UK PubMed Central (United Kingdom)

AbstractStudies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been...Full Text Available

UK PubMed Central (United Kingdom)

Chemoprevention, especially through the use of naturally occurring phytochemicals capable of impeding the process of carcinogenesis at one or more steps, is an ideal approach for cancer management....Full Text Available

UK PubMed Central (United Kingdom)

Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib,...Full Text Available

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 ...

British Library Electronic Table of Contents (United Kingdom)

The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...

Energy Technology Data Exchange (ETDEWEB)

Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of /sup 125/I/sup -/ during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ) or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three ..cap alpha..-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the ..cap alpha.. 1 and ..cap alpha.. 2 subtypes in the sympathetic regulation of the blood flow in the ...

DEFF Research Database (Denmark)

Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse ...

British Library Electronic Table of Contents (United Kingdom)

ObjectivesTo assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. MethodsProstate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potenti...

British Library Electronic Table of Contents (United Kingdom)

9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 ?mg/kg/day to CD? rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglo...

British Library Electronic Table of Contents (United Kingdom)

In previous studies we have demonstrated that prion protein (PrP) interacts with tubulin and disrupts microtubular cytoskeleton by inducing tubulin oligomerization. These observations may explain the molecular mechanism of toxicity of cytoplasmic PrP in transmissible spongiform encephalopathies (TSEs). Here, we check whether microtubule associated proteins (MAPs) that regulate microtubule stability, influence the PrP-induced oligomerization of tubulin. We show that tubulin preparations depleted of MAPs are more prone to oligomerization by PrP than those containing traces of MAPs. Tau protein, a major neuronal member of the MAPs family, reduces the effect of PrP. Importantly, phosphorylation of Tau abolishes its ability to affect the PrP-induced oligomerization of tubulin. We propose that t...

British Library Electronic Table of Contents (United Kingdom)

Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NFkB-induced PLD1 expression vi...

British Library Electronic Table of Contents (United Kingdom)

In an environment of rapid technological change, countries in the developed and developing worlds need to improve the population's skills and competences. Since 1992, education reforms and various education sector documents and policy frameworks have been implemented to improve quality of education by getting more children into school through the abolishing of school fees, and the school feeding programme, whilst special efforts are made to deal with issues of gender inequality and the empowerment of women to meet the goals of Education for All and the education-related Millennium Development Goals 2 and 3. Though gains have been made in the area of gross enrolment ratio, there are still gross disparities in net enrolment and completion rates at regional level, with girls lagging behind bo...

Energy Technology Data Exchange (ETDEWEB)

Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg/sup 2 +/ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.

Energy Technology Data Exchange (ETDEWEB)

Since June 1997 the standards/specifications and inspection/certification of various products in Japan have been reviewed by Ministries and Agencies, with the aim of reducing direct government intervention to a necessary minimum and creating a free and fair socio-economic system that is fully opened to the international community and based on the rules of self-responsibility and market principles. Reflecting this policy the administrative regulations which prescribe technical standards as specific requirements have been revised by degrees into performance prescriptions. Detailed provisions in ordinances and notices have been abolished gradually to utilize voluntary standards and rules. In the nuclear energy field voluntary standards are being developed to make up statutory performance requirements by the Atomic Energy Society of Japan (AESJ) and the Japan Society of Mechanical Engineers (JSME) together with other organizations such as the Japan Electric ...

Energy Technology Data Exchange (ETDEWEB)

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former of which appeared to ...

Energy Technology Data Exchange (ETDEWEB)

Small unilamellar vesicles which form when gel-state long-chain phosphatidylcholines are mixed with micellar short-chain lecithins undergo an increase in size as the long-chain species melts to its liquid-crystalline form. Analysis of the vesicle population with quasi-elastic light scattering shows that the particle size increases from 90-A radius to greater than 5000-A radius. Resonance energy transfer experiments show total mixing of lipid probes with unlabeled vesicles only when the Tm of the long-chain phosphatidylcholine is exceeded. This implies that the large size change represents a fusion process. Aqueous compartments are also mixed during this transition. 31P NMR analysis of the vesicle mixtures above the phase transition shows a great degree of heterogeneity with large unilamellar particles coexisting with oligo- and multilamellar structures. Upon cooling the vesicles below the Tm, the original size distribution (e.g., small unilamellar vesicles) is obtained, as monitored by ...

Science.gov (United States)

In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell migration and MMP-2 activity as well as the binding capability of ...

International Nuclear Information System (INIS)

This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of _8_6Rb and 9-microns spheres labeled with "1"4"1Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia ...

Science.gov (United States)

beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH cells as beta-Bgt did. Abolishment of PLA(2) activity ...

International Nuclear Information System (INIS)

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not bind to soluble and ...

International Nuclear Information System (INIS)

We have previously shown that avian reovirus (ARV) #sigma#A and #sigma#NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on #sigma#A (I and II) and three epitopes (A, B, and C) on #sigma#NS. To further define the location of epitopes on #sigma#A and #sigma#NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of #sigma#A and #sigma#NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on #sigma#A was located at amino acid residues ...