The impact of temperature and urinary constituents on urine viscosity and its relevance to bladder hyperthermia treatment

Inman, Brant A.; Etienne, Wiguins; Rubin, Rainier; Owusu, Richmond; Oliveira, Tiago; Rodriques, Dario B; Maccarini, Paolo F.; Stauffer, Paul R.; Mashal, Alireza; Dewhirst, Mark W.

doi:10.3109/02656736.2013.775355

Cited by 68 publications

(35 citation statements)

References 24 publications

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“…The increase in hydraulic conductivity is the result of enhanced permeability in the interstitium and reduced fluid viscosity. Hyperthermia (42 C) has been shown to decrease urine viscosity by approximately 10%, as compared with 37 C [23]. This combination of effects could contribute to increased drug penetration into the bladder wall.…”

Section: Hyperthermia Enhances Drug Diffusionmentioning

confidence: 99%

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Heijden

Dewhirst

2016

International Journal of Hyperthermia

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Non-muscle-invasive bladder cancer is a challenging disease, even given its superficial nature. It is prone to multiple recurrences and progression to muscle-invasive cancer. These features of this disease contribute significantly to reduced quality of life as well as creating significant morbidity and even mortality. Randomised trials demonstrate that when hyperthermia is added to conventional mitomycin-C treatment that local control rates and progression-free survival are substantially improved. In this review we consider how hyperthermia can exert such beneficial effects. Some of the mechanisms presented are theoretical, while others are facts. It is hoped that this review will contribute rationale for further examination of mechanisms, because an understanding of such mechanisms may lead to even better chemotherapeutic approaches, as well as potential biomarkers for predicting and monitoring treatment success.ARTICLE HISTORY

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Section: Hyperthermia Enhances Drug Diffusionmentioning

confidence: 99%

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Heijden

Dewhirst

2016

International Journal of Hyperthermia

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“…Human urine at 20 C (density ¼ 1.015 g/cm 3 and kinematic viscosity ¼ 1.0700 cSt; ref. 18) was used as the matrix fluid with a flow rate of 500 mL/s and the outlet set as an open boundary. From our computational simulations, we obtained the shear stresses and shear rates in the capture chamber of the chip.…”

Section: Simulation Of Urine Flow Inside the Microfluidic Chipmentioning

confidence: 99%

Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single-Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells

Chen

et al. 2018

Cancer Research

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The increasing incidence of bladder cancer and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention; however, they suffer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETC), either individually or in clusters, in a clean and segregated environment, which is crucial to minimize crosscontamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression, and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 patients with bladder cancer and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably higher UETC counts in patients with bladder cancer versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; P < 0.0001]. For bladder cancer detection, a stratified 10-fold cross-validation of training data reveals an overall predictive accuracy of 0.84 [95% confidence interval (CI), 0.76-0.93] with an 89.8% (95% CI, 71.5%-86.4%) for sensitivity and 71.5% (95% CI, 59.7%-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity compared with other techniques for the detection of bladder cancer.Significance: A unique and promising diagnostic assay for bladder cancer is proposed with potential clinical utility as a complement for cytology. Cancer Res; 78(14); 4073-85. Ó2018 AACR.

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“…Although urine is a diluted solution with a density and viscosity close to water we noticed that when the tip of the dialysis bag is immersed in water the stream of urine flowing from the tube sank on the bottom of the cylinder. Factors affecting the viscosity of urine include temperature, protein content (114), and hydration status (115). These are of pivotal importance when a comparative analysis between different subjects and patients’ samples with different grade of hydration and proteinuria are compared and a differential centrifugation protocol is employed.…”

Section: Bottlenecks Of Uev Isolation and Future Aspectsmentioning

confidence: 99%

Use and Isolation of Urinary Exosomes as Biomarkers for Diabetic Nephropathy

2014

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Diabetes represents a major threat to public health and the number of patients is increasing alarmingly in the global scale. Particularly, the diabetic kidney disease (nephropathy, DN) together with its cardiovascular complications cause immense human suffering, highly increased risk of premature deaths, and lead to huge societal costs. DN is first detected when protein appears in urine (microalbuminuria). As in other persisting proteinuric diseases (like vasculitis) it heralds irreversible damage of kidney functions up to non-functional (end-stage) kidney and ultimately calls for kidney replacement therapy (dialysis or kidney transplantation). While remarkable progress has been made in understanding the genetic and molecular factors associating with chronic kidney diseases, breakthroughs are still missing to provide comprehensive understanding of events and mechanisms associated. Non-invasive diagnostic tools for early diagnostics of kidney damage are badly needed. Exosomes – small vesicular structures present in urine are released by all cell types along kidney structures to present with distinct surface assembly. Furthermore, exosomes carry a load of special proteins and nucleic acids. This “cargo” faithfully reflects the physiological state of their respective cells of origin and appears to serve as a new pathway for downstream signaling to target cells. Accordingly, exosome vesicles are emerging as a valuable source for disease stage-specific information and as fingerprints of disease progression. Unfortunately, technical issues of exosome isolation are challenging and, thus, their full potential remains untapped. Here, we review the molecular basis of exosome secretion as well as their use to reveal events along the nephron. In addition to novel molecular information, the new methods provide the needed accurate, personalized, non-invasive, and inexpensive future diagnostics.

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The impact of temperature and urinary constituents on urine viscosity and its relevance to bladder hyperthermia treatment

Cited by 68 publications

References 24 publications

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single-Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells

Use and Isolation of Urinary Exosomes as Biomarkers for Diabetic Nephropathy

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