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Significant Growth Inhibition (significant + growth_inhibition)
Selected AbstractsReduced growth of rainbow trout (Oncorhynchus mykiss) fed a live invertebrate diet pre-exposed to metal-contaminated sedimentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2004James A. Hansen Abstract Juvenile rainbow trout (Oncorhynchus mykiss) were fed live diets of Lumbriculus variegatus cultured in metal-contaminated sediments from the Clark Fork River Basin (MT, USA), an uncontaminated reference sediment, or an uncontaminated culture medium. Fish were tested in individual chambers; individual growth as well as the nutritional quality and caloric value of each trout's consumed diet were determined. Growth was measured following 14, 28, 42, 56, and 67 d of exposure. A subset of fish was sampled at 35 d for whole-body metals. Metals (whole body, digestive tract, and liver) and histology were measured at the end of the test. We observed significant growth inhibition in trout fed the contaminated diets; growth inhibition was associated with reductions in conversion of food energy to biomass rather than with reduced food intake. Growth inhibition was negatively correlated with As in trout tissue residues. Histological changes in contaminated treatments included hepatic necrosis and degenerative alterations in gallbladder. The present study provides evidence that metal-contaminated sediments can pose a hazard to trout health through a dietary exposure pathway. [source] Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growthINTERNATIONAL JOURNAL OF CANCER, Issue 5 2003Kelli M. Bullard Abstract HA is a glycosaminoglycan that is synthesized on the inner surface of the plasma membrane and secreted into the pericellular matrix. HA and its biosynthetic enzymes (HAS1, HAS2 and HAS3) are thought to participate in tumor growth and cancer progression. In our study, colon carcinoma cells isolated from a lymph node metastasis (SW620) produced more pericellular HA and expressed higher levels of HAS3 mRNA compared to cells isolated from a primary colon carcinoma (SW480). To assess functionality, HAS3 expression in SW620 cells was inhibited by transfection with an asHAS3 construct. Decreased HA secretion and cell-surface retention by asHAS3 transfectants were confirmed using competitive binding and particle exclusion assays. Anchorage-independent growth, a correlate of tumor growth in vivo, was assessed by colony formation in soft agar. SW620 cells stably transfected with asHAS3 demonstrated significant growth inhibition, as evidenced by fewer colonies and smaller colony area than either SW620 cells or cells transfected with vector alone. Addition of exogenous HA restored growth in asHAS3 transfectants. Thus, we demonstrate that pericellular HA secretion and retention and HAS3 expression are increased in metastatic colon carcinoma cells relative to cells derived from a primary tumor. Inhibition of HAS3 expression in these cells decreased the pericellular HA matrix and inhibited anchorage-independent growth. These data suggest that HA and HAS3 function in the growth and progression of colon carcinoma. © 2003 Wiley-Liss, Inc. [source] Cooperative inhibitory effect of ZD1839 (Iressa) in combination with 17-AAG on glioma cell growth,MOLECULAR CARCINOGENESIS, Issue 5 2006Daniel R. Premkumar Abstract ZD1839 ("Iressa") is an orally active, selective epidermal growth factor (EGF) receptor-tyrosine kinase inhibitor. We evaluated the antitumor activity of ZD1839 in combination with HSP90 antagonist, 17-AAG in malignant human glioma cell lines. ZD1839 independently produced a dose-dependent inhibition of cellular proliferation in glioma cells grown in culture with time- and dose-dependent accumulation of cells in G1 phase of the cell cycle on flow cytometric analysis, although the concentrations required for optimal efficacy were at or above the limits of clinically achievable levels. Because the heat shock protein (HSP) is involved in the conformational maturation of a number of signaling proteins critical to the proliferation of malignant glioma cells, we hypothesized that the HSP90 inhibitor 17-AAG would potentiate ZD 1839-mediated glioma cytotoxicity by decreasing the activation status of EGF receptor, as well as downregulating the levels of other relevant signaling effectors. We, therefore, examined the effects of ZD1839 and 17-AAG, alone and in combination, on signal transduction and apoptosis in a series of malignant glioma cell lines. Simultaneous exposure to these inhibitors significantly induced cell death and quantitative analysis revealed that interaction between ZD1839 and 17-AAG-induced cytotoxicity was synergistic, leading to a pronounced increase in active caspase-3 and PARP cleavage. No significant growth inhibition or caspase activation was seen in control cells. The enhanced cytotoxicity of this combination was associated with diminished Akt activation and a significant downregulation of EGFR receptor, Raf-1 and mitogen activated protein kinase (MAPK). Cells exposed to 17-AAG and ZD1839 displayed a significant reduction in cell cycle regulatory proteins, such as CDK4 and CDK6. Taken together, these findings suggest that ZD1839, an EGF receptor tyrosine kinase inhibitor, plays a critical role in regulating the apoptotic response to 17-AAG and that multi-site targeting of growth signaling and cell survival pathways could provide a potent strategy to treat patients with malignant gliomas. © 2006 Wiley-Liss, Inc. [source] Cleavage of mRNAs and role of tmRNA system under amino acid starvation in Escherichia coliMOLECULAR MICROBIOLOGY, Issue 2 2008Xia Li Summary We have shown previously that ribosome stalling during translation caused by various reasons leads to mRNA cleavage, resulting in non-stop mRNAs that are eliminated in a tmRNA-dependent manner. Amino acid starvation is a physiological condition in which ribosome stalling is expected to occur more frequently. Here we demonstrate that mRNA cleavage is induced by amino acid starvation, resulting in accumulation of truncated mRNAs in cells lacking tmRNA. The truncated mRNAs are eliminated in wild-type cells, indicating that the tmRNA system rapidly degrade the truncated mRNAs. The cleavage pattern of model mRNAs in which serine codons were replaced with threonine codons indicated that mRNA cleavage occurs near serine codons in response to serine starvation. Cells lacking all of the five known toxin loci were proficient in mRNA cleavage, showing that toxin,antitoxin systems are not responsible for the cleavage. A mild serine starvation caused a significant growth inhibition in cells lacking tmRNA but not in wild-type cells. The ribosome-mediated mRNA cleavage along with the tmRNA system is an important mechanism that enables cells to adapt to amino acid starvation conditions. [source] Effects of fluorides on Candida albicansORAL DISEASES, Issue 4 2008S Flisfisch Aims:, To assess whether a short exposure of Candida albicans to commonly used fluorides would affect growth, cell surface hydrophobicity, and adherence to buccal epithelial cells. Methods:,Candida albicans ATCC 90028 and 11 clinical isolates were used. Minimal inhibitory concentrations (MICs) of sodium fluoride (NaF) and of an amine fluoride,/,stannous fluoride combination (AmF,/,SnF2) were determined. Yeasts were exposed to MICs of tested agents for 1 h. Subsequently, their growth was recorded spectrophotometrically. Their cell surface hydrophobicity was assessed with n -hexadecane. Adherence to buccal epithelial cells was determined microscopically. Phosphate buffered saline (PBS) and chlorhexidine digluconate (CHX) served as controls. All results were analyzed by one-way ANOVA. Results:, MICs of AmF,/,SnF2 and CHX varied between 1 and 4 ,g ml,1, whereas those of NaF were 15 000 ,g ml,1. Statistically significant growth inhibition was detected after AmF,/,SnF2 (OD24 h ± SD 0.457 ± 0.059) and CHX (0.175 ± 0.065) in comparison with PBS (0.925 ± 0.087) and NaF (0.813 ± 0.081). All strains demonstrated uniform behavior. Only minor changes in cell surface hydrophobicity and adherence to buccal epithelial cells (BEC) were detected. Conclusion:, Growth inhibition of AmF,/,SnF2 was comparable with that of CHX whereas NaF had a weaker effect. Exposure to the fluorides did not seem to alter the cell surface hydrophobicity nor adherence to BEC. [source] Chemical modification of chitosan: synthesis and biological activity of new heterocyclic chitosan derivativesPOLYMER INTERNATIONAL, Issue 2 2008Mohamed EI Badawy Abstract BACKGROUND: Numerous works have been published on the chemical modification of chitosan; this polymer is still being modified, leading to various derivatives with improved properties. In the present study, heterocyclic aldehydes including furan-2-carbaldehyde, 5-methylfuran-2-carbaldehyde, 3-pyridine carboxyaldehyde, benzo[d][1,3]dioxole-5-carbaldehyde and 4-oxo-4H -chromene-3-carbaldehyde were reacted with chitosan by a reductive alkylation reaction to produce for the first time five new N -heterocyclic chitosan derivatives to improve the biological activity of chitosan against the most important economic plant pests including fungi and insects, in particular the cotton leafworm Spodoptera littoralis. RESULTS: The chemical structures of the synthesized compounds were confirmed by 1H NMR spectroscopy and the degree of substitution ranged from 0.30 to 0.43. The fungicidal assessment was investigated in vitro using a mycelia radial growth inhibition technique against soil-borne pathogenic fungi Fusarium oxysporum and Pythium debaryanum and the rice leaf blast Pyricularia grisea. The results showed that N -[(5-methylfuran-2-yl)methyl] chitosan was the most active against P. grisea with an EC50 value of 0.919 mg mL,1 while N -(benzo[d][1,3]dioxol-5-ylmethyl) chitosan and N -(methyl-4H -chromen-4-one) chitosan exhibited the most potent fungicidal activity against P. debaryanum and F. oxysporum. An insecticidal bioassay against the larvae of S. littoralis showed that N -(methyl-4H -chromen-4-one) chitosan exhibited a significant growth inhibition and antifeedant activity among the synthesized compounds. CONCLUSION: The chemical modification of chitosan molecule with a heterocyclic moiety led to an enhancement in the biological activity against the plant pathogenic fungi F. oxysporum, P. debaryanum and P. grisea and the cotton leafworm insect S. littoralis. Copyright © 2007 Society of Chemical Industry [source] Acetate-inducible protein overexpression from the glnAp2 promoter of Escherichia coliBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2001William R. Farmer Abstract The Ntr regulon in Escherichia coli has previously been engineered to control the expression of a heterologous metabolic pathway. In this study, we reengineered the same system for protein production. In the absence of NRII (glnL gene product), we showed that glnAp2 can be an effective promoter for protein production that is inducible by exogenous acetate, but both the induction ratio and the range of modulation are low. To deal with this issue, we inactivated phosphotransacetylase (pta gene product), which disrupts the acetate pathway and denies the cell the ability to synthesize acetate. With this additional modification, gene expression from glnAp2 can be controlled by directly adding acetate into the growth medium. Using a lacZ reporter fusion, we found that glnAp2 induction was modulatable over a range of potassium acetate concentrations, and the induction/noninduction ratio increased to 77 in the absence of pta. The extracellular acetate required for maximal induction is lower than the concentration that causes toxicity, and thus growth inhibition by acetate addition was not a matter of concern. Furthermore, compared to the Ptac promoter, overexpression of a model protein using the modified glnAp2 promoter system did not cause significant growth inhibition, although a higher level of protein expression was achieved. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 504,509, 2001. [source] Raloxifene, an oestrogen-receptor-,-targeted therapy, inhibits androgen-independent prostate cancer growth: results from preclinical studies and a pilot phase II clinical trialBJU INTERNATIONAL, Issue 4 2006RONALD L. SHAZER OBJECTIVES To determine, in preclinical in vivo animal and in clinical studies, whether raloxifene (a selective oestrogen-receptor (ER) modulator that targets ER-, and induces apoptosis in vitro in androgen-independent prostate cancer, AIPC cells) affects prostate cell differentiation, proliferation and carcinogenesis, and in the pilot phase II clinical trial, the response rate and duration of patients with AIPC treated with a daily oral dose of raloxifene. PATIENTS, MATERIALS AND METHODS Tumour proliferation rate in response to raloxifene treatment, and molecular markers of cell cycle and apoptosis, were evaluated in established ER-,-positive androgen-dependent (AD) CWR22 and AI CWRSA9 human xenograft prostate cancer models. Twenty-one patients with AIPC and evidence of disease progression were enrolled into the clinical trial and given daily oral raloxifene. RESULTS There was significant growth inhibition by raloxifene in the ADPC and AIPC xenograft models (CWR22 68%, P < 0.010; CWRSA9 64%, P < 0.001), with no tumour regression. There was evidence of G1 arrest by increased p27kip1 expression in the raloxifene-treated group. Eighteen patients comprised the efficacy analysis, as three withdrew before the first evaluation. At the first evaluation, five men had stable disease and continued on the study for a median of five cycles. The longest response was 17 cycles. Drug related toxicity was minimal. CONCLUSION Raloxifene has activity in xenograft models, slowing disease progression. This translated to possible disease stabilization in patients with AIPC. Further studies are warranted. [source] Amrubicin, a novel 9-aminoanthracycline, enhances the antitumor activity of chemotherapeutic agents against human cancer cells in vitro and in vivoCANCER SCIENCE, Issue 3 2007Mitsuharu Hanada Amrubicin, a completely synthetic 9-aminoanthracycline derivative, is an active agent in the treatment of untreated extensive disease-small-cell lung cancer and advanced non-small-cell lung cancer. Amrubicin administered intravenously at 25 mg/kg substantially prevented the growth of five of six human lung cancer xenografts established in athymic nude mice, confirming that amrubicin as a single agent was active in human lung tumors. To survey which antitumor agent available for clinical use produces a synergistic interaction with amrubicin, we examined the effects in combinations with amrubicinol, an active metabolite of amrubicin, of several chemotherapeutic agents in vitro using five human cancer cell lines using the combination index (CI) method of Chou and Talalay. Synergistic effects were obtained on the simultaneous use of amrubicinol with cisplatin, irinotecan, gefitinib and trastuzumab, with CI values after 3 days of exposure being <1. Additive effect was observed with the combination containing vinorelbine with CI values indistinguishable from 1, while the combination of amrubicinol with gemcitabine was antagonistic. All combinations tested in vivo were well tolerated. The combinations of cisplatin, irinotecan, vinorelbine, trastuzumab, tegafur/uracil, and to a lesser extent, gemcitabine with amrubicin caused significant growth inhibition of human tumor xenografts without pronouncedly enhancing body weight loss, compared with treatment using amrubicin alone at the maximum tolerated dose. Growth inhibition of tumors by gefitinib was not antagonized by amrubicin. These results suggest that amrubicin appears to be a possible candidate for combined use with cisplatin, irinotecan, vinorelbine, gemcitabine, tegafur/uracil or trastuzumab. (Cancer Sci 2007; 98: 447,454) [source] | |||||||||||||