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Inhibition of Cancer Cell Growth by GRP78 siRNA Lipoplex via Activation of Unfolded Protein Response.
Abstract Proteasome inhibitors are a novel class of molecular-targeted anti-cancer drugs that suppress the degradation of malfolded proteins, trigger endoplasmic reticulum (ER) stress, and activate apoptosis signals. Glucose-regulated protein 78 (GRP78), a major ER chaperone, is one of the most important molecules for transduction of unfolded protein response (UPR) signals. In accordance with past findings that expression of GRP78 is elevated in cancer cells and helps to resist stress-induced apoptosis, GRP78 knockdown could be effective in anticancer therapy. We tested this hypothesis and found that transfection ...
Source: Biological and Pharmaceutical Bulletin - April 6, 2014 Category: Drugs & Pharmacology Authors: Matsumura K, Sakai C, Kawakami S, Yamashita F, Hashida M Tags: Biol Pharm Bull Source Type: research

Reduced plasma glucose by asparagine synthetase knockdown in the mouse liver.
Abstract Expression of the asparagine synthetase gene is dependent on extracellular glucose concentration. This gene was knocked-down in livers of male Balb/c mice by a hydrodynamic tail vein injection of small interfering RNA (siRNA) against the gene. This knockdown resulted in a significant decrease in plasma glucose concentration. These results suggested that asparagine synthetase is a novel protein that regulates plasma glucose levels. PMID: 24292060 [PubMed - in process]
Source: Biological and Pharmaceutical Bulletin - December 4, 2013 Category: Drugs & Pharmacology Authors: Iida S, Kamiya H, Nakaya A, Hayashi Y, Sawada A, Kaji N, Baba Y, Harashima H Tags: Biol Pharm Bull Source Type: research

The Development of Ternary Nanoplexes for Efficient siRNA Delivery.
Abstract Targeted posttranscriptional gene silencing by RNA interference (RNAi) has garnered considerable interest as an attractive new class of drugs for several diseases, such as cancer. Chitosan and protamine are commonly used as a vehicle to deliver and protect small interfering RNA (siRNA), but the strong interaction still remains to be modulated for efficient siRNA uptake and silencing. Therefore, in this study, ternary nanoplexes containing chitosan and protamine were designed to substantially enhance the siRNA efficiency. Binary and ternary nanoplexes were prepared at different the ratios of moles of the a...
Source: Biological and Pharmaceutical Bulletin - October 3, 2013 Category: Drugs & Pharmacology Authors: Salva E, Turan SO, Akbuğa J Tags: Biol Pharm Bull Source Type: research

Gene silencing in a mouse lung metastasis model by an inhalable dry small interfering RNA powder prepared using the supercritical carbon dioxide technique.
In this study, a novel dry small interfering RNA (siRNA) powder for inhalation, containing chitosan and mannitol, was prepared using the supercritical carbon dioxide (CO2) technique. Although the siRNA/chitosan powder was difficult to disperse because of a long needle-like structure, it could be reduced to fragments of 10-20 µm by manual grinding, which allowed for administration into mice. Electrophoresis revealed that the supercritical CO2 technique and manual grinding didn't greatly affect the integrity of the siRNA. Furthermore, the siRNA was more stable in the lungs than in blood, suggesting the utility of pulmonar...
Source: Biological and Pharmaceutical Bulletin - July 6, 2013 Category: Drugs & Pharmacology Authors: Okuda T, Kito D, Oiwa A, Fukushima M, Hira D, Okamoto H Tags: Biol Pharm Bull Source Type: research

Glycolaldehyde induces cytotoxicity and increases glutathione and multidrug-resistance-associated protein levels in schwann cells.
Abstract Schwann cell injury is observed in diabetic neuropathy. It is speculated that glycolaldehyde (GA), a precursor of advanced glycation end products (AGEs), contributes to the pathogenesis and development of diabetic neuropathy. Here, we demonstrated for the first time that GA at near-physiological concentration decreased the viability of rat Schwann cells. In contrast, methylglyoxal, glyoxal, and 3-deoxyglucosone, all of which are AGE precursors, had no effects on cell viability. It is well known that methylglyoxal causes oxidative damage. In the present study, however, GA failed to induce reactive oxygen s...
Source: Biological and Pharmaceutical Bulletin - July 6, 2013 Category: Drugs & Pharmacology Authors: Sato K, Tatsunami R, Yama K, Tampo Y Tags: Biol Pharm Bull Source Type: research

Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes.
Abstract We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-l-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol). The ternary complexes were constructed by the addition of γ-polyglutamic acid (γ-PGA) t...
Source: Biological and Pharmaceutical Bulletin - June 8, 2013 Category: Drugs & Pharmacology Authors: Kodama Y, Harauchi S, Kawanabe S, Ichikawa N, Nakagawa H, Muro T, Higuchi N, Nakamura T, Kitahara T, Sasaki H Tags: Biol Pharm Bull Source Type: research

Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy.
Abstract Novel polycation liposomes decorated with cyclic(Cys-Arg-Gly-Asp-D-Phe) peptide (cyclicRGD)-polyethylene glycol (PEG) (RGD-PEG-polycation liposomes (PCL)) were previously developed for cancer therapy based on RNA interference. Here, we demonstrate the in vivo delivery of small interfering RNA (siRNA) to tumors by use of RGD-PEG-PCL in B16F10 melanoma-bearing mice. Pharmacokinetic data obtained by positron emission tomography showed that cholesterol-conjugated siRNA formulated in RGD-PEG-PCL markedly accumulated in the tumors. Delivered by RGD-PEG-PCL, a therapeutic cocktail of siRNAs composed of cholester...
Source: Biological and Pharmaceutical Bulletin - February 10, 2013 Category: Drugs & Pharmacology Authors: Kenjo E, Asai T, Yonenaga N, Ando H, Ishii T, Hatanaka K, Shimizu K, Urita Y, Dewa T, Nango M, Tsukada H, Oku N Tags: Biol Pharm Bull Source Type: research

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