Publications
-
Huynh, Hang Minh; Nawaz, Meh Sameen; Jabeen, Shakila; Bjørnetrø, Tonje; Geisler, Jürgen & Kristensen, Vessela
[Show all 7 contributors for this article]
(2026).
Analysis of circulatory extracellular vesicle–associated cytokines as candidate disease-associated markers in ER-positive breast cancer.
BMC Cancer.
p. 1–27.
doi:
10.1186/s12885-026-17052-5.
Full text in Research Archive
Show summary
Abstract Introduction Cytokines are signaling molecules produced by various cell types, including immune cells, and play important roles in tumor development and progression. Extracellular vesicles (EVs) are small membrane-bound particles secreted by all cell types, including cancer cells. EVs mediate intercellular communication through the transfer of proteins, lipids and nucleic acids, affecting many cellular processes. EV-associated cytokines may therefore represent a novel source of circulatory biomarkers in cancer. In this study, we investigated EV-associated cytokines obtained from estrogen receptor-positive (ER+) breast cancer (BC) patients and healthy individuals and evaluated treatment-associated changes during neoadjuvant endocrine therapy (NET). Materials and methods EVs were isolated from plasma samples of BC patients, healthy individuals, and from breast cell lines through ultracentrifugation. EVs were characterized by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis and western blotting. EV-associated cytokines were profiled using Luminex multiplex assay in plasma samples of ER + BC patients ( n = 46) enrolled in the Neoletexe clinical trial. EV-associated cytokine levels were analyzed at three timepoints, before (T0) and after NET (T1 and T2), and in healthy individuals ( n = 13). EV-associated cytokine levels were compared with free-circulating cytokines in blood and with cytokine gene expression in tumor tissue from a subset of the same patients from the Neoletexe cohort. Results Three EV-associated cytokines, interleukin 10 (IL-10), interleukin 12 (IL-12) and interferon gamma inducible protein 10 (IP-10), were significantly elevated in ER + BC patients compared to healthy individuals. CXCL10 (IP-10) gene expression was also found to be overexpressed in breast cancer tissue relative to normal and benign tissue, supporting the EV-associated IP-10 findings. Levels of EV-associated IL-10 and IL-12 decreased significantly during NET, but only eotaxin was associated with Ki-67 treatment response. Treatment-associated changes were more pronounced in EV-associated cytokines than for corresponding free-circulating cytokines and tumor gene expression. Conclusion EV-associated cytokines differ between ER + BC patients and healthy individuals and change during NET in ER+ LABC patients. These findings suggest that EV-associated cytokines may reflect disease and treatment related changes and provide complementary information to free-circulating cytokines and tumor gene expression. Further studies are required to determine their potential clinical relevance as biomarkers. Trial registration The Neoletexe study was approved on March 19th, 2015, by the Regional Ethics Committee (REC) of Southeast Norway in Oslo (national registration number: 2015/84).
-
Kong, Xiang Yi; Huse, Camilla; Yang, Kuan; Øgaard, Jonas; Jimenez, Natalia Berges & Vik, Erik Sebastian
[Show all 24 contributors for this article]
(2021).
Endonuclease v regulates atherosclerosis through c-c motif chemokine ligand 2-mediated monocyte infiltration.
Journal of the American Heart Association (JAHA).
10(14).
doi:
10.1161/JAHA.120.020656.
Full text in Research Archive
Show summary
Background:
In cardiovascular diseases, atherosclerotic disorder are the most frequent and important with respect to morbidity and mortality. Inflammation mediated by immune cells is central in all parts of the atherosclerotic progress, and further understanding of the underlying mechanisms is needed. Growing evidence suggests that deamination of adenosine‐to‐inosine in RNA is crucial for a correct immune response; nevertheless, the role of adenosine‐to‐inosine RNA editing in atherogenesis has barely been studied. Several proteins have affinity for inosines in RNA, one being ENDOV (endonuclease V), which binds and cleaves RNA at inosines. Data on ENDOV in atherosclerosis are lacking.
Methods and Results:
Quantitative polymerase chain reaction on ENDOV mRNA showed an increased level in human carotid atherosclerotic plaques compared with control veins. Inosine‐ribonuclease activity as measured by an enzyme activity assay is detected in immune cells relevant for the atherosclerotic process. Abolishing EndoV in atherogenic apolipoprotein E‐deficient (ApoE−/−) mice reduces the atherosclerotic plaque burden, both in size and lipid content. In addition, in a brain stroke model, mice without ENDOV suffer less damage than control mice. Finally, lack of EndoV reduces the recruitment of monocytes to atherosclerotic lesions in atherogenic ApoE−/− mice.
Conclusions:
ENDOV is upregulated in human atherosclerotic lesions, and data from mice suggest that ENDOV promotes atherogenesis by enhancing the monocyte recruitment into the atherosclerotic lesion, potentially by increasing the effect of CCL2 activation on these cells.
-
Kong, Xiang Yi; Vik, Erik Sebastian; Nawaz, Meh Sameen; Berges, Natalia; Dahl, Tuva Børresdatter & Vågbø, Cathrine
[Show all 17 contributors for this article]
(2020).
Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma.
Nucleic Acids Research (NAR).
ISSN 0305-1048.
48(8),
p. 4463–4479.
doi:
10.1093/nar/gkaa115.
Full text in Research Archive
Show summary
Endonuclease V (EndoV) is a conserved inosine-specific ribonuclease with unknown biological function. Here, we present the first mouse model lacking EndoV, which is viable without visible abnormalities. We show that endogenous murine EndoV cleaves inosine-containing RNA in vitro, nevertheless a series of experiments fails to link an in vivo function to processing of such transcripts. As inosine levels and adenosine-to-inosine editing often are dysregulated in hepatocellular carcinoma (HCC), we chemically induced HCC in mice. All mice developed liver cancer, however, EndoV−/− tumors were significantly fewer and smaller than wild type tumors. Opposed to human HCC, adenosine deaminase mRNA expression and site-specific editing were unaltered in our model. Loss of EndoV did not affect editing levels in liver tumors, however mRNA expression of a selection of cancer related genes were reduced. Inosines are also found in certain tRNAs and tRNAs are cleaved during stress to produce signaling entities. tRNA fragmentation was dysregulated in EndoV−/− livers and apparently, inosine-independent. We speculate that the inosine-ribonuclease activity of EndoV is disabled in vivo, but RNA binding allowed to promote stabilization of transcripts or recruitment of proteins to fine-tune gene expression. The EndoV−/− tumor suppressive phenotype calls for related studies in human HCC.
-
Berges, Natalia; Nawaz, Meh Sameen; Dahl, Tuva Børresdatter; Hagen, Lars; Bjørås, Magnar & Lærdahl, Jon Kristen
[Show all 7 contributors for this article]
(2019).
Complex alternative splicing of human Endonuclease V mRNA, but evidence for only a single protein isoform.
PLOS ONE.
14(11).
doi:
10.1371/journal.pone.0225081.
Full text in Research Archive
Show summary
Endonuclease V (ENDOV) is a ribonuclease with affinity for inosine which is the deamination product of adenosine. The genomes of most organisms, including human, encode ENDOV homologs, yet knowledge about in vivo functions and gene regulation is sparse. To contribute in this field, we analyzed mRNA and protein expression of human ENDOV (hENDOV). Analyses of public sequence databases revealed numerous hENDOV transcript variants suggesting extensive alternative splicing. Many of the transcripts lacked one or more exons corresponding to conserved regions of the ENDOV core domain, suggesting that these transcripts do not encode for active proteins. Three complete transcripts were found with open reading frames encoding 282, 308 and 309 amino acids, respectively. Recombinant hENDOV 308 and hENDOV 309 share the same cleavage activity as hENDOV 282 which is the variant that has been used in previous studies of hENDOV. However, hENDOV 309 binds inosine-containing RNA with stronger affinity than the other isoforms. Overexpressed GFP-fused isoforms were found in cytoplasm, nucleoli and arsenite induced stress granules in human cells as previously reported for hENDOV 282. RT-qPCR analysis of the 3’-termini showed that hENDOV 308 and hENDOV 309 transcripts are more abundant than hENDOV 282 transcripts in immortalized cell lines, but not in primary cells, suggesting that cells regulate hENDOV mRNA expression. In spite of the presence of all three full-length transcripts, mass spectrometry analyses identified peptides corresponding to the hENDOV 309 isoform only. This result suggests that further studies of human ENDOV should rather encompass the hENDOV 309 isoform.
-
-
-
View all works in NVA
-
Nawaz, Meh Sameen
(2026).
Mandatory vs. Optional: How Course Integration Drives Student Engagement with Virtual Laboratory Simulations.
Full text in Research Archive
-
-
-
-
-
-
-
Fjermeros, Kamilla; Ghannoum, Salim; Geisler, Stephanie; Bhargava, Sameer; Tahiri, Andliena & Klajic, Jovana
[Show all 32 contributors for this article]
(2024).
The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer.
Future Oncology.
ISSN 1479-6694.
20(32),
p. 2457–2466.
doi:
10.1080/14796694.2024.2377531.
Full text in Research Archive
Show summary
Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.
-
Strand, Martin Frank; Skjerve, Hilde; Nawaz, Meh Sameen & Aqrawi, Lara Adnan
(2024).
Studentaktiviserende semesteroppgave med muntlig justering innen biomedisinske fag.
Full text in Research Archive
-
View all works in NVA
Published
Oct. 31, 2022 10:18 AM
- Last modified
Oct. 31, 2022 10:19 AM