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An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction

Untersuchung der Wirkung von Bortezomib auf die strahleninduzierte Harnblasenfunktionsstörung

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Abstract

Purpose

The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation. This study evaluates the effect of bortezomib as an anti-proliferative and anti-inflammatory compound in an established mouse bladder model. The early radiation-induced bladder dysfunction in the mouse occurs in two phases during the first month after irradiation (phase I: day 0–15, phase II: days 16–30).

Materials and methods

Daily bortezomib injections (0.02 mg/ml, subcutaneously) were administered between days 0–15 or 15–30 in separate groups. Single graded radiation doses were administered in five dose groups. Cystometry was carried out before (individual control) and during the first month after irradiation. When bladder capacity was decreased by ≥50%, mice were considered as responders. Statistical analysis was performed by the SPSS software version 24.

Results

Daily bortezomib injections between days 0–15 resulted in a significant decrease in responders for phase I. There was no significant effect with daily bortezomib injections between days 16–30.

Conclusion

Two separate waves of acute radiation-induced urinary bladder dysfunction have distinct mechanisms that need further biological studies.

Zusammenfassung

Zielsetzung

Die Harnblase ist ein wichtiges Risikoorgan bei der Strahlentherapie von Malignomen im Beckenbereich. Die Strahlungsreaktion äußert sich in frühen und chronischen Veränderungen der Blasenfunktion. Diese basieren auf entzündlichen Effekten und Änderungen in der Funktion und Proliferation der Urothelzellen. In dieser Studie wird die Wirkung von Bortezomib als antiproliferative und entzündungshemmende Verbindung in einem etablierten Mausblasenmodell untersucht. Die frühe strahleninduzierte Blasenfunktionsstörung der Maus tritt im ersten Monat nach der Bestrahlung in zwei Phasen auf (Phase I: Tag 0–15, Phase II: Tag 16–30).

Material und Methoden

Tägliche Bortezomibinjektionen (0,02 mg/ml, subkutan) wurden an den Tagen 0–15 oder 16–30 in separaten Gruppen angewendet. Einzelne abgestufte Bestrahlungsdosen wurden in fünf Dosisgruppen angewendet. Zystometrien wurden vor (Einzelkontrolle) und im ersten Monat nach der Bestrahlung durchgeführt. Wenn die Blasenkapazität um ≥50 % verringert wurde, wurden Mäuse als Responder betrachtet. Die statistische Analyse wurde mit der SPSS-Software Version 24 durchgeführt.

Ergebnisse

Tägliche Bortezomibinjektionen an den Tagen 0–15 führten zu einer signifikanten Abnahme der Responder in Phase I. Bei den täglichen Bortezomibinjektionen zwischen den Tagen 16 und 30 gab es keine signifikante Wirkung.

Schlussfolgerung

Zwei getrennte Wellen einer akuten strahleninduzierten Harnblasenfunktionsstörung haben unterschiedliche Mechanismen, die weitere biologische Studien erfordern.

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Authors and Affiliations

  1. Department of Molecular Medicine, Iran University of Medical Science, 14496-14530, Tehran, Iran

    Sina Sarsarshahi &  Zahra Madjd MD PhD

  2. ATRAB-Applied and Translational Radiobiology, Department of Radiation Oncology, Medical University of Vienna, Waehringer Guertel 18–20, 1090, Vienna, Austria

    Sina Sarsarshahi, Eva Bozsaky, Jakob Kowaliuk &  Wolfgang Doerr DVM, PhD

  3. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Zahra Madjd MD PhD

  4. Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna, Austria

    Peter Kuess

  5. Department of Pharmacology-Toxicology, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran

    Mohammad Hossein Ghahremani

  6. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran

    Mohammad Hossein Ghahremani

Authors
  1. Sina Sarsarshahi
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  2. Zahra Madjd MD PhD
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  3. Eva Bozsaky
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  4. Jakob Kowaliuk
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  6. Mohammad Hossein Ghahremani
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  7. Wolfgang Doerr DVM, PhD
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Corresponding authors

Correspondence to Zahra Madjd MD PhD or Wolfgang Doerr DVM, PhD.

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Conflict of interest

S. Sarsarshahi, Z. Madjd, E. Bozsaky, J. Kowaliuk, P. Kuess, M.H. Ghahremani, and W. Doerr declare that they have no competing interests.

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Sarsarshahi, S., Madjd, Z., Bozsaky, E. et al. An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction. Strahlenther Onkol 195, 934–939 (2019). https://doi.org/10.1007/s00066-019-01497-8

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  • DOI: https://doi.org/10.1007/s00066-019-01497-8

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