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Abstract 5148: Liposomal gemcitabine, FF-10832, improves gemcitabine (GEM) pharmacokinetics (PK) and increases anti-tumor efficacy
No full textAbstract
Introduction: FF-10832 is a liposome suspension optimized by Fujifilm nanotechnology containing 0.5 mg/mL GEM, cholesterol, HSPC, N-MPEG-DSPE. FF-10832 is expected to improve GEM PK and have strong anti-tumor effects. The PK and anti-tumor effects of FF-10832 were studied in mice and human pancreatic cancer xenograft models.
Methods: Single-dose murine plasma PK of FF-10832 1 mg/kg was compared to GEM 240mg/kg. In vivo activity of GEM 240 mg/kg and FF-10832 1-5 mg/kg IV once weekly were compared in human pancreatic cancer murine xenograft models; 2 subcutaneous (Capan-1 [GEM-sensitive] and BxPC-3 [GEM-resistant]), and 1 orthotopic (SUIT-2) model. The active form of GEM (GEM triphosphate [dFdCTP]) inhibits DNA synthesis. dFdCTP tissue concentrations following FF-10832 4mg/kg and GEM 240mg/kg were compared in these models.
Results: An extended plasma t½ (10.6 vs. 2.9 hours), lower clearance, and smaller volume of distribution were observed with FF-10832 vs. GEM, which correlated with greater dose exposure achieved with FF-10832 compared to GEM (AUClast 186000 vs. 73000 hr·ng/mL). FF-10832 demonstrated increased in vivo activity in SUIT-2, Capan-1, and BxPC-3 models at significantly lower doses compared to GEM. In the Capan-1 and BxPC3 models, FF-10832 showed dose-dependent tumor growth suppression with FF-10832 4 mg/kg and 5 mg/kg superior to that of GEM (p<0.001), respectively. Following 11 weekly doses in the SUIT-2 model, the survival rate was 0% and 20% for vehicle and GEM 240 mg/kg vs. 13% and 60% for 2 and 4 mg/kg FF-10832, respectively. Median survival time was 60 (FF-10832 2 mg/kg) and 73 (GEM 240 mg/kg) vs. 26 days (vehicle) (p <0.001). Median survival was not reached at FF-10832 4 mg/kg. In all models, FF-10832 2 mg/kg (equivalent efficacy to GEM 240 mg/kg) showed no body weight gain suppression. The dFdCTP tumor/bone marrow AUC ratio was significantly higher following FF-10832 (dFdCTP AUC ratio = 7) compared with non-liposomal GEM (0.8).
Conclusions: FF-10832 is a stable liposomal GEM formulation demonstrating potent anti-tumor efficacy in solid tumor models with a favorable pharmacokinetic profile compared to non-liposomal GEM. Increased exposure achieved at lower GEM doses may potentially result in superior efficacy and a more tolerable safety profile for FF-10832 compared to non-liposomal GEM.
Citation Format: Takeshi Matsumoto, Tsukasa Kitahashi, Takashi Komori, Hiromu Kitahara, Kohei Ono, Naoki Yamada, Hiroyuki Iwamura, Kiyohito Takada, Shinji Hagiwara, Yasuhiro Shimada. Liposomal gemcitabine, FF-10832, improves gemcitabine (GEM) pharmacokinetics (PK) and increases anti-tumor efficacy [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 5148. doi:10.1158/1538-7445.AM2017-5148</jats:p
Cadmium inhibition of the erythrocyte Ca2+ pump. A molecular interpretation
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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
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Evaluation of coated QCM for the detection of atmospheric ozone
Get PDFA coated acoustic wave sensor has been developed to selectively detect atmospheric ozone. The selective detection has been assessed using a variety of coatings: beeswax, gallic acid, indigo carmine, polybutadiene, potassium iodide and sodium nitrite. Polybutadiene was the most sensitive with a limit of detection of 55 ppb. The sensitivity was improved by operating at higher harmonics and was shown to increase linearly with harmonic up to the 11th harmonic. This novel work shows that ozone detection can be improved by operating at the crystals' harmonic frequencies and in conjunction with a suitable flow rate, a potentially highly sensitive and fast response sensor can be created based on acoustic wave technolog
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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