High expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor has been found in myelomonocytic or monocytic subtypes (M4/M5) of acute myeloid leukemia. Herein, we aimed to improve the effect of CAG [Ara-C, ACR, and G-CSF (granulocyte colony-stimulating factor)] regimen for acute monocytic leukemia by replacing G-CSF with GM-CSF. Results showed that the percentage of cells in S phase was higher with GM-CSF than with G-CSF treatment at 20 ng/mL (P < 0.05). When THP-1 and SHI-1 cells were primed with 20 ng/mL G-CSF or GM-CSF followed by Ara-C and ACR, cell proliferation rate in the CAGM (Ara-C, ACR, and GM-CSF) regimen was lower than in the CAG regimen (P < 0.05). Furthermore, CAGM regimen induced more obvious cell apoptosis than CAG regimen probably by reducing Bcl-2/Bax ratio (P < 0.05). Similar results were seen in primary cells from M5 patients. Collectively, our study suggests that priming with GM-CSF may be more effective than G-CSF in CAG regimen in acute monocytic leukemia.
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http://dx.doi.org/10.1007/s00280-019-03857-8 | DOI Listing |
Melanoma Res
February 2025
Department of Public Health, College of Medicine, Taipei Medical University.
Melanoma is an aggressive tumor that is challenging to treat. Talimogene laherparepvec (T-VEC), the first oncolytic virus treatment approved by the US Food and Drug Administration to treat unresectable melanoma, was recently used in recurrent tumors after initial surgery. Our network meta-analysis aimed to compare T-VEC treatment of metastatic melanoma with treatment of granulocyte-macrophage colony-stimulating factor (GM-CSF) and control group.
View Article and Find Full Text PDFJ Interferon Cytokine Res
January 2025
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous promoter. Homozygous Halo-SOCS1 mice () were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, China.
Background: Microglia play a critical role in the pathogenesis and development of Alzheimer's disease (AD). Selective small-molecule colony-stimulating factor 1 receptors (CSF1R) inhibitor, designed to deplete microglia, could be used to meliorate AD. This study aimed to investigate the effects and mechanisms of chimeric antigen receptor T (CAR-T) cells targeting CSF1R in 6-month-old APP/PS1 male mice.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Immunology and.
Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibited a sustained inhibitory effect against colony-stimulating factor 1 receptor by forming a covalent bond and reduced immunosuppressive TAMs in the TME, which led to strong antitumor immunity.
View Article and Find Full Text PDFBackground: Microglial activation is one of the neuropathological hallmarks of Alzheimer's disease (AD). Evidence suggest that chronic activation of microglia cause neuroinflammation and neuronal injuries, contributing to cognitive impairment. Therefore, modulation of microglial pathway like CSF-1R represents an attractive therapeutic strategy.
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