1,724,205 research outputs found
Abstract 4143: Mastl, a novel therapeutic target in colon cancer
No full textAbstract
Combining chemoradiation with agents that modulate tumor-specific pathways such as cell cycle checkpoints has shown immense promise in preclinical and clinical studies. To ensure that only healthy cells proliferate, checkpoints have evolved that induce cell-cycle arrest in response to the detection of defects that may have arisen during DNA replication or other steps leading to mitosis. The G2/M checkpoint Mastl in mammals (and Greatwall in Xenopus and Drosophila) prevents cells from premature entry into mitosis, and thus minimizes chromosome mis-segregation. Our preliminary data demonstrate that Mastl not only plays a key role in regulating cell cycle and mitosis but also regulates key oncogenic signaling pathways and assists therapy resistance in cancer cells. Interestingly, genetic elimination of Mastl expression in vivo compromised survival in young mice, however, only mild alterations were found when deleted in adult mice.
Here we show using two clinical and genomic databases using a total of 265 patient samples that Mastl expression increases in colon cancer across all cancer stages compared with the normal colon tissue (P < 0.001). Moreover, high Mastl expression associates with high-risk colorectal cancer patients and poor prognosis. Silencing of Mastl expression using gene-specific shRNA, in two different colon cancer cells with high endogenous expression of Mastl, induced cell death/apoptosis supporting important role of Mastl in colon cancer cell survival. To further determine molecular mechanism/s by which Mastl regulates cell survival, we screened a panel of oncogenes. It was interesting that the knock-down of Mastl expression sharply inhibited β-catenin/c-myc signaling, key regulators of colon carcinogenesis, in both cell types. To further expand the breadth of this investigation and to identify additional key players in Mastl dependent regulation of colon cancer cell survival, we performed an oncogenic array analysis using above cell lines with or without stable inhibition of Mastl expression. Here, we observed robust effects of inhibiting Mastl upon anti-apoptotic proteins Bcl-xl and survivin. Notably, c-myc regulates survivin and Bcl-xl expressions.
Additional studies, where colon cancer cells were subjected to 5-FU treatment sharply induced Mastl expression and combinational therapy using 5FU and (targeting) Mastl resulted in significantly increased death among these cells (P>0.0025; versus control). Taken together, we here report a novel and previously undescribed role of Mastl in colon cancer progression, malignancy and therapy resistance potentially by regulating cell survival in manners dependent on β-catenin/c-Myc/Survivin/Bcl-xl signaling.
Citation Format: JayaPrakash Uppada, SaiPrasad Gowrikumar, Rizwan Ahmad, Steven Chen, J Joshua Smith, Amar B. Singh, Punita Dhawan. Mastl, a novel therapeutic target in colon cancer [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 4143. doi:10.1158/1538-7445.AM2017-4143</jats:p
Y(4143) is probably a molecular partner of Y(3930)
No full textAfter discussing the various possible interpretations of the Y(4143) signal observed by the CDF collaboration in the J/Sigma phi mode, we tend to conclude that Y(4143) is probably a D(s)(*)D(s)(*) molecular state with J(PC)=0(++) or 2(++) while Y(3930) is its D(*)D(*) molecular partner as predicted in our previous work [X. Liu, Z. G. Luo, Y. R. Liu, and Shi-Lin Zhu, Eur. Phys. J. C 61, 411 (2009)]. Both the hidden-charm and open-charm two-body decays occur through the rescattering of the vector components within the molecular states while the three- and four-body open-charm decay modes are forbidden kinematically. Hence, their widths are narrow naturally. CDF, BABAR and Belle collaborations may have discovered heavy molecular states already. We urge experimentalists to measure their quantum numbers and explore their radiative decay modes in the future.Astronomy & AstrophysicsPhysics, Particles & FieldsSCI(E)50ARTICLE1null8
Block Card 4143 Commonwealth 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: dwelling | 4143 Commonwealth Avenue (Toledo, Ohio) | Bungalow Style | Craftsman Style | Commonwealth Addition (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio
Block Card 4143 Cypress 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: Ranch Style | 4143 Cypress Avenue (Toledo, Ohio) | Dwelling | Estero Place (Toledo, Ohio) | Trilby Area (Toledo, Ohio)
Block Card 4143 Birchall 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: Dwelling (Toledo, Ohio) | multi-family | cleveland double | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4143 Birchall Road (Toledo, Ohio
Block Card 4143 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) | Side gabled | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4143 East Way (Toledo, Ohio) | Dutch Colonial Styl
Linked collectors and determiners for: The Pisces Collection at the Staatssammlung für Anthropologie und Paläoanatomie München.
No full textNatural history specimen data linked to collectors and determiners held within, "The Pisces Collection at the Staatssammlung für Anthropologie und Paläoanatomie München". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/ed820bdb-4345-4143-a280-4fbffaacd31d">https://bionomia.net/dataset/ed820bdb-4345-4143-a280-4fbffaacd31d</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/ed820bdb-4345-4143-a280-4fbffaacd31d">https://gbif.org/dataset/ed820bdb-4345-4143-a280-4fbffaacd31d</a>. Formatted as a Frictionless Data package
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
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