Integrated nanoscale deterministic lateral displacement arrays for separation of extracellular vesicles from clinically-relevant volumes of biological samples.

Extracellular vesicles (EVs) offer many opportunities in early-stage disease diagnosis, treatment monitoring, and precision therapy owing to their high abundance in bodily fluids, accessibility from liquid biopsy, and presence of nucleic acid and protein cargo from their cell of origin. Despite their growing promise, isolation of EVs for analysis remains a labor-intensive and time-consuming challenge given their nanoscale dimensions (30-200 nm) and low buoyant density. Here, we report a simple, size-based EV separation technology that integrates 1024 nanoscale deterministic lateral displacement (nanoDLD) arrays on a single chip capable of parallel processing sample fluids at rates of up to 900 μL h-1.

Hydrodynamics of diamond-shaped gradient nanopillar arrays for effective DNA translocation into nanochannels.

Effective DNA translocation into nanochannels is critical for advancing genome mapping and future single-molecule DNA sequencing technologies. We present the design and hydrodynamic study of a diamond-shaped gradient pillar array connected to nanochannels for enhancing the success of DNA translocation events. Single-molecule fluorescence imaging is utilized to interrogate the hydrodynamic interactions of the DNA with this unique structure, evaluate key DNA translocation parameters, including speed, extension, and translocation time, and provide a detailed mapping of the translocation events in nanopillar arrays coupled with 10 and 50 μm long channels.

The impact of frailty on postoperative delirium in cardiac surgery patients.

Objective: To determine if adding frailty measures to the EuroSCORE II improves model performance in predicting postoperative delirium.

Methods: In a prospective observational study in elective cardiac surgery patients, frailty was defined using the Modified Fried Criteria (MFC), the Short Physical Performance Battery (SPPB) and a 35-item Frailty Index (FI). The primary outcome was postoperative delirium, assessed using the Confusion Assessment Method (CAM).

Chemopreventive efficacy of Targretin in rodent models of urinary bladder, colon/intestine, head and neck and mammary cancers.

The chemopreventive efficacy of Targretin was evaluated in various rodent cancer models. In the rat model of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced urinary bladder cancer, it was found that Targretin administered in the diet (beginning one week after the last OH-BBN treatment) for 5.5 months increased the number and size of urinary bladder cancers.

Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin.

Atorvastatin and suberoylanilide hydroxamic acid (SAHA) were evaluated for chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg atorvastatin, and combinations containing SAHA and atorvastatin administered in their diet. SAHA and both combinations, but not atorvastatin, decreased the multiplicity of lung tumors, including large adenomas and adenocarcinomas with the combinations demonstrating the greatest efficacy.

Prevention of mouse lung tumors by combinations of chemopreventive agents using concurrent and sequential administration.

Background: Concurrent and sequential administration of combinations of budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin were evaluated in A/J mice for prevention of lung tumors initiated by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK).

Materials And Methods: Individual drugs and their combinations were administered for 26 weeks after NNK initiation. For sequential administration, budesonide was given for 21 weeks followed by a second drug.

Catechin degradation with concurrent formation of homo- and heterocatechin dimers during in vitro digestion.

Catechins were subjected to in vitro gastric and small intestinal digestion. EGCG, EGC, and ECG were significantly degraded at all concentrations tested, with losses of 71-91, 72-100, and 60-61%, respectively. EC and C were comparatively stable, with losses of 8-11 and 7-8%, respectively.

Modulation by bexarotene of mRNA expression of genes in mouse lung tumors.

Bexarotene has demonstrated chemopreventive and therapeutic efficacy towards mouse lung tumors. Using specimens from our published study that demonstrated the efficacy of bexarotene, we report herein its ability to modulate mRNA expression of genes in both lung and lung tumors. Strain A/J mice were administered vinyl carbamate to induce lung tumors.

Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra).

As part of a search for new cancer chemopreventive agents, a new chalcone derivative (1), a novel group of neolignan lipid esters (2), and seven known phenolic compounds (formononetin, glabridin, hemileiocarpin, hispaglabridin B, isoliquiritigenin, 4'-O-methylglabridin, and paratocarpin B) (3-9) were isolated from the roots and stolons of licorice (Glycyrrhiza glabra). The structures of compound 1 and the individual components of isolate 2 were elucidated using various spectroscopic and chemical methods. All isolates were tested in an authentic peroxynitrite anti-oxidant assay.

Modulation by budesonide of a CpG endonuclease in mouse lung tumors.

CpG endonuclease activity was identified in nuclear extracts obtained from mouse lung tumors. Enzyme activity was determined using a 333 bp polymerase chain reaction product of the estrogen receptor-alpha gene that contained either radiolabeled cytosine or tritium-labeled methyl groups at CpG sites. Activity was measured as the release of radioactivity from the substrate.

Modulation by budesonide of DNA methylation and mRNA expression in mouse lung tumors.

Biomarkers are being developed that can aid in the evaluation of cancer therapeutic and chemopreventive drugs. Two suggested biomarkers found in mouse lung tumors are DNA hypomethylation and alterations in mRNA expression of genes, such as 18S RNA, caspase 3, cyclin B2, cyclin E1, iNOS and survivin. Budesonide is very efficacious in preventing lung tumors in mice, so that its ability to modulate biomarkers in lung tumors was determined.

Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (Zarnestra MT).

Budesonide (an anti-inflammatory glucocorticoid), R115777 (a farnesyl transferase inhibitor, Zarnestra, Tipifarnib) or combinations of them were evaluated for prevention of lung tumors and for modulation of DNA methylation in tumors. Lung tumors were induced by vinyl carbamate in female strain A mice. One week later, mice received 60 or 100 mg/kg R115777 by oral gavage and 5 days/week, 0.

Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (ZarnestraMT).

Budesonide (an anti-inflammatory glucocorticoid), R115777 (a farnesyl transferase inhibitor, Zarnestra, Tipifarnib) or combinations of them were evaluated for prevention of lung tumors and for modulation of DNA methylation in tumors. Lung tumors were induced by vinyl carbamate in female Strain A mice. One week later, mice received 60 or 100 mg/kg R115777 by oral gavage and 5 days/week, 0.

Prevention of mouse lung tumors by targretin.

Targretin has indicated chemotherapeutic activity against nonsmall-cell lung cancer and chemoprevention in rat mammary gland. Therefore, targretin was evaluated for the prevention of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) and vinyl carbamate-induced lung tumors in female strain A mice. Three experiments were performed: (i) a dose-response study with vinyl carbamate-induced tumors; (ii) a limited treatment study also with vinyl carbamate and (iii) prevention of NNK-induced tumors.

DNA hypomethylation induced by drinking water disinfection by-products in mouse and rat kidney.

Bromodichloromethane (BDCM), chloroform, dibromoacetic acid (DBA), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are chlorine disinfection by-products (DBPs) found in drinking water that have indicated renal carcinogenic and/or tumor promoting activity. We have reported that the DBPs caused DNA hypomethylation in mouse liver, which correlated with their carcinogenic and tumor promoting activity. In this study, we determined their ability to cause renal DNA hypomethylation.

Chemoprevention: mouse colon and lung tumor bioassay and modulation of DNA methylation as a biomarker.

Lung and colon tumors were induced in A/J, C3H, and A/J X C3H (AC3) mice by administering 16 mg/kg vinyl carbamate followed by 6 weekly doses of 12 mg/kg azoxymethane (AOM). Beginning 1 week after carcinogen treatment, the mice received chemopreventive agents, dexamethasone or piroxicam, at 0.1 and 75 mg/kg in the diet, respectively.

Effect of dibromoacetic acid on DNA methylation, glycogen accumulation, and peroxisome proliferation in mouse and rat liver.

Dibromoacetic acid (DBA) is a drinking water disinfection by-product. Its analogs, dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are liver carcinogens in rodents. We evaluated the ability of DBA to cause DNA hypomethylation, glycogen accumulation, and peroxisome proliferation that are activities previously reported for the two other haloacetic acids.

DNA hypomethylation induced by non-genotoxic carcinogens in mouse and rat colon.

The ability of non-genotoxic colon carcinogens to induce DNA hypomethylation was evaluated. Administering 0, 0.2 and 0.

Modulation by celecoxib and difluoromethylornithine of the methylation of DNA and the estrogen receptor-alpha gene in rat colon tumors.

The ability of celecoxib and alpha-difluoromethylornithine (DFMO) to modulate the DNA hypomethylation and the hypermethylation of the estrogen receptor (ER)-alpha gene in colon tumors was evaluated as potential biomarkers for chemoprevention. Colon tumors were induced in rats by azoxymethane. Celecoxib (500 mg/kg), DFMO (100, 1000 and 3000 mg/kg) or celecoxib + 1000 mg/kg DFMO were administered in the diet for 7 or 28 days prior to death at week 37.

Hypomethylation of DNA and the insulin-like growth factor-II gene in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors.

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens. DNA hypomethylation is a common molecular event in cancer that is induced by DCA and TCA. Hypomethylation of DNA and the insulin-like growth factor-II (IGF-II) gene was determined in DCA- and TCA-promoted liver tumors.

Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer.

Surrogate end-point biomarkers are being developed as indicators of the efficacy of chemopreventive agents. These biomarkers are molecular and biological end-points that can be modulated by chemopreventive agents in accordance with their efficacy to prevent cancer. DNA hypomethylation is a common alteration found in colon tumors that has the potential of being modulated by chemopreventive agents and thus being useful as a surrogate end-point biomarker.

Prevention by methionine of dichloroacetic acid-induced liver cancer and DNA hypomethylation in mice.

Dichloroacetic acid (DCA) is a liver carcinogen that induces DNA hypomethylation in mouse liver. To test the involvement of DNA hypomethylation in the carcinogenic activity of DCA, we determined the effect of methionine on both activities. Female B6C3F1 mice were administered 3.

Chemoprevention of benzo(a)pyrene-induced lung tumors in mice by the farnesyltransferase inhibitor R115777.

Purpose: Inhibitors of farnesyltransferase (e.g., R115777) are being developed for therapy and prevention of various cancers.

Effect of budesonide on the methylation and mRNA expression of the insulin-like growth factor 2 and c-myc genes in mouse lung tumors.

The use of surrogate end-point biomarkers could help in the development of chemopreventive agents. To define potential surrogate end-point biomarkers, the ability of budesonide to decrease mRNA expression of the insulin-like growth factor-2 (Igf-II) and c-myc genes and to cause the remethylation of the genes was investigated in lung tumors. Lung tumors were induced in female strain A mice by administering i.

Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents.

Modulation of gene expression in tumors has the potential of being a surrogate end-point biomarker for chemoprevention. Thus, we determined the modulation by chemopreventive agents of the protein and mRNA expression of genes in rat colon tumors. Male F344 rats were administered three weekly injections of 15 mg/kg azoxymethane.