رسالة جامعية
Molecular Markers and Hypoxia in Renal Cell Carcinoma
| العنوان: | Molecular Markers and Hypoxia in Renal Cell Carcinoma |
|---|---|
| المؤلفون: | de Alwis, Roger |
| المصدر: | Lund University, Faculty of Medicine Doctoral Dissertation Series; (2023:69) (2023) ; ISSN: 1652-8220 |
| بيانات النشر: | Lund University, Faculty of Medicine |
| سنة النشر: | 2023 |
| المجموعة: | Lund University Publications (LUP) |
| مصطلحات موضوعية: | Clinical Laboratory Medicine, Kidney cancer, CTC, RCC, Hypoxia, SEMA5B, Prognostic markers |
| الوصف: | Renal cell carcinomas (RCCs) are a group of tumours that arise from the nephron within the kidney. They are characterised by an indolent growth pattern and do not display overt clinical symptoms in patients with early to locally advanced tumours. Furthermore, the global average age of a RCC patient at diagnosis is 75 and they usually present with co-morbidities that may render invasive surgical/biopsy approaches risky. The most prevalent form of RCC is the clear cell RCC (ccRCC) subtype that displays pseudohypoxic activation of the two transcription factors HIF- 1α and HIF-2α as the result of a non-functional pVHL protein. Although the general influence of these two transcription factors has been deciphered, the full extent of the tumour-promoting activities of HIF-2α via its target genes have not been elucidated. Given these limitations in the clinical management of RCC and understanding of its biology, we set out to address these issues through the papers included in this thesis.In our first paper we aimed to decipher HIF-2α specific target genes operating in normal renal proximal tubule epithelial cells as well as ccRCC tumour cells. We pharmacologically emulated the loss of functional pVHL in renal proximal tubule cells whilst inhibiting HIF-2α transcriptional activity. Subsequent RNA-sequencing revealed potentially HIF-2α specific genes of which we selected SEMA5B, where its protein expression pattern matched our RNA-sequencing findings. We verified the HIF-2α regulatory specificity to SEMA5B in ccRCC cell lines, with other lines of evidence definitively demonstrating that HIF-2α but not HIF-1α specifically regulates the expression of SEMA5B in renal proximal tubule and ccRCC cells. Therefore, SEMA5B may have important role(s) in the context of ccRCC tumour vascularity and microenvironment.With papers two and three, we sought to address issues in RCC prognostication and detection. In paper two, we analysed transcription factor network and regulon activity in RCC subtypes using publicly available datasets. ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://lup.lub.lu.se/record/5a23146d-a6ae-4fd0-a536-2443fae37b1dTest; urn:isbn:9789180214094; https://portal.research.lu.se/files/145747827/Thesis_for_lucris.pdfTest |
| الإتاحة: | https://lup.lub.lu.se/record/5a23146d-a6ae-4fd0-a536-2443fae37b1dTest https://portal.research.lu.se/files/145747827/Thesis_for_lucris.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.17E5311C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |