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Pparg Drives Luminal Differentiation and Luminal Tumor Formation in the UrotheliumTate, Tiffany January 2021 (has links)
The urothelium is a crucial stratified epithelial barrier that protects the urinary tract. It consists of basal cells in the lower layers and intermediate and superficial cells in the luminal layer. These urothelial cells can be identified by their distinct gene expression patterns. Superficial cells are terminally differentiated, binucleated, post-mitotic cells that are responsible for the barrier function of the urothelium via the production of uroplakin proteins. Intermediate cells act as the progenitor cells for superficial cells during development, homeostasis, and after acute injury. Basal cells consist of two populations, K14-basal cells and K5-basal cells. K14- basal cells have been shown to be progenitors that can repopulate the urothelium after chronic injury and are the cells of origin that produce bladder cancer. Bladder cancer can be classified as basal subtype or luminal subtype. The basal subtype is generally immune infiltrated, aggressive, and invasive with a poor prognosis. The luminal subtype is generally immune poor, less aggressive, and non-invasive with a better prognosis compared to basal tumors.
Pparg is a nuclear hormone receptor that has been described as a master regulator of adipogenesis and cellular differentiation that also carries out important anti-inflammatory functions (in part by antagonizing the NFKB pathway). Pparg is downregulated in basal subtype muscle invasive bladder cancer and amplified in luminal subtype bladder cancer. In vivo we find that Pparg is a master regulator of cell specification during urothelial development, homeostasis, regeneration, and cancer. When Pparg is ablated in the entire urothelium, Pparg KO mutants lack mature superficial cells and undergo squamous differentiation, with an expansion of the K14-basal cell population. These Pparg KO mutants also display persistent inflammation and squamous metaplasia after injury by urinary tract infection (UTI), due to unregulated NFKB signaling. However, the squamous differentiation in the Pparg KO mutants did not progress to bladder cancer.
Constitutive activation of Pparg in basal cells using a novel VP16;Pparg transgenic mouse line crossed to an Krt5CreERT2 driver induces basal cells to undergo a luminal differentiation program towards post-mitotic S-cells during homeostasis. Not surprisingly, these cells did not progress to form bladder cancer on their own. Interestingly, expression of VP16;Pparg in basal cells only drives tumor formation when the basal cells are in an “activated state,” induced by 1 month of BBN treatment. In a BBN mouse model which produces basal subtype bladder cancer in wild type animals, expression of the VP16;Pparg transgene in activated basal cells drives the formation of luminal tumors with papillary morphology, suggesting that this transcription factor is a master regulator of urothelial luminal differentiation, as has been suggested from previous in vitro studies. Like their human counterparts, these VP16;Pparg luminal tumors are immune cold. Additionally, these VP16;Pparg luminal tumors have different domains; a top domain that is “luminal,” and a bottom domain that is “basal”, suggesting the luminal tumors produced by activation of Pparg are not homogenous and undergo a phenotypic shift that mimics what has previously been reported in patient-derived organoids. Understanding the molecular mechanism that drives luminal bladder cancer provides critical information in bettering our approach in diagnosing and treating MIBCs.
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Smooth Muscle Modeling : Activation and contraction of contractile units in smooth muscleMurtada, Sae-Il January 2009 (has links)
No description available.
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Semi-Automated Detection of Bladder Neck Funneling and Measurement of Posterior Urethrovesical Angle in FemalesVandermolen, Megan 29 April 2022 (has links)
The pathophysiology of stress urinary incontinence is poorly understood but bladder neck funneling (BNF) and posterior urethrovesical angle (PUVA) enlargement have been implicated. Methods to measure these phenomena are poorly established. The aim of this thesis was to develop and evaluate a semi-automated method to analyze BNF and PUVA from ultrasound images acquired transperineally and test its repeatability and concurrent validity compared to manual segmentation. Agreement between the semi-automated and manual methods was assessed by kappa statistics and intraclass correlation coefficients (ICCs). The repeatability of detection of BNF using the semi-automated approach was almost perfect (ĸC = 1.00 (p<0.001)), while the reliability of semi-automated detection of PUVA was good (ICC(3,1) = 0.860 (0.784 – 0.910)). Concurrent validity of BNF classification was almost perfect (ĸL = 1.00 (p<0.001)), while PUVA estimation was moderate (ICC(2,1) = 0.610 (0.514 – 0.705)). The method presented here is an acceptable proof of concept; further development is recommended.
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Microvascular Architecture of Mouse Urinary Bladder Described With Vascular Corrosion Casting, Light Microscopy, SEM, and TEMHossler, Fred E., Lametschwandtner, Alois, Kao, Race, Finsterbusch, Friederike 01 December 2013 (has links)
The urinary bladder is a unique organ in that its normal function is storage and release of urine, and vasculature in its wall exhibits specialized features designed to accommodate changes in pressure with emptying and filling. Although we have previously described the fine details of the microvasculature of the urinary bladder of the rabbit and dog, information on the fine details of the microvasculature of the mouse bladder were deemed to be of value because of the increasing use of this species in developing genetic models for studying human disorders. The present study shows that many of the special features of the microvasculature of the mouse urinary bladder are similar to those described in the rabbit and dog, including vessel coiling, abundant collateral circulation, arterial sphincters, and a dense mucosal capillary plexus.
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Microvascular Architecture of Mouse Urinary Bladder Described With Vascular Corrosion Casting, Light Microscopy, SEM, and TEMHossler, Fred E., Lametschwandtner, Alois, Kao, Race, Finsterbusch, Friederike 01 December 2013 (has links)
The urinary bladder is a unique organ in that its normal function is storage and release of urine, and vasculature in its wall exhibits specialized features designed to accommodate changes in pressure with emptying and filling. Although we have previously described the fine details of the microvasculature of the urinary bladder of the rabbit and dog, information on the fine details of the microvasculature of the mouse bladder were deemed to be of value because of the increasing use of this species in developing genetic models for studying human disorders. The present study shows that many of the special features of the microvasculature of the mouse urinary bladder are similar to those described in the rabbit and dog, including vessel coiling, abundant collateral circulation, arterial sphincters, and a dense mucosal capillary plexus.
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Botulinum Neurotoxin: Evolution From Poison, to Research Tool - Onto Medicinal Therapeutic and Future Pharmaceutical PanaceaKostrzewa, Richard M., Segura-Aguilar, Juan 01 December 2007 (has links)
Botulinum neurotoxin (BoNT), for more than a hundred years, has been a recognized poisonous principle in spoiled food. As its chemical structure became unraveled, and as more knowledge was gained over its mechanism of toxicity, it became clear that BoNT had the potential to act therapeutically as a targeted toxin that could inactivate specific nerve populations, and thus achieve a therapeutic goal. BoNT has evolved over the past 25 years into a viable therapeutic, now being a first line treatment for dystonia, overtly altering the course of progression of this disorder. BoNT is used for hyperhidrosis and gustatory sweating syndrome, alleviation of pain, as a treatment for overactive bladder, achalasia and anal fissure; and it has gained popularity as a cosmetic aid. Many other possible uses are being explored. The greatest potential for BoNT may lie in its being a molecular Trojan Horse - able to carry a specific enzyme or specific drug to the inside of a cancer or other type of cell while bypassing other cells and thereby having little or no ill effect. BoNTs pharmaceutical potential is boundless.
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Microvasculature of the Urinary Bladder of the Dog: A Study Using Vascular Corrosion CastingHossler, Fred E., Kao, Race L. 01 June 2007 (has links)
The urinary bladder is an unusual organ in that its normal function includes filling and emptying with alternating changes in internal pressure. Although fluctuations in blood flow to the bladder wall are known to accompany these changes, detailed descriptions of the bladder microvasculature are sparse. The present study uses vascular corrosion casting and scanning electron microscopy to describe the three-dimensional anatomy of the microvasculature of the urinary bladder of the dog. Specialized features of that microvasculature, including collateral circulation, vessel folding, vessel orientation, the presence of valves and sphincters, and mucosal capillary density, that may enhance and control blood flow during normal bladder function, are described and discussed.
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Machine Learning for Responsiveness of Medication in Bladder and Prostate SyndromesJu, Mingxuan 01 June 2020 (has links)
No description available.
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Analýza volných nukleových kyselin v moči urologických pacientů. / Analysis of cell-free nucleic acids in urine of urological patients.Šantorová, Šárka January 2019 (has links)
The two studies follow free nucleic acids in urine in search for biomarkers to distinguish urinary bladder cancer patients from controls. Bladder cancer forms 4 % of newly diagnosed oncological diseases in the Czech Republic. Nowadays, there is no accredited non-invasive method for its diagnosis, which is sufficiently accurate. Urine supernatant, which is washing the bladder mucosa and which does not contain cell debris, seems to be an appropriate source of biomarkers for non-invasive diagnosis. miRNAs, as a non-invasive biomarker of urinary bladder cancer, were studied in one of the studies. miRNAs are short noncoding RNA, which block the process of translation. miRNAs occur in all body fluids and are relatively stable. A study with three phases was assessed to find a suitable miRNA marker. 109 individuals were examined in total (36 controls and 73 bladder cancer patients). The analysis of miRNAs was based on RT-PCR (Reverse Transcription Polymerase Chain Reaction). In the first phase, the urine of 59 individuals was analyzed on TaqMan array card with 381 miRNAs. In the second phase, the results of the first phase were confirmed on the same cohort by a single miRNA assay. In the third phase, a new cohort was used (23 controls and 27 bladder cancer patients), analyzed by a single miRNA assay again....
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Prognostic and Predictive Computational Pathology-Based Companion Diagnostics for Genitourinary CancersLeo, Patrick J. 25 January 2022 (has links)
No description available.
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