Correction to: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells.

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IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells.

BACKGROUND: Natural killer (NK) cells are an emerging new tool for cancer immunotherapy. To develop NK cell therapeutics from peripheral blood mononuclear cells (PBMCs) of healthy donors, substantial expansion of primary NK cells is necessary because of the very low number of these cells in peripheral blood. In this study, we aimed to investigate the effect of various cytokine alone or combinations, in expanded NK cells and to analyze the synergetic effect of cytokine combinations. METHODS: Human NK cells were isolated from healthy donor PBMC. Purified NK cells were stimulated with single cytokines or combinations of IL-2, IL-15, IL-18, and IL-27. The expanded NK cells were characterized by flow cytometry, cytotoxicity assay, calcein AM assay and Western blot. RESULTS: We investigated the synergistic effects of each cytokine, namely, IL-2, IL-15, IL-18, and IL-27, on human NK cells isolated from PBMCs of healthy donors and cultured for 21 days. We identified that IL-15/IL-18/IL-27-mediated activation of NK cells most potently increased NK cell proliferation, cytotoxicity, and IFN-É£ secretion compared with the activation observed with other treatments, including IL-2, IL-15, and IL-15/IL-18. Additionally, the expression of DNAM-1, NKG2D, CD69, and natural cytotoxicity receptors (NCRs; NKp30 and NKp44) increased on day 21 compared to that on day 0, demonstrating the activation of NK cells. In vitro, expanded NK cells were highly cytotoxic against cancer cells, displaying increased perforin and granzyme B accumulation. CONCLUSIONS: Taken together, these results indicated that IL-27 can synergize on NK cell expansion and activation with IL-15 and IL-18. In addition, we described an improved culture method for ex vivo expansion of human NK cells with IL-15/IL-18/IL-27 stimulation and characterized the response of NK cells to this stimulation.

Desmoplastic fibroblastoma mimicking tenosynovial giant cell tumor encasing a tendon of the foot.

Desmoplastic fibroblastoma is an uncommon, benign fibrous soft tissue tumor that usually occurs in the arms, shoulders, neck, hands, and feet in the fifth to seventh decades of life. In general, it is commonly located in the subcutaneous tissue and skeletal muscle. The authors report an unusual case of a desmoplastic fibroblastoma mimicking tenosynovial giant cell tumor encasing a tendon of the foot in a 72-year-old woman. Ultrasonography revealed an inhomogeneously hypoechoic lobulated soft tissue lesion completely wrapped around the extensor digitorum longus tendon. Color Doppler study revealed increased vascularity in the internal and peripheral portions of the lesion. Magnetic resonance imaging revealed a well-defined, lobulated soft tissue mass encasing the extensor digitorum longus tendon with predominantly isointense signal with some areas of hypointense signal on T1-weighted images, predominantly hyperintense signal with some areas of hypointense signal on T2-weighted images, and inhomogeneous enhancement on fat-suppressed contrast-enhanced T1-weighted images. Surgical excision was performed, and the mass was diagnosed on pathological examination as a desmoplastic fibroblastoma. There has been no previously published radiologic case of a desmoplastic fibroblastoma encasing a tendon of the foot in the literature.

miR-150 enhances apoptotic and anti-tumor effects of paclitaxel in paclitaxel-resistant ovarian cancer cells by targeting Notch3.

Tumor recurrence by obtaining chemoresistance is a major obstacle to treating ovarian cancer. By TargetScan database and a luciferase reporter assay, we identified miR-150 directly targets Notch3, which is a key oncogene in ovarian cancer. We, therefore, investigated the role of miR-150 in ovarian cancer cells, and the usefulness of miR-150 as a therapeutic target in chemoresistant ovarian cancer, through examining miR-150 expression by qRT-PCR in ovarian cancer cell lines and tissues, and assessing the gain-of-function effect by WST, colony forming, TUNEL, wound healing and angiogenesis assays. Western blotting was performed to evaluate its downstream targets. The miR-150 expression was significantly downregulated in ovarian cancers. Treatment with pre-miR-150 significantly inhibited cancer cell proliferation, and induced apoptosis in PTX (paclitaxel) -resistant SKpac cells, which was not seen by PTX only treatment. On spheroid forming assay, an additional pre-miR-150 treatment with PTX decreased cancer stem cell activation in PTX-resistant SKpac cells. An experimental upregulation of miR-150 also decreased cancer cell migration and angiogenesis in SKpac cells. The Notch3 downstream proteins(NICD3 and HEY2), and cell cycle-related proteins (cyclinD3, pS6, and NF-kB), and apoptosis-related proteins (BCL-2 and BCL-W) were significantly downregulated by pre-miR-150 transfection. Taken together, miR-150 is related with PTX-resistance in ovarian cancer, and treatment with pre-miR-150 resensitizes cancer cells to PTX. Therefore, it may be a promising treatment strategy in chemoresistant and recurrent ovarian cancer.