1,723,078 research outputs found
Engine #5902
No full textEngine #5902 in unidentified yard (likely Field). Snow plow blade and front end covered in snow
Pearce, John Edward, 5902
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/410019Surname: PEARCE. Given Name(s) or Initials: JOHN EDWarD. Military Service Number or Last Known Location: 5902. Missing, Wounded and Prisoner of War Enquiry Card Index Number: 27701.225735
Item: [2016.0049.42288] "Pearce, John Edward, 5902
OLPD 5902 Leading Change in Private Colleges Syllabus
No full textSyllabus for OLPD 5902 Leading Change in Private Colleges - one of four courses that comprise the Private College Leadership Certificate program.Center for Innovative Higher Education. (2017). OLPD 5902 Leading Change in Private Colleges Syllabus. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/194748
Block Card 5902 Curson 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: Dwelling | 5902 Curson Drive (Toledo, Ohio) | Colonial Revival Style | McLains Hopewell Heights (Toledo, Ohio) | Greenwood Area (Toledo, Ohio) | West Toledo Area (Toledo, Ohio
OLPD 5902 Leading Change in Private Colleges Modules, Readings, Assignments
No full textModules, Readings, and Assignments for OLPD 5902 Leading Change in Private Colleges - one of four courses that comprise the Private College Leadership Certificate program.Center for Innovative Higher Education. (2017). OLPD 5902 Leading Change in Private Colleges Modules, Readings, Assignments. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/194749
Block Card 5902 East Heights 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 houses | Dwelling | Whitmer Heights Addition (Toledo, Ohio) | Trilby Area (Toledo, Ohio)) | 5902 East Heights Drive (Toledo, Ohio
Abstract P5-21-16: Preclinical studies of RX-5902, a beta-catenin modulator in triple negative breast cancer
No full textAbstract
Background: RX-5902 (Supinoxin) is a novel anti-cancer compound that targets phosphorylated p68 RNA helicase, a member of the DEAD box family of helicases, affecting upstream and downstream molecules in the Wnt canonical pathway. As a single agent, RX-5902 exhibits strong growth inhibition in both in vitro and in vivo settings. Specifically, RX-5902 enhances survival and tumor growth inhibition in numerous xenograft models, including ovarian, renal and breast. We have previously shown RX-5902 inhibits cell growth in a dose-dependent fashion in the triple-negative breast cancer (TNBC) xenograft MDA-MB231. In the current study, we have expanded our investigation of the therapeutic potential of RX-5902 against TNBC using both in vitro and in vivo preclinical models.
Methods: RX-5902 was provided by Rexahn, Inc. (Rockville, MD). Cell proliferation was measured using the Cell-Titer Glo luminescent cell viability assay (Promega). Apoptosis was assessed using Incucyte Caspase 3/7 Green apoptosis assay (Essenbioscience). Immunoblots of MDA-MB-231 cell line were probed for ß-catenin (Cell Signaling). Syngeneic 4T1 murine TNBC mice were obtained from Sippr-BK Laboratory Animal Co (Shanghai, China) and tumor volumes were measured twice a week. When the mean tumor volumes reached ˜90 mm3, mice were randomized and treated with vehicle or RX-5902 PO daily alone or in combination with anti-CTLA4 or anti-PD-1 BIW for 3 weeks. Tumor growth inhibition (TGI) was calculated at Day 25.
Results: A panel of 18 TNBC cell lines were treated with RX-5902 and effects on cell proliferation were measured by the Cell Titer-Glo assay. Using 100nM as a cutoff, 14 sensitive lines and 4 resistant lines were identified, with an average IC50 of 56 nM in the sensitive lines. Of these, we chose 2 sensitive lines (MDA-MB-231, HCC1806) and 2 resistant lines (MDA-MB-436 and CAL-120) and assessed induction of apoptosis by the Incucyte caspase activity assay. Robust induction of apoptosis was observed in both sensitive lines (N=3). These lines were then subjected to cell cycle analysis by flow cytometry, which revealed a pronounced G2/M cell cycle arrest and aneuploidy following exposure to RX-5902. Western blot analysis of the MDA-MB-231 cell line showed decreases in the Wnt pathway-related protein nuclear ß-catenin in doses ranging from 20 nM to 200 nM. Finally, the therapeutic efficacy of RX-5902 was assessed as a single agent and in combination with two immune-oncology agents in the treatment of the TNBC 4T1 animal model. RX-5902 as a single agent showed dose dependency in the 4T1 model, and when given in combination with either anti-CTLA4 or anti-PD1 showed an additive effect (p<0.001). All the treatments were well-tolerated and no severe body weight loss was observed in this study.
Conclusions: RX-5902 showed efficacy against several in vitro and in vivo preclinical models of TNBC. RX-5902 resulted in G2/M arrest and induced apoptosis in sensitive TNBC cell lines and decreases in nuclear beta-catenin. In vivo, RX-5902 demonstrated additive anti-tumor effects when combined with either anti-CTLA4 or anti-PD1 immunotherapies. Together, these finding indicate that RX-5902 may have important clinical implications for the treatment of TNBC. A phase 2a clinical study in metastatic TNBC is ongoing..training_cert
Citation Format: Tentler JJ, Frank JG, Kim DJ, George C, Lee YB, Ely B, Tan AC, Kim J, Pitts TM, Capasso A, Dailey KL, Eckhardt G, Diamond JR. Preclinical studies of RX-5902, a beta-catenin modulator in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-16.</jats:p
RX-5902: A phosphorylated p68 targeting agent to treat subjects with advanced solid tumors.
No full text TPS778 Background: Phosphorylated p68 may play a vital role in cell proliferation and tumor/cancer progression. RX-5902 is a novel compound that targets phosphorylated p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. As a single agent, RX-5902 inhibits tumor growth and enhances survival in a variety of xenograft tumor models (e.g., pancreatic, renal, ovarian, melanoma). Methods: This Phase 1, open-label, multicenter study evaluates the efficacy and safety of RX-5902 in subjects with solid tumors. RX-5902 is administered orally 1, 3 or 5 times per week for 3 weeks with 1 week of rest in each 4 week cycle. Dose escalation starts with an accelerated design treating 1 subject per dose followed by a standard 3 + 3 design using a modified Fibonacci sequence after the occurrence of a single Grade 2 or greater adverse event that is considered at related to RX-5902. The primary endpoint is the overall safety profile characterized by the type, frequency, severity, timing of onset, duration and relationship to study therapy of any adverse events, or abnormalities of laboratory tests or electrocardiograms as well as the description of any dose limiting toxicities that occur during Cycle 1, serious adverse events, or adverse events leading to discontinuation of study treatment. Secondary endpoints include pharmacokinetic parameters (e.g., time to maximum observed concentration [Tmax], maximum observed plasma concentration [Cmax], trough concentration [Ctrough], area under the concentration-time curve [AUC]) and Indices of anti-tumor activity (e.g., overall response rate, time to response, duration of response, and progression-free survival during treatment. Exploratory endpoints are biochemical levels of drug targets in blood and tumor samples. Eligible subjects must have confirmed histologic or cytologic evidence of metastatic or locally advanced solid neoplasm that has failed to respond to standard therapy, progressed despite standard therapy or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens. Clinical trial information: NCT02003092. </jats:p
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