Chip-Based Nanostructured Sensors Enable Accurate Identification and Classification of Circulating Tumor Cells in Prostate Cancer Patient Blood Samples

2012 ◽  
Vol 85 (1) ◽  
pp. 398-403 ◽  
Author(s):  
Ivaylo Ivanov ◽  
Jessica Stojcic ◽  
Aleksandra Stanimirovic ◽  
Edward Sargent ◽  
Robert K. Nam ◽  
...  
Author(s):  
Estrelania S. Williams ◽  
Veronica Rodriquez-Bravo ◽  
Uma Chippada-Venkata ◽  
Janis De Ia Iglesia-Vicente ◽  
Yixuan Gong ◽  
...  

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 112-112
Author(s):  
Avani Atul Shah ◽  
Zhigang Kang ◽  
Ravi Amrit Madan ◽  
Jennifer L. Marte ◽  
James L. Gulley ◽  
...  

112 Background: Increased androgen receptor (AR) expression and signaling is associated with the progression of prostate cancer. Constitutively active AR splice variants (ARVs) are thought to arise following castration and play a key role in progression. The most well studied variant, ARv567es, lacks portions of the ligand-binding domain, increasing expression of full-length AR and transcriptional activity of AR in human prostate cancer cell lines. Tumor-derived tissue can be difficult to obtain for molecular studies on patients (pts) with castration-resistant prostate cancer (CRPC), with circulating tumor cells (CTCs) representing a unique avenue to investigate changes at the molecular level. Methods: Forty-seven whole blood samples drawn from 36 pts with metastatic CRPC (mCRPC) were processed for CTC isolation followed by molecular characterization of cDNA using epithelial tumor markers and prostate cancer specific markers. Microfluidics devices used in this study for CTCs isolation and retrieval is a surface marker independent, label-free cell trap system developed to isolate CTCs based on cell size and deformability (Clearbridge Biomedics). The ARv567eswas detected by multiplex digital PCR System (BioMark HD, Fluidigm) and confirmed by Sanger sequencing. Results: Four out of 36 pts and 6 out of 47 samples had the ARv567es.. The ARv567esamplified from three pts was confirmed by Sanger sequencing in which the ligand binding domain of the receptor was absent. Metastatic disease on presentation was seen in three out of four pts with the ARVs. The ARVs were detected late in the disease course, with the survival after assessment being brief (49, 106, and 200 days) for three out of four pts. One patient is still at 343 days. Due to the nature of this analysis it is unclear when these ARVs developed since baselines samples were not available. Conclusions: This is the first report of the ARv567es found in CTC-enriched peripheral blood samples from CRPC pts. This methodology can also be employed to find other ARVs, which could serve as potential biomarkers in pts, allowing for more appropriate treatment selection based on tumor evolution. This noninvasive method could significantly impact the molecular characterization and potentially the treatment science of CRPC.


2008 ◽  
Vol 123 (8) ◽  
pp. 1968-1973 ◽  
Author(s):  
Wei He ◽  
Sumith A. Kularatne ◽  
Kimberly R. Kalli ◽  
Franklyn G. Prendergast ◽  
Robert J. Amato ◽  
...  

2019 ◽  
Vol 8 (9) ◽  
pp. 1473 ◽  
Author(s):  
Tamasa De ◽  
Shina Goyal ◽  
Gowri Balachander ◽  
Kaushik Chatterjee ◽  
Prashant Kumar ◽  
...  

The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45− (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial–mesenchymal transition (EMT) in CTCs for clinical association.


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