717 research outputs found

    The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

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    Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

    Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids

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    BACKGROUND: Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells. METHODS: In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (Curcuma longa Linn), were compared for their potential ability to modulate the human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR. RESULTS: Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures. CONCLUSION: These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased MDR-1 gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents

    Anthocyanins and Proanthocyanidins in Natural Pigmented Rice and Their Bioactivities

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    Natural pigmented rice is mainly black, red, and dark purple and contains a variety of flavones, tannins, phenolic, sterols, oryzanols, and essential oils. Anthocyanins and proanthocyanidins belonging to plant flavonoids are thought of as the major functional components found in black, red, and purple rice and contribute to the intense color of many fruits, vegetables, and pigmented cereals such as blueberries, grapes, red cabbages, and purple sweet potatoes. Recent data have indicated the potential for isolating and characterizing the nutrition and non-nutritive components in colored fruits, vegetables, and cereals for their potential chemopreventive and pharmaceutical agents. This chapter provides up-to-date coverage of pigmented rice in terms of the bioactive constituents, isolation, extraction and analytical methods, and related bioactivities. Special focus has been placed on the anti-inflammation, anticancer, and antiaging processes of the major components found in pigmented rice, especially with regard to germ and bran extracts

    Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade

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    OBJECTIVE: Acquired chemoresistance is a major obstacle in the clinical management of ovarian cancer. Therefore, searching for alternative therapeutic modalities is urgently needed. Bitter melon (Momordica charantia) is a traditional dietary fruit, but its extract also shows potential medicinal values in human diabetes and cancers. Here, we sought to investigate the extract of bitter melon (BME) in antitumorigenic and cisplatin-induced cytotoxicity in ovarian cancer cells. METHODS: Three varieties of bitter melon were used to prepare the BME. Ovarian cancer cell lines, human immortalized epithelial ovarian cells (HOSEs), and nude mice were used to evaluate the cell cytotoxicity, cisplatin resistance, and tumor inhibitory effect of BME. The molecular mechanism of BME was examined by Western blotting. RESULTS: Cotreatment with BME and cisplatin markedly attenuated tumor growth in vitro and in vivo in a mouse xenograft model, whereas there was no observable toxicity in HOSEs or in nude mice in vivo. Interestingly, the antitumorigenic effects of BME varied with different varieties of bitter melon, suggesting that the amount of antitumorigenic substances may vary. Studies of the molecular mechanism demonstrated that BME activates AMP-activated protein kinase (AMPK) in an AMP-independent but CaMKK (Ca2+/calmodulin-dependent protein kinase)-dependent manner, exerting anticancer effects through activation of AMPK and suppression of the mTOR/p70S6K and/or the AKT/ERK/FOXM1 (Forkhead Box M1) signaling cascade. CONCLUSION: BME functions as a natural AMPK activator in the inhibition of ovarian cancer cell growth and might be useful as a supplement to improve the efficacy of cisplatin-based chemotherapy in ovarian cancer.published_or_final_versio

    Reviews on Physically Based Controllable Fluid Animation

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    In computer graphics animation, animation tools are required for fluid-like motions which are controllable by users or animator, since applying the techniques to commercial animations such as advertisement and film. Many developments have been proposed to model controllable fluid simulation with the need in realistic motion, robustness, adaptation, and support more required control model. Physically based models for different states of substances have been applied in general in order to permit animators to almost effortlessly create interesting, realistic, and sensible animation of natural phenomena such as water flow, smoke spread, etc. In this paper, we introduce the methods for simulation based on physical model and the techniques for control the flow of fluid, especially focus on particle based method. We then discuss the existing control methods within three performances; control ability, realism, and computation time. Finally, we give a brief of the current and trend of the research areas

    Influence of Carbon Black/Silica Hybrid Ratio on Properties of Passenger Car Tire Sidewall

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    Influence of carbon black (CB)/precipitated silica (SiO2) hybrid ratio on properties of a passenger car tire (PCT) sidewall based on natural rubber (NR) and butadiene rubber (BR) blend was investigated. Rubbers filled with various hybrid filler ratios at a constant loading of 50 phr were prepared and tested. The filler reinforcement efficiency in association with crucial properties of the tire sidewall were of interest. Results show the enhanced rubber–filler interaction with increasing SiO2 fraction leading to the improvement in many vulcanizate properties including hardness, tensile strength, tear strength and fatigue resistance, at the expense of cure efficiency and hysteretic behaviors (i.e., reduced heat build-up resistance and increased dynamic set). The results also suggest the improvement in tire sidewall performance of the NR/BR vulcanizates reinforced with CB/SiO2 hybrid filler, compared to that of the CB-filled vulcanizate

    Thermal stabilization of thin gold nanowires by surfactant-coating: a molecular dynamics study

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    The thermal stabilization of thin gold nanowires with a diameter of about 2 nm by surfactants is investigated by means of classical molecular dynamics simulations. While the well-known melting point depression leads to a much lower melting of gold nanowires compared to bulk gold, coating the nanowires with surfactants can reverse this, given that the attractive interaction between surfactant molecules and gold atoms lies beyond a certain threshold. It is found that the melting process of coated nanowires is dominated by surface instability patterns, whereas the melting behaviour of gold nanowires in vacuum is dominated by the greater mobility of atoms with lower coordination numbers that are located at edges and corners. The suppression of the melting by surfactants is explained by the isotropic pressure acting on the gold surface (due to the attractive interaction) which successfully suppresses large-amplitude thermal motions of the gold atoms. (Note that this is a pre-peer-reviewed version which has been submitted to Nanoscale.)Comment: 13 pages, 7 figure

    Theoretical Study of the Adsorption of Ethylene on Alkali-Exchanged Zeolites

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    ABSTRACT: The structures of alkali-exchanged faujasite (X-FAU, X ϭ Li ϩ or Na ϩ ion) and ZSM-5 (Li-ZSM-5) zeolites and their interactions with ethylene have been investigated by means of quantum cluster and embedded cluster approaches at the B3LYP/6-31G (d, p) level of theory. Inclusion of the Madelung potential from the zeolite framework has a significant effect on the structure and interaction energies of the adsorption complexes and leads to differentiation of different types of zeolites (ZSM-5 and FAU) that cannot be drawn from a typical quantum cluster model, H 3 SiO(X)Al(OH) 2 OSiH 3 . The Li-ZSM-5 zeolite is predicted to have a higher Lewis acidity and thus higher ethylene adsorption energy than the Li-FAU zeolites (16.4 vs. 14.4 kcal/mol), in good agreement with the known acidity trend of these two zeolites. On the other hand, the cluster models give virtually the same adsorption energies for both zeolite complexes (8.9 vs. 9.1 kcal/mol). For the larger cation-exchanged Na-FAU complex, the adsorption energy (11.6 kcal/mol) is predicted to be lower than that of Li-FAU zeolites, which compares well with the experimental estimate of about 9.6 kcal/ mol for ethylene adsorption on a less acidic Na-X zeolite

    Distribution of TGF-β1 C-509T polymorphism in Thai population

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    Transforming growth factor beta 1 (TGF-β1) C-509T gene polymorphism has been found to be associated with severity and susceptibility of many diseases. To examine the distribution of TGF-β1 C-509T (rs1800469) gene polymorphism in Thai population, 56 samples from unrelated healthy Thai volunteers were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype frequencies of TGF-β1 C-509T polymorphisms were as follows: CC 12.5%, CT 39.3% and TT 48.2%, which showed no statistically  significant differences to those of Chinese (Han) (p=0.390), Italian (p=0.057), Serbian (p=0.554) and Brazilian (p=0.442) population. However, a statistically significant difference was observedbetween the genotype frequencies found in this study and those of Indian (p=0.005), Russian  (p=0.048), English (p=0.006), German (p=0.014), and Egyptian (p<0.0001) population. In addition, statistically significant differences were also observed between allele frequencies in Thai population in this study and those of other reported groups; including, Chinese (Han), Indian,Russian, Italian, English, German, Serbian, Egyptian, and Brazilian (p<0.05). The frequency of Tallele in Thai was significantly higher than that of C allele, whereas in other reported groups, the Callele frequencies were significantly higher than T allele frequencies (p<0.05). From the above data, it is likely that the distribution of TGF-β1 C-509T gene polymorphisms in Thai population is different from those of Asian, Caucasian, Egyptian, and Brazilian population. This observation may be useful and could be applied for treatment and prognostic of disease in the future. However, further studies in larger numbers of Thai subjects are required for confirmation
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