This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although it is generally accepted that estrogens potentiate the development of cancer by a receptor-mediated process, many recent studies suggest that estrogens are complete (but extremely weak) carcinogens capable of tumor initiation. It is believed that estrogens, including the natural hormones estrone (E1) and estradiol (E2), are associated with increased risk of breast and other types of human cancer. That is, catechol estrogen quinones (CEQ) derived from 4-hydroxyestrone (4-OHE1) and 4-hydroxyestradiol (4-OHE2) react with DNA and form depurinating -N7Gua and -N3Ade adducts that may be responsible for tumor initiation [Cavalieri, E.L., et al. (2000) JNCI Monograph, 27,75]. To determine whether this type of DNA damage occurs in humans, urine samples from prostate and breast cancer patients and healthy individuals will be analyzed in a blind study. A primary objective is determining whether any of the cancer patients had formed 4-OHE1(E2)-1-N3Ade, suspected to be one of the major adducts formed by CEQ. This is of great interest as it could provide a new biomarker(s) for cancer detection and prognosis. The methods for testing the hypothesis that metabolically activated endogenous estrogens are involved in the initiation of breast and prostate cancers include capillary electrophoresis (CE) with field amplified sample stacking (FASS) interfaced with low temperature (T) laser-induced phosphorescence (LIP) detection and a new biosensor methodology suitable for room-temperature detection of various CEQ-derived biomarkers in nipple aspirate, urine, and tissue samples from breast cancer cases and control women, as well as in prostate fluid from prostate cancer cases and control men. Detection in biochips will be based on a novel first-come-first-served approach and fluorescence based imaging. The technical merit and the potential of this approach for high throughput screening and future cancer risk assessment will be evaluated.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-8 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kansas Lawrence
Schools of Pharmacy
United States
Zip Code
Subramanian, Chitra; Grogan, Patrick T; Opipari, Valerie P et al. (2018) Novel natural withanolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-?B activation. Oncotarget 9:14509-14523
Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro et al. (2018) Co-treatment with a C1B5 peptide of protein kinase C? and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation. Biochem Biophys Res Commun 495:962-968
He, Chenchen; Duan, Shaofeng; Dong, Liang et al. (2017) Characterization of a novel p110?-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate 77:1187-1198
White, Peter T; Subramanian, Chitra; Zhu, Qing et al. (2016) Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery 159:142-51
Ohta, Naomi; Ishiguro, Susumu; Kawabata, Atsushi et al. (2015) Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One 10:e0123756
Li, Benyi; Thrasher, James Brantley; Terranova, Paul (2015) Glycogen synthase kinase-3: a potential preventive target for prostate cancer management. Urol Oncol 33:456-63
Ishiguro, Susumu; Yoshimura, Kiyoshi; Tsunedomi, Ryouichi et al. (2015) Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice. Cancer Biol Ther 16:307-16
Li, Benyi; Sun, Aijing; Jiang, Wencong et al. (2014) PI-3 kinase p110?: a therapeutic target in advanced prostate cancers. Am J Clin Exp Urol 2:188-98
Bibis, Stergios S; Dahlstrom, Kelly; Zhu, Tongtong et al. (2014) Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs. Mol Biochem Parasitol 196:90-9
Subramanian, Chitra; Zhang, Huaping; Gallagher, Robert et al. (2014) Withanolides are potent novel targeted therapeutic agents against adrenocortical carcinomas. World J Surg 38:1343-52

Showing the most recent 10 out of 240 publications