Browsing by Author "Petricoin, EF"

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    Serum proteomic patterns for detection of prostate cancer
    (OXFORD UNIV PRESS INC, 2002) Petricoin, EF; Ornstein, DK; Paweletz, CP; Ardekani, A; Hackett, PS; Hitt, BA; Velassco, A; Trucco, C; Wiegand, L; Wood, K; Simone, CB; Levine, PJ; Linehan, WM; Emmert Buck, MR; Steinberg, SM; Kohn, EC; Liotta, LA
    Pathologic states within the prostate may be reflected by changes in serum proteomic patterns. To test this hypothesis, we analyzed serum proteomic mass spectra with a bioinformatics tool to reveal the most fit pattern that discriminated the training set of sera of men with a histopathologic diagnosis of prostate cancer (serum prostate-specific antigen [PSA] greater than or equal to 4 ng/mL) from those men without prostate cancer (serum PSA level < 1 ng/mL). Mass spectra of blinded sera (N = 266) from a test set derived from men with prostate cancer or men without prostate cancer were matched against the discriminating pattern revealed by the training set. A predicted diagnosis of benign disease or cancer was rendered based on similarity to the discriminating pattern discovered from the training set. The proteomic pattern correctly predicted 36 (95%, 95% confidence interval [CI] = 82% to 99%) of 38 patients with prostate cancer, while 177 (78%, 95% CI = 72% to 83%) of 228 patients were correctly classified as having benign conditions. For men with marginally elevated PSA levels (4-10 ng/mL; n = 137), the specificity was 71%. If validated in future series, serum proteomic pattern diagnostics may be of value in deciding whether to perform a biopsy on a man with an elevated PSA level.
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    Signal pathway profiling of prostate cancer using reverse phase protein arrays
    (2003) Grubb, RL; Calvert, VS; Wulkuhle, JD; Paweletz, CP; Linehan, WM; Phillips, JL; Chuaqui, R; Valasco, A; Gillespie, J; Emmert-Buck, M; Liotta, LA; Petricoin, EF
    Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phosphospecific endpoints revealed changes in cellular signaling events through disease progression and, between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.