scholarly journals Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells**This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.).

Endocrinology ◽  
1998 ◽  
Vol 139 (12) ◽  
pp. 4881-4889 ◽  
Author(s):  
Bhumsoo Kim ◽  
Phillip S. Leventhal ◽  
Morris F. White ◽  
Eva L. Feldman
Keyword(s):  
Kinase Inhibitors ◽  
Neuroblastoma Cells ◽  
Juvenile Diabetes ◽  
Mitogen Activated Protein Kinase ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
University Of Michigan ◽  
Human Neuroblastoma ◽  
Mitogen Activated Protein ◽  
The University

Creating an Effort Tracking Tool to Improve Therapeutic Cancer Clinical Trials Workload Management and Budgeting

2011 ◽  
Vol 9 (11) ◽  
pp. 1228-1233 ◽  
Author(s):  
Pam James ◽  
Patty Bebee ◽  
Linda Beekman ◽  
David Browning ◽  
Mathew Innes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Data Management ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
University Of Michigan ◽  
Web Based ◽  
Workload Management ◽  
Effective Cost ◽  
The University

Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.

Predicting Patient Treatment Deferrals at an Outpatient Chemotherapy Infusion Center: A Statistical Approach

2017 ◽  
pp. 1-8
Author(s):  
Donald B. Richardson ◽  
Seth D. Guikema ◽  
Amy E.M. Cohn
Keyword(s):  
Treatment Protocol ◽  
Regression Tree ◽  
Comprehensive Cancer Center ◽  
Patient Specific ◽  
Brier Score ◽  
Cancer Center ◽  
University Of Michigan ◽  
Wide Range ◽  
Patient Will ◽  
The University

Purpose Patients scheduled for outpatient infusion sometimes may be deferred for treatment after arriving for their appointment. This can be the result of a secondary illness, not meeting required bloodwork counts, or other medical complications. The ability to generate high-quality predictions of patient deferrals can be highly valuable in managing clinical operations, such as scheduling patients, determining which drugs to make before patients arrive, and establishing the proper staffing for a given day. Methods In collaboration with the University of Michigan Comprehensive Cancer Center, we have developed a predictive model that uses patient-specific data to estimate the probability that a patient will defer or not show for treatment on a given day. This model incorporates demographic, treatment protocol, and prior appointment history data. We tested a wide range of predictive models including logistic regression, tree-based methods, neural networks, and various ensemble models. We then compared the performance of these models, evaluating both their prediction error and their complexity level. Results We have tested multiple classification models to determine which would best determine whether a patient will defer or not show for treatment on a given day. We found that a Bayesian additive regression tree model performs best with the University of Michigan Comprehensive Cancer Center data on the basis of out-of-sample area under the curve, Brier score, and F1 score. We emphasize that similar statistical procedures must be taken to reach a final model in alternative settings. Conclusion This article introduces the existence and selection process of a wide variety of statistical models for predicting patient deferrals for a specific clinical environment. With proper implementation, these models will enable clinicians and clinical managers to achieve the in-practice benefits of deferral predictions.

Effort Tracking Metrics Provide Data for Optimal Budgeting and Workload Management in Therapeutic Cancer Clinical Trials

2011 ◽  
Vol 9 (12) ◽  
pp. 1343-1352 ◽  
Author(s):  
Pam James ◽  
Patricia Bebee ◽  
Linda Beekman ◽  
David Browning ◽  
Mathew Innes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Management ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
University Of Michigan ◽  
Workload Management ◽  
Aggregated Data ◽  
Personnel Costs ◽  
Accrual Rate ◽  
The University

Clinical trials operations struggle to achieve optimal distribution of workload in a dynamic data management and regulatory environment, and to achieve adequate cost recovery for personnel costs. The University of Michigan Comprehensive Cancer Center developed and implemented an effort tracking application to quantify data management and regulatory workload to more effectively assess and allocate work while improving charge capture. Staff recorded how much time they spend each day performing specific study-related and general office tasks. Aggregated data on staff use of the application from 2006 through 2009 were analyzed to gain a better understanding of what trial characteristics require the most data management and regulatory effort. Analysis revealed 4 major determinants of staff effort: 1) study volume (actual accrual), 2) study accrual rate, 3) study enrollment status, and 4) study sponsor type. Effort tracking also confirms that trials that accrued at a faster rate used fewer resources on a per-patient basis than slow-accruing trials. In general, industry-sponsored trials required the most data management and regulatory support, outweighing other sponsor types. Although it is widely assumed that most data management efforts are expended while a trial is actively accruing, the authors learned that 25% to 30% of a data manager's effort is expended while the study is either not yet open or closed to enrollment. Through the use of a data-driven effort tracking tool, clinical research operations can more efficiently allocate workload and ensure that study budgets are negotiated to adequately cover study-related expenses.

scholarly journals 2043

2017 ◽  
Vol 1 (S1) ◽  
pp. 30-30
Author(s):  
Daniel L. Hertz ◽  
Kelley M. Kidwell ◽  
Kiran Vangipuram ◽  
Duxin Sun ◽  
N. Lynn Henry
Keyword(s):  
Treatment Cycle ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
University Of Michigan ◽  
Breast Cancer Patients ◽  
Patient Reported ◽  
Study Population ◽  
The University ◽  
Dose Limiting Toxicity ◽  
Paclitaxel Treatment

OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.

scholarly journals Taurine and Ginsenoside Rf Induce BDNF Expression in SH-SY5Y Cells: A Potential Role of BDNF in Corticosterone-Triggered Cellular Damage

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2819
Author(s):  
Won Jin Lee ◽  
Gyeong Hee Lee ◽  
Jinwoo Hur ◽  
Hyuk Gyoon Lee ◽  
Eunsu Kim ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Neuroblastoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Damage ◽  
Dependent Manner ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Human Neuroblastoma ◽  
Lactate Dehydrogenase Release ◽  
Mitogen Activated Protein

This study shows that taurine and ginsenoside Rf act synergistically to increase the expression of brain-derived neurotrophic factor (BDNF) in SH-SY5Y human neuroblastoma cells in a dose- and time-dependent manner. The increase of BDNF mRNA by taurine and ginsenoside Rf was markedly attenuated by inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. In addition, taurine and ginsenoside Rf protected cells from corticosterone-induced BDNF suppression and reduced cell viability and lactate dehydrogenase release. The results from this study showed that combined treatment with both taurine and ginsenoside Rf enhanced BDNF expression and protected cells against corticosterone-induced damage.

Involvement of Ras/MAP Kinase in the Regulation of Ca2+ Channels in Adult Bullfrog Sympathetic Neurons by Nerve Growth Factor

1998 ◽  
Vol 80 (3) ◽  
pp. 1352-1361 ◽  
Author(s):  
Saobo Lei ◽  
William F. Dryden ◽  
Peter A. Smith
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Map Kinase ◽  
Kinase Inhibitors ◽  
Sympathetic Neurons ◽  
Mitogen Activated Protein Kinase ◽  
Nerve Growth ◽  
Channel Current ◽  
Mitogen Activated Protein

Lei, Saobo, William F. Dryden, and Peter A. Smith. Involvement of Ras/MAP kinase in the regulation of Ca2+ channels in adult bullfrog sympathetic neurons by nerve growth factor. J. Neurophysiol. 80: 1352–1361, 1998. The cellular mechanisms that underlie nerve growth factor (NGF) induced increase in Ca2+-channel current in adult bullfrog sympathetic B-neurons were examined by whole cell recording techniques. Cells were maintained at low density in neuron-enriched, defined-medium, serum-free tissue culture for 6 days in the presence or absence of NGF (200 ng/ml). The increase in Ba2+ current ( I Ba) density induced by NGF was attenuated by the RNA synthesis inhibitor cordycepin (20 μM), by the DNA transcription inhibitor actinomycin D (0.01 μg/ml), by inhibitors of Ras isoprenylation (perillic acid 0.1–1.0 mM or α-hydroxyfarnesylphosphonic acid 10–100 μM), by tyrosine kinase inhibitors genistein (20 μM) or lavendustin A (1 μM), and by PD98059 (10–100 μM), an inhibitor of mitogen-activated protein kinase kinase. Inhibitors of the phosphatidylinositol 3-kinase (PI3K) pathway (wortmannin, 100 nM, or LY29400, 100 μM) were ineffective as were inhibitors of phospholipase Cγ (U73122 or neomycin, both 100 μM). The effect of NGF persisted in Ca2+-free medium that contained 1.8 mM Mg2+ and 2 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid. It was mimicked by a Trk antibody that was capable of inducing neurite outgrowth in explant cultures of bullfrog sympathetic ganglion. Antibodies raised against the low-affinity p75 neurotrophin receptor were ineffective in blocking the effect of NGF on I Ba. These results suggest that NGF-induced increase in Ca2+ channel current in adult sympathetic neurons results, at least in part, from new channel synthesis after Trk activation of Ras and mitogen activated protein kinase by a mechanism that is independent of extracellular Ca2+.

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