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Dehlin, Eva
Publications (6 of 6) Show all publications
Molin, J., Vanky, E., Løvvik, T. S., Dehlin, E. & Bixo, M. (2022). Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: A longitudinal, placebo-controlled study. British Journal of Obstetrics and Gynecology, 129(7), 1112-1121
Open this publication in new window or tab >>Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: A longitudinal, placebo-controlled study
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2022 (English)In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 129, no 7, p. 1112-1121Article in journal (Refereed) Published
Abstract [en]

Objective: To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls.

Design: Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls).

Setting: Eleven Norwegian, Swedish, and Icelandic hospitals.

Population: Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15).

Methods: Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters.

Main Outcome Measures: Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels.

Results: The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (< 0.001), and lower third trimester allopregnanolone levels (= 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2–0.8, = 0.005). FLI decreased during pregnancy in PCOS-M (= 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy.

Conclusion: Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-191090 (URN)10.1111/1471-0528.17042 (DOI)000734689400001 ()34865304 (PubMedID)2-s2.0-85122031307 (Scopus ID)
Funder
Region Västerbotten, 310426013The Research Council of Norway, 213497
Available from: 2022-01-14 Created: 2022-01-14 Last updated: 2022-07-12Bibliographically approved
Israelsson, P., Dehlin, E., Nagaev, I., Lundin, E., Ottander, U. & Mincheva-Nilsson, L. (2020). Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses. American Journal of Reproductive Immunology, 84(1), Article ID e13249.
Open this publication in new window or tab >>Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses
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2020 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, no 1, article id e13249Article in journal (Refereed) Published
Abstract [en]

Problem: To get a comprehensive picture of cytokine expression in health and disease is difficult, cytokines are transiently and locally expressed, and protein analyses are burdened by biological modifications, technical issues, and sensitivity to handling of samples. Thus, alternative methods, based on molecular techniques for cytokine mRNA analyses, are often used. We compared cytokine mRNA and protein expression to evaluate whether cytokine mRNA profiles can be used instead of protein analyses.

Method of study: In kinetic experiments, cytokine mRNA and protein expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta/LTA were studied using real-time RT-qPCR and Luminex(R) microarrays in the ovarian cancer cell lines OVCAR-3, SKOV-3 and the T-cell line Jurkat, after activation of transcription by thermal stress. In addition, we analyzed IL-6 and IL-8 mRNA and protein in a small number of ovarian cancer patients.

Results: Ovarian cancer cells can express cytokines on both mRNA and protein level, with 1-4 hours' time delay between the mRNA and protein peak and a negative Spearman correlation. The mRNA and protein expression in patient samples was poorly correlated, reflecting previous studies.

Conclusion: Cytokine mRNA and protein expression levels show diverging results, depending on the material analyzed and the method used. Considering the high sensitivity and reproducibility of real-time RT-qPCR, we suggest that cytokine mRNA profiles could be used as a proxy for protein expression for some specific purposes, such as comparisons between different patient groups, and in defining mechanistic pathways involved in the pathogenesis of cancer and other pathological conditions.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
cytokine, mRNA, ovarian cancer, protein, protein microarray, real-time polymerase chain reaction
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-171392 (URN)10.1111/aji.13249 (DOI)000530699700001 ()32307767 (PubMedID)2-s2.0-85085074930 (Scopus ID)
Available from: 2020-06-12 Created: 2020-06-12 Last updated: 2023-03-24Bibliographically approved
Israelsson, P., Labani-Motlagh, A., Nagaev, I., Dehlin, E., Nagaeva, O., Lundin, E., . . . Mincheva-Nilsson, L. (2019). Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary. International Journal of Gynecological Cancer, 29, A138-A138
Open this publication in new window or tab >>Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
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2019 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, p. A138-A138Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction/Background Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient‘s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment.

Methodology Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses.

Results The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity.

Conclusion Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-170021 (URN)10.1136/ijgc-2019-ESGO.191 (DOI)000523502500191 ()
Note

Supplement: 4

Meeting Abstract: P129

Available from: 2020-05-05 Created: 2020-05-05 Last updated: 2020-05-05Bibliographically approved
Israelsson, P., Labani-Motlagh, A., Nagaev, I., Dehlin, E., Nagaeva, O., Lundin, E., . . . Mincheva-Nilsson, L. (2017). Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary. Journal of Cancer Science & Therapy, 9(5), 422-429
Open this publication in new window or tab >>Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
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2017 (English)In: Journal of Cancer Science & Therapy, ISSN 1948-5956, Vol. 9, no 5, p. 422-429Article in journal (Refereed) Published
Abstract [en]

Objective: Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient’s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment. Methods: Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses. Results: The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity. Conclusions: Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

Keywords
Cytokines, High-grade serous ovarian carcinoma (HGSC), EOC, Tumor microenvironment, Tumor inflammation, Immune suppression
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-138256 (URN)10.4172/1948-5956.1000453 (DOI)
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2021-03-02Bibliographically approved
Labani-Motlagh, A., Israelsson, P., Ottander, U., Lundin, E., Nagaev, I., Nagaeva, O., . . . Mincheva-Nilsson, L. (2016). Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumor Biology, 37(4), 5455-5466
Open this publication in new window or tab >>Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity
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2016 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 4, p. 5455-5466Article in journal (Refereed) Published
Abstract [en]

Cancers constitutively produce and secrete into the blood and other biofluids 30-150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand-bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor-ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain.

Keywords
Epithelial ovarian cancer/EOC, Tumor, Exosomes, NKG2D, DNAM-1/CD266, Cytotoxicity, MICA/B, ULBP, PVR, Nectin-2
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-118529 (URN)10.1007/s13277-015-4313-2 (DOI)000374904500128 ()26563374 (PubMedID)2-s2.0-84946924480 (Scopus ID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2023-03-23Bibliographically approved
Mincheva-Nilsson, L., Baranov, V., Nagaeva, O. & Dehlin, E. (2016). Isolation and characterization of exosomes from cultures of tissue explants and cell lines. Current Protocols in Immunology, 2016, 14.42.1-14.42.21
Open this publication in new window or tab >>Isolation and characterization of exosomes from cultures of tissue explants and cell lines
2016 (English)In: Current Protocols in Immunology, ISSN 1934-3671, Vol. 2016, p. 14.42.1-14.42.21Article in journal (Refereed) Published
Abstract [en]

Exosomes are specialized, nanometer-sized extracellular vesicles of endosomal origin actively secreted into the extracellular space by a variety of cells under normal and pathological conditions. Exosomes have recently emerged as important intercellular communicators and modulators of diverse mechanisms and cellular responses. Characterization of their composition and functionwill open possibilities for new diagnostic methods and promising therapeutic approaches based on nanobiology. This unit provides a standard isolation procedure for purification of exosomes based on density gradient ultracentrifugation with sucrose. The process of isolating exosomes relies on obtaining proper source fluids/supernatants as well as qualitative and quantitative assessment of the isolated vesicles. The methodological procedures here can be divided in three parts: (1) pre-isolation procedures aiming to obtain fluids containing exosomes, with a focus on protocols for organ explants and cell cultures; (2) a procedure for exosome isolation with several gradient alternatives; and (3) post-isolation procedures for estimating the purity and yield of the exosomal fraction.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
density ultracentrifugation, exosomes, Extracellular vesicles, flow cytometry, negative contrast staining, Organ explant culture, sucrose gradient, TEM
National Category
Immunology in the medical area Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-200033 (URN)10.1002/cpim.17 (DOI)27801511 (PubMedID)2-s2.0-85018275366 (Scopus ID)
Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2022-10-10Bibliographically approved
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