Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies.

Histone deacetylase inhibitors represent a promising new class of anticancer agents. In the current investigation, we examined the activity of PXD101, a potent histone deacetylase inhibitor, used alone or in combination with clinically relevant chemotherapeutics (docetaxel, paclitaxel, and carboplatin), in preclinical in vitro and in vivo models of ovarian cancer. In vitro activity was examined in ovarian cancer and multidrug-resistant cell lines grown in monolayer culture, and in primary clinical ovarian cancer specimens grown in three-dimensional organoid culture.

Macroencapsulation protects against sensitization after allogeneic islet transplantation in rats.

Background: The aim of this study was to evaluate the risks of sensitization by islet grafts encapsulated in a bilaminar immunoprotective membrane.

Methods: We studied five groups of Lewis rats: one control group (no islets), two groups that received free islets (200 or 1000 s.c.

Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats.

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons.

Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits bone resorption. Identification of cardiotoxins as non-RGD integrin-binding proteins of the Ly-6 family.

Severe tissue necrosis with a retarded wound healing process is a major symptom of a cobra snakebite. Cardiotoxins (CTXs) are major components of cobra venoms that belong to the Ly-6 protein family and are implicated in tissue damage. The interaction of the major CTX from Taiwan cobra, i.

Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential.

Purpose: Little information is available on the heterogeneity of the vascular endothelium in hepatocellular carcinoma. The aim of this study was to identify the differentially expressed genes in tumor endothelial cells from highly metastatic hepatocellular carcinoma.

Experimental Design: Magnetic beads conjugated with anti-CD31 antibody were used to isolate vascular endothelial cells from hepatocellular carcinoma xenografts with different metastatic potentials in nude mice.

Effect of the selective estrogen receptor modulator arzoxifene on repopulation of hormone-responsive breast cancer xenografts between courses of chemotherapy.

Selective inhibition of repopulation of clonogenic tumor cells between courses of chemotherapy has potential to improve the effectiveness of treatment. Here we study arzoxifene, a short-acting selective estrogen receptor modulator, for its potential to inhibit repopulation in estrogen-dependent human breast cancer MCF-7 xenografts between courses of chemotherapy. Proliferation of tumor cells was evaluated by cyclin D1 expression and uptake of 5-bromo-2'-deoxyuridine.

Prostate secretory protein of 94 amino acids (PSP-94) and its peptide (PCK3145) as potential therapeutic modalities for prostate cancer.

This review focuses on the promising roles of prostate secretory protein of 94 amino acids (PSP-94) and one of its derived peptides (PCK3145) as potential therapeutic modalities for prostate cancer and its associated complications. Evaluation of these compounds was carried out in vitro and in vivo using syngeneic models of rat prostate cancer. Overproduction of parathyroid hormone-related protein (PTHrP) results in the development of hypercalcemia of malignancy in several malignancies including prostate cancer.

Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS.

Objective: To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS).

Methods: The study involved 21 SPMS patients who received subcutaneous (s.c.

[Ginseng modulates the immune response via its effect on cytokine production--secondary publication].

Ginseng has been shown to modulate the immune system. In this study, ginseng"s effects against chronic P. aeruginosa lung infection in animal models and its cytokine-modulating effects on leukocytes were investigated.

VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth.

Purpose: We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (VEGI, TL1), with a Lewis lung cancer murine tumor model.

Experimental Design: Recombinant human VEGI-192 was produced in Escherichia coli and purified to apparent homogeneity. The protein was given systemically via i.

Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor.

The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that the lymphangiogenic growth factor, vascular endothelial growth factor-C (VEGF-C), and its receptor, VEGF receptor-3 (VEGFR3), may play a pivotal role in the promotion of metastasis to regional lymph nodes. In this study, human prostate and melanoma tumor models that preferentially metastasize to the lymph nodes following s.

[Anti-tumor effect of anti-dsDNA autoantibodies].

Objective: To investigate effects of anti-dsDNA autoantibodies on growth of tumor in vitro and in vivo.

Methods: BALB/c mice were inoculated with inactivated tumor cells and challenged s.c.

Activation of mitochondrial ATP-sensitive potassium channels improves rotenone-related motor and neurochemical alterations in rats.

Our previous studies revealed that activation of mitochondrial ATP-sensitive potassium channels exerted protective effects on rotenone-treated rats and cultured cells. The aim of the present study is to examine the potential therapeutic effects of iptakalim, an ATP-sensitive potassium-channel opener, and diazoxide, a selective mitochondrial ATP-sensitive potassium-channel opener, on Parkinsonian symptoms in rats induced by rotenone. Rats were treated with rotenone (2.

In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors.

Purpose: The type I insulin-like growth factor receptor (IGF-IR) and its ligands have been shown to play a critical role in prostate carcinoma development, growth, and metastasis. Targeting the IGF-IR may be a potential treatment for prostate cancer. A fully human monoclonal antibody, A12, specific to IGF-IR, has shown potent antitumor effects in breast, colon, and pancreatic cancers in vitro and in vivo.

Poly(ethylene glycol)-poly(ester-carbonate) block copolymers carrying PEG-peptidyl-doxorubicin pendant side chains: synthesis and evaluation as anticancer conjugates.

Water soluble polymer anticancer conjugates can improve the pharmacokinetics of covalently bound drugs by limiting cellular uptake to the endocytic route, thus prolonging plasma circulation time and consequently facilitating tumor targeting by the enhanced permeability and retention (EPR) effect. Many of the first generation antitumor polymer conjugates used nonbiodegradable polymeric carriers which limits the molecular weight that can be safely used to <40,000 g/mol. The aim of this ambitious study was to synthesize and evaluate a novel, prototype biodegradable polymeric system based on high molecular weight, water-soluble functionalized polyesters.

[Protective effect of Armillaria mellea polysaccharide on mice bone marrow cell damage caused by cyclophosphamide].

Objective: To observe the effect of Armillaria mellea polysaccharide on mice bone marrow cells damage caused by Cyclophosphamide.

Method: Kunming purebred mice were used and stochastic divided into 5 groups: normal control group, positive control group (rhG-CSF 20 microg x kg(-1) x d(-1)), damage group of Cyclophosphamide (150 mg x kg(-1) x d(-1)), the protective group with A. mellea polysaccharide, low dose (25.

[Effect of Rhizoma pinelliae on vomiting in minks].

Objective: To study emetic and anti-emetic effects of Rhizoma pinelliae in minks.

Method: The emetic effect of raw pinellia 2 g kg(-1) (i.g.

Is risk-adjustor selection more important than statistical approach for provider profiling? Asthma as an example.

Objectives: To examine how the selections of different risk adjustors and statistical approaches affect the profiles of physician groups on patient satisfaction.

Data Sources: Mailed patient surveys. Patients with asthma were selected randomly from each of 20 California physician groups between July 1998 and February 1999.

Value of portal hemodynamics and hypersplenism in cirrhosis staging.

Aim: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging.

Methods: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices.

Effects of clozapine, olanzapine and haloperidol on ethanol-induced ascorbic acid release in mouse striatum.

The effects of clozapine, olanzapine and haloperidol on ethanol-induced striatal ascorbic acid (AA) release in mice were compared by using microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (4.0 g/kg i.

A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in rats.

The effect of A-317491 (5-([(3-Phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid), a recently described selective P2X3 and P2X(2/3) receptor antagonist, on inflammatory mechanical hyperalgesia was examined. In the rat Freund's complete adjuvant model of inflammatory pain, s.c.

Monitoring the response of orthotopic bladder tumors to granulocyte macrophage colony-stimulating factor therapy using the prostate-specific antigen gene as a reporter.

Purpose: Although orthotopic animal models of cancer best reflect the disease in humans, a major drawback of these models is the inability to monitor tumor growth accurately. Our aims were to produce a bladder tumor cell line (MB49) that secreted human prostate-specific antigen (PSA), analyze the feasibility and accuracy of PSA as a biomarker for monitoring orthotopic bladder tumor growth, and evaluate the effectiveness of granulocyte macrophage colony-stimulating factor (GM-CSF) gene therapy using this model.

Experimental Design: PSA secretion was assessed after both s.

Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice.

Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism.

Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent.

I.v. injection of secretin activates neurons in brain areas controlling autonomic function and emotion.

Isomers of HSCO: IR absorption spectra of t-HSCO in solid Ar.

Irradiation of an Ar matrix sample containing H2S and CO (or OCS) with an ArF excimer laser at 193 nm yields trans-HSCO (denoted t-HSCO). New lines at 1823.3, 931.