Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Sci Rep ; 12(1): 12748, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35882949

ABSTRACT

While radioembolization with yttrium-90 (Y-90) microspheres is a promising treatment for hepatocellular carcinoma (HCC), lower responses in advanced and high-grade tumors present an urgent need to augment its tumoricidal efficacy. The purpose of this study was to determine whether clinically used Y-90 microspheres activate light-responsive nano-photosensitizers to enhance hepatocellular carcinoma (HCC) cell oxidative stress and cytotoxicity over Y-90 alone in vitro. Singlet oxygen and hydroxyl radical production was enhanced when Y-90 microspheres were in the presence of several nano-photosensitizers compared to either alone in cell-free conditions. Both the SNU-387 and HepG2 human HCC cells demonstrated significantly lower viability when treated with low activity Y-90 microspheres (0.1-0.2 MBq/0.2 mL) and a nano-photosensitizer consisting of both titanium dioxide (TiO2) and titanocene (TC) labelled with transferrin (TiO2-Tf-TC) compared to Y-90 microspheres alone or untreated cells. Cellular oxidative stress and cell death demonstrated a linear dependence on Y-90 at higher activities (up to 0.75 MBq/0.2 mL), but was significantly more accentuated in the presence of increasing TiO2-Tf-TC concentrations in the poorly differentiated SNU-387 HCC cell line (p < 0.0001 and p = 0.0002 respectively) but not the well-differentiated HepG2 cell line. Addition of TiO2-Tf-TC to normal human hepatocyte THLE-2 cells did not increase cellular oxidative stress or cell death in the presence of Y-90. The enhanced tumoricidal activity of nano-photosensitizers with Y-90 microspheres is a potentially promising adjunctive treatment strategy for certain patient subsets. Applications in clinically relevant in vivo HCC models are underway.


Subject(s)
Carcinoma, Hepatocellular , Embolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Cell Death , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Microspheres , Oxidative Stress , Photosensitizing Agents , Yttrium Radioisotopes
2.
PLoS One ; 16(7): e0254242, 2021.
Article in English | MEDLINE | ID: mdl-34237100

ABSTRACT

Microglia are the resident immune cell of the brain involved in the development and progression of Alzheimer's disease (AD). Modulation of microglia activity represents a potential mechanism for treating AD. Herein, the compound NNC 26-9100 (NNC) was evaluated in toxicity, nitric oxide release, Aß1-42 uptake and cytosolic calcium assays during lipopolysaccharide (LPS)-activated conditions using mouse BV2 microglia cells. After 24 hours, LPS increased cell toxicity in the alamar blue and lactate dehydrogenase assays, increased nitrite release, and increase cytoplasmic calcium. Addition of NNC decreased the LPS-induce lactate dehydrogenase release, had no effect in the alamar blue assay, decreased nitrite release and decreased cytosolic calcium. In the absence of LPS, NNC increased uptake of FITC-tagged Aß1-42. These data demonstrate that NNC treatment decreases nitrosative stress and microglia cell damage during LPS-induced activation and enhances phagocytosis of Aß1-42 during non-inflammatory conditions. Thus, NNC 26-9100 may have beneficial effects in AD and in inflammatory diseases of the brain through enhancement of microglial Aß clearance, and cell protective effects through prevention of elevated cytosolic calcium and inhibition of nitric oxide release.


Subject(s)
Aminopyridines/pharmacology , Amyloid beta-Peptides/metabolism , Calcium/metabolism , Microglia/drug effects , Nitric Oxide/metabolism , Peptide Fragments/metabolism , Phagocytosis/drug effects , Thiourea/analogs & derivatives , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Cell Line , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Mice , Microglia/metabolism , Thiourea/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...