1,720,955 research outputs found
Cellular and molecular surrogate markers to monitor targeted and non-targeted antiangiogenic drug activity and determine optimal biologic dose
Perhaps the most significant recent advance in oncology therapeutics has been the approval of
various “molecularly targeted” anti-cancer drugs. Currently, there are a large number of similar drugs in early or
late stage development, including antiangiogenic agents. Clinical development of such drugs suffers from
several handicaps including determining whether a patient’s cancer expresses the target and is functionally
contributing to cancer growth, monitoring biologic activity, and determining optimal biologic dose. The last
problem is related to the low frequency of objective tumor responses (tumor shrinkage) caused by such drugs,
or the lack of dose limiting toxicities necessary to define a maximum tolerated dose (MTD), or expression of
optimal therapeutic activity at doses below the MTD, when one can be defined. These problems necessitate the
development of alternative pharmacodynamic surrogate markers.
Here we summarize several such promising markers for monitoring targeted antiangiogenic activity, and
establishing optimal therapeutic/biologic dosing. The first is molecular - plasma VEGF – levels of which are
rapidly and significantly increased in a dose dependent manner after injection of normal or tumor bearing mice
with anti-VEGFR-2 antibodies. The second is a cellular marker, and more generic in nature - circulating VEGF
receptor-2 positive cells found in peripheral blood, some of which may be circulating endothelial progenitor
cells. Levels of such cells are suppressed in a dose dependent manner which correlate with previously
determined optimal biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or treatments.
Finally, another promising marker we discuss is soluble VEGFR-2
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Tumor growth kinetics of human LM2-4LUC+ triple negative breast carcinoma cells
Cell culture and data set
Tumor growth data used in this study were obtained from experiments involving the use of a LM2-4LUC+ cells (or LM2-4), a metastatic variant of the human triple-negative breast carcinoma MDA-MB-231 cells. Animal studies were performed as described previously under Roswell Park Comprehensive Cancer Center (RPCCC) Institutional Animal Care and Use Committee (IACUC) protocol number 1227M [1-6]. Tumor growth data were pooled from eight separate experiments conducted with a total of 581 observations, and represent control (vehicle-treated) animals from published studies [1-6]. Vehicle formulation was carboxymethylcellulose sodium (USP, 0.5% w/v), NaCl (USP, 1.8% w/v), Tween-80 (NF, 0.4% w/v), benzyl alcohol (NF, 0.9% w/v), and reverse osmosis deionized water (added to final volume) and adjusted to pH 6 (see [3]) and was given at 10ml/kg/day for 7-14 days prior after tumor implantation and before tumor resection [1-6].
Tumor injections
LM2-4LUC+ cells were orthotopically implanted (106 cells per injection) into the right inguinal mammary fat pads of 6- to 8-week-old female severe combined immunodeficient (SCID) mice.
Tumor measurements
Tumor size was measured regularly with calipers to a maximum volume of 2 cm3, calculated by the formula
(ellipsoid) where L is the largest and w is the smallest tumor diameter.
References
[1] Benzekry, S., Lamont, C., Beheshti, A., Tracz, A., Ebos, J. M. L., Hlatky, L., & Hahnfeldt, P. (2014). Classical mathematical models for description and prediction of experimental tumor growth. PLoS Comput Biol, 10(8), e1003800. http://doi.org/10.1371/journal.pcbi.1003800
[2] Benzekry S, Tracz A, Mastri M, Corbelli R, Barbolosi D, Ebos JML. (2016) Modeling Spontaneous Metastasis Following Surgery: An In Vivo-In Silico Approach. Cancer Res.;76(3):535–547. doi:10.1158/0008-5472.CAN-15-1389.
[3] Ebos JML, Lee CR, Bogdanovic E, Alami J, Van Slyke P, Francia G, et al. (2008) Vascular Endothelial Growth Factor-Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth. Cancer Res.;68(2):521–529. doi:10.1158/0008-5472.CAN-07-3217.
[4] Ebos JML, Mastri M, Lee CR, Tracz A, Hudson JM, Attwood K, et al. (2014) Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy. EMBO Mol Med;6:1561–76. https://doi.org/10.15252/emmm.201403989
[5] Ebos JML, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell;15:232–9. https://doi.org/10.1016/j.ccr.2009.01.021
[6] Mastri M, Tracz A, Lee CR, Dolan M, Attwood K, Christensen JG, et al. (2018) A Transient Pseudosenescent Secretome Promotes Tumor Growth after Antiangiogenic Therapy Withdrawal. Cell Rep.; 25 (13):3706–20 e8. Epub 2018/12/28. https://doi.org/10.1016/j.celrep.2018.12.017</p
Dispelling the Myths Behind First-author Citation Counts
We 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
- …
