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Torosyan Y.,Bethesda University | Dobi A.,Center for Prostate Disease Research | Glasman M.,Bethesda University | Mezhevaya K.,Bethesda University | And 6 more authors.
Oncogene | Year: 2010

Annexin-A7 (ANXA7) tumor suppressor role has been shown in various tumors, and ANXA7 expression has been particularly lost in androgen-resistant prostate cancers. In this study, we studied ANXA7 regulation in normal prostate versus androgen-sensitive and-resistant prostate cancer cells. Deletion mapping analysis showed lowest ANXA7-promoter activities in androgen-sensitive LNCaP prostate cancer cells. Genomatix analysis of ANXA7 promoter identified a cluster of steroid nuclear hormone receptor elements, including VGREF (VGRE.02/ARE.02). Gelshift analysis clearly indicated distinct nuclear protein occupancy at this ANXA7-promoter site (1086/890) in prostate cancer (LNCaP, DU145, and PC3) versus normal prostate (PrEC) cells. In matrix-assisted laser desorption time-of-flight mass spectrometry-based search for ANXA7 nuclear regulators, we identified several heterogeneous nuclear ribonucleoproteins (hnRNPs) (A1, A2/B1 and K) attached to the steroid-associated ANXA7-promoter site in the androgen-resistant PC3 prostate cancer cells with high ANXA7 gene copy number, but not in PrEC. The hnPNP role in ANXA7 regulation (that was validated by hnRNPA2/B1 antibody interference) resulted in multiple ANXA7 cDNA and protein products in PC3, but not in PrEC. Ingenuity pathways analysis showed plausible molecular paths between ANXA7 and the hnRNP-associated network in prostate cancer progression. Thus, a multi-hnRNP complex can be responsible for aberrant ANXA7 transcription and splicing, thereby affecting ANXA7 expression pattern and tumor suppressor function in prostate cancer. © 2010 Macmillan Publishers Limited All rights reserved.

Rhim J.S.,Center for Prostate Disease Research
Methods in Molecular Biology | Year: 2013

Prostate cancer is the most common male cancer in the United States. Research on the mechanisms of prostate cancer progression has been limited by the lack of suitable in vitro systems. A hurdle in understanding the molecular genetic changes in prostate cancer has been the difficulty in establishing premalignant lesions and primary prostate tumors as in vitro cell cultures. Primary prostate epithelial cells grow for a finite life span and then senesce. Immortalization is defined by continuous growth of otherwise senescing cells and is believed to represent an early stage in tumor progression. To examine these early stages, we and others have developed in vitro models of prostate epithelial cell immortalization. Methods are described for the processing of primary human prostate biopsy samples and the generation of human prostate epithelial (HPE) cells in serum-free conditions. Retrovirus containing human telomerase reverse transcriptase (hTERT) is used for the immortalization of primary HPE cells, and the methods for the characterization of HPE cell lines are discussed. These in vitro prostate cell culture models are useful for the study of prostate normal and cancer stem cells, are critical for defining the mechanisms of prostate cancer progression and for testing preventive and therapeutic regimens. © 2013 Springer Science+Business Media, LLC.

Schully S.D.,U.S. National Cancer Institute | Carrick D.M.,U.S. National Cancer Institute | Mechanic L.E.,U.S. National Cancer Institute | Srivastava S.,U.S. National Cancer Institute | And 19 more authors.
Journal of the National Cancer Institute | Year: 2015

Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. © 2015 Published by Oxford University Press.

Vallone D.M.,American Legacy Foundation | Niederdeppe J.,Cornell University | Richardson A.K.,American Legacy Foundation | Patwardhan P.,Schroeder Institute for Tobacco Research and Policy Studies | And 2 more authors.
American Journal of Health Promotion | Year: 2011

Purpose. To assess the effectiveness of a large-scale, national smoking cessation media campaign, the EX campaign, across racial/ethnic and educational subgroups. Design. A longitudinal random-digit-dial panel study conducted prior to and 6 months following the national launch of the campaign. Setting. The sample was drawn from eight designated media markets in the United States. Subjects. The baseline survey was conducted on 5616 current smokers, aged 18 to 49 years, and 4067 (73% follow-up response rate) were resurveyed at the 6-month follow-up. Measures. The primary independent variable is confirmed awareness of the campaign advertising, and the outcome variables are follow-up cessation-related cognitions index score and quit attempts. Analysis. Multivariable logistic and linear regression analyses were conducted within racial/ ethnic and educational strata to assess the strength of association between confirmed awareness of campaign advertising and cessation-related outcomes. Results. Confirmed awareness of campaign advertising increased favorable cessation-related cognitions among Hispanics and quit attempts among non-Hispanic blacks, and increased favorable cessation-related cognitions and quit attempts among smokers with less than a high school education. Conclusions. These results suggest that the EX campaign may be effective in promoting cessationrelated cognitions and behaviors among minority and disadvantaged smokers who experience a disproportionate burden of tobacco-related illness and mortality. Copyright © 2011 by American Journal of Health Promotion, Inc.

Kim J.,University of Houston | Ebertowski J.,San Antonio Military Medical Center | Janiga M.,60th Medical Group | Arzola J.,Wright Medical Group | And 9 more authors.
BJU International | Year: 2013

What's known on the subject? and What does the study add? Little is known as to the potential for over-treatment of young men diagnosed with prostate cancer. We show that for men aged ≤55 years with PSA screen-detected disease, 45% of the tumours are classified as very low risk and 85% of these have favourable pathology, yet most are actively treated. These findings raise the spectre of over-treatment for a group of men likely to be affected by treatment side-effects. Objective To identify a population of young men (aged <55 years at diagnosis) with very-low-risk prostate cancer (stage cT1c, with prostate-specific antigen [PSA] density of <0.15 ng/mL/g, Gleason score ≤6, and ≤2 positive biopsy cores with <50% tumour involvement) that may be candidates for active surveillance (AS). Patients and Methods We queried a Department of Defense tumour registry and hard-copy records for servicemen diagnosed with prostate cancer from 1987 to 2010. Statistical analyses were undertaken using Fisher's exact and chi-square testing. Results From 1987-1991 and 2007-2010, PSA screen-detected tumours diagnosed in men aged ≤55 years rose >30-fold. Data for a subset of men (174) with PSA screen-detected cancer were evaluable for disease risk assessment. Of the 174 men with screen-detected disease, 81 (47%) had very-low-risk disease. Of that group, 96% (78/81) selected treatment and, of 57 men undergoing radical prostatectomy (RP), the tumours of 49 (86%) carried favourable pathology (organ confined, <10% gland involvement, Gleason ≤6). Conclusions Nearly half of young men with PSA screen-detected prostate cancer are AS candidates but the overwhelming majority seek treatment. Considering that many tumours show favourable pathology at RP, there is a possibility that these patients may benefit from AS management. © 2013 BJU International.

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