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Kamali-Moghaddam, MasoodORCID iD iconorcid.org/0000-0002-1303-2218
Alternative names
Publications (10 of 55) Show all publications
Franzen, B., Kamali-Moghaddam, M., Alexeyenko, A., Hatschek, T., Becker, S., Wik, L., . . . Lewensohn, R. (2018). A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions. Molecular Oncology, 12(9), 1415-1428
Open this publication in new window or tab >>A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions
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2018 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, Vol. 12, no 9, p. 1415-1428Article in journal (Refereed) Published
Abstract [en]

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and to follow-up personalized cancer therapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissues; however, the minute sample amounts require sensitive multiplex molecular analysis to achieve clinical utility. We have applied proximity extension assays (PEA) and NanoString (NS) technology for analyses of proteins and of RNA, respectively, in FNA samples. Using samples from patients with breast cancer (BC, n=25) or benign lesions (n=33), we demonstrate that these FNA-based molecular analyses (a) can offer high sensitivity and reproducibility, (b) may provide correct diagnosis in shorter time and at a lower cost than current practice, (c) correlate with results from routine analysis (i.e., benchmarking against immunohistochemistry tests for ER, PR, HER2, and Ki67), and (d) may also help identify new markers related to immunotherapy. A specific 11-protein signature, including FGF binding protein 1, decorin, and furin, distinguished all cancer patient samples from all benign lesions in our main cohort and in smaller replication cohort. Due to the minimally traumatic sampling and rich molecular information, this combined proteomics and transcriptomic methodology is promising for diagnostics and evaluation of treatment efficacy in BC.

Keywords
breast cancer diagnosis, fine-needle aspiration, protein biomarker, proximity extension assay
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-364195 (URN)10.1002/1878-0261.12350 (DOI)000443402000002 ()30019538 (PubMedID)
Funder
VINNOVA, 201600595Swedish Research CouncilEU, FP7, Seventh Framework Programme, 316929 294409Stockholm County Council, 20151043The Breast Cancer FoundationSwedish Cancer SocietyThe Cancer Research Funds of Radiumhemmet
Available from: 2018-10-29 Created: 2018-10-29 Last updated: 2018-11-16Bibliographically approved
de Oliveira, F. M., Mereiter, S., Lönn, P., Siart, B., Shen, Q., Heldin, J., . . . Kamali-Moghaddam, M. (2018). Detection of post-translational modifications using solid-phase proximity ligation assay. New Biotechnology, 45, 51-59
Open this publication in new window or tab >>Detection of post-translational modifications using solid-phase proximity ligation assay
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2018 (English)In: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 45, p. 51-59Article in journal (Refereed) Published
Abstract [en]

Post-translational modifications (PTMs) regulate protein activities to help orchestrate and fine-tune cellular processes. Dysregulation of PTMs is often related with disorders and malignancies, and may serve as a precise biomarker of disease. Developing sensitive tools to measure and monitor low-abundant PTMs in tissue lysates or serum will be instrumental for opening up new PTM-based diagnostic avenues. Here, we investigate the use of solid-phase proximity ligation assay (SP-PLA) for detection of different PTMs. The assay depends on the recognition of the target protein molecule and its modification by three affinity binders. Using antibodies and lectins, we applied the method for detection of glycosylated CD44 and E-Cadherin, and phosphorylated p53 and EGFR. The assay was found to have superior dynamic range and limit of detection compared to standard ELISAs. In summary, we have established the use of SP-PLA as an appropriate method for sensitive detection of PTMs in lysates and sera, which may provide a basis for future PTM-based diagnostic and prognostic biomarkers

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-334520 (URN)10.1016/j.nbt.2017.10.005 (DOI)000441913800008 ()29101055 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 316929
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-10-05Bibliographically approved
Bhandage, A. K., Jin, Z., Korol, S. V., Shen, Q., Pei, Y., Deng, Q., . . . Birnir, B. (2018). GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes. EBioMedicine, 30, 283-294
Open this publication in new window or tab >>GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30, p. 283-294Article in journal (Refereed) Published
Abstract [en]

The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. In anti-CD3 stimulated PBMCs, GABA (100nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4+ T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100nM, 500nM) on the cell proliferation. In the responder T cells, GABA decreased proliferation, and inhibited secretion of 37 cytokines in a concentration-dependent manner. In the non-responder T cells, GABA modulated release of 8 cytokines. GABA concentrations in plasma from T1D patients and ND individuals were correlated with 10 cytokines where 7 were increased in plasma of T1D patients. GABA inhibited secretion of 5 of these cytokines from both T1D PBMCs and ND responder T cells. The results identify GABA as a potent regulator of both Th1- and Th2-type cytokine secretion from human PBMCs and CD4+ T cells where GABA generally decreases the secretion.

Keywords
PBMCs, Immune cells, Proliferation, Cytokine, GABAA receptor, Diabetes, T1D, Autoimmune disease, T cell
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Research subject
Biology; Physiology
Identifiers
urn:nbn:se:uu:diva-348232 (URN)10.1016/j.ebiom.2018.03.019 (DOI)000430303000033 ()
Funder
Swedish Research Council, 2015-02417Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved
Bränn, E., Fransson, E., White, R. A., Papadopoulos, F. C., Edvinsson, Å., Kamali-Moghaddam, M., . . . Skalkidou, A. (2018). Inflammatory markers in women with postpartum depressive symptoms. Journal of Neuroscience Research
Open this publication in new window or tab >>Inflammatory markers in women with postpartum depressive symptoms
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2018 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547Article in journal (Refereed) Epub ahead of print
Abstract [en]

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

Keywords
cytokines, immune system, inflammation, maternal depression, pregnancy, protein markers
National Category
Psychiatry Immunology in the medical area Psychology
Identifiers
urn:nbn:se:uu:diva-362471 (URN)10.1002/jnr.24312 (DOI)30252150 (PubMedID)
Funder
Swedish Research Council, 521-2013-2339Swedish Research Council, 523-2014-2342Marianne and Marcus Wallenberg Foundation, 2011-Skalkidou
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-12-10Bibliographically approved
Birgisson, H., Tsimogiannis, K., Freyhult, E. & Kamali-Moghaddam, M. (2018). Plasma Protein Profiling Reveal Osteoprotegerin as a Marker of Prognostic Impact for Colorectal Cancer. Translational Oncology, 11(4), 1034-1043
Open this publication in new window or tab >>Plasma Protein Profiling Reveal Osteoprotegerin as a Marker of Prognostic Impact for Colorectal Cancer
2018 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 11, no 4, p. 1034-1043Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Due to difficulties in predicting recurrences in colorectal cancer stages II and III, reliable prognostic biomarkers could be a breakthrough for individualized treatment and follow-up. OBJECTIVE: To find potential prognostic protein biomarkers in colorectal cancer, using the proximity extension assays. METHODS: A panel of 92 oncology-related proteins was analyzed with proximity extension assays, in plasma from a cohort of 261 colorectal cancer patients with stage II-IV. The survival analyses were corrected for disease stage and age, and the recurrence analyses were corrected for disease stage. The significance threshold was adjusted for multiple comparisons. RESULTS: The plasma proteins expression levels had a greater prognostic relevance in disease stage III colorectal cancer than in disease stage II, and for overall survival than for time to recurrence. Osteoprotegerin was the only biomarker candidate in the protein panel that had a statistical significant association with overall survival (P = .00029). None of the proteins were statistically significantly associated with time to recurrence. CONCLUSIONS: Of the 92 analyzed plasma proteins, osteoprotegerin showed the strongest prognostic impact in patients with colorectal cancer, and therefore osteoprotegerin is a potential predictive marker, and it also could be a target for treatments.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-361500 (URN)10.1016/j.tranon.2018.05.012 (DOI)000438977600023 ()29982101 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-09-28 Created: 2018-09-28 Last updated: 2018-09-28Bibliographically approved
Thulin, Å., Yan, J., Åberg, M., Christersson, C., Kamali-Moghaddam, M. & Siegbahn, A. (2018). Sensitive detection of platelet-derived and tissue factor positive extracellular vesicles in plasma using solid-phase proximity ligation assay. Paper presented at 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA. Cardiovascular Research, 114, S132-S132
Open this publication in new window or tab >>Sensitive detection of platelet-derived and tissue factor positive extracellular vesicles in plasma using solid-phase proximity ligation assay
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2018 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, p. S132-S132Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357493 (URN)000430678500388 ()
Conference
5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
Caja, L., Tzavlaki, K., Dadras, M. S., Tan, E.-J., Hatem, G., Maturi, N. P., . . . Moustakas, A. (2018). Snail regulates BMP and TGF beta pathways to control the differentiation status of glioma-initiating cells. Oncogene, 37(19), 2515-2531
Open this publication in new window or tab >>Snail regulates BMP and TGF beta pathways to control the differentiation status of glioma-initiating cells
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2018 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 37, no 19, p. 2515-2531Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor beta (TGF beta) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGF beta 1 signaling activity. Exogenous TGF beta 1 counteracts Snail function in vitro, and in vivo promotes proliferation and re-expression of Nestin, confirming the importance of TGFB1 gene repression by Snail. In conclusion, novel insight highlights mechanisms whereby Snail differentially regulates the activity of the opposing BMP and TGF beta pathways, thus promoting an astrocytic fate switch and repressing stemness in GSCs.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-355463 (URN)10.1038/s41388-018-0136-0 (DOI)000431873400005 ()29449696 (PubMedID)
Funder
Swedish Research Council, K2013-66X-14936-10-5Swedish Research Council, 2015-02757
Note

Andra och tredje författare delar andra författarskapet.

Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-12-03Bibliographically approved
Shen, Q., Björkesten, J., Galli, J., Ekman, D., Broberg, J., Nordberg, N., . . . Landegren, U. (2018). Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays. Clinical Chemistry and Laboratory Medicine, 56(4), 582-594
Open this publication in new window or tab >>Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays
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2018 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, no 4, p. 582-594Article in journal (Refereed) Published
Abstract [en]

Background: A number of factors regarding blood collection, handling and storage may affect sample quality. The purpose of this study was to assess the impact on plasma protein profiles by delayed centrifugation and plasma separation and multiple freeze-thaw cycles.

Methods: Blood samples drawn from 16 healthy individuals were collected into ethylenediaminetetraacetic acid tubes and kept either at 4 degrees C or 22 degrees C for 1-36 h prior to centrifugation. Plasma samples prepared 1 h after venipuncture were also subjected to two to eight cycles of freezing at -80 degrees C and thawing at 22 degrees C. Multiplex proximity extension assay, an antibody-based protein assay, was used to investigate the influence on plasma proteins.

Results: Up to 36 h delay before blood centrifugation resulted in significant increases of 16 and 40 out of 139 detectable proteins in samples kept at 4 degrees C or 22 degrees C, respectively. Some increases became noticeable after 8 h delay at 4 degrees C but already after 1 h at 22 degrees C. For samples stored at 4 degrees C, epidermal growth factor (EGF), NF-kappa-B essential modulator, SRC, interleukin 16 and CD6 increased the most, whereas the five most significantly increased proteins after storage at 22 degrees C were CD40 antigen ligand (CD40-L), EGF, platelet-derived growth factor subunit B, C-X-C motif chemokine ligand 5 and matrix metallopeptidase 1 (MMP1). Only matrix metallopeptidase 7 (MMP7) decreased significantly over time and only after storage at 22 degrees C. No protein levels were found to be significantly affected by up to eight freeze-thaw cycles.

Conclusions: Plasma should be prepared from blood after a limited precentrifugation delay at a refrigerated temperature. By contrast, the influence by several freeze-thaw cycles on detectable protein levels in plasma was negligible.

Place, publisher, year, edition, pages
WALTER DE GRUYTER GMBH, 2018
Keywords
biobank, protein detection, proteome, proximity extension assay (PEA), sample collection and handling
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-350276 (URN)10.1515/cclm-2017-0648 (DOI)000426657400016 ()29040064 (PubMedID)
Funder
Swedish Research Council, 829-2009-6285EU, European Research Council, 313010, 294409
Available from: 2018-05-14 Created: 2018-05-14 Last updated: 2018-05-14Bibliographically approved
Ebai, T., de Oliveira, F. M., Löf, L., Wik, L., Schweiger, C., Larsson, A., . . . Kamali-Moghaddam, M. (2017). Analytically Sensitive Protein Detection in Microtiter Plates by Proximity Ligation with Rolling Circle Amplification. Clinical Chemistry, 63(9), 1497-1505
Open this publication in new window or tab >>Analytically Sensitive Protein Detection in Microtiter Plates by Proximity Ligation with Rolling Circle Amplification
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2017 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 9, p. 1497-1505Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Detecting proteins at low concentrations in plasma is crucial for early diagnosis. Current techniques in clinical routine, such as sandwich ELISA, provide sensitive protein detection because of a dependence on target recognition by pairs of antibodies, but detection of still lower protein concentrations is often called for. Proximity ligation assay with rolling circle amplification (PLARCA) is a modified proximity ligation assay (PLA) for analytically specific and sensitive protein detection via binding of target proteins by 3 antibodies, and signal amplification via rolling circle amplification (RCA) in microtiter wells, easily adapted to instrumentation in use in hospitals.

METHODS: Proteins captured by immobilized antibodies were detected using a pair of oligonucleotide-conjugated antibodies. Upon target recognition, these PLA probes guided oligonucleotide ligation, followed by amplification via RCA of circular DNA strands that formed in the reaction. The RCA products were detected by horseradish peroxidase-labeled oligonucleotides to generate colorimetric reaction products with readout in an absorbance microplate reader.

RESULTS: We compared detection of interleukin (IL)-4, IL-6, IL-8, p53, and growth differentiation factor-15 by PLARCA and conventional sandwich ELISA or immuno RCA. PLARCA detected lower concentrations of proteins and exhibited a broader dynamic range compared ELISA and iRCA using the same antibodies. IL-4 and IL-6 were detected in clinical samples at femtomolar concentrations, considerably lower than for ELISA.

CONCLUSIONS: PLARCA offers detection of lower protein levels and increased dynamic ranges compared to ELISA. The PLARCA procedure may be adapted to routine instrumentation available in hospitals and research laboratories.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-326672 (URN)10.1373/clinchem.2017.271833 (DOI)000408421200013 ()28667186 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, 294409 264737 313010
Available from: 2017-07-21 Created: 2017-07-21 Last updated: 2018-09-17Bibliographically approved
Löf, L., Arngården, L., Olsson-Strömberg, U., Siart, B., Jansson, M., Dahlin, J. S., . . . Kamali-Moghaddam, M. (2017). Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia. Scientific Reports, 7, 1-9, Article ID 623.
Open this publication in new window or tab >>Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, p. 1-9, article id 623Article in journal (Refereed) Published
Abstract [en]

Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-319726 (URN)10.1038/s41598-017-00755-y (DOI)000398162400034 ()28377570 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 294409Swedish Cancer SocietySwedish Research Council
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-05-15Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-1303-2218

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