scholarly journals Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bernadette M. M. Zwaans ◽  
Alexander L. Carabulea ◽  
Sarah N. Bartolone ◽  
Elijah P. Ward ◽  
Michael B. Chancellor ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Hemorrhagic Cystitis ◽  
Chronic Phase ◽  
Temporary Increase ◽  
Preclinical Model ◽  
Cancer Therapies ◽  
Radiation Cystitis ◽  
Barrier Defect ◽  
Tissue Changes ◽  
Micturition Frequency

AbstractLong term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4–8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell–cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.

64: Intravesical Instillation of Epinephrine in Patients with Intractable Hemorrhagic Cystitis Due to Radiation Cystitis

2007 ◽  
Vol 177 (4S) ◽  
pp. 22-22
Author(s):  
Yung C. Chow ◽  
Jong M. Hsu ◽  
Wen C. Lin ◽  
Huang K. Chang ◽  
Yuh C. Yang ◽  
...  
Keyword(s):  
Hemorrhagic Cystitis ◽  
Intravesical Instillation ◽  
Radiation Cystitis

scholarly journals Radiation Induced Hemorrhagic Cystitis: Current Treatments

2017 ◽  
Vol 35 (4) ◽  
pp. 391
Author(s):  
Chaiyut Kongseang ◽  
Worapat Attawettayanon ◽  
Watid Kanchanawanichkul
Keyword(s):  
Mortality Rate ◽  
Hemorrhagic Cystitis ◽  
Moderate Degree ◽  
Gross Hematuria ◽  
Current Management ◽  
Correct Treatment ◽  
Radiation Cystitis ◽  
Common Presentation ◽  
Genitourinary Cancer ◽  
Radiation Induced

Gross hematuria is the most common presentation in genitourinary cancer patients. Patient with radiation cystitis also have similar presentation. Radiation cystitis can cause hematuria in various degrees, most of patients usually had mild to moderate degree which can be successfully treated with conservative treatment. In some patients, degree of hematuria may be severe that leads to mortality, correct treatment may decrease mortality rate. We review the current literature regarding the current management of radiation cystitis.

BMI1 collaborates with BCR-ABL in leukemic transformation of human CD34+ cells

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4621-4630 ◽  
Author(s):  
Aleksandra Rizo ◽  
Sarah J. Horton ◽  
Sandra Olthof ◽  
Bert Dontje ◽  
Albertina Ausema ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Blast Crisis ◽  
Severe Combined Immunodeficiency ◽  
Chronic Phase ◽  
Cancer Therapies ◽  
Human Cd34 ◽  
Cd34 Cells

Abstract The major limitation for the development of curative cancer therapies has been an incomplete understanding of the molecular mechanisms driving cancer progression. Human models to study the development and progression of chronic myeloid leukemia (CML) have not been established. Here, we show that BMI1 collaborates with BCR-ABL in inducing a fatal leukemia in nonobese diabetic/severe combined immunodeficiency mice transplanted with transduced human CD34+ cells within 4-5 months. The leukemias were transplantable into secondary recipients with a shortened latency of 8-12 weeks. Clonal analysis revealed that similar clones initiated leukemia in primary and secondary mice. In vivo, transformation was biased toward a lymphoid blast crisis, and in vitro, myeloid as well as lymphoid long-term, self-renewing cultures could be established. Retroviral introduction of BMI1 in primary chronic-phase CD34+ cells from CML patients elevated their proliferative capacity and self-renewal properties. Thus, our data identify BMI1 as a potential therapeutic target in CML.

scholarly journals Anticancer Role of PPARγAgonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-36 ◽  
Author(s):  
P. J. Simpson-Haidaris ◽  
S. J. Pollock ◽  
S. Ramon ◽  
N. Guo ◽  
C. F. Woeller ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Radiation Treatment ◽  
Inflammatory Responses ◽  
Combined Therapy ◽  
Chemotherapeutic Agents ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Peroxisome Proliferator Activated Receptor ◽  
Treatment And Prevention

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-γagonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγagonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγagonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγand/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

scholarly journals Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model

2021 ◽  
Vol 22 (8) ◽  
pp. 4248
Author(s):  
Andrea Friedmann ◽  
Andre Baertel ◽  
Christine Schmitt ◽  
Christopher Ludtka ◽  
Javorina Milosevic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intervertebral Disc ◽  
Disc Height ◽  
Preclinical Model ◽  
Test Model ◽  
Adipose Derived Stem Cells ◽  
Sheep Model ◽  
Collagen Hydrogel ◽  
Intervertebral Disc Regeneration ◽  
Tissue Changes

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant’s therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant’s influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.

Experimental combination therapy using low doses of benznidazole and allopurinol in mouse models of Trypanosoma cruzi chronic infection

Parasitology ◽  
2018 ◽  
Vol 146 (3) ◽  
pp. 305-313 ◽  
Author(s):  
Marcela Silvina Rial ◽  
María Luján Scalise ◽  
Micaela López Alarcón ◽  
Mónica Inés Esteva ◽  
Jacqueline Búa ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chronic Infection ◽  
Chronic Phase ◽  
Preclinical Model ◽  
Low Doses ◽  
Positive Interaction ◽  
Continuous Administration ◽  
Conventional Dose ◽  
Antibody Titres ◽  
Parasitic Effect

AbstractThis study evaluated the effectiveness of low doses of benznidazole (BNZ) on continuous administration (BNZc), combined with allopurinol (ALO), in C57BL/6J and C3H/HeN mice infected with Trypanosoma cruzi Nicaragua strain and T. cruzi Sylvio-X10/4 clone. TcN-C57BL/6J was also treated with intermittent doses of BNZ (BNZit). The drug therapy started 3 months post infection (pi) in the chronic phase of mice with heart disease progression, followed-up at 6 months pi. TcN-C57BL/6J treated with BNZc was also monitored up to 12 months pi by serology and electrocardiogram. These mice showed severe electrical abnormalities, which were not observed after BNZc or BNZit. ALO only showed positive interaction with the lowest dose of BNZ. A clear parasitic effect, with significant reductions in antibody titres and parasitic loads, was achieved in all models with low doses of BNZ, and a 25% reduction of the conventional dose showed more efficacy to inhibit the development of the pathology. However, BNZ 75 showed partial efficacy in the TcSylvio-X10/4-C3H/HeN model. In our experimental designs, C57BL/6J allowed to clearly define a chronic phase, and through reproducible efficacy indicators, it can be considered a good preclinical model.

Humanized NOD-SCID IL2rg –/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies

2014 ◽  
Vol 344 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Qianjun Zhou ◽  
John Facciponte ◽  
Min Jin ◽  
Qiang Shen ◽  
Qiang Lin
Keyword(s):  
Cancer Research ◽  
Preclinical Model ◽  
Cancer Therapies ◽  
Potential Use

A retrospective case series looking at the effectiveness of hyperbaric oxygen in treating radiation cystitis.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 127-127 ◽  
Author(s):  
Scott Gorenstein ◽  
Aaron Katz ◽  
Kimberly Regan ◽  
Donna Hangan
Keyword(s):  
Radiation Therapy ◽  
Hyperbaric Oxygen ◽  
Hyperbaric Oxygen Therapy ◽  
Oxygen Therapy ◽  
Radiation Treatment ◽  
Case Series ◽  
University Hospital ◽  
Radiation Cystitis ◽  
Patient Reported ◽  
Radiation Induced

127 Background: A side effect of radiation therapy to treat genitourinary cancers is radiation-induced cystitis, which in its most severe form can be hemorrhagic cystitis (HC). Some studies have found the incidence of HC in radiation patients to range from 3% to 6.5% after radiation therapy and can develop anywhere from 6 months after radiation therapy to 10 years or more after the last treatment. The severity of symptoms, which includes hematuria, may drastically reduce quality of life. Recent studies have shown that hyperbaric oxygen therapy has improved symptoms of radiation cystitis in around 80% of patients. Methods: Sixty patients who received hyperbaric oxygen therapy (HBOT) for radiation-induced cystitis since 2010 at Winthrop University Hospital were identified. IRB approval was obtained for contacting these patients to gather outcome data. Patient reported outcomes were evaluated using a questionnaire that assessed the type and duration of radiation treatment, treatment other than HBOT for HC symptoms, surgical intervention, and patient perceived outcomes of HBOT. Results: 36 patients were consented. The average age of the patient was 71 with a range from 29-91. The majority of the patients 78% had prostate cancer with the Colon, Uterinem, Bladder and Testicular cancer also included The average time from completion of radiation to onset of symptoms was 3 years. The mean number of treatments was 35 with a range of 18-120 treatments. All treatments were for 90 minutes at 2.4 ATA. The majority of the patients (24) had external beam radiaiation and 12 patients had a urological procedure after completion of their therapy. 78 % of the patients reports either moderate improvement or complete resolution of symptoms. Conclusions: This case series seems to demonstrate that Hyperbaric Oxygen Therapy appears to be an effective treatment for radiation cystitis, however additional studies are necessary.

Fine Structural Changes in the Microvasculature of the Mouse Pinna: Aging and Radiation Injury

1974 ◽  
Vol 32 ◽  
pp. 54-55
Author(s):  
S. Phyllis Steamer ◽  
Rosemarie L. Devine
Keyword(s):  
Structural Changes ◽  
Radiation Treatment ◽  
Arterial Stenosis ◽  
Ultrastructural Changes ◽  
Vascular Effects ◽  
Microvascular Changes ◽  
Surrounding Connective Tissue ◽  
Fission Neutrons ◽  
Total Body

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.

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