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Stanford University

 

Bladder cancer diagnostics

Bladder cancer is the 5th most common cancer and has one of the highest recurrence rates of all cancers. White light cystoscopy (WLC) plays the integral role in the diagnosis, surveillance, resection, and local staging of bladder cancer.  However, WLC is invasive and has suboptimal diagnostic accuracy for non-papillary, high-grade tumors that have significant potential to recur and progress. Our goal is to improve bladder cancer diagnosis and treatment through development of urine based tests and improved imaging modalities.

 

Urine biomarks for bladder cancer detection and surveillance

 

Development of urine-based tests for bladder cancer detection, surveillance and prognosis have the potential to improve patient care and reduce morbidity. For development of a urine-based test, we think that direct analysis of exfoliated urothelial cells, rather than tissue biopsies, will yield higher translation al potential for biomarker discovery. Therefore, we have applied RNA-seq to urinary cells to assess bladder cancer specific gene expression. We are testing a 3-marker panel for bladder cancer detection identified by RNA-seq analysis. Ongoing work is using RNA-seq of urinary cells to identify prognostic biomarkers and biomarkers of treatment response.

 

 

Real-time diagnosis and grading of bladder cancer with in vivo microscopy

 

We are investigating confocal laser endomicroscopy (CLE) to augment the diagnostic accuracy of standard WLC and provide intraoperative surgical guidance.  CLE is based on a miniaturized fiberoptic imaging probe compatible with standard endoscopes, with the capability to provide real-time in vivo microscopy of suspected mucosal lesions.    Current projects include development of computer-based image processing algorithms for real-time image interpretation, developing confocal imaging standards and diagnostic criteria, and multi-modal imaging with other optical imaging technologies.

 

 

 

 

Molecular imaging of bladder cancer

Molecular imaging of bladder cancer could greatly improve on current methods of diagnosis, which rely on white light -based imaging that looks for superficial tissue changes, such as color and texture. Our recent work indicates that CD47 targeted molecular imaging has the potential to improve bladder cancer diagnosis.  CD47 is present on the surface of most solid tumors, including in the bladder, and inhibits macrophage engulfment. In our ex vivo model using human bladders recently removed form patients for bladder cancer and a fluorescently label anti-CD47 we have demonstrated a sensitivity of 82.9% and a specificity of 90.5% for CD47 targeted imaging.  Because this approach only requires topical administration of a fluorescent antibody and the use of already available clinical tools, it is hoped that this molecular imaging approach to diagnosing various bladder cancers will translate after further optimization.

 

Scheme for ex vivo imaging

 

 

Urinary Tract Infection

Point-of care diagnosis of urinary tract infections using molecular biosensors

Urinary tract infection (UTI) is among the most common bacterial infections and poses a significant healthcare burden.  Standard culture-based diagnosis has a delay of two to three days, which contributes to widespread injudicious use of broad-spectrum antibiotics by clinicians and the emergence of multi-drug resistant pathogens.  We are developing an integrated diagnostic biosensor capable of point-of-care (POC) diagnosis of UTI, including pathogen identification and antimicrobial susceptibility testing.  The detection strategy is based on an electrochemical biosensor array functionalized with pathogen-specific probes targeting bacterial 16S rRNA.