Shedding Light on Bladder Cancer Diagnosis in Urine

Chan, Kit Man; Gleadle, Jonathan; Li, Jordan; Vasilev, Krasimir; MacGregor, Melanie

doi:10.3390/diagnostics10060383

Cited by 15 publications

(15 citation statements)

References 79 publications

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“…While cystoscopy remains the gold standard evaluation modality in the diagnosis of UC, it is invasive, costly, and the procedure is uncomfortable for the patient. Urine biomarkers offer a non-invasive approach to detect UC, especially for high-grade lesions and CIS, with higher sensitivity but lower specificity than urine cytology [ 50 ].…”

Section: Current Research Gaps In Uc Diagnosismentioning

confidence: 99%

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Hong¹,

Goh

et al. 2021

Cancers

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Urothelial carcinoma (UC) is the most frequent malignancy of the urinary system and is ranked the sixth most diagnosed cancer in men worldwide. Around 70–75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer (NMIBC) subtype, which can be treated by a transurethral resection of the tumor. However, patients require life-long monitoring due to its high rate of recurrence. The current gold standard for UC diagnosis, prognosis, and disease surveillance relies on a combination of cytology and cystoscopy, which is invasive, costly, and associated with comorbidities. Hence, there is considerable interest in the development of highly specific and sensitive urinary biomarkers for the non-invasive early detection of UC. In this review, we assess the performance of current diagnostic assays for UC and highlight some of the most promising biomarkers investigated to date. We also highlight some of the recent advances in single-cell technologies that may offer a paradigm shift in the field of UC biomarker discovery and precision diagnostics.

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Section: Current Research Gaps In Uc Diagnosismentioning

confidence: 99%

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Hong¹,

Goh

et al. 2021

Cancers

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“…Deposition of plasma polymers was carried out in a custommade reactor that has been previously described previously (Chan K. M. et al, 2020). The plasma was ignited with a 13.56 MHz Radio Frequency generator coupled to a matching network (Coaxial Power System).…”

Section: Plasma Depositionmentioning

confidence: 99%

“…Building on this discovery, immunosensing substrates were developed using PPOx to immobilise cancer specific antibodies for application in non-invasive diagnostic devices. The biocompatibility of the films has been previously investigated using both noncancerous and cancerous prostatic cell lines, fibroblasts, and bladder carcinoma cell lines (Chan K. M. et al, 2020). Cell viability was determined through a resazurin assay and the results showed that PPOx films are biocompatible.…”

Section: Introductionmentioning

confidence: 99%

“…In previous work, PPOx coatings have been used in commercial microfluidic chips for selective isolation of both bladder and prostate cancer cells from urine samples (Macgregor-Ramiasa et al, 2017;Hanieh Safizadeh Shirazi, 2020;Macgregor et al, 2021). These urothelial cancers readily shed cancer cells in urine, so detecting these cancer cells from urine samples could become an alternative to the current invasive diagnostic methods which consist of cystoscopy and/or biopsy (Chan et al, 2020). Urine samples can also be investigated for biomarkers such as exosomes.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Deposited Polyoxazoline Films Integration Into Spiral Microfluidics for the Targeted Capture of Size Selected Cells

et al. 2021

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Biomolecules readily and irreversibly bind to plasma deposited Polyoxazoline thin films in physiological conditions. The unique reactivity of these thin films toward antibodies is driving the development of immunosensing platforms for applications in cancer diagnostics. However, in order for these coatings to be used as advanced immunosensors, they need to be incorporated into microfluidic devices that are sealed via plasma bonding. In this work, the thickness, chemistry and reactivity of the polyoxazoline films were assessed following plasma activation. Films deposited from methyl and isopropenyl oxazoline precursors were integrated into spiral microfluidic devices and biofunctionalized with prostate cancer specific antibodies. Using microbeads as model particles, the design of the spiral microfluidic was optimised to enable the size-based isolation of cancer cells. The device was tested with a mixed cell suspension of healthy and malignant prostate cells. The results showed that, following size-specific separation in the spiral, selective capture was achieved on the immunofunctionalised PPOx surface. This proof of concept study demonstrates that plasma deposited polyoxazoline can be used for immunosensing in plasma bonded microfluidic devices.

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“…The immunofunctionalisation is capable of withstanding the harsh urine environment (high ionic strength, acidic) thanks to the plasma deposited polyoxazoline coating (POx) used to covalently bind bioactive anti-EpCAM antibodies, as previously demonstrated 25 , 26 . The captured cancer cells are then distinguished from healthy cells by using Hexaminolevulinate (HAL) which induce cancer specific protoporphyrin IX fluorescence 27 . HAL is a derivative of 5-ALA, a precursor of protoporphyrin IX (PpIX) in the heme biosynthetic pathway 28 .…”

Section: Introductionmentioning

confidence: 99%

Improving hexaminolevulinate enabled cancer cell detection in liquid biopsy immunosensors

Chan

Gleadle

et al. 2021

Sci Rep

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Hexaminolevulinate (HAL) induced Protoporphyrin IX (PpIX) fluorescence is commonly used to differentiate cancer cells from normal cells in vivo, as for instance in blue light cystoscopy for bladder cancer diagnosis. A detailed approach is here provided to use this diagnostic principle ex vivo in an immunosensor device, towards enabling non-invasive cancer diagnostic from body fluids, such as urine. Several factors susceptible to affect the applicability of HAL-assisted diagnosis in body fluids were tested. These included the cell viability and its impact on PpIX fluorescence, the storage condition and shelf life of HAL premix reagent, light exposure (360–450 nm wavelengths) and its corresponding effect on both intensity and bleaching of the PpIX fluorescence as a function of the microscopy imaging conditions. There was no significant decrease in the viability of bladder cancer cells after 6 h at 4 °C (student’s t-test: p > 0.05). The cellular PpIX fluorescence decreased in a time-dependent manner when cancer cells were kept at 4 °C for extended period of time, though this didn’t significantly reduce the fluorescence intensity contrast between cancer and non-cancer cells kept in the same condition for 6 h. HAL premix reagent kept in long term storage at 4 °C induced stronger PpIX fluorescence than reagent kept in the − 20 °C freezer. The PpIX fluorescence was negatively affected by repeated light exposure but increased with illumination intensity and exposure time. Though this applied to both healthy and cancer cell lines, and therefore did not statistically improved the differentiation between cell types. This study revealed important experimental settings that need to be carefully considered to benefit from the analytical potential of HAL induced fluorescence when used in technologies for the diagnosis of cancer from body fluids.

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Shedding Light on Bladder Cancer Diagnosis in Urine

Cited by 15 publications

References 79 publications

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Plasma Deposited Polyoxazoline Films Integration Into Spiral Microfluidics for the Targeted Capture of Size Selected Cells

Improving hexaminolevulinate enabled cancer cell detection in liquid biopsy immunosensors

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