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10.1021/mp5002697

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C4186679!4186679!25179345
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suck abstract from ncbi


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pmid25179345      Mol+Pharm 2014 ; 11 (10): 3484-91
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  • Adjuvant Cationic Liposomes Presenting MPL and IL-12 Induce Cell Death, Suppress Tumor Growth, and Alter the Cellular Phenotype of Tumors in a Murine Model of Breast Cancer #MMPMID25179345
  • Meraz IM; Savage DJ; Segura-Ibarra V; Li J; Rhudy J; Gu J; Serda RE
  • Mol Pharm 2014[Oct]; 11 (10): 3484-91 PMID25179345show ga
  • Dendritic cells (DC) process and present antigens to T lymphocytes, inducing potent immune responses when encountered in association with activating signals, such as pathogen-associated molecular patterns. Using the 4T1 murine model of breast cancer, cationic liposomes containing monophosphoryl lipid A (MPL) and interleukin (IL)-12 were administered by intratumoral injection. Combination multivalent presentation of the Toll-like receptor-4 ligand MPL and cytotoxic 1,2-dioleoyl-3-trmethylammonium-propane lipids induced cell death, decreased cellular proliferation, and increased serum levels of IL-1? and tumor necrosis factor (TNF)-?. The addition of recombinant IL-12 further suppressed tumor growth and increased expression of IL-1?, TNF-?, and interferon-?. IL-12 also increased the percentage of cytolytic T cells, DC, and F4/80+ macrophages in the tumor. While single agent therapy elevated levels of nitric oxide synthase 3-fold above basal levels in the tumor, combination therapy with MPL cationic liposomes and IL-12 stimulated a 7-fold increase, supporting the observed cell cycle arrest (loss of Ki-67 expression) and apoptosis (TUNEL positive). In mice bearing dual tumors, the growth of distal, untreated tumors mirrored that of liposome-treated tumors, supporting the presence of a systemic immune response.
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