Welcome to the UA Campus Repository, a service of the University of Arizona Libraries. The repository shares, archives and preserves unique digital materials from faculty, staff, students and affiliated contributors. Contact us at repository@u.library.arizona.edu with any questions.

 

Featured submissions

January 2021

  • More than 8,400 journal articles from University of Arizona faculty, staff and researchers have been made available since the implementation of the UA Open Access Policy (April 2016). You can find these articles in the UA Faculty Publications collection - thank you to all our article authors and contributors!

December 2020

 

  • Delivering Gridded Map and Products

    OSIRIS-REx Asteroid Sample Return Mission (2019)
  • Deliverablility Weighted Unresolved Material Quantification (C Code)

    OSIRIS-REx Asteroid Sample Return Mission (2019)
  • Ground EPR December 2014

    OSIRIS-REx Asteroid Sample Return Mission (2014)
  • Debris 2 Movie

    OSIRIS-REx Asteroid Sample Return Mission; OSIRIS-REx Asteroid Sample Return Mission (2019)
  • A pilot clinical trial of the cytidine deaminase inhibitor tetrahydrouridine combined with decitabine to target DNMT1 in advanced, chemorefractory pancreatic cancer

    Sohal, Davendra; Krishnamurthi, Smitha; Tohme, Rita; Gu, Xiaorong; Lindner, Daniel; Landowski, Terry H; Pink, John; Radivoyevitch, Tomas; Fada, Sherry; Lee, Zhenghong; et al. (E-CENTURY PUBLISHING CORP, 2020-09-01)
    DNA methyltransferase 1 (DNMT1) is scientifically validated as a molecular target to treat chemo-resistant pancreatic ductal adenocarcinoma (PDAC). Results of clinical studies of the pyrimidine nucleoside analog decitabine to target DNMT1 in PDAC have, however, disappointed. One reason is high expression in PDAC of the enzyme cytidine deaminase (CDA), which catabolizes decitabine within minutes. We therefore added tetrahydrouridine (THU) to inhibit CDA with decitabine. In this pilot clinical trial, patients with advanced chemorefractory PDAC ingested oral THU ~10 mg/kg/day combined with oral decitabine ~0.2 mg/kg/day, for 5 consecutive days, then 2X/week. We treated 13 patients with extensively metastatic chemo-resistant PDAC, including 8 patients (62%) with ascites: all had received ≥ 1 prior therapies including gemcitabine/nab-paclitaxel in 9 (69%) and FOLFIRINOX in 12 (92%). Median time on THU/decitabine treatment was 35 days (range 4-63). The most frequent treatment-attributable adverse event was anemia (n=5). No deaths were attributed to THU/decitabine. Five patients had clinical progressive disease (PD) prior to week 8. Eight patients had week 8 evaluation scans: 1 had stable disease and 7 PD. Median overall survival was 3.1 months. Decitabine systemic exposure is expected to decrease neutrophil counts; however, neutropenia was unexpectedly mild. To identify reasons for limited systemic decitabine effect, we measured plasma CDA enzyme activity in PDAC patients, and found a > 10-fold increase in those with metastatic vs resectable PDAC. We concluded that CDA activity is increased not just locally but also systemically in metastatic PDAC, suggesting a need for even higher CDA-inhibitor doses than used here.

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