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https://hdl.handle.net/1889/3805
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DC Field | Value | Language |
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dc.contributor.advisor | Quaini, Federico | - |
dc.contributor.author | Ghidini, Michele | - |
dc.date.accessioned | 2019-04-16T10:26:31Z | - |
dc.date.available | 2019-04-16T10:26:31Z | - |
dc.date.issued | 2019-03 | - |
dc.identifier.uri | http://hdl.handle.net/1889/3805 | - |
dc.description.abstract | Liquid biopsies are informative in regard to tumour heterogeneity and allow the contemporary evaluation of genetically different and co-occurring cell clones during tumour. In colorectal cancer (CRC), circulating-free DNA (cfDNA) and microRNAs (miRNAs) can be relevant for early diagnosis, identification of minimal residual disease and estimation of recurrence risk of disease. Aim of the study was to monitor cfDNA mutations and changes in the expression of miRNAs during treatment with targeted agents (bevacizumab, cetuximab and panitumumab) in metastatic CRC. Plasma and urine from patients undergoing treatment were collected at different timepoints during treatment. MiRNA let-7g-5p was evaluated in patients treated with cetuximab/panitumumab using digital droplet PCR (ddPCR). In five cases, let 7g-5p expression followed and sometimes anticipated radiological disease progression, increasing its expression before or concurrently with disease progression. Trend in urine was specular to plasma in some cases and parallel in other situations. Then, we assessed RAS and BRAF mutations in patients treated with bevacizumab using ddPCR. Mutation load followed clinical history in four cases only. Moreover, plasma samples of patients with uncommon and long duration of treatment with bevacizumab were evaluated with next generation sequencing (NGS). TP53 was the acquired mutation promoting progression in two cases, while APC was detected together with KRAS mutation in a third case. Furthermore, NGS was performed on pre-surgical samples of three patients undergoing radical surgery for advanced disease and relapsing after operation. All three cases were found to have one or more mutations expressed before surgery. One patient showed a mutation pattern shift before and after surgery, with acquisition of APC and TP53 mutations at high frequencies. Liquid biopsies may have a prognostic and predictive role in the management of patients with advanced CRC receiving active treatment. Tracking of known cfDNA mutations, detection of new mutations and evaluation of miRNA expression levels can become of high importance in predicting clinical trend of the disease and may be used in anticipating therapeutic decisions as well as suitable candidates for radical surgery. | it |
dc.language.iso | Inglese | it |
dc.publisher | Università degli Studi di Parma. Dipartimento di Medicina e chirurgia | it |
dc.publisher | ASST di Cremona. Dipartimento di Oncologia. Unità Operativa di Oncologia Medica | it |
dc.publisher | Gastrointestinal Cancer Biology and Genomic Group. Centre for Molecular Pathology. Institute of Cancer Research | it |
dc.relation.ispartofseries | Dottorato di ricerca in Scienze mediche | it |
dc.rights | © Michele Ghidini, 2019 | it |
dc.subject | Liquid Biopsies | it |
dc.subject | MicroRNAs | it |
dc.subject | Circulating DNA | it |
dc.subject | Colorectal Cancer | it |
dc.subject | Mutations | it |
dc.subject | Let-7g-5p | it |
dc.subject | Anti-EGFR | it |
dc.subject | Anti-VEGF | it |
dc.subject | Monoclonal Antibodies | it |
dc.subject | Cancer Cells | it |
dc.subject | Cancer Exosomes | it |
dc.subject | Resistance | it |
dc.title | Prognostic and predictive role of liquid biopsies in advanced colorectal carcinoma: circulating tumour mutations and microRNAs | it |
dc.title.alternative | Ruolo predittivo e prognostico delle biopsie liquide nell'adenocarcinoma colorettale avanzato: mutazioni circolanti e microRNAs | it |
dc.type | Doctoral thesis | it |
dc.subject.miur | MED/06 | it |
dc.subject.miur | BIO/12 | it |
dc.subject.miur | MED/03 | it |
Appears in Collections: | Medicina clinica e sperimentale. Tesi di dottorato |
Files in This Item:
File | Description | Size | Format | |
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Dottorato III anno relazione finale.pdf Until 2100-01-01 | Relazione finale | 195.4 kB | Adobe PDF | View/Open Request a copy |
Ghidini Dottorato finale.pdf | Tesi dottorato | 3.6 MB | Adobe PDF | View/Open |
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