MRI monitoring of monocytes to detect immune stimulating treatment response in brain tumor

Yang, Runze; Sarkar, Susobhan; Korchinski, Daniel; Wu, Ying; Yong, V. Wee; Dunn, Jeff F.

doi:10.1093/neuonc/now180

Cited by 17 publications

(15 citation statements)

References 27 publications

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“…Increased tumor infiltration of Iba1 + microglial cells and macrophages was detected in AmpB treated animals. This effects has been recently confirmed using ultrasmall iron oxide nanoparticles as contrast agents for magnetic resonance imaging, in order to detect monocyte infiltration into brain tumors [53] . In addition, tumor infiltrating Iba1 + cells in response to AmpB showed a significant up-regulation of iNOS, that most likely results in increased production of cytotoxic nitric oxide (NO) [52] Beneficial effects of AmpB were also observed in immunocompe-tent C57BL/6 mice, against highly aggressive tumors derived from enriched stem-like CD133 + GL261 glioma cells.…”

Section: Drugs That Interfere With Gams' Inflammatory Activation and mentioning

confidence: 80%

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Russo¹,

Cappoli²

2018

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Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, particularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a specific phenotype of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma. Therefore, treatments that limit or prevent GAMs' recruitment at the tumor site or modulate their immune activation promoting antitumor activities are expected to exert beneficial effects in glioblastoma. In the present paper, we aim at the revision of pharmacological strategies that interfere with GAMs' function and are currently proposed as an alternative/additional option to current approved cytotoxic regimens.

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Section: Drugs That Interfere With Gams' Inflammatory Activation and mentioning

confidence: 80%

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Russo¹,

Cappoli²

2018

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“…BTICs generated from human glioma patients BTICs were generated and stable lines were formed from resected specimens of patients with malignant glioma as described before (39,40). We used two BTIC lines for most of the tissue culture experiments in the present study designated BT025 and BT048 with divergent genetic background; these lines have been referred to previously as 25EF and 48EF, respectively (39).…”

Section: Methodsmentioning

confidence: 99%

Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells

et al. 2017

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Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC) in malignant glioma, but the mechanism of its activation is unknown. Here we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We demonstrate the proximal localization of TNC and BTIC in human glioblastoma specimens and in orthotopic murine xenografts of human BTIC implanted intracranially. In tissue culture, TNC was superior amongst several extracellular matrix proteins in enhancing the sphere-forming capacity of glioma patient-derived BTIC. Exogenously applied or autocrine TNC increased BTIC growth through an α2β1 integrin-mediated mechanism that elevated NOTCH ligand Jagged1 (JAG1). Microarray analyses and confirmatory PCR and Western analyses in BTIC determined that NOTCH signaling components including JAG1, ADAMTS15, and NICD1/2 were elevated in BITC after TNC exposure. Inhibition of γ-secretase and metalloproteinase proteolysis in the NOTCH pathway, or silencing of α2β1 integrin or JAG1, reduced the proliferative effect of TNC on BTIC. Collectively, our findings identified TNC as a pivotal initiator of elevated NOTCH signaling in BTIC and define the establishment of a TN-α2β1-JAG1-NOTCH signaling axis as a candidate therapeutic target in glioma patients. .

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“…Contrast MRI uses exogenous cell labels, such as superparamagnetic iron oxide (SPIOs) nanoparticles or Fluorine-19 ( 19 F)-based perfluorocarbon (PFC) nanoemulsions[184]. Iron oxide nanoparticles have already been used to image monocyte dynamics in a rodent model of glioblastoma[185] and in patients with myocardial infarction[186]. Alternatively, 19 F-MRI allows direct detection and imaging of labeled cells for unambiguous identification and quantification unlike iron oxide-based MRI [187].…”

Section: Applying Nanomedicine In Inflammation Dynamicsmentioning

confidence: 99%

Applying nanomedicine in maladaptive inflammation and angiogenesis

Alaarg

Pérez-Medina

Metselaar

et al. 2017

Advanced Drug Delivery Reviews

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Inflammation and angiogenesis drive the development and progression of multiple devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and inflammatory bowel disease. Though these diseases have very different phenotypic consequences, they possess several common pathophysiological features in which monocyte recruitment, macrophage polarization, and enhanced vascular permeability play critical roles. Thus, developing rational targeting strategies tailored to the different stages of the journey of monocytes, from bone marrow to local lesions, and their extravasation from the vasculature in diseased tissues will advance nanomedicine. The integration of in vivo imaging uniquely allows studying nanoparticle kinetics, accumulation, clearance, and biological activity, at levels ranging from subcellular to an entire organism, and will shed light on the fate of intravenously administered nanomedicines. We anticipate that convergence of nanomedicines, biomedical engineering, and life sciences will help to advance clinically relevant therapeutics and diagnostic agents for patients with chronic inflammatory diseases.

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MRI monitoring of monocytes to detect immune stimulating treatment response in brain tumor

Abstract: USPIO-MRI is a promising method of rapidly assessing the efficacy of anticancer drugs that stimulate innate immunity.

Cited by 17 publications

References 27 publications

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells

Applying nanomedicine in maladaptive inflammation and angiogenesis

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