Prostate cancer is the most common cancer among American men and African American men have the highest incidence of any population in the world. Three percent of all deaths in men over 50 years old are attributed to prostate cancer, an estimated 33,000 in 1991. As the population ages, the number of patients will increase steadily over the next decade. Yet prostate cancer is unique among the potentially lethal human malignancies in the wide discrepancy between the high prevalence of histologic changes recognizable as cancer (""""""""latent cancer"""""""") and the much lower prevalence of the clinically recognizable disease (""""""""clinical cancer"""""""") (see Spore Program Description Section II.A.2., Introduction. Fig. 1, Multistep Progression of Human Prostate Cancer). Tests are available to detect prostate cancer early: digital rectal examination, prostate specific antigen, and transrectal ultrasonography. Yet physicians are uncertain about the clinical importance of some cancers detected with such techniques. These cancers are usually low grade and low stage and there are no objective markers able to distinguish stable from unstable latent cancers or to predict the rate of progression of the cancer -- the prognosis of the patient -- so that appropriate intervention can be recommended. We propose to identify effective markers of progression in human prostate cancer by analyzing the pathologic features (stage, grade, zone of origin, extraprostatic spread), the DNA ploidy value, and the presence and distribution in tissue sections of a panel of interrelated markers (the growth control gene products TGF-beta1, p53, c-myc and RB; and the fibronectin-like mesenchymal marker tenascin) in prostate cancers found in: (1) radical prostatectomy specimens from patients with early stage clinical prostate cancer; and, (2) prostates removed during cystoprostatectomy for bladder cancer. Studies in the mouse prostate reconstitution model of prostate cancer [1,2], supported by preliminary data in human prostate cancer [3], suggest that increased expression of transforming growth factor-beta (TGF-beta1) may serve as an early marker of progression. Absence of the retinoblastoma (RB) gene product allows unsuppressed growth in a human prostate cancer cell line [4] and our preliminary studies show a discordance of RB staining and histologic grade. The presence and location of these markers in human prostate cancers will be determined by immunohistochemistry using specific antibodies. Whole mount prostatectomy specimens from the 2 sources listed above will allow us to correlate the expression of these markers with the detailed pathologic features and DNA ploidy of each cancer, and to compare these features in rapid vs. slow (or non-) progressors in our large patient population in order to determine whether any one or a combination of the markers in our panel can be used as objective markers of progression predictive of the biological behavior of the tumor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA058204-03S2
Application #
3731461
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Olar, Adriana; He, Dandan; Florentin, Diego et al. (2014) Biological correlates of prostate cancer perineural invasion diameter. Hum Pathol 45:1365-9
Olar, Adriana; He, Dandan; Florentin, Diego et al. (2014) Biologic correlates and significance of axonogenesis in prostate cancer. Hum Pathol 45:1358-64
Sonpavde, Guru; Wang, Mingjun; Peterson, Leif E et al. (2014) HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer. Invest New Drugs 32:235-242
Nakka, Manjula; Agoulnik, Irina U; Weigel, Nancy L (2013) Targeted disruption of the p160 coactivator interface of androgen receptor (AR) selectively inhibits AR activity in both androgen-dependent and castration-resistant AR-expressing prostate cancer cells. Int J Biochem Cell Biol 45:763-72
Ding, Yi; He, Dandan; Florentin, Diego et al. (2013) Semaphorin 4F as a critical regulator of neuroepithelial interactions and a biomarker of aggressive prostate cancer. Clin Cancer Res 19:6101-11
Feng, Shu; Dakhova, Olga; Creighton, Chad J et al. (2013) Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression. Cancer Res 73:2551-62
Yang, Feng; Zhang, Yongyou; Ressler, Steven J et al. (2013) FGFR1 is essential for prostate cancer progression and metastasis. Cancer Res 73:3716-24
Yang, Guang; Goltsov, Alexei A; Ren, Chengzhen et al. (2012) Caveolin-1 upregulation contributes to c-Myc-induced high-grade prostatic intraepithelial neoplasia and prostate cancer. Mol Cancer Res 10:218-29
Sonpavde, Guru; Thompson, Timothy C; Jain, Rajul K et al. (2011) GLIPR1 tumor suppressor gene expressed by adenoviral vector as neoadjuvant intraprostatic injection for localized intermediate or high-risk prostate cancer preceding radical prostatectomy. Clin Cancer Res 17:7174-82
Wang, Jianghua; Cai, Yi; Shao, Long-Jiang et al. (2011) Activation of NF-{kappa}B by TMPRSS2/ERG Fusion Isoforms through Toll-Like Receptor-4. Cancer Res 71:1325-33

Showing the most recent 10 out of 262 publications