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Kamali-Moghaddam, MasoodORCID iD iconorcid.org/0000-0002-1303-2218
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Publications (10 of 67) Show all publications
Shen, Q., Polom, K., Williams, C., de Oliveira, F. M., Guergova-Kuras, M., Lisacek, F., . . . Kamali-Moghaddam, M. (2019). A targeted proteomics approach reveals a serum protein signature as diagnostic biomarker for resectable gastric cancer. EBioMedicine, 44, 322-333
Open this publication in new window or tab >>A targeted proteomics approach reveals a serum protein signature as diagnostic biomarker for resectable gastric cancer
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2019 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 44, p. 322-333Article in journal (Refereed) Published
Abstract [en]

Background: Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. Methods: We retrospectively collected pre- and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. Findings: We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCPI, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0.99 (95% CI: 0.98-1). Moreover, the 19-serum protein signature pro-vided an increased diagnostic capacity in patients at TNMI-II stage (sensitivity 89%, specificity 100%, AUC 0.99) and in patients with high miaosatellite instability (MSI) (91%. 98%, and 0.99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. Interpretation: Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. (C) 2019 The Authors. Published by Elsevier B.V.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Gastric cancer, Diagnosis, Biomarker, PEA, Proteomics
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-390592 (URN)10.1016/j.ebiom.2019.05.044 (DOI)000472768900038 ()31151932 (PubMedID)
Funder
EU, Horizon 2020, 316929
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Djureinovic, D., Pontén, V., Landelius, P., Al Sayegh, S., Kappert, K., Kamali-Moghaddam, M., . . . Ståhle, E. (2019). Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung. BMC Cancer, 19, Article ID 741.
Open this publication in new window or tab >>Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 741Article in journal (Refereed) Published
Abstract [en]

Background:The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relevance. The aim of this study was to identify and validate novel protein markers in plasma using the highly sensitive DNA-assisted multiplex proximity extension assay (PEA) to discriminate NSCLC from other lung diseases. 

Methods:Plasma samples were collected from a total of 343 patients who underwent surgical resection for different lung diseases, including 144 patients with lung adenocarcinoma (LAC),68 patients with non-malignant lung disease, 83 with lung metastasis of colorectal cancers and 48 patients with typical carcinoid. One microliter of plasma was analyzed using PEA, allowing detection and quantification of 92 established cancer related proteins. The concentrations of the plasma proteins were compared between disease groups.

Results:The comparison between LAC and benign samples revealed significantly different plasma levels for four proteins; CXL17, CEACAM5, VEGFR2 and ERBB3 (adjusted p-value < 0.05). A multi-parameter classifier was developed to discriminate between samples from LAC patients and from patients with non-malignant lung conditions. With a bootstrap aggregated decision tree algorithm (TreeBagger) a sensitivity of 93% and specificity of 64% was achieved to detect LAC in this risk population. 

Conclusion:By applying the highly sensitive PEA, reliable protein profiles could be determined in microliter amounts of plasma. We further identified proteins that demonstrated different plasma concentration in defined disease groups and developed a signature that holds potential to be included in a screening assay for early lung cancer detection. 

Keywords
lung cancer, tumor markers, blood, serum, screening, biomarker
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-347805 (URN)10.1186/s12885-019-5943-3 (DOI)000477815100004 ()31357969 (PubMedID)
Funder
Swedish Cancer Society, 2012/738
Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2019-09-09Bibliographically approved
Herr, A. E., Kitamori, T., Landegren, U. & Kamali-Moghaddam, M. (2019). Next wave advances in single-cell analyses. The Analyst, 144(3), 735-737
Open this publication in new window or tab >>Next wave advances in single-cell analyses
2019 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 144, no 3, p. 735-737Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2019
National Category
Analytical Chemistry Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-377491 (URN)10.1039/c9an90011j (DOI)000457394400001 ()30656308 (PubMedID)
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Siart, B., de Oliveira, F. M., Shen, Q., Björkesten, J., Pekar, T., Steinborn, R., . . . Wallner, B. (2019). Protein measurements in venous plasma, earlobe capillary plasma and in plasma stored on filter paper. Analytical Biochemistry, 566, 146-150
Open this publication in new window or tab >>Protein measurements in venous plasma, earlobe capillary plasma and in plasma stored on filter paper
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2019 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 566, p. 146-150Article in journal (Refereed) Published
Abstract [en]

In this study, levels of inflammatory protein biomarkers in venous plasma, plasma derived from capillary blood from the earlobe, and capillary plasma stored as dried plasma spots (DPS) were compared. Samples from 12 male individuals were assessed with a panel of 92 inflammation-related proteins using multiplex proximity extension assay. Correlations between sample types varied greatly between analytes. A high correlation of rho > 0.8 was observed between capillary plasma and DPS for 32 analytes. At this level of correlation, 13 analytes correlated between venous and capillary plasma and 5 analytes in the comparison of venous blood with DPS.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019
Keywords
Cytokines, Earlobe capillary, Dried plasma spots, Extension assay, Inflammation protein 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-376729 (URN)10.1016/j.ab.2018.11.016 (DOI)000456354900024 ()30472219 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 316929
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved
Franzen, B., Alexeyenko, A., Kamali-Moghaddam, M., Hatschek, T., Kanter, L., Ramqvist, T., . . . Lewensohn, R. (2019). Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer. Molecular Oncology, 13(2), 376-391
Open this publication in new window or tab >>Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer
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2019 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, Vol. 13, no 2, p. 376-391Article in journal (Refereed) Published
Abstract [en]

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow-up of personalized cancer therapy, including immunotherapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL-6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune-related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
breast cancer subtypes, fibroadenomas, fine-needle aspiration, immune-related protein biomarker, proximity extension assay
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-377673 (URN)10.1002/1878-0261.12410 (DOI)000457747900016 ()30451357 (PubMedID)
Funder
VINNOVA, 2016-00595Swedish Foundation for Strategic Research Swedish Research CouncilEU, FP7, Seventh Framework Programme, 316929EU, FP7, Seventh Framework Programme, 294409Stockholm County Council, 20151043Stockholm County Council, 20160287Swedish Cancer Society, 170246Swedish Foundation for Strategic Research The Breast Cancer Foundation
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
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
Dubois, L., Löf, L., Larsson, A., Hultenby, K., Waldenström, A., Kamali-Moghaddam, M., . . . Ronquist, K. G. (2018). Human erythrocyte-derived nanovesicles can readily be loaded with doxorubicin and act as anticancer agents. Cancer Research Frontiers, 4(1), 13-26
Open this publication in new window or tab >>Human erythrocyte-derived nanovesicles can readily be loaded with doxorubicin and act as anticancer agents
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2018 (English)In: Cancer Research Frontiers, ISSN 2328-5249, Vol. 4, no 1, p. 13-26Article in journal (Refereed) Published
Abstract [en]

Purpose: In future therapeutics new formulas are needed that assure lower doses, fewer side effects, targeted administration and protection of the drug from degradation. In a first step to fulfil the requirements defined above, we carried out an in vitro study by developing a new procedure to encapsulate drugs using native vesicles first from prostasomes and then from erythrocyte membranes known to be well tolerated. The new method for production of drug delivery vesicles utilized osmotic loading of detergent resistant membranes (DRMs).

Materials and methods: DRMs of prostasomes and prepared human erythrocyte membranes were extracted and separated in a sucrose gradient at a density of 1.10 g/mL containing 1% Triton X-100. These DRMs were characterized by electron microscopy (transmission and scanning EM) and loaded with low and high molecular compounds. PC3 prostate cancer cells were treated with doxorubicin loaded DRMs in triplicate. DAPI (nuclear fluorescent stain) was included and fluorescence microscopic pictures were taken before the cells were trypsinized and counted after 48h.

Results: The content of the well separated band was observed ultrastructurally as small spherical, double layered membrane vesicles, (DRM vesicles) which harbored hyperosmolar sucrose of the gradient. Encapsulated hyperosmolar sucrose induced a transient osmotic lysis of the DRM vesicles when suspended in isotonic buffer containing loading molecules allowing vesicular inclusion. After this proof of concept, the method was finally employed for doxorubicin loading of DRM vesicles from human erythrocytes. When incubating such vesicles with PC3 cells a complete arrest of growth was observed in sharp contrast to PC3 cells incubated with plain doxorubicin in similar conditions.

Conclusion: The present results open up new possibilities for using DRM vesicles as drug delivery vesicles.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-364780 (URN)10.17980/2018.13 (DOI)
Note

Louise Dubois and Liza Löf contributed equally to this work.

Available from: 2018-11-02 Created: 2018-11-02 Last updated: 2019-01-31Bibliographically approved
Palma, M., Krstic, A., Perez, L. P., Bergloef, A., Meinke, S., Wang, Q., . . . Smith, C. I. (2018). Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes. British Journal of Haematology, 183(2), 212-224
Open this publication in new window or tab >>Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes
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2018 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 183, no 2, p. 212-224Article in journal (Refereed) Published
Abstract [en]

In chronic lymphocytic leukaemia (CLL) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes (LN) to peripheral blood (PB). Here, we characterized in depth the dynamics of ibrutinib-induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Changes in plasma inflammation-related biomarkers, CLL cell RNA expression, B-cell activation and migration markers expression, and PB mononuclear cell populations were assessed. A significant reduction of 10 plasma inflammation markers, the majority of which were chemokines and not CLL-derived, was observed within hours, and was paralleled by very early increase of CD19(+) circulating cells. At the RNA level, significant and continuous changes in transcription factors and signalling molecules linked to B-cell receptor signalling and CLL biology was observed in both PB and LN CLL cells already after 2 days of treatment. In conclusion, ibrutinib seems to instantly shut off an ongoing inflammatory response and interfere with diverse sensitive pathways in the LN.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
chronic lymphocytic leukaemia, ibrutinib, chemokines, RNA sequencing, flow-cytometry
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-387259 (URN)10.1111/bjh.15516 (DOI)000449671500007 ()30125946 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-1303-2218

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