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The Effect of an Angiogenesis Inhibitor on Tumor-Associated Immune Cells in a Murine Neuroblastoma Model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Nuriddin Mahmudov)
2023 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Neuroblastoma (NB) is a prevalent extracranial solid cancer in children with a relatively low post-treatment survival rate for high-risk cases which underlines the need for new treatment modalities. Studies are emerging that elucidate the role of tumor stroma and the associated immune cells in poor survival rates in cancer patients indicating these as important new targets in the treatment arsenal for these patients. In an earlier study using a murine orthotopic model of NB, treatment with angiogenesis inhibitor SU11248 showed to disrupted vascularity and tumor growth. 

The aims of current study were to determine the effects of SU11248 on other components of tumor stroma (other than tumor vessels), specially focusing on TAMs and TANs by developing an automated cell counting method for these analyses. Tumor sections from above mentioned study stained for specific macrophage antibody F4/80 were therefore scanned and analyzed on bioimage analysis software, QuPath. Treated group showed a statistically insignificant decrease in TAMs, 23% (p=0.088; two-tailed t-test) and 34% (p=0.02, two-tailed t-test) by manual and automated countings respectively.  These results might be of great clinical significance due to importance of TAMs for tumor growth and poor survival rates in cancer patients. 

TANs on the other hand were stained with hematoxylin and eosin (H&E) and counted manually under a light microscope. A 12% reduction in TANs was also noted without reaching statistical significance (p=0,6). Hence, that this part of the study should be repeated to find a more reliable and specific antibody for detection of TANs. 

Place, publisher, year, edition, pages
2023. , p. 33
Keywords [en]
neuroblastoma, tumor-associated macrophages, tumor associated neutrophils, tumor angiogenesis, SU11248, tumor stroma
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-507234OAI: oai:DiVA.org:uu-507234DiVA, id: diva2:1779207
Subject / course
Toxicology
Educational program
Master of Science Programme in Pharmacy
Presentation
(English)
Supervisors
Examiners
Available from: 2023-07-04 Created: 2023-07-03 Last updated: 2023-07-04Bibliographically approved

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CiteExportLink to record
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Citation style
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