Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

Zwaans, Bernadette; Wegner, Kyle A; Bartolone, Sarah N.; Vezina, Chad M.; Chancellor, Michael B.; Lamb, Laura E.

doi:10.14814/phy2.14377

Cited by 21 publications

(24 citation statements)

References 33 publications

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“…Soler's study measured the number of vessels, while Jaal's study quantified the total surface area of the vessels, not their number. Therefore, there was a decrease in the number of vessels, but these vessels were wider, which was in agreement with the telangiectasias visible in the Zwaans [15,20] and Kohler studies [64].…”

Section: Vascular Lesions: Key Factor In the Onset Of Crcsupporting

confidence: 85%

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Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis

Brossard

Lefranc

Simon

et al. 2022

IJMS

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Chronic radiation cystitis (CRC) is a consequence of pelvic radiotherapy and affects 5–10% of patients. The pathology of CRC is without curative treatment and is characterized by incontinence, pelvic pain and hematuria, which severely degrades patients’ quality of life. Current management strategies rely primarily on symptomatic measures and have certain limitations. Thanks to a better understanding of the pathophysiology of radiation cystitis, studies targeting key manifestations such as inflammation, neovascularization and cell atrophy have emerged and are promising avenues for future treatment. However, the mechanisms of CRC are still better described in animal models than in human models. Preclinical studies conducted to elucidate the pathophysiology of CRC use distinct models and are most often limited to specific processes, such as fibrosis, vascular damage and inflammation. This review presents a synthesis of experimental studies aimed at improving our understanding of the molecular mechanisms at play and identifying key processes in CRC.

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Section: Vascular Lesions: Key Factor In the Onset Of Crcsupporting

confidence: 85%

“…The early effects are damage to the urothelium and microvasculature. Microvascularization damage induces the development of edema in the bladder wall [15]. Edema of the mucosa, submucosa and lamina propria develops, accompanied by acute inflammation.…”

Section: Pathophysiology Of Crc In Patientsmentioning

confidence: 99%

Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis

Brossard

Lefranc

Simon

et al. 2022

IJMS

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“…When bladder drainage is obstructed either anatomically or functionally, as seen in spinal cord injuries, muscle contractions continue but they are no longer synchronized with urethral sphincter opening. The bladder wall becomes thicker with a marked increase in ECM in the lamina propria and muscle [6][7][8][9]. This results in a high-pressure bladder that is stiff and unable to empty.…”

Section: Introductionmentioning

confidence: 99%

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder

Murugapoopathy

Cammisotto

Mossa

et al. 2021

IJMS

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The extracellular matrix of the bladder consists mostly of type I and III collagen, which are required during loading. During bladder injury, there is an accumulation of collagen that impairs bladder function. Little is known about the genes that regulate production of collagens in the bladder. We demonstrate that the transcription factor Odd-skipped related 1 (Osr1) is expressed in the bladder mesenchyme and epithelium at the onset of development. As development proceeds, Osr1 is mainly expressed in mesenchymal progenitors and their derivatives. We hypothesized that Osr1 regulates mesenchymal cell differentiation and production of collagens in the bladder. To test this hypothesis, we examined newborn and adult mice heterozygous for Osr1, Osr1+/−. The bladders of newborn Osr1+/− mice had a decrease in collagen I by western blot analysis and a global decrease in collagens using Sirius red staining. There was also a decrease in the cellularity of the lamina propria, where most collagen is synthesized. This was not due to decreased proliferation or increased apoptosis in this cell population. Surprisingly, the bladders of adult Osr1+/− mice had an increase in collagen that was associated with abnormal bladder function; they also had a decrease in bladder capacity and voided more frequently. The results suggest that Osr1 is important for the differentiation of mesenchymal cells that give rise to collagen-producing cells.

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“…The cytokines IL-1a, IL-6, IL-8 and MIP-1a were detectable in one or two RC patients with gross hematuria and high symptom scores. Likewise, pre-clinical models of RC have not demonstrated a chronic inflammatory response to radiation [ 32 – 36 ]. One study did identify elevated levels of macrophage migration inhibitory factor (MIF) in patients with RC.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine

et al. 2020

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Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch’s t-test. In prostate cancer survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments.

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Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

Cited by 21 publications

References 33 publications

Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis

Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder

Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine

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