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  1. Article ; Online: Elevated plasma interleukin 6 predicts poor response in patients treated with sunitinib for metastatic clear cell renal cell carcinoma.

    Pilskog, Martin / Nilsen, Gry Hilde / Beisland, Christian / Straume, Oddbjørn

    Cancer treatment and research communications

    2019  Volume 19, Page(s) 100127

    Abstract: Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type among renal cell carcinomas, and anti-angiogenic treatment is currently first line therapy in metastatic ccRCC (mccRCC). Response rates and duration of response show ... ...

    Abstract Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type among renal cell carcinomas, and anti-angiogenic treatment is currently first line therapy in metastatic ccRCC (mccRCC). Response rates and duration of response show considerable variation, and adverse events have major influence on patient's quality of life. The need for predictive biomarkers to select those patients most likely to respond to receptor tyrosine kinase inhibitors (rTKI) upfront is urgent. We investigated the predictive value of plasma interleukin-6 (pIL6), interleukin-6 receptor α (pIL6Rα) and interleukin 6 signal transducer (pIL6ST) in mccRCC patients treated with sunitinib.
    Material and methods: Forty-six patients with metastatic or non-resectable ccRCC treated with sunitinib were included. Full blood samples were collected at baseline before start of sunitinib and after every second cycle of treatment during the study time. pIL6, pIL6R and pIL6ST at baseline and week 12 samples were analysed by ELISA. The predictive potential of the candidate markers was assessed by correlation with response rates (RECIST). In addition, progression free survival (PFS) and overall survival (OS) were analysed.
    Results: Low pIL6 at baseline was significantly associated with improved response to sunitinib (Fisher's exact test, p < 0.01). Furthermore, low pIL6 at baseline was significantly associated with improved PFS (log rank, p = 0.04). In addition, patients with a decrease in concentration of pIL6R between baseline and week 12 showed significantly improved PFS (log rank, p = 0.04) and patients with high pIL6ST at baseline showed significantly improved OS (log rank, p = 0.03).
    Conclusion: Low pIL6 at baseline in mccRCC patients treated with sunitinib predicts improved treatment response, and might represent a candidate predictive marker.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/blood ; Carcinoma, Renal Cell/blood ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/secondary ; Cytokine Receptor gp130/blood ; Female ; Follow-Up Studies ; Humans ; Interleukin-6/blood ; Kidney Neoplasms/blood ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Prognosis ; Quality of Life ; Receptors, Interleukin-6/blood ; Sunitinib/therapeutic use ; Survival Rate
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; IL6 protein, human ; IL6R protein, human ; IL6ST protein, human ; Interleukin-6 ; Receptors, Interleukin-6 ; Cytokine Receptor gp130 (133483-10-0) ; Sunitinib (V99T50803M)
    Language English
    Publishing date 2019-03-14
    Publishing country England
    Document type Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2468-2942
    ISSN (online) 2468-2942
    DOI 10.1016/j.ctarc.2019.100127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Differential transcript usage in the Parkinson's disease brain.

    Dick, Fiona / Nido, Gonzalo S / Alves, Guido Werner / Tysnes, Ole-Bjørn / Nilsen, Gry Hilde / Dölle, Christian / Tzoulis, Charalampos

    PLoS genetics

    2020  Volume 16, Issue 11, Page(s) e1009182

    Abstract: Studies of differential gene expression have identified several molecular signatures and pathways associated with Parkinson's disease (PD). The role of isoform switches and differential transcript usage (DTU) remains, however, unexplored. Here, we report ...

    Abstract Studies of differential gene expression have identified several molecular signatures and pathways associated with Parkinson's disease (PD). The role of isoform switches and differential transcript usage (DTU) remains, however, unexplored. Here, we report the first genome-wide study of DTU in PD. We performed RNA sequencing following ribosomal RNA depletion in prefrontal cortex samples of 49 individuals from two independent case-control cohorts. DTU was assessed using two transcript-count based approaches, implemented in the DRIMSeq and DEXSeq tools. Multiple PD-associated DTU events were detected in each cohort, of which 23 DTU events in 19 genes replicated across both patient cohorts. For several of these, including THEM5, SLC16A1 and BCHE, DTU was predicted to have substantial functional consequences, such as altered subcellular localization or switching to non-protein coding isoforms. Furthermore, genes with PD-associated DTU were enriched in functional pathways previously linked to PD, including reactive oxygen species generation and protein homeostasis. Importantly, the vast majority of genes exhibiting DTU were not differentially expressed at the gene-level and were therefore not identified by conventional differential gene expression analysis. Our findings provide the first insight into the DTU landscape of PD and identify novel disease-associated genes. Moreover, we show that DTU may have important functional consequences in the PD brain, since it is predicted to alter the functional composition of the proteome. Based on these results, we propose that DTU analysis is an essential complement to differential gene expression studies in order to provide a more accurate and complete picture of disease-associated transcriptomic alterations.
    MeSH term(s) Case-Control Studies ; Computational Biology ; Genome-Wide Association Study ; Humans ; Models, Genetic ; Parkinson Disease/genetics ; Parkinson Disease/pathology ; Prefrontal Cortex/pathology ; Protein Isoforms/genetics ; RNA-Seq ; Transcriptome/genetics
    Chemical Substances Protein Isoforms
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009182
    Database MEDical Literature Analysis and Retrieval System OnLINE

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