The goal of this SBIR project is to develop a multiplexing method to simultaneously quantify the expression levels of biomarkers in heterogeneous tumor tissue. The current method for diagnostic and prognostic classifications of biomarkers is based on immunohistochemistry (IHC). However, the immunoenzyme (HRP- based) IHC method has a single color nature and is unable to perform multiplexed molecular profiling. Moreover, IHC remains semi-quantitative and subjective, resulting in considerable inter-observer variation in results. Quantum dots (QD) are a new class of biological detection labels which present a broad range of biomedical applications. It allows biomarker detection and analysis in highly heterogeneous samples and rare cell populations. The multiplexed QD technology can be used to examine a panel of cancer biomarkers on the level of single cells (in situ analysis), which is not possible with other types of nanotechnology-based assays. This NIH SBIR project intends to develop a QDs-based nanotyping method to monitor the chemotherapy efficacy in prostate cancer. Specifically, activation of the anti-apoptotic bradykinin-survivin signaling pathway was found to be critical to Docetaxel (Taxotere) resistance in prostate cancer cells, therefore, bradykinin- survivin could be used as novel biomarkers to predict the chemotherapy response in hormone-refractory prostate cancer patients. We will establish a multiplexed QDs-based, minimally-invasive technology to monitor the activation status of the bradykinin-survivin pathway for evaluating chemotherapy efficacy in prostate cancer models. In this SBIR phase I project, we will prepare high quality QDs with high bio-affinities and low non- specific binding. Furthermore, the QD-antibody conjugates will be tested in the prediction of response to docetaxel chemotherapy in a human prostate cancer xenograft model. In Phase II, our focus will be shifted to improving the sensitivity of the proposed system and developing a quantification method. The final delivery of this project will be a highly sensitive, clinically applicable Ab-QD conjugation kit for prostate tumor imaging that will predict the response of chemotherapy.
Prostate cancer (PCa) is the most common cancer occurring among men in the United States. In 2007, an estimated 218,890 new cases of PCa were diagnosed in the U.S. Enhancing monitoring cancer therapy is very critical to increase the survival rate of patients. The proposed QD nanotyping technology will provide a platform to monitor chemotherapy efficacy and guide physicians in making decisions for the appropriate therapy. The successful development of this project can greatly increase the survival rate of these patients.
|Zhang, Shumin; Wang, Yanru; Chen, Zhengjia et al. (2013) Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells. Prostate 73:1681-9|
|Xu, Hong; Xu, Jing; Wang, Xu et al. (2013) Quantum dot-based, quantitative, and multiplexed assay for tissue staining. ACS Appl Mater Interfaces 5:2901-7|
|Zhang, Shumin; Wang, Xu; Iqbal, Shareen et al. (2013) Epidermal growth factor promotes protein degradation of epithelial protein lost in neoplasm (EPLIN), a putative metastasis suppressor, during epithelial-mesenchymal transition. J Biol Chem 288:1469-79|
|Iqbal, Shareen; Zhang, Shumin; Driss, Adel et al. (2012) PDGF upregulates Mcl-1 through activation of ýý-catenin and HIF-1ýý-dependent signaling in human prostate cancer cells. PLoS One 7:e30764|
|Zhang, S; Wang, X; Osunkoya, A O et al. (2011) EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene 30:4941-52|
|Zhang, Shumin; Zhau, Haiyen E; Osunkoya, Adeboye O et al. (2010) Vascular endothelial growth factor regulates myeloid cell leukemia-1 expression through neuropilin-1-dependent activation of c-MET signaling in human prostate cancer cells. Mol Cancer 9:9|