1B), and the combination of clodrolip or ZA with sorafenib further inhibited lung metastasis compared with sorafenib alone (integrated absorbance: 36.17 ± 6.36 and 3.67 ± 2.28 versus 58.0 ± 3.65, P < 0.05 and P < 0.001, respectively).

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Aging and cancer: The role of macrophages and neutrophils.

Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice.

Jackaman C, Tomay F, Duong L, Abdol Razak NB, Pixley FJ, Metharom P, Nelson DJ. eISSN: 1557-3265 Exp Gerontol. Ly6C is a monocyte/macrophage and endothelial cell differentiation antigen regulated by interferon gamma and is thought to play a role in the development and maturation of lymphocytes. No potential conflicts of interest were disclosed. 2020 Aug 31;11:1037. doi: 10.3389/fphys.2020.01037. The Regulatory Status Adopted by Lymph Node Dendritic Cells and T Cells During Healthy Aging Is Maintained During Cancer and May Contribute to Reduced Responses to Immunotherapy. injection of PBS-containing liposome (control group), (b) a daily oral dose of sorafenib at 30 mg/kg (sorafenib group), (c) i.p. Targeting macrophages rescues age-related immune deficiencies in C57BL/6J geriatric mice. Final dosing solutions were prepared on the day of use by dilution to 1× with endotoxin-free distilled water (Life Technologies) and mixed by vortexing immediately before dosing.

Ageing Res Rev. The effect of macrophage depletion on tumor angiogenesis and metastasis after sorafenib treatment, using two drug target macrophages, zoledronic acid (ZA) and clodrolip, was measured in the two models of hepatocellular carcinoma. The NIMP-R14 antibody has been shown to be useful for depletion of neutrophils in mice.

Depletion of macrophages using F4/80 antibody in elderly, but not young mice, improved IL-2/anti-CD40 immunotherapy up to 78% tumor regression.

Front Physiol. A to C, protein level of CSF-1, SDF-1α, and VEGF by Western blotting of LM3-R tumor (A), and mRNA level of M-CSF, SDF-1, and VEGF of sorafenib-treated tumor by quantitative PCR were normalized to control (B and C). Original magnification, ×100. Patients with lung metastasis had a poorer response to sorafenib treatment (3). Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity.


Sections of lung were stained with H&E to pathologically determine the presence of lung metastasis. -, Barns M., Gondro C., Tellam R. L., Radley-Crabb H. G., Grounds M. D., Shavlakadze T. (2014).

4D and E), when compared with that of the nontreated mice. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail.

In both models, although clodrolip alone did not inhibit tumor growth, it significantly enhanced the antitumor effects of sorafenib (Fig.

Clodrolip and PBS-containing liposome were gifts of Roche Diagnostics GmbH. CSF-1 can activate macrophages, thereby contributing to macrophage-tumor interaction, and may finally lead to tumor progression (9).

We found that sorafenib caused severe hypoxia and necrosis in the treated tumor, as indicated by pimonidazole and hypoxia-inducible factor 1α staining (see Supplementary Figure). *, P < 0.05; **, P < 0.01; ***P < 0.001. Mice treated with ZA alone had a significantly smaller tumor volume compared with that of controls (Fig. Epub 2017 Apr 6. Hypoxia-inducible factor 1α has been found to induce the recruitment of bone marrow–derived vascular modulatory cells, including F4/80- and CD11b-positive cells, to regulate tumor angiogenesis and invasion (36). B, quantitation of tumor vasculature indicated that clodrolip and ZA inhibited angiogenesis in combination with sorafenib.

Hepatocellular carcinoma (HCC) is currently a major public health problem and the fifth most common cause of cancer-related death among men in the United States. With the depletion of macrophages by clodrolip or ZA, tumor progression, tumor angiogenesis, and metastasis were significantly inhibited.

5C).

Original magnification, ×100. https://doi.org/10.1016/j.ccr.2014.05.016. However, we do agree that this conclusion needs to be validated in an immunity-competent mouse model. The present study used orthotropic nude mouse model with two human HCC cell lines to investigate the role of macrophages in tumor progression under sorafenib treatment. The membranes were blocked for 1 hour at room temperature in 5% nonfat dry milk in TBS containing 0.05% Tween 20, followed by overnight incubation at 4°C with primary antibodies.

Oncol. C and D, percent of F4/80-positive cells (C) and CD11b-positive cells (D) in LM3-R tumor. Administration of RG7155 to patients led to striking reductions of CSF-1R+CD163+ macrophages in tumor tissues, which translated into clinical objective responses in diffuse-type giant cell tumor (Dt-GCT) patients. Stable red fluorescent protein–expressing HCCLM3 (LM3-R) cells by infection with lentivirus containing full-length cDNA of red fluorescent protein were established by our institute (27). Data were collected after each annealing step.

Interestingly, in tumor-bearing mice, bone marrow macrophages increased proliferation whilst splenic macrophages had reduced proliferation in elderly compared with young mice, and macrophage depletion using the F4/80 antibody slowed tumor growth in young and elderly mice.

A, sorafenib significantly inhibited tumor growth, and clodrolip and ZA enhanced the tumor inhibitory effect of sorafenib. This Antibody Is Useful For: in vivo neutrophil depletion However, immunosuppressive macrophages can constitute up to 50% of the tumor burden and impair anti-tumor T cell activity.

Another 24 hours later, the conditioned medium was collected and added to RAW 264.7 cells (mouse leukemic monocyte macrophage cell line, established by the Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai), which were seeded in six-well plates. 28 ED2 antibody, which recognises a membrane bound antigen similar to human CD163, has been commonly used as a specific maker for resident macrophages. Sorafenib prolonged time to progression and overall survival of HCC patients by only 3 months, and patients with metastasis had a poorer response to sorafenib treatment.

2020 Jun 13;12(11):11152-11160. doi: 10.18632/aging.103492. For quantitation of mean vessel density in sections stained for CD31, five fields at ×100 magnification in the “hotspot” were captured for each tumor, and microvessel density (MVD) was quantitated as CD31-positive area/total area. The experimental protocol was approved by the Shanghai Medical Experimental Animal Care Committee. Macrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. 2020 Aug 1;484:29-39. doi: 10.1016/j.canlet.2020.04.017.
Macrophages are also instrumental in shaping developing organs and repairing tissues during life. 10.1016/j.biocel.2014.04.025 Quantitation of F4/80- or CD11b-positive cells in an HCC graft was calculated as F4/80- or CD11b-positive area/total area. In the present study, CSF-1, SDF-1α, and VEGF, all chemokines for macrophages (37, 38), were elevated in sorafenib-treated tumor.

*, P < 0.05; **, P < 0.01. Two HCC cell lines were used in this study. Depletion of macrophages by clodrolip or ZA in combination with sorafenib significantly inhibited tumor progression, tumor angiogenesis, and lung metastasis compared with mice treated with sorafenib alone. Copyright © 2014 Elsevier Inc. All rights reserved. Consult the supplier page to verify the identity of the desired antibody target and learn more detailed product information, such as species reactivity, antibody features, and validated applications. Serial sections were cut at 5 μm for histologic study.

After 5 weeks of treatment, sorafenib-treated mice had a smaller tumor volume compared with that of mice in the control group in the LM3-R model (1.03 ± 0.05 cm3 versus 3.37 ± 0.23 cm3, P < 0.001) and in the SMMC7721 model (1.02 ± 0.1cm3 versus 1.86 ± 0.3 cm3, P < 0.05). We do not retain these email addresses.

Recent studies reveal the direct communication between macrophages and tumor cells that leads to the invasion and egress of tumor cells into blood vessels (9). Young (. D and E, plasma CSF-1 level were also significantly elevated in sorafenib-treated mice compared with control in the LM3-R tumor (D) and SMMC7721 tumor (E), and the combination of clodrolip and ZA significantly reduced plasma VEGF in both models and also reduced plasma CSF-1 in the SMMC7721 model. Sorafenib significantly inhibited tumor angiogenesis as indicated by reduced MVD in the LM3-R model (1.28% ± 0.15% versus 3.77% ± 0.44%, P < 0.001), and sorafenib combined with clodrolip or ZA further inhibited tumor angiogenesis (0.69% ± 0.08% or 0.3% ± 0.07% versus 1.28% ± 0.15%, P < 0.01 or P < 0.001, respectively), suggesting that macrophages play a role in tumor angiogenesis (Fig. IBA-1 Documentation of Macrophage Depletion.

Rabbit anti-rat IgG/horseradish peroxidase (1:100; Serotec) or rabbit anti-rat FITC antibody (1:100; Santa Cruz) were applied as secondary antibodies.

Macrophage-produced VEGF regulates malignant progression through stimulation of tumor angiogenesis and tumor cell invasion (34).

Male athymic BALB/c nu/nu mice (5-wk-old) were obtained from the Shanghai Institute of Materia Medica, Chinese Academy of Science. Purpose: To investigate the role of macrophages in tumor progression under sorafenib treatment and to explore whether combination of drugs that deplete macrophages improved the antitumor effect of sorafenib. To assess the distribution of CD31 and F4/80, we stained sections with rat anti-CD31 (1:200; BD Pharmingen), rat anti-F4/80 antibody (1:50; Serotec), and rat anti-CD11b antibody (1:50; Serotec).

VEGF mRNA was elevated by 1.65-fold in SMMC7721 tumor. Recruitment of F4/80- and CD11b-positive cells in peripheral blood. As an example, a 5-ml kit is composed of 5 ml Clodrosome® and 5 ml Encapsome®. 2017 Jul;36:105-116. doi: 10.1016/j.arr.2017.03.008.