Browsing by Author "Wiebke, Eric A."

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    Depletion of the Chimeric Drug Rituximab from Biological Samples
    (Elsevier, 2017) Book, Benita K.; Pescovitz, Mark D.; Guo, Lili; Wiebke, Eric A.; Department of Surgery, IU School of Medicine
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    The Effects of a Novel MEK Inhibitor PD184161 on MEK–ERK Signaling and Growth in Human Liver Cancer
    (Elsevier, 2006-01) Klein, Patrick J.; Schmidt, C. Max; Wiesenauer, Chad A.; Choi, Jennifer N.; Gage, Earl A.; Yip-Schneider, Michele T.; Wiebke, Eric A.; Wang, Yufang; Omer, Charles; Sebolt-Leopold, Judith S.; Biochemistry and Molecular Biology, School of Medicine
    The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentrationdependent manner more effectively than PD098059 or U0126. PD184161 inhibited cell proliferation and induced apoptosis at concentrations of ≥ 1.0 µM in a time- and concentration-dependent manner. In vivo, tumor xenograft P-ERK levels were significantly reduced 3 to 12 hours after an oral dose of PD184161 (P< .05). Contrarily, tumor xenograft P-ERK levels following long-term (24 days) daily dosing of PD184161 were refractory to this signaling effect. PD184161 significantly suppressed tumor engraftment and initial growth (P<.0001); however, established tumors were not significantly affected. In conclusion, PD184161 has antitumor effects in HCC in vitro and in vivo that appear to correlate with suppression of MEK activity. These studies demonstrate that PD184161 is unable to suppress MEK activity in HCC xenografts in the long term. Thus, we speculate that the degree of success of MEKtargeted treatment in HCC and other cancers may, in part, depend on the discovery of mechanisms governing MEK inhibitor signaling resistance.
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    Optimizing Perioperative Decision Making: Improved Information for Clinical Workflow Planning
    (2012-11) Doebbeling, Bradley N.; Burton, Matthew M.; Wiebke, Eric A.; Miller, Spencer; Baxter, Laurence; Miller, Donald; Alvarez, Jorge; Pekny, Joseph
    Perioperative care is complex and involves multiple interconnected subsystems. Delayed starts, prolonged cases and overtime are common. Surgical procedures account for 40–70% of hospital revenues and 30–40% of total costs. Most planning and scheduling in healthcare is done without modern planning tools, which have potential for improving access by assisting in operations planning support. We identified key planning scenarios of interest to perioperative leaders, in order to examine the feasibility of applying combinatorial optimization software solving some of those planning issues in the operative setting. Perioperative leaders desire a broad range of tools for planning and assessing alternate solutions. Our modeled solutions generated feasible solutions that varied as expected, based on resource and policy assumptions and found better utilization of scarce resources. Combinatorial optimization modeling can effectively evaluate alternatives to support key decisions for planning clinical workflow and improving care efficiency and satisfaction.
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    Recurrent pneumonia and colobronchial fistula from Crohn’s disease: Infliximab alters and simplifies surgical management
    (Hellenic Society of Gastroenterology, 2012) Mercadal, Nuria Rosa; Wiebke, Eric A.; Surgery, School of Medicine
    We report a rare case of right-sided colobronchial fistula in a 47-year-old, severely malnourished male with a history of regional enteritis and recurrent right lower and middle lobe pneumonias medically managed with the addition of the immunomodulator infliximab prior to surgery. On admission, evaluation of sputum cultures and chest radiograph pattern of pneumonia led to the suspicion of colobronchial fistula. This diagnosis was confirmed by abdominal CT enteroclysis. This patient's pneumonia was initially treated with empiric antibiotics, then focused antibiotics based on culture results. The treatment for the regional enteritis and the secondary colobronchial fistula consisted of immunosuppression with infliximab, bowel rest, and total parenteral nutrition. The patient was discharged on a limited course of prednisone and received maintenance therapy with 3mg/kg IV infliximab infusions for four additional treatments with dramatic improvement in his clinical condition. Surgical therapy consisted of only bowel resection; no thoracic surgery or lung resection was necessary. The patient has had a dramatic improvement in his clinical condition and is currently disease-free on no maintenance therapy. The use of TNF-blocking agents such as infliximab may simplify the surgical approach in patients with complicated fistulous Crohn's disease.