Vincent Navarro
Cornell University
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Publication
Featured researches published by Vincent Navarro.
Proceedings of the National Academy of Sciences of the United States of America | 2011
Michael J. Evans; Peter Smith-Jones; John Wongvipat; Vincent Navarro; Sae Kim; Neil H. Bander; Steven M. Larson; Charles L. Sawyers
Despite encouraging clinical results with next generation drugs (MDV3100 and abiraterone) that inhibit androgen receptor (AR) signaling in patients with castration-resistant prostate cancer (CRPC), responses are variable and short-lived. There is an urgent need to understand the basis of resistance to optimize their future use. We reasoned that a radiopharmaceutical that measures intratumoral changes in AR signaling could substantially improve our understanding of AR pathway directed therapies. Expanding on previous observations, we first show that prostate-specific membrane antigen (PSMA) is repressed by androgen treatment in multiple models of AR-positive prostate cancer in an AR-dependent manner. Conversely, antiandrogens up-regulate PSMA expression. These expression changes, including increased PSMA expression in response to treatment with the antiandrogen MDV3100, can be quantitatively measured in vivo in human prostate cancer xenograft models through PET imaging with a fully humanized, radiolabeled antibody to PSMA, 64Cu-J591. Collectively, these results establish that relative changes in PSMA expression levels can be quantitatively measured using a human-ready imaging reagent and could serve as a biomarker of AR signaling to noninvasively evaluate AR activity in patients with CRPC.
The Prostate | 2009
Kenji Kuroda; He Liu; Sae Kim; Ming Guo; Vincent Navarro; Neil H. Bander
Docetaxel (DOC) has potent anti‐tumor efficacy as a result of promoting microtubule assembly and microtubule bundling thereby impairing mitosis. Knowing that some anti‐microtubule agents affect the polarity of prostate‐specific membrane antigen (PSMA) expression and that androgen ablation can up‐regulate PSMA expression, we sought to determine any effect of DOC on PSMA expression in prostate cancer (PC) cell lines as a prelude to a clinical effort. As controls, we also looked at the expression of androgen receptor (AR) and prostate‐specific antigen (PSA).
The Prostate | 2010
Kenji Kuroda; He Liu; Sae Kim; Ming Guo; Vincent Navarro; Neil H. Bander
Prostate‐specific membrane antigen (PSMA) provides an attractive target for monoclonal antibody targeted therapies in the treatment of prostate cancer (PC). In this study, we generated an immunotoxin by linking a humanized anti‐PSMA monoclonal antibody (hJ591) to the ribosome‐inactivating protein toxin saporin. The hJ591–saporin immunoconjugate was evaluated for antitumor activity against PC cells.
Cancer Research | 2011
Matthew Loftus; Mona Jodari-Karimi; Gunjan Gakhar; Erica D. Pratt; Steven M. Santana; Mark A. Rubin; Neil H. Bander; Vincent Navarro; Scott T. Tagawa; Brian J. Kirby; David M. Nanus; Paraskevi Giannakakou
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Prostate cancer (PC) is the most common type of cancer in males and the second leading cause of male cancer deaths in the United States. Circulating tumor cells (CTCs) are commonly found in the blood of metastatic patients and the capture of these cells is important in the study of disease progression. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device coated with the prostate-specific membrane antigen (PSMA) which captures prostate CTCs with high purity and efficiency. This device is designed with a staggered obstacle array in order to maximize the capture efficiency (>80%) and purity (70%) of CTCs. We have used this device to capture, enumerate and molecularly characterize CTCs isolated from 1 ml of blood from patients with castrate resistant prostate cancer (CRPC). First, we compared the capture efficiency from 16 CRPC patients’ blood and subjected it to CTC enumeration by either the GEDI device or the FDA approved CellSearch technology (EpCAM-based immunocapture). Our results showed a 2-350 fold enrichment in CTC counts by the GEDI (range 15-1200 CTCs/ml, median 54). In addition, there was minimal false positive CTC detection in healthy donor blood analyzed by the GEDI. Next we sought to characterize the captured CTCs using multiplex immunofluorescence for proteins specific for PC like androgen receptor (AR), PSMA, TMPRSS2-ERG, EpCAM and other markers involved in epithelial to mesenchymal transition (EMT). We observed low or lack of EpCAM expression in the captured PSMA+/CD45- CTCs, concomitant with high vimentin expression, suggesting that our device may be preferentially capturing CTCs that have undergone EMT. Using the GEDI device, we are able to detect a known single point mutation in the AR using cDNA extracted from approximately 50 C4-2 cells spiked into 1 ml of blood from a healthy donor. Importantly, we have captured CTCs from different CRPC patients and treated them ex vivo with docetaxel to assess effective drug-target engagement by determining the extent of microtubule (MT) stabilization and apoptotic cell death. Our results showed non-uniform CTC response to drug treatment, such that a subset of PSMA+/CD45- CTCs showed MT bundling, indicating tumor heterogeneity and further suggesting that we can potentially use this device to predict patient response to taxane-based chemotherapy. In summary, the GEDI microfluidic device is a novel and specific technology to isolate and characterize PC CTCs at the molecular level. We plan to use this device in prospective clinical studies in order to understand the molecular basis of disease progression and response to taxane-based chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4891. doi:10.1158/1538-7445.AM2011-4891
Cancer Research | 1997
He Liu; Peggy Moy; Sae Kim; Yan Xia; Ayyappan K. Rajasekaran; Vincent Navarro; Beatrice Knudsen; Neil H. Bander
Cancer Research | 1998
He Liu; Ayyoppan K. Rajasekaran; Peggy Moy; Yan Xia; Sae Kim; Vincent Navarro; Rahmatullah Rahmati; Neil H. Bander
Cancer Research | 2000
Peter Smith-Jones; Shankar Vallabahajosula; Stanley J. Goldsmith; Vincent Navarro; Catherine J. Hunter; Diego Bastidas; Neil H. Bander
The Journal of Nuclear Medicine | 2003
Peter Smith-Jones; Shankar Vallabhajosula; Vincent Navarro; Diego Bastidas; Stanley J. Goldsmith; Neil H. Bander
The Prostate | 2004
Shankar Vallabhajosula; Peter Smith-Jones; Vincent Navarro; Stanley J. Goldsmith; Neil H. Bander
Cancer Research | 2006
Sharron X. Lin; Vincent Navarro; He Liu; Neil H. Bander