Chemotherapy-induced intestinal mucositis: characterization and treatment strategies

Terrmin

HT21

Beskrivning

Background
An important function of the intestinal mucosa is to maintain a dynamic barrier between the complex and potentially hazardous luminal intestinal contents and the underlying submucosal tissue. A common toxicity of anti-cancer drugs is chemotherapeutics-induced intestinal mucositis (CIM), which is a complex gastrointestinal (GI) complication 1. It results from an inability to resist and/or rapidly repair these off-target effects, which results in various pathologies, including anorexia, ulceration, pain, diarrhea, and sepsis 2. It affects up to 90% of all cancer patients dosed with anti-neoplastic drugs, adding up to approximated 1 million patients annually in US and Europe 3. As there are no treatment options available today, there is a strong consensus that effective strategies for its prevention and management are needed 4.

Aim
The overall aim of this project is to improve the mechanistic understanding of chemotherapeutics-induced intestinal mucositis associated with different classes of cytotoxic drugs and to identify treatments that can protect and/or improve the repair processes of the intestinal mucosa. This will be done by coupling rat in vivo models to a range of bioanalytical, histological, and immunological assays. Specifically, we will quantify and describe the timeline of a range of immunological, apoptotic and proliferative processes in the intestine following treatment with different cytostatics.

Methods
The experimental work that will be carried may include the following
(i) sampling and preparation of intestinal tissue sample from rat
(ii) histological and quantitative analysis of intestinal tissue samples using staining, immunohistochemistry, as well as protein and RNA quantification
The definitive study plan will be decided together with the student.

References
1. Dahlgren D, Sjöblom M, Hellström PM, Lennernäs H. Chemotherapeutics-Induced Intestinal Mucositis: Pathophysiology and Potential Treatment Strategies. Front Pharmacol. 2021;12:1020.
2. Keefe DM, Gibson RJ, Hauer-Jensen M. Gastrointestinal mucositis. Paper presented at: Seminars in oncology nursing2004.
3. Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2020;126(10):2225-2249.
4. Scarpignato C, Bjarnason I. Drug-induced small bowel injury: a challenging and often forgotten clinical condition. Current gastroenterology reports. 2019;21(11):1-12.

Huvudområde

Farmaceutisk vetenskap

Ämne

Biofarmaci

Typ

Laborativ studie

Företag

Uppsala University

Ort/Plats

Uppsala

Handledarens namn

David Dahlgren

Handledarens e-post

david.dahlgren@farmbio.uu.se

Institution

Program

Kurs

Omfattning/hp

30hp

Hur många studenter kan antagas för detta projekt?

1

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