• W4229050525 cites W3002902597 @default.
• W4229050525 cites W3006438030 @default.
• W4229050525 cites W3015655761 @default.
• W4229050525 cites W3017336166 @default.
• W4229050525 cites W3024629180 @default.
• W4229050525 cites W3092622132 @default.
• W4229050525 cites W3110005995 @default.
• W4229050525 cites W3119005666 @default.
• W4229050525 cites W3129982058 @default.
• W4229050525 cites W3146001933 @default.
• W4229050525 cites W3181592021 @default.
• W4229050525 cites W4210987384 @default.
• W4229050525 cites W68151451 @default.
• W4229050525 doi "https://doi.org/10.1186/s12885-022-09612-2" @default.
• W4229050525 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35513776" @default.
• W4229050525 hasPublicationYear "2022" @default.
• W4229050525 type Work @default.
• W4229050525 citedByCount "10" @default.
• W4229050525 countsByYear W42290505252022 @default.
• W4229050525 countsByYear W42290505252023 @default.
• W4229050525 crossrefType "journal-article" @default.

• next