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Chemotherapy induced intestinal mucositis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (translational drug discovery and development. Uppsala university)
2022 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction: With an aging population, cancer is a growing concern worldwide. Chemotherapyremains a common anti-cancer treatment, inducing apoptosis in rapidly dividing cells. However,the treatment also affects rapidly proliferating cells in healthy organs, such as the gastrointestinal tract, where diarrhea and ulcers are observed. This condition is called chemotherapyinduced intestinal mucositis, and it has an incidence over 40%. Despite many advances in cancertherapy, this gastro-intestinal side effect remains a significant problem. Causing decreasedquality of life, unscheduled interruptions in cancer treatments and increased the well fare costsby hospitalization.

Aim: Investigate the progressing pathogenesis of chemotherapy induced mucositis.

Methods: Jejunal rat tissue sampled at 6, 24, 72 and 168 hours after IV administration of 10mg/kg of doxorubicin were sliced in 5 µm thick sections and stained to study changes in mucosalmorphology. Additionally, using Ki67 and TUNEL assay we investigated the effect on mucosalstem cell proliferation and apoptosis, respectively.

Results: A reduction in villus length by mean 39 % was observed 72 hours after administrationof doxorubicin with a near restore to baseline after 168 hours. Increased apoptosis and reducedproliferation were observed 24 hours after administration, both with normalizing values 72 hoursafter administration.

Conclusion: Doxorubicin induced significant morphological signs of chemotherapy inducedmucositis, primarily with jejunal villus atrophy. This was a result from apoptosis in the basal stemcells causing loss of proliferating activity. Consequently, disrupting the homeostasis in theepithelium and illustrating the relationship between crypt apoptosis and proliferation. 

Place, publisher, year, edition, pages
2022. , p. 26
Keywords [en]
chemotherpy induced mucositis, chemotherapy, mucositis, doxorubicin, rat, jejunum
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-476494OAI: oai:DiVA.org:uu-476494DiVA, id: diva2:1667184
Subject / course
Pharmaceutical Biosciences
Educational program
Master of Science Programme in Pharmacy
Presentation
2022-06-01, BMC A3:203, husargatan 3, Uppsala, 10:00 (English)
Supervisors
Examiners
Available from: 2022-06-10 Created: 2022-06-09 Last updated: 2022-06-10Bibliographically approved

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CiteExportLink to record
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