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J Neurooncol ; 146(3): 417-426, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32020472


INTRODUCTION: The failure of immune checkpoint inhibitor (ICPi) on glioblastoma (GBM) treatment underscores the need for improving therapeutic strategy. We aimed to change tumor associated macrophage (TAM) from M2 type (anti-inflammatory) to M1 (pro-inflammatory) type to increase the therapeutic response of ICPi. We proposed that combined rapamycin (R) and hydroxychloroquine (Q) preferentially induce M2 cells death, as fatty acid oxidation was their major source of energy. METHODS: Macrophage polarization was characterized on mice and human macrophage cell lines by specific cytokines stimulation with or without RQ treatment under single culture or co-culture with GBM cell lines. Tumor sizes were evaluated on subcutaneous and intracranial GL261 mice models with or without RQ, anti-PD1 mAb treatment. Tumor volumes assessed by MRI scan and proportions of tumor infiltrating immune cells analyzed by flow cytometry were compared. RESULTS: In vitro RQ treatment decreased the macrophages polarization of M2, increased the phagocytic ability, and increased the lipid droplets accumulation. RQ treatment decreased the expression levels of CD47 and SIRPα on tumor cells and macrophage cells in co-culture experiments. The combination of RQ and anti-PD1 treatment was synergistic in action. Enhanced the intra-tumoral M1/M2 ratio, the CD8/CD4 ratio in the intracranial GL261 tumor model after RQ treatment were evident. CONCLUSION: We provide a rationale for manipulating the macrophage phenotype and increased the therapeutic effect of ICPi. To re-educate and re-empower the TAM/microglia opens an interesting avenue for GBM treatment.

Medicine (Baltimore) ; 98(4): e14205, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681595


RATIONALE: Traumatic hemipelvectomy is a rare but lethal catastrophic injury. PATIENT CONCERNS: A case of a very young child with open fracture of left sacroiliac joint dislocation and pubic symphysis diastasis, suffered from a severe large-size soft tissue defects. DIAGNOSIS: Traumatic hemipelvectomy. INTERVENTIONS: Complete amputation was performed and three kinds of surgical techniques including regulated negative pressure-assisted wound therapy (RNPT), TopClosure device, and Ilizarov technique were jointly utilized to secure closure in the further revisions of the soft tissue injury and reconstruct reconstructive surgery. OUTCOMES: Six months after hospital discharge, the patient was able to ambulate with a single limb and a prosthesis and she is independent in many activities of daily living currently. LESSONS: We report this case to share experience with other clinicians in the management of this deadly extensive defects after traumatic hemipelvectomy in patients.

Amputação Traumática/cirurgia , Fraturas Expostas/cirurgia , Técnica de Ilizarov , Luxações Articulares/cirurgia , Tratamento de Ferimentos com Pressão Negativa/métodos , Diástase da Sínfise Pubiana/cirurgia , Articulação Sacroilíaca/lesões , Lesões dos Tecidos Moles/cirurgia , Amputação Traumática/complicações , Pré-Escolar , Feminino , Fraturas Expostas/etiologia , Humanos , Luxações Articulares/etiologia , Diástase da Sínfise Pubiana/etiologia , Articulação Sacroilíaca/cirurgia , Lesões dos Tecidos Moles/etiologia