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Ufuk Eryilmaz Buket Demirci Saliha Aksun Murat Boyacioglu Cagdas Akgullu Tevfik Fikret Ilgenli Hande Sultan Yalinkilinc Mehmet Bilgen 《PloS one》2015,10(12)
This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against. 相似文献
53.
The role of phosphatidylinositol 3-kinase, rho family GTPases, and STAT3 in Ros-induced cell transformation. 总被引:3,自引:0,他引:3
Kevin T Nguyen Cong S Zong Shailaja Uttamsingh Pallavi Sachdev Monica Bhanot Mai-Thao Le Joseph L-K Chan Lu-Hai Wang 《The Journal of biological chemistry》2002,277(13):11107-11115
Using loss-of-function mutants of Ros and inducible epidermal growth factor receptor-Ros chimeras we investigated the role of various signaling pathways in Ros-induced cell transformation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway with the MEK (MAP/extracellular signal-regulated kinase kinase) inhibitor PD98059 had little effect on the Ros-induced monolayer and anchorage-independent growth of chicken embryo fibroblasts and NIH3T3 cells even though more than 70% of the MAPK was inhibited. In contrast, inhibiting the phosphatidylinositol 3-kinase (PI3K) pathway with the drug LY294002, a dominant negative mutant of PI3K, Deltap85, or the phosphatidylinositol phosphatase PTEN (phosphatase and tensin homologue deleted in chromosome ten) resulted in a dramatic reduction of v-Ros- and epidermal growth factor receptor-Ros-promoted anchorage-independent growth of chicken embryo fibroblasts and NIH3T3 cells, respectively. Parallel and downstream components of PI3K signaling such as the Rho family GTPases (Rac, Rho, Cdc42) and the survival factor Akt were all shown to contribute to Ros-induced anchorage-independent growth, although Rac appeared to be less important for Ros-induced colony formation in NIH3T3 cells. Furthermore, the transformation-attenuated v-Ros mutants F419 and DI could be complemented by constitutively active mutants of PI3K and Akt. Finally, we found that overexpressing a constitutively active mutant of STAT3 (STAT3C) conferred a resistance to the inhibition of Ros-induced anchorage-independent growth by LY294002, suggesting a possible overlap of functions between PI3K and STAT3 signaling in mediating Ros-induced anchorage-independent growth. 相似文献
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Nilantha Sirisoma Azra Pervin Bao Nguyen Candace Crogan-Grundy Shailaja Kasibhatla Ben Tseng John Drewe Sui Xiong Cai 《Bioorganic & medicinal chemistry letters》2009,19(8):2305-2309
As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl)pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048–0.024 μM in the apoptosis induction assay against T47D cells, were identified through the SAR studies. In a tubulin polymerization assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited tubulin polymerization with an IC50 value of 0.5 μM, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the tubulin assay at up to 50 μM. 相似文献
57.
William Kemnitzer Jared Kuemmerle Han-Zhong Zhang Shailaja Kasibhatla Ben Tseng John Drewe Sui Xiong Cai 《Bioorganic & medicinal chemistry letters》2009,19(15):4410-4415
As a continuation of our efforts to discover and develop the 3-aryl-5-aryl-1,2,4-oxadiazole series of apoptosis inducers as potential anticancer agents, we explored substitutions at the 2- and 3-positions of the 3-aryl group to improve the aqueous solubility properties and identify development candidates. A small substitution such as methyl or hydroxymethyl at the 2-position was well tolerated. This modification, in combination with a 3-substituted furan ring as the 5-aryl group, resulted in 4g and 4h, which have improved solubility properties. Compound 4g was found to have good in vivo efficacy in animal studies via intravenous administration. 相似文献
58.
Pérez Velasco R Praditsitthikorn N Wichmann K Mohara A Kotirum S Tantivess S Vallenas C Harmanci H Teerawattananon Y 《PloS one》2012,7(2):e30333
Background
Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted.Methods
The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers.Results
44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries.Conclusion
The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies. 相似文献59.
Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin-1 and reduced Kirrel-2 expressions. Kirrel-2-mediated cell adhesion influences odorant receptor-specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide-gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channel-deficient mice further indicated that RAR-regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid-degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs. 相似文献
60.
Self-organized flocking in mobile robot swarms 总被引:1,自引:0,他引:1
In this paper, we study self-organized flocking in a swarm of mobile robots. We present Kobot, a mobile robot platform developed specifically for swarm robotic studies. We describe its infrared-based short range sensing system, capable of measuring the distance from obstacles and detecting kin robots, and a novel sensing system called the virtual heading system (VHS) which uses a digital compass and a wireless communication module for sensing the relative headings of neighboring robots. We propose a behavior based on heading alignment and proximal control that is capable of generating self-organized flocking in a swarm of Kobots. By self-organized flocking we mean that a swarm of mobile robots, initially connected via proximal sensing, is able to wander in an environment by moving as a coherent group in open space and to avoid obstacles as if it were a “super-organism”. We propose a number of metrics to evaluate the quality of flocking. We use a default set of behavioral parameter values that can generate acceptable flocking in robots, and analyze the sensitivity of the flocking behavior against changes in each of the parameters using the metrics that were proposed. We show that the proposed behavior can generate flocking in a small group of physical robots in a closed arena as well as in a swarm of 1000 simulated robots in open space. We vary the three main characteristics of the VHS, namely: (1) the amount and nature of noise in the measurement of heading, (2) the number of VHS neighbors, and (3) the range of wireless communication. Our experiments show that the range of communication is the main factor that determines the maximum number of robots that can flock together and that the behavior is highly robust against the other two VHS characteristics. We conclude by discussing this result in the light of related theoretical studies in statistical physics. 相似文献