1,724,079 research outputs found
Abstract 4525: Targeting ROS to kill cisplatin-resistant cells
No full textAbstract
Cisplatin (CP) resistance remains a major problem in the treatment of both small cell and non small cell lung cancer. We have previously shown that inhibiting mTOR can restore CP sensitivity; however, not all CP resistant cell lines are sensitive to mTOR inhibitor. Our findings have led us to search for an alternative target in these CP resistant cells. We have discovered that CP resistant cells share one common biochemical parameter which is increased reactive oxygen species (ROS) when compared to normal cells and their parental cells counterpart. Thus, further increased ROS in these CP resistant cells can push them beyond their tolerance limit which ultimately leads to cell death. We have found that increased expression of NADPH oxidase 4 (NOX4) and lower levels of thioredoxin (Trx) correlate with the high levels of ROS seen in CP resistant cell lines. Using elesclomol (N′1, N′3-dimethyl-N′1, N′3- bis [phenylcarbonothioyl] propanedihydrazide (formerly STA-4783, provided by Synta Pharmaceuticals)), an agent which is known to increase ROS, we demonstrated that elesclomol can increase H2O2 levels in CP resistant lung cancer cell lines (CP-R). Moreover, elesclomol is also significantly more cytotoxic toward CP-R with the ID50 dosage of 4-10 fold less than their parental cells (PC) counterpart and normal cells, BJ-1 (see table below). The percentage of apoptosis is also significantly higher in CP-R (65%) vs. PC (3%). The cytotoxic effect of elesclomol in CP-R is accompanied by further decrease in Trx and glutathione (GSH) antioxidant systems, while opposite results were found in PC and normal cells. This cytotoxic effect can be reversed by an antioxidant, N-acetylcysteine (NAC, 0.1mM). Furthermore, we have also found that elesclomol also increased intracellular CP and hence enhanced CP sensitivity in CP-R cells. We conclude that elesclomol is highly effective in CP resistant cells which express high basal levels of ROS and should be considered for treatment of CP resistant tumor.ID50 Dosage of Elesclomol in Parental (PC) vs. Cisplatin Resistant (CP-R) Lung Cancer Cell Lines SCLC1(PC)SCLCSR2(CP-R)SCLCB(PC)SCLCBC (CP-R)NSCLCS(PC)NSCLCSC(CP-R)BJ1Elesclomol(nM)50+/−2.55+/−0.541+/−3.89+/−1.259+/−4.610+/−2.265+/−5.5
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4525.</jats:p
Block Card 4525 McKain Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 4525 McKain Drive (Toledo, Ohio) | Dwelling | Greenbush Knolls Addition (Toledo, Ohio) | Trilby Area (Toledo, Ohio)
Block Card 4525 Carskaddon Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Garrison Colonial Style | 4525 Carskaddon Avenue (Toledo, Ohio) | Dwelling | Corey Woods Addition (Toledo, Ohio) | Westgate Area (Toledo, Ohio
Block Card 4525 Granville Court
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Modern Colonial Style | 4525 Granville Court (Toledo, Ohio) | Dwelling | Corey Woods Addition (Toledo, Ohio) | Westgate Area (Toledo, Ohio
Block Card 4525 Eddington Court
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Cape Cod Style | 4525 Eddington Court (Toledo, Ohio) | Dwelling | Corey Woods Addition (Toledo, Ohio) | Westgate Area (Toledo, Ohio
Block Card 4525 Penridge Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 4525 Penridge Road (Toledo, Ohio) | Dwelling | Corey Woods Addition (Toledo, Ohio) | Westgate Area (Toledo, Ohio
Flint Vehicle City at 4525 Driveway, Flint, Mich.
No full text3.5x5.5 color postcard of 4525 Driveway in Flint, Michigan with horse-drawn buggies, seen through wrought iron arch with sign 'Flint Vehicle City.
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Un-weighted and weighted characteristics of study population in Jamaica’s National Drug Survey, 2016 (N = 4525).
No full textUn-weighted and weighted characteristics of study population in Jamaica’s National Drug Survey, 2016 (N = 4525).</p
- …
