Tissue morphology and gene expression characterisation of transplantable adenocarcinoma bearing mice exposed to fluorodeoxyglucose-conjugated magnetic nanoparticles

Fluorodeoxyglucose-conjugated magnetic nanoparticles, designed to target cancer cells with high specificity when heated by an alternating magnetic field, could provide a low-cost, non-toxic treatment for cancer. However, it is essential that the in vivo impacts of such technologies on both tumour and healthy tissues are characterised fully. Profiling tissue gene expression by semi-quantitative reverse transcriptase real-time PCR can provide a sensitive measurement of tissue response to treatment. However, the accuracy of such analyses is dependent on the selection of stable reference genes. In this study, we determined the impact of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and non-tumour tissue gene expression and morphology in MAC16 adenocarcinoma established male NMRI mice. Mice received an injection of 8mg / kg body weight fluorodeoxyglucose-conjugated magnetic nanoparticles either intravenously in to the tail vein, directly into the tumour or subcutaneously directly overlying the tumour. Tissues from mice were sampled between 70 minutes and 12 hours post injection. Using the bioinformatic geNorm tool, we established the stability of six candidate reference genes (Hprt, Pgk1, Ppib, Sdha, Tbp and Tuba); we observed Pgk1 and Ppib to be the most stable. We then characterised the expression profiles of several apoptosis genes of interest in our adenocarcinoma samples, observing differential expression in response to mode of administration and exposure duration. Using histological assessment and fluorescent TUNNEL staining, we observed no detrimental impact on either tumour or non-tumour tissue morphology or levels of apoptosis. These observations define the underlying efficacy of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and non-tumour tissue morphology and gene expression, setting the basis for future studies

An in-vivo pilot study into the effects of FDG-mNP in cancer in mice

Purpose Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice. Materials and methods FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points. Results In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months. Conclusion Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice

Effects of fluorodeoxyglucose magnetic nanoparticles on NCI-H727 and SH-SY5Y cancer cells

We present a report regarding the cytotoxic effects of iron-based magnetic nanoparticles conjugated with fluorodeoxyglucose (FDG-mNPs) on the viability of NCI-H727 and SH-SY5Y cancer cells. MTT assays were performed to determine cell viability in treated cancer cells grown under standard 2D culture conditions. FDG-mNP concentrations of 0.075 mg/mL, 0.15 mg/mL, and 0.3 mg/mL decreased mean cell viability of NCI-H727 cells to 92.5%, 82.9%, and 75% respectively. FDG-mNPs was also shown to have a detrimental effect on the viability of SY5Y cells: a decrease of 5.7%, 18.6%, and 36.4% was found for SY5Y cells treated with 0.075 mg/mL, 0.15 mg/mL, and 0.3 mg/mL concentrations of FDG-mNPs, respectively. When NCI-H727 and SH-SY5Y cancer cells were grown as 3D spheroids, morphology was visibly changed and the number of viable cells was decerased in spheroids treated with FDG-mNPs compared with untreated spheroids. The results of our study demonstrated that FDG-mNP has toxic effects on NCI-H7272 and SY5Y cancer cells, and we conclude that conjugated FDG-mNPs are promising in the development of clinical applications for the destruction of cancer cells

Chemical constituent and radical scavenging antioxidant activity of Anthemis kotschyana Boiss

WOS:000513121200001PubMed: 32028798Phenolic content and antioxidant activity of Anthemis kotschyana Boiss. var. discoidea (A. kotschyana) were reported in this study. The ethanol extract of Anthemis kotschyana (EEA) and the water extract of Anthemis kotschyana (WEA) were prepared and used for biochemical analyses. Radical scavenging antioxidant capacities of EEA and WEA were evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging method. Another goal of the study was to evaluate the phenolic compositions of A. kotschyana by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Rhamnetin (5.484 +/- 0.020 ppm; mu g/g extract) and quinic acid (2.251 +/- 0.012 ppm; mu g/g extract) were identified as major two compounds in the plant sample. This study will be a scientific base for further studies about A. kotschyana for plant biochemistry and plant-based pharmacological industry

Changes in mean platelet volume in the course of upper gastrointestinal bleeding

In this study, we retrospectively evaluated patients with upper gastrointestinal bleeding (UGB) who were followed up at our center over a 3 year period and aimed to determine the factors affecting mean platelet volume (MPV) in patients with UGB, temporal changes in MPV during UGB, and the relationship between MPV values and the severity of UGB. Patients and methods: A total of 170 patients who were hospitalized between January 2010 and December 2013 with a diagnosis of UGB, completed a 72-hour follow up, and had a baseline blood count performed within 6 months were evaluated retrospectively. Demographic, clinical, and laboratory data, along with MPV values at baseline, on admission, and at 4 hours, 1 day, 2 days, 3 days, and discharge, were evaluated. Number Cruncher Statistical System (NCSS) 2007 was used for statistical analyses. Results: Women and patients with comorbid diseases had higher baseline MPV values; this effect disappeared after admission for UGB and reappeared at discharge. MPV values were lowest at the start of the bleeding and significantly increased during the course of UGB. Baseline MPV and MPV at discharge values were similar. There was no statistically significant relationship between any MPV measurement and transfusion amount. Conclusion: The effects of gender and comorbid diseases were negated by the presence of UGB and returned after UGB was controlled. MPV levels exhibited temporal changes during the course of UGB, indicating that MPV can be used as a marker; however, no statistical relationship was found between temporal MPV values and transfusion amount, a marker for UGB severity. [Med-Science 2020; 9(4.000): 1036-40

Technetium-99m and ICG-labeled HPG (hyperbranched polyglycerol) as a SPECT/FL dual imaging nanoprobe for imaging blood cells: in vitro investigation using myelogenous leukemia cells

This study aimed to develop a single photo emission computed tomography/fluorescence (SPECT/FL) bimodal imaging probe to image blood cells. Hyperbranched polyglycerol (HPG) was synthesized by anionic ring-opening polymerization. Succinic anhydride was used to functionalize HPG. Then, indocyanine green (ICG) was bound to HPG, with a 73.59% binding yield. Deferoxamine (DFO) was subsequently bound to ICG-HPG, and DFO-ICG-HPG was radiolabeled with technetium-99m, with 100% yield. The molecular weight of HPG in this study was found to be 6.8 kDa. In in vitro studies, the radiolabeled nanoconjugates remained stable even after 6 h (last timepoint when stability was assessed), and when the nanoconjugates were applied to K562 chronic myeloid leukemia cells, the highest cell viability was observed at a concentration of 5 mu g/mL and binding efficiency increased over time, reaching 30% at 6 h (last timepoint when binding efficiency was assessed). The results support the feasibility of the developed probe to image blood cells, which would be useful for applications such as detecting internal bleeding. [GRAPHICS] .Ege University Research Fund [2018 FBE 006]; NIH/NCI Cancer Support Grant [P30 CA008748]This work was financially supported by Ege University Research Fund (2018 FBE 006) and partially presented at HEZARFEN International Congress of Science, Mathematics, and Engineering Sciences held in Izmir/Turkey on November 8-10, 2019. Dr. Omer Aras was partially supported through the NIH/NCI Cancer Support Grant P30 CA008748

(225)Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to Ac-225-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive Lu-177-PSMA-617. In addition, the patient's baseline germline mutation likely predisposed him to more aggressive disease