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Cytostatic Effects (cytostatic + effects)

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Medical Sciences100%

Selected Abstracts

Evaluation of Cytotoxic and Cytostatic Effects in Saccharomyces cerevisiae by Poissoner Quantitative Drop Test

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2009
Nadine Paese Poletto
Current assay techniques, however, typically require the use of expensive technological equipment or chemical reagents, or they lack adequate testing sensitivity. The poissoner quantitative drop test (PQDT) assay is a sensitive, inexpensive and accurate method for evaluation of cytotoxicity and/or cytostatic effects of multiple chemical compounds in a single experiment. In this study, the sensitivity of the PQDT assay was evaluated in a wild-type Saccharomyces cerevisiae strain using 4-nitroquinoline-N - oxide (4-NQO) and methyl methanesulfonate (MMS), both cytotoxic and genotoxic standard compounds, and cytostatic 5-fluorouracil, an antitumoral drug. Yeast cell colony growth was measured in culture media containing increasing concentrations of the three chemical agents. The results showed that the PQDT assay was able to clearly differentiate the cytotoxic effect of 4-NQO and MMS from the cytostatic effect of 5-fluorouracil. Interestingly, the cytostatic effect of 5-fluorouracil followed an exponential decay curve with increasing concentrations, a phenomenon not previously described for this drug. The PQDT assay, in this sense, can be applied not only for cytotoxic/cytostatic assays, but also for pharmacodynamic studies using Saccharomyces cerevisiae as a model. [source]

Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2006
Seungwon Kim MD
Abstract Background. A preclinical evaluation of CPT-1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR-2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice. Methods. The cytotoxic and cytostatic effects of CPT-11 on ATC cell lines were evaluated. The antitumor effects of CPT-11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied. Results. CPT-11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT-11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT-11 and CPT-11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR-2 on tumor endothelium and decrease the tumor microvessel density. Conclusions. The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC. © 2005 Wiley Periodicals, Inc. Head Neck27: 389,399, 2006 [source]

Evaluation of Cytotoxic and Cytostatic Effects in Saccharomyces cerevisiae by Poissoner Quantitative Drop Test

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2009
Nadine Paese Poletto
Current assay techniques, however, typically require the use of expensive technological equipment or chemical reagents, or they lack adequate testing sensitivity. The poissoner quantitative drop test (PQDT) assay is a sensitive, inexpensive and accurate method for evaluation of cytotoxicity and/or cytostatic effects of multiple chemical compounds in a single experiment. In this study, the sensitivity of the PQDT assay was evaluated in a wild-type Saccharomyces cerevisiae strain using 4-nitroquinoline-N - oxide (4-NQO) and methyl methanesulfonate (MMS), both cytotoxic and genotoxic standard compounds, and cytostatic 5-fluorouracil, an antitumoral drug. Yeast cell colony growth was measured in culture media containing increasing concentrations of the three chemical agents. The results showed that the PQDT assay was able to clearly differentiate the cytotoxic effect of 4-NQO and MMS from the cytostatic effect of 5-fluorouracil. Interestingly, the cytostatic effect of 5-fluorouracil followed an exponential decay curve with increasing concentrations, a phenomenon not previously described for this drug. The PQDT assay, in this sense, can be applied not only for cytotoxic/cytostatic assays, but also for pharmacodynamic studies using Saccharomyces cerevisiae as a model. [source]

Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2007
M Kobori
Background and purpose: 5,,8,-Epidioxy-22E -ergosta-6, 22-dien-3,-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol peroxide. Experimental approach: After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS-induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT-PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells. Key results: Ergosterol peroxide suppressed LPS-induced TNF-, secretion and IL-1,/, expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS-induced DNA binding activity of NF-,B and C/EBP,, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down-regulated the expression of low-density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG-CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress-inducible genes, and the cyclin-dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon-inducible genes. Conclusion and Implication: Our results suggest that ergosterol peroxide and ergosterol suppress LPS-induced inflammatory responses through inhibition of NF-,B and C/EBP, transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells. British Journal of Pharmacology (2007) 150, 209,219. doi:10.1038/sj.bjp.0706972 [source]

Blue Light Inhibits the Growth of B16 Melanoma Cells

CANCER SCIENCE, Issue 5 2002
Masayuki Ohara
Although a number of studies have been carried out to examine the biological effects of radiation and ultraviolet radiation (UV), little is known concerning the effects of visible light. In the present study, exposure of B16 melanoma cells to blue light (wavelength 470 nm, irradiance 5.7 mW/cm2) from a light-emitting diode (LED) inhibited cell growth in proportion to the period of exposure, with no increase observed in the number of dead cells. The number of B16 melanoma colonies that formed after exposure to blue light for 20 min was only slightly less than that in non-exposed controls, but the colony size as assessed by the area covered by colonies and cell counts per colony were markedly decreased. The percentages of G0/G1 and G2/M phase cells were markedly increased, with a reduction in S phase cells as determined by flow cytometry after exposure to blue light. Furthermore, analysis of the incorporation of 5,bromo,2,,deoxyuridine (BrdU) into DNA also showed a reduction in the percentage of S phase cells after exposure. These results indicate that blue light exerts cytostatic effects, but not a cytocidal action, on B16 melanoma cells. [source]