1,725,460 research outputs found
Grain size composition of sediment core DM49-4404-1
No full textGrain size composition of sediment core DM49-4404-
Abstract 4404: Novel approach to circumvent cisplatin resistant lung cancer by targeting metabolism
No full textAbstract
For the past three decades, there are no drugs which could reverse cisplatin resistance or selectively kill these resistant cells. We have discovered that cisplatin resistant (CR) lung cancer shares one common factor which is increase in reactive oxygen species (ROS). Decreased intracellular thioredoxin-1(TRX1) due to excessive secretion was found in vitro and in vivo, as well as in patients’ serum which could be a primary contributory factor to higher mitochondria-ROS levels. Furthermore, CR cells possess significantly increased number of mitochondria and consume higher rates of oxygen. Key glycolytic enzymes (HKII and LDHA) and lactate production were decreased in CR cells which suggests rewiring of tumor metabolic pathways. NAD+, crucial co-factor of all redox systems, is significantly reduced in all CR cells. Importantly, treatment with riluzole (the FDA approved drug that interferes with cystine/glutamate pump and results in reduced intracellular glutathione (GSH) levels) led to further decrease in NAD+ and LDHA, as well as heightened oxidative stress in CR cells. ROS levels were increased (2-3X) more in resistant cells after riluzole treatment while no significant change occurred in parental cells. The ID50 dosage of parental cells were 3-4 fold more than theirs CR cell counterparts and no cytotoxicity were found in normal lung fibroblast (n=8; p<0.05). Addition of 200 µM NAD+ re-stabilized LDHA, reduced ROS, and reversed riluzole induced cell death. To further determine whether LDHA correlates with ROS levels and sensitivity to riluzole, we inhibited LDHA expressions in parental cell lines S and H460 using siRNA. Lactate productions were decreased in knockdown cells and further attenuated upon riluzole treatment when compared with scrambled control. Higher basal levels of ROS were obtained from S+siLDHA and H460+siLDHA and further increased in ROS levels were observed when treated with riluzole. We then evaluated the viability of these cells under riluzole treatment. Both siLDHA clones were sensitive to riluzole particularly in S+siLDHA which showed 4 fold more sensitivity. Importantly, treatment of riluzole also led to further decrease in LDHA expressions at both protein and mRNA levels. Using riluzole in 2 mouse xenograft models (H460CR (KRAS mutant) and SC (wt)) resulted in completely disappeared in wild type mice and were significant reduced in KRAS mutant mice (n=5 per treatment group; p<0.002). Repurpose of riluzole should be considered for future treatment of CR lung cancer patients. Supported by Department of Veterans Affairs, CDA2 award (1K2BX001289) and Woman Cancer Association Fund.
Citation Format: Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Lynn G. Feun, Macus T. Kuo, Niramol Savaraj. Novel approach to circumvent cisplatin resistant lung cancer by targeting metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4404. doi:10.1158/1538-7445.AM2017-4404</jats:p
St. Louis & San Francisco (SLSF) "Frisco" 4404
No full textA photograph print showing the St. Louis and San Francisco (SLSF) "Frisco" 4404, 4-8-2, Tulsa, OK
Block Card 4404 Springbrook 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 house | Dwelling | Talmadge Gardens Addition (Toledo, Ohio) | Westgate Area (Toledo, Ohio) | 4404 Springbrook Drive (Toledo, Ohio
Block Card 4404 Willys Parkway
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: Dwelling (Toledo, Ohio) | Side gabled | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4404 Willys Parkway (Toledo, Ohio) | Folk House Styl
Block Card 4404 East Way
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: Dwelling (Toledo, Ohio) | Cape Cod style | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4404 East Way (Toledo, Ohio
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
(Table 3a) Methane concentrations, its oxidation rate, Eh, and organic carbon contents in bottom sediments of the Kara Sea at Station DM49-4404-1b
No full text(Table 3a) Methane concentrations, its oxidation rate, Eh, and organic carbon contents in bottom sediments of the Kara Sea at Station DM49-4404-1
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