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Melanoma B16-F10 in sepsis surviving mice: role of tumor associated macrophages

Abstract

The description that post-sepsis patients develop immunosuppression has risen the interestabout this phenomenon. Recently, it has been established the role of T regulator lymphocytes, as well anti-inflammatory cytokines and alternatively activated macrophage. In that phase,established cancer could expand, possibly worsening outcomes. Tumor-associatedmacrophages (TAM) are key pieces in orchestrating immune escapes and tumoralprogression, characterizing a bad prognostic marker in many tumor types. Our hypothesis isthat this period may facilitate expansion of tumors through a TAM-dependent mechanism. Totest that hypothesis, sepsis will be induced in C57 mice by the cecal and ligation puncturemodel. In the 15th day after the procedure, the surviving or naïve animals will receive asubcutaneous inoculum of B16-F10-luc melanoma. Tumor progression will be measuredthrough volume and bioluminescent signal. In the 21st day after inoculation, TAM from naïveor post-septic mice will be isolated for RNA extraction and microarray for gene expressionprofiling. Representative differentially expressed genes will be confirmed through RT-PCR.Additionally, we will isolate bone marrow-derived macrophage from post-septic or naïvemice, in order to perform co-inoculation with B16 cells and evaluate the role of post-septicmacrophage in the neoplastic growth after sepsis. Data will be analyzed utilizing GraphPadPrism version 3.0. It will be considered significant P-values<0.05. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MOTA, JOSE M.; LEITE, CAIO A.; SOUZA, LUCAS E.; MELO, PAULO H.; NASCIMENTO, DANIELE C.; DE-DEUS-WAGATSUMA, VIRGINIA M.; TEMPORAL, JESSICA; FIGUEIREDO, FLORENCIO; NOUSHMEHR, HOUTAN; ALVES-FILHO, JOSE C.; CUNHA, FERNANDO Q.; REGO, EDUARDO M. Post-Sepsis State Induces Tumor-Associated Macrophage Accumulation through CXCR4/CXCL12 and Favors Tumor Progression in Mice. CANCER IMMUNOLOGY RESEARCH, v. 4, n. 4, p. 312-322, APR 2016. Web of Science Citations: 11.

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