Publications by authors named "Robert E Hurst"
Article Synopsis
- The review focuses on the challenges of preclinical research related to bladder pain syndrome/interstitial cystitis (IC/BPS), specifically studying the urothelial barrier's role in the disease.
- Recent models have successfully replicated IC/BPS by using toxic substances to induce temporary impairment in the urothelial barrier, revealing potential treatments like glycosaminoglycan replenishment.
- There’s a need for more research to understand the interplay between barrier permeability, inflammation, and nerve factors in the development of IC/BPS.
MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies.
Diagnostics (Basel)
December 2021
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, often incapacitating condition characterized by pain seeming to originate in the bladder in conjunction with lower urinary tract symptoms of frequency and urgency, and consists of a wide range of clinical phenotypes with diverse etiologies. There are currently no diagnostic tests for IC/BPS. Magnetic resonance imaging (MRI) is a relatively new tool to assess IC/BPS.
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- - Cancer survivors often fear recurrence, especially since metastasis is responsible for about 90% of cancer deaths, highlighting the need for improved strategies to prevent metastatic recurrence.
- - The review explores several methods to target dormant disseminated tumor cells (DTCs) that may cause cancer to return, including keeping them inactive, promoting dormancy, and making them more vulnerable to therapies.
- - It also discusses the potential for using already approved drugs, identifies biomarkers for high-risk patients, and critiques current clinical trial designs aimed at addressing dormant DTCs.
Article Synopsis
- The study develops a new high molecular weight biopolymer called "SuperGAG" to treat Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by restoring bladder impermeability and reducing associated pain.
- SuperGAG was tested on OVX female rats and URO-MCP1 genetically modified mice, showing significant improvement in bladder function and pain reduction after treatment.
- This research suggests that SuperGAG, especially when paired with contrast-enhanced MRI, could serve as a promising therapeutic option for patients with IC/BPS.
Objectives: To determine if the URO-MCP-1 mouse model for bladder IC/BPS is associated with in vivo bladder hyper-permeability, as measured by contrast-enhanced MRI (CE-MRI), and assess whether molecular-targeted MRI (mt-MRI) can visualize in vivo claudin-2 expression as a result of bladder hyper-permeability. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, painful condition of the bladder that affects primarily women. It is known that permeability plays a substantial role in IC/BPS.
View Article and Find Full Text PDFAssessing bladder hyper-permeability biomarkers using molecularly-targeted MRI.
Am J Nucl Med Mol Imaging
February 2020
Article Synopsis
- - The study aimed to see if molecularly-targeted magnetic resonance imaging (mt-MRI) could visualize key molecular markers linked to bladder hyper-permeability in interstitial cystitis/bladder pain syndrome (IC/BPS), a painful condition primarily affecting women.
- - Key molecular markers like VEGF-R1, decorin, and claudin-2 were assessed in a rat model induced by protamine sulfate, revealing that decorin and VEGF-R1 levels decreased, while claudin-2 levels increased after hyper-permeability was induced.
- - The successful detection of these biomarkers using mt-MRI suggests this imaging technique could help deepen our understanding of bladder hyper-permeability in IC/BPS patients.
Systemic side effects and high hydrophobicity are major disadvantages of paclitaxel (PTX), one of the most popular anticancer drugs. Here, we present singlet oxygen (SO)-activatable and mitochondria-targeted PTX prodrugs to overcome these problems and boost the cytotoxic effect of photodynamic therapy (PDT). Three PTX prodrugs were prepared by conjugating PTX with various cationic groups.
View Article and Find Full Text PDFBladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence.
View Article and Find Full Text PDFAugmentation enterocystoplasty remains the gold standard surgical bladder reconstruction procedure to increase the capacity and compliance of dysfunctional bladders. Since the use of the patient's intestine has severe risks of complications, alternative biodegradable matrices have been explored. Porcine small intestinal submucosa (SIS) has gained immense interests in bladder reconstruction due to its favorable properties.
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- The study introduces a method to release drugs using photo-unclick chemistry, triggered by singlet oxygen (SO), which can be activated by visible light and near-infrared light.
- The research combines a photosensitizer and an SO-cleavable drug linker into one molecule or within drug delivery systems to enhance localized drug activation.
- The results demonstrate successful activation of a specific prodrug using a mitochondria-targeting photosensitizer, highlighting a novel approach to controlled drug release.
Article Synopsis
- Cancer survival rates have only improved slightly over the years primarily because research has focused on primary tumors rather than disseminated dormant cancer cells, which contribute to recurrence.
- The paper highlights the need to better understand how these dormant cells work in order to find effective treatments and discusses potential drugs currently available or in clinical trials aimed at preventing metastasis.
- It also presents new research from the authors' labs that demonstrates a successful screening method for targeting these dormant cancer cells, suggesting that addressing micrometastatic cells is achievable.
Article Synopsis
- The study highlights the importance of the glycosaminoglycan (GAG) layer in the urothelium, which is crucial for maintaining the bladder's protective barrier against dysfunction.* -
- Researchers used protamine sulfate and chondroitinase ABC on rat bladders to demonstrate that the degradation of the GAG layer increases permeability and inflammation, while preserving tight junctions.* -
- Overall findings suggest that loss of the GAG layer may contribute to symptoms in patients with interstitial cystitis/painful bladder syndrome, emphasizing the need for further exploration in this area.*
Article Synopsis
- The definition of interstitial cystitis (IC) has shifted from a specific condition defined by Hunner's ulcer to a diagnosis based on symptoms being similar to painful bladder syndrome (PBS).
- The cause of IC is still unknown, but research indicates that increased permeability of the bladder is linked to its symptoms.
- The article also discusses how different organs and systems in the body, like the bladder and bowel, communicate with each other, suggesting that IC/PBS may be a systemic issue rather than just a localized problem.
Purpose: Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes.
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- The study focuses on how urothelial cells from patients with interstitial cystitis/painful bladder syndrome (IC/PBS) manage prostaglandin E2 (PGE2), which is crucial for regulating urine flow into the bladder.
- Researchers measured the expression of proteins involved in PGE2 synthesis and degradation, such as COX-2 and PGES, in normal and IC/PBS urothelial cells during their differentiation process.
- Findings revealed that normal urothelial cells showed increased COX-2 and PGES expression during differentiation, while cells from IC/PBS patients often lacked COX-2 expression and didn't release PGE2 in response to stimuli, suggesting impaired bladder function in these patients.
Article Synopsis
- Cancer-specific survival rates have not improved much over the last 50 years due to the hidden and resilient nature of dormant micrometastases that manifest long after initial treatment.
- Researchers developed a new screening method to test drug effects on cancer cells grown in a natural extracellular matrix (ECM) versus traditional plastic dishes, finding that some compounds were more effective in the ECM environment.
- Two promising compounds were identified that significantly reduced dormant cancer cells and large metastases in mice, showing potential for better management of metastatic cancer compared to standard chemotherapeutics.
Article Synopsis
- Researchers studied cats with feline interstitial cystitis to identify protein expression abnormalities in their urothelium and compared it to human interstitial cystitis cases.
- Analysis involved examining biopsies from 8 affected cats and 7 healthy controls using immunohistochemistry, revealing significant differences in protein expression patterns.
- The findings indicated that a majority of feline cystitis samples showed abnormal protein expression, indicating similarities between feline and human interstitial cystitis mechanisms, thus supporting the cat model for future research.
Article Synopsis
- Interstitial cystitis/painful bladder syndrome is a debilitating condition diagnosed primarily through symptoms like pain and urgency, without a definitive diagnostic test currently available.* -
- In a rat study, researchers used contrast-enhanced magnetic resonance imaging (MRI) with a special contrast agent to visualize bladder and colon effects after inducing interstitial cystitis with protamine sulfate.* -
- The results showed significant changes in bladder permeability and colon uptake of the contrast agent, suggesting this MRI technique could be a promising diagnostic tool for interstitial cystitis and help understand the interactions between different organs.*
Introduction: Hyaluronic acid (HA), a non-sulfated glycosaminoglycan, is an essential component of the extracellular matrix (ECM). Since HA is involved in many phases of wound healing and may play a key role in tissue repair and regeneration, this study was intended to understand temporal and spatial expression of HA and HA receptors (HARs) during the course of bladder regeneration in rats.
Materials And Methods: Sprague-Dawley rats were subjected to partial cystectomy followed by augmentation with porcine small intestinal submucosal (SIS) prepared from distal sections of the small intestine.
Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor.
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- The pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS) involves issues with urothelial cells and the accumulation of mast cells in the bladder wall, which release inflammatory mediators like histamine and tryptase.
- Tryptase stimulation led to increased activation of ERK 1/2 and p38 MAP kinases in urothelial cells from IC/PBS patients compared to normal cells, indicating a heightened response.
- The study suggests that ERK 1/2 activation in response to tryptase may support wound healing and cell movement in inflammatory conditions of the bladder associated with IC/PBS.
A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa (SIS), in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest these suppressed cells can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 bladder cancer cells and highly metastatic JB-V bladder cancer cells in nude mouse flank xenografts.
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- The study aimed to determine if glycosaminoglycan (GAG) replenishment therapy affects inflammatory cell recruitment in a model of acute bladder damage.
- Rat bladders were induced with damage using HCl, followed by treatment with chondroitin sulfate, and then analyzed for inflammatory cell presence.
- Results showed that chondroitin sulfate significantly reduced the recruitment of certain inflammatory cells, indicating its potential effectiveness in treating bladder conditions linked to uroepithelial damage.
Background: This work tests the hypothesis that increased levels of vascular endothelial growth factor (VEGF) observed during bladder inflammation modulates nerve plasticity.
Methods: Chronic inflammation was induced by intravesical instillations of Bacillus Calmette-Guérin (BCG) into the urinary bladder and the density of nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) or pan-neuronal marker PGP9.5 was used to quantify alterations in peripheral nerve plasticity.
Article Synopsis
- The study investigates the gene expression changes in mouse bladder mucosa at different juvenile and adult ages to understand bladder growth and function, which could help in regeneration efforts, especially for elderly individuals with bladder issues.
- Using microarray technology to analyze RNA, the researchers found that while no genes were significantly up-regulated with maturation, 66 genes showed a significant downward trend, affecting processes like transcription and cell differentiation.
- Key genes identified include collagens and various transcription factors, suggesting that these down-regulated genes could be important targets for future bladder regeneration strategies.