1,724,791 research outputs found
Jungfraubahn, Jungfraujoch 3467 M, Hofer & Co. Zürich
No full textJUNGFRAUBAHN, JUNGFRAUJOCH 3467 M, HOFER & CO. ZÜRICH
Jungfraubahn, Jungfraujoch 3467 M, Hofer & Co. Zürich ( -
Astronomische Nachrichten, nos 3459-3467
No full textR. R. Astronomische Nachrichten, nos 3459-3467. In: Bulletin astronomique, tome 15, 1898. pp. 431-437
Block Card 3467 Goddard 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 | 3467 Goddard Road (Toledo, Ohio) | Georgian Revival Style | Leesdale Extension (Toledo, Ohio) | Westgate Area (Toledo, Ohio) | West Toledo (Toledo, Ohio
Abstract 3467: Inhibition of AURKA targets gastrointestinal cancer cells with activated KRAS by inhibiting RPS6KB1
No full textAbstract Background & Aims: Amplifications and mutations of KRAS play essential roles in resistance to chemotherapeutics in luminal gastrointestinal cancers. We investigated the regulation of ribosomal protein S6 kinase B1 (RPS6KB1) by AURKA and the effects of knockdown AURKA or its inhibitions using alisertib, an AURKA inhibitor, in human gastrointestinal cancer cells with amplified or mutant activated forms of KRAS. Methods: We performed CellTiter-Glo luminescence and clonogenic cell survival assays using 10 upper gastrointestinal or colon cancer cell lines with KRAS mutations or amplifications to test the effects of alisertib, AURKA overexpression or knock down. To determine protein co-localization, we used proximity ligation in situ and immunoprecipitation assays. Nude mice with xenograft tumors grown from HCT116, SNU-601, SW480, or SNU-1 cells were given oral alisertib (40 mg/kg, 5 times/week) for 4 weeks. Tumor samples were collected and analyzed by immunoblots and immunohistochemistry. In addition, immunohistochemistry was performed using AURKA antibody on tissue microarrays containing 151 paraffin-embedded human colon tumors with adjacent normal and adenomas. Results: AURKA knockdown or inhibition with alisertib reduced Alisertib reduced proliferation and survival of cell lines tested. In addition, we detected a decrease in the levels of phosphorylated RPS6KB1 (at T389), and increased levels of proteins that induce apoptosis including BIM, cleaved PARP, and cleaved caspase 3. Proximity ligation assay and immunoprecipitation indicated that AURKA co-localized and interacted with RPS6KB1, mediating RPS6KB1 phosphorylation at T389. We detected AURKA-dependent phosphorylation of RPS6KB1 in cell lines with mutations in KRAS, but not in cells with wild-type Ras. Administration of alisertib to mice with xenograft tumors significantly reduced tumor volumes (P < .001). These effects were associated with reduced phosphorylation of RPS6KB1 and Ki-67, and increased levels of cleaved caspase 3, in tumor xenograft tissues. The tissue microarrays demonstrated significant overexpression of AURKA in gastrointestinal tumor tissues compared with non-tumor tissues (P=.0003). Conclusion: Our studies indicate that AURKA can phosphorylate RPS6KB1 in cancer cells with activated KRAS to promote cell proliferation and survival and growth of xenograft tumors in mice. AURKA inhibitors such as alisertib might slow the growth of gastrointestinal tumors with activation of KRAS. Citation Format: Zheng Chen, Lihong W. Bishop, Ahmed Gomaa, Albert C. Lockhart, Safia Salaria, Jeffrey Ecsedy, Kay Washington, Robert D. Beauchamp, Wael El-Rifai. Inhibition of AURKA targets gastrointestinal cancer cells with activated KRAS by inhibiting RPS6KB1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3467
Cemeteries - Horse Cave, Kentucky (SC 3467)
Full text linkFinding aid and scan (Click on Additional Files below) for Manuscripts Small Collection 3467. Deed, 15 July 1911, from the Trustees of the Town of Horse Cave, Kentucky to Mrs. Minnie Hendrick of Lot No. 168 in the “public white cemetery” of Horse Cave. Includes an endorsement giving two grave sites on the lot to the grantee’s sister and brother-in-law
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
Role of 4-Thiazolidinone–Pyrazoline/Indoline Hybrids Les-4369 and Les-3467 in BJ and A549 Cell Lines
No full textCancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells
Role of 4-Thiazolidinone–Pyrazoline/Indoline Hybrids Les-4369 and Les-3467 in BJ and A549 Cell Lines
Full text linkCancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator
receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and
their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM
(ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells
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