Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine

Microglia are resident macrophages of the CNS that are involved in its development, homeostasis and response to infection and damage. Microglial activation is a common feature of neurological disorders, and although in some instances this activation can be damaging, protective and regenerative functions of microglia have been revealed. The most prominent example of the regenerative functions is a role for microglia in supporting regeneration of myelin after injury, a process that is critical for axonal health and relevant to numerous disorders in which loss of myelin integrity is a prevalent feature, such as multiple sclerosis, Alzheimer disease and motor neuron disease. Although drugs that are intended to promote remyelination are entering clinical trials, the mechanisms by which remyelination is controlled and how microglia are involved are not completely understood. In this Review, we discuss work that has identified novel regulators of microglial activation - including molecular drivers, population heterogeneity and turnover - that might influence their pro-remyelination capacity. We also discuss therapeutic targeting of microglia as a potential approach to promoting remyelination.

The pro-remyelination properties of microglia in the central nervous system

The immune contexture, a composition of the tumor microenvironment, plays multiple important roles in cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT), and hence critically influences tumor initiation, progression and patient outcome. Tumor-associated macrophages (TAMs) are abundant in immune contexture, however their roles in CSC, EMT and prognosis of colorectal cancer (CRC) have not been elucidated. In 419 colorectal carcinomas, immune cell types (CD68+ macrophages, CD3+, CD4+ or CD8+ T lymphocytes, CD20+ B lymphocytes), EMT markers (E-cadherin and Snail) as well as the stem cell marker (CD44v6) were detected in tumor center (TC) and tumor invasive front (TF) respectively by immunohistochemistry. Tumor buds, that represent EMT phenotype, were also counted. It was found CD68+ macrophages were the most infiltrating immune cells in CRC. By correlation analysis, more CD68+TF macrophages were associated with more CD44v6 expression (p < 0.001), lower SnailTF expression (p = 0.08) and fewer tumor buds (p < 0.001). More CD68+TF macrophages were significantly related to more CD3+TF T lymphocytes (p = 0.002), CD8+TF T lymphocytes (p < 0.001) and CD20+TF B lymphocytes counts (p = 0.004). Strong CD68+TF macrophages infiltration also predicted long term overall survival. CRC patients with more tumor buds had worse survival. However, strong CD68+TF macrophages infiltration could reverse the unfavorable results since patients with more tumor buds but increasing CD68+TF macrophages infiltration had the favorable outcome, similar to lower tumor buds groups. This study provided direct morphological evidence that tumor-associated macrophages in the invasive front play critical roles in fighting with the unfavorable results of tumor buds, thus resulting favorable outcomes for CRC patients.

https://www.tandfonline.com/doi/pdf/10.1080/2162402X.2017.1380765

Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma.

Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.

The Glioblastoma Microenvironment: Morphology, Metabolism, and Molecular Signature of Glial Dynamics to Discover Metabolic Rewiring Sequence.

Background Complementary therapy (CAM) is common in cancer patients. We undertook this study to assess the association of complementary therapy usage with mortality in glioblastoma (GBM) patients. Methods The analysis was based on 470 patients. Information on current use of CAM was collected in structured interviews conducted a median of 6 weeks following GBM diagnosis. Proportional hazards regression was used to estimate hazard ratios (HRs) for GBM-related death according to the use of individual supplements with multivariate adjustment for known prognostic factors including age, KPS, and extent of tumor resection (ESR). Results Use of CAM agents was common, with 77% of the cohort reporting CAM usage. No mortality association was observed with the use of multivitamins (HR = 0.91; P = .40) or omega-3 fatty acids (HR = 1.07; P = .69). Patients taking vitamin D as an individual supplement (containing higher dosages than in a multivitamin) had reduced mortality when compared with nonusers (age-adjusted HR = 0.68; P = .02). However, the association was diminished after adjustment for KPS and ESR (HR = 0.74; P = .09). Use of herbal supplements was also associated with reduced mortality (HR = 0.58; P = .04). Vitamin E users had a nonsignificantly higher mortality when compared with nonusers (HR = 1.54; P = .09). Conclusions Use of CAM is common in GBM patients. These exploratory analyses suggest no mortality association with the use of multivitamins or omega-3 fatty acids. Associations observed with vitamins D and E merit further investigation.

/pdf/complementary-therapy-and-survival-in-glioblastoma-1znh5kl5pq.pdf

Complementary therapy and survival in glioblastoma.

Glioblastoma is a ferociously expanding form of tumor with a grim prognosis even after surgical removal.  The tumor most frequently returns after surgery, which may point to a population of cells that have the capacity to initiate a relapse. Resident macrophage population of the brain should tame tumor growth but glioma seems to be interfering with their normal response hence growing even in their presence. Artificial activation of macrophages has been shown to decelerate the growth of glioma in mouse model. doi : 10.5214/ans.0972.7531.200407

/pdf/therapeutic-activation-of-macrophages-and-microglia-to-3rthtio4zz.pdf

Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells.

Liposomes are used as carriers of drugs intended to manipulate macrophage functions. The normal in vivo fate of liposomes is phagocytosis, followed by phospholipase-mediated disruption of their phospholipid bilayers and intracellular release of their contents. Using this method for intracellular delivery of drugs, we have developed an approach for in vivo depletion of macrophages. Phagocytosis also forms a major feature of parasitic amoebae. In the present experiments, we investigated whether amoebae could be killed using the same approach (liposome-mediated "suicide" of amoebae). The results confirm that liposomes are ingested by Ent-amoeba invadens cultured under routine laboratory conditions. From various chelator molecules and their metalion complexes that were active in the liposome-mediated elimination of macrophages, Cu-ethylenediaminetetraacetic acid (EDTA) complexes appeared to be the most efficacious compounds in the elimination of E. invadens.

Killing of Entamoeba invadens using liposome-encapsulated drugs.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

van Rooijen N

Author Tools

Chat about Author

Papers

Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells.

Killing of Entamoeba invadens using liposome-encapsulated drugs.