Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2006
2006
INTRODUCTION
Stated preference studies for cancer screening programs are used to understand how the programs can be improved to maximize usage. Our objectives were to conduct a systematic review of stated preference studies for cancer screening, identify gaps in the literature, and determine which types of research should be conducted in the future.
METHODS
We considered all studies in the PubMed database through May 2005 that measured utility-based stated preferences for cancer screening using contingent valuation or conjoint analysis. We abstracted data on 1) study characteristics and 2) study results and policy implications.
RESULTS
We found eight (of 84 identified) preference studies for cancer screening. The most commonly studied cancer was breast cancer, and the most commonly used method was contingent valuation. We found no studies for prostate cancer or physician preferences. Studies demonstrated that although individuals are able to state their preferences for cancer screening, they do not weigh test benefits and harms, and a significant percentage would choose to have no screening at all. Several studies found that test accuracy and reduction in mortality risk were important for determining preferences.
CONCLUSION
Few studies of cancer screening preferences exist. The available studies examine only a few types of cancer and do not explore practice and policy implications in depth. The results of this review will be useful in identifying the focus of future research, identifying which screening methods may be more preferred to increase use of the programs, and developing interventions and policies that could facilitate informed and shared decision making for screening.
View on PubMed2006
2006
2006
OBJECTIVE
N, N-Dimethylsphingosine (DMS) is recognized as an inhibitor of sphingosine kinase (SphK), a key enzyme responsible for the formation of sphingosine-1-phosphate (S1P). We previously showed that S1P was cardioprotective and that SphK was critical for myocardial ischemic preconditioning. Although DMS is an endogenous sphingolipid, its effect on cardiac function and cardioprotection at low concentration has not been studied.
METHODS
In Langendorff-perfused wild-type and protein kinase C (PKC)epsilon-null mouse hearts, cardiac function, infarction size, and SphK activity were measured.
RESULTS
Pretreatment with 0.3 microM and 1 microM DMS for 10 min protected against ischemia/reperfusion injury. Cardiac function (LVDP, +/-dP/dtmax) was improved and infarction size was reduced. The cardiac protection induced by DMS was abolished in PKCepsilon-null mouse hearts. Administration of 1 microM DMS ex vivo increased cytosolic SphK activity. This enhanced SphK activity was abolished in PKCepsilon-null mouse hearts. DMS also increased PKCepsilon translocation from the particulate to the cytosolic fraction with no effect on PKCalpha distribution. Co-immunoprecipitation showed that SphK1 interacted with PKCepsilon phosphorylated on Ser729. DMS also increased cytosolic Akt phosphorylation (Ser 473) and Akt translocation from a Triton-insoluble fraction to the cytosol.
CONCLUSIONS
DMS has a biphasic effect on cardioprotection. Higher concentrations (10 microM) are inhibitory, whereas a low concentration (0.3 microM and 1 microM) of DMS protects murine hearts against ischemia/reperfusion injury. DMS activates SphK in the cytosol via a PKCepsilon dependent mechanism. The PKCepsilon-SphK-S1P-Akt pathway is involved in the cardiac protection induced by DMS.
View on PubMed2006
2006
2006
2006
2006
PURPOSE
To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo.
PATIENTS AND METHODS
Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination.
RESULTS
When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib.
CONCLUSION
Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC.
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