Carbone, D. P., Salmon, J. S., Billheimer, D., Chen, H., Sandler, A., Roder, H., Roder, J., Tsypin, M., Herbst, R. S., Tsao, A. S., Tran, H. T., & Dang, T. P. (2010). VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab. Lung Cancer, 69(3), 337-340.
PMID: 20036440;PMCID: PMC2891357;Abstract:
We applied an established and commercially available serum proteomic classifier for survival after treatment with erlotinib (VeriStrat®) in a blinded manner to pretreatment sera obtained from recurrent advanced NSCLC patients before treatment with the combination of erlotinib plus bevacizumab. We found that VeriStrat® could classify these patients into two groups with significantly better or worse outcomes and may enable rational selection of patients more likely to benefit from this costly and potentially toxic regimen. © 2009 Elsevier Ireland Ltd.
Yankeelov, T. E., DeBusk, L. M., Billheimer, D. D., Luci, J. J., Lin, P. C., Price, R. R., & Gore, J. C. (2006). Repeatability of a reference region model for analysis of murine DCE-MRI data at 7T. Journal of Magnetic Resonance Imaging, 24(5), 1140-1147.
PMID: 17024660;Abstract:
Purpose: To test the repeatability of a reference region (RR) model for the analysis of dynamic contrast-enhanced MRI (DCE-MRI) in a mouse model of cancer at high field. Materials and Methods: Seven mice were injected with 10 6 4T1 mammary carcinoma cells and imaged eight to 10 days later on a Varian 7.0T scanner. Two DCE-MRI studies were performed for each mouse (separated by 2.5 hours). The RR model was used to analyze the data, and returned estimates on the perfusion-permeability index (Ktrans) for the RR and the tissue of interest (TOI), as well as the extravascular extracellular volume fraction (ve) for the TOI. Results: When the first injection was compared with the second injection, all parameters tested were highly correlated (r2 = 0.90, 0.62, 0.82 for the RR K trans, TOI Ktrans, and TOI ve, respectively, with P 0.001 for all). To observe a statistically significant change (at the 5% level) in a treatment study with seven animals in each group, log 10 changes of 0.084 and 0.077 in the tumor Ktrans and ve. respectively, are required. Conclusion: If a reliable arterial input function (AIF) is unavailable, the RR model is a reasonable alternative to measuring MRI contrast-agent (CA) kinetics in mouse models of cancer at high field. © 2006 Wiley-Liss, Inc.
Tsiatis, A. C., Manes, B., Calder, C., Billheimer, D., Wilkerson, K. S., & Frangoul, H. (2004). Incidence and clinical complications of vancomycin-resistant enterococcus in pediatric stem cell transplant patients. Bone Marrow Transplantation, 33(9), 937-941.
PMID: 15034540;Abstract:
Vancomycin-resistant enterococcus (VRE) are increasingly important pathogens in stem cell transplant (SCT). In all, 61 pediatric SCT patients had surveillance stool cultures for VRE between July 1999 and November 2002. When VRE was identified, the patients were placed on strict contact isolation. VRE was detected in 15 patients (24.6%). The median age was 3.6 years (range 0.6-18.5 years). Of the 15, 13 (87%) received an allogeneic transplant (six unrelated and seven related). Five of the 15 (33%) colonized patients developed VRE bacteremia. The bacteremia resolved in all five patients after therapy with quinupristin/dalfopristin; three patients required central line removal. Four patients died (38-153 days) post-SCT due to relapse or transplant complication not related to VRE. Of the 11 surviving patients, seven cleared the colonization at a median of 144 days (range 61-198 days) postcolonization. Four patients remain colonized at 68-702 days after the first positive culture. Intestinal colonization with VRE occurred commonly in pediatric SCT patients. Although the morbidity from VRE was not substantial, transplant patients were colonized for prolonged periods. Our results indicate that surveillance for VRE is an effective way to identify colonized patients and may lead to a decrease in transmission to other patients. © 2004 Nature Publishing Group. All rights reserved.
Micalizzi, D. S., Christensen, K. L., Jedlicka, P., Coletta, R. D., Barón, A. E., Harrell, J. C., Horwitz, K. B., Billheimer, D., Heichman, K. A., Welm, A. L., Schiemann, W. P., & Ford, H. L. (2009). The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-β signaling. Journal of Clinical Investigation, 119(9), 2678-2690.
PMID: 19726885;PMCID: PMC2735914;Abstract:
Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases TGF-β signaling in human breast cancer cells and induces an epithelial-mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-β signaling. TGF-β signaling and EMT have been implicated in metastatic dissemination of carcinoma. Accordingly, we used spontaneous and experimental metastasis mouse models to demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-β signaling. Importantly, in human breast cancers Six1 correlated with nuclear Smad3 and thus increased TGF-β signaling. Further, breast cancer patients whose tumors overexpressed Six1 had a shortened time to relapse and metastasis and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlated with adverse outcomes in numerous other cancers including brain, cervical, prostate, colon, kidney, and liver. Our findings indicate that Six1, acting through TGF-β signaling and EMT, is a powerful and global promoter of cancer metastasis.
Lake, A., Novak, P., Fisher, C., Jackson, J., Hardwick, R., Billheimer, D., Klimecki, W., & Cherrington, N. (2011). Analysis of Global and ADME Gene Expression In the Progressive Stages of Human Non-Alcoholic Fatty Liver Disease. Drug Metab Dispos, 39(10), 1954-1960.
