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Publikasjoner (10 av 49) Visa alla publikasjoner
Hui, Z., Wang, B., Liu, Z., Wei, J., Gan, J., Landström, M., . . . Zang, G. (2024). TGFβ-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model. International Journal of Cancer, 154(10), 1814-1827
Åpne denne publikasjonen i ny fane eller vindu >>TGFβ-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model
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2024 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 154, nr 10, s. 1814-1827Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed-1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient-derived organoids (PDOs). TGFβ-induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ-induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2024
Emneord
adenoid cystic carcinoma, EN1, organoid model, salivary gland tumors, TGFβ, tumor budding
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-220756 (URN)10.1002/ijc.34856 (DOI)001152380300001 ()38282121 (PubMedID)2-s2.0-85183662155 (Scopus ID)
Forskningsfinansiär
Cancerforskningsfonden i Norrland, LP20-2255
Tilgjengelig fra: 2024-02-12 Laget: 2024-02-12 Sist oppdatert: 2024-05-13bibliografisk kontrollert
Zymovets, V., Rakhimova, O., Wadelius, P., Schmidt, A., Brundin, M., Kelk, P., . . . Romani Vestman, N. (2023). Exploring the impact of oral bacteria remnants on stem cells from the Apical papilla: mineralization potential and inflammatory response. Frontiers in Cellular and Infection Microbiology, 13, Article ID 1257433.
Åpne denne publikasjonen i ny fane eller vindu >>Exploring the impact of oral bacteria remnants on stem cells from the Apical papilla: mineralization potential and inflammatory response
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2023 (engelsk)Inngår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 13, artikkel-id 1257433Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Introduction: Bacterial persistence is considered one of the main causal factors for regenerative endodontic treatment (RET) failure in immature permanent teeth. This interference is claimed to be caused by the interaction of bacteria that reside in the root canal with the stem cells that are one of the essentials for RET. The aim of the study was to investigate whether prolonged exposure of stem cells from the apical papilla (SCAP) to bacterial remnants of Fusobacterium nucleatum, Actinomyces gerensceriae, Slackia exigua, Enterococcus faecalis, Peptostreptococcaceae yurii, commonly found in infected traumatized root canals, and the probiotic bacteria Lactobacillus gasseri and Limosilactobacillus reuteri, can alter SCAP’s inflammatory response and mineralization potential.

Methods: To assess the effect of bacterial remnants on SCAP, we used UV-C–inactivated bacteria (as cell wall-associated virulence factors) and bacterial DNA. Histochemical staining using Osteoimage Mineralization Assay and Alizarin Red analysis was performed to study SCAP mineralization, while inflammatory and osteo/odontogenic-related responses of SCAPs were assessed with Multiplex ELISA.

Results: We showed that mineralization promotion was greater with UV C–inactivated bacteria compared to bacterial DNA. Immunofluorescence analysis detected that the early mineralization marker alkaline phosphatase (ALP) was increased by the level of E. coli lipopolysaccharide (LPS) positive control in the case of UV-C–inactivated bacteria; meanwhile, DNA treatment decreased the level of ALP compared to the positive control. SCAP’s secretome assessed with Multiplex ELISA showed the upregulation of pro-inflammatory factors IL-6, IL-8, GM-CSF, IL-1b, neurotrophic factor BDNF, and angiogenic factor VEGF, induced by UV-C–killed bacteria.

Discussion: The results suggest that long term stimulation (for 21 days) of SCAP with UV-C–inactivated bacteria stimulate their mineralization and inflammatory response, while DNA influence has no such effect, which opens up new ideas about the nature of RET failure.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2023
Emneord
bacterial DNA, bacterial remnants, inflammation, mineralization, oral bacteria, SCAP
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-218290 (URN)10.3389/fcimb.2023.1257433 (DOI)38089810 (PubMedID)2-s2.0-85179354108 (Scopus ID)
Forskningsfinansiär
Knut and Alice Wallenberg Foundation, 7003503Region Västerbotten, 7004361Region Västerbotten, 98263The Kempe Foundations, SMK-1966Region Västerbotten, 7003459Region Västerbotten, 7003589
Tilgjengelig fra: 2023-12-22 Laget: 2023-12-22 Sist oppdatert: 2023-12-22bibliografisk kontrollert
Zymovets, V., Razghonova, Y., Rakhimova, O., Aripaka, K., Manoharan, L., Kelk, P., . . . Romani Vestman, N. (2022). Combined Transcriptomic and Protein Array Cytokine Profiling of Human Stem Cells from Dental Apical Papilla Modulated by Oral Bacteria. International Journal of Molecular Sciences, 23(9), Article ID 5098.
Åpne denne publikasjonen i ny fane eller vindu >>Combined Transcriptomic and Protein Array Cytokine Profiling of Human Stem Cells from Dental Apical Papilla Modulated by Oral Bacteria
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2022 (engelsk)Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, nr 9, artikkel-id 5098Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Stem cells from the apical papilla (SCAP) are a promising resource for use in regenerative endodontic treatment (RET) that may be adversely affected by oral bacteria, which in turn can exert an effect on the success of RET. Our work aims to study the cytokine profile of SCAP upon exposure to oral bacteria and their supernatants—Fusobacterium nucleatum and Enterococcus faecalis—as well as to establish their effect on the osteogenic and immunogenic potentials of SCAP. Further, we target the presence of key proteins of the Wnt/β-Catenin, TGF-β, and NF-κB signaling pathways, which play a crucial role in adult osteogenic differentiation of mesenchymal stem cells, using the Western blot (WB) technique. The membrane-based sandwich immunoassay and transcriptomic analysis showed that, under the influence of F. nucleatum (both bacteria and supernatant), the production of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 occurred, which was also confirmed at the mRNA level. Conversely, E. faecalis reduced the secretion of the aforementioned cytokines at both mRNA and protein levels. WB analysis showed that SCAP co-cultivation with E. faecalis led to a decrease in the level of the key proteins of the Wnt/β-Catenin and NF-κB signaling pathways: β-Catenin (p = 0.0068 *), LRP-5 (p = 0.0059 **), and LRP-6 (p = 0.0329 *), as well as NF-kB (p = 0.0034 **) and TRAF6 (p = 0.0285 *). These results suggest that oral bacteria can up-and downregulate the immune and inflammatory responses of SCAP, as well as influence the osteogenic potential of SCAP, which may negatively regulate the success of RET.

sted, utgiver, år, opplag, sider
MDPI, 2022
Emneord
cytokine secretion, endodontics, Fusobacterium nucleatum, IL-6, IL-8, immune response, osteogenic potential, regenerative endodontic treatment (RET), stem cells from the apical papilla (SCAP), transcriptome analysis
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-194879 (URN)10.3390/ijms23095098 (DOI)000799319900001 ()35563488 (PubMedID)2-s2.0-85129389469 (Scopus ID)
Forskningsfinansiär
Swedish Research Council, 2018-05973Knut and Alice Wallenberg Foundation, 7003503Region Västerbotten, 7004361The Kempe Foundations, SMK-1966Region Västerbotten, 7003459Region Västerbotten, 7003589
Tilgjengelig fra: 2022-06-09 Laget: 2022-06-09 Sist oppdatert: 2023-05-23bibliografisk kontrollert
Fioretos, T., Wirta, V., Cavelier, L., Berglund, E., Friedman, M., Akhras, M., . . . Rosenquist, R. (2022). Implementing precision medicine in a regionally organized healthcare system in Sweden [Letter to the editor]. Nature Medicine, 28, 1980-1982
Åpne denne publikasjonen i ny fane eller vindu >>Implementing precision medicine in a regionally organized healthcare system in Sweden
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2022 (engelsk)Inngår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 28, s. 1980-1982Artikkel i tidsskrift, Letter (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
Nature Publishing Group, 2022
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-199913 (URN)10.1038/s41591-022-01963-4 (DOI)000857867600001 ()36123428 (PubMedID)2-s2.0-85138201780 (Scopus ID)
Forskningsfinansiär
Science for Life Laboratory, SciLifeLabVinnovaSwedish Childhood Cancer FoundationRegion SkåneRegion VästerbottenRegion ÖstergötlandRegion StockholmRegion UppsalaRegion Örebro County
Tilgjengelig fra: 2022-10-06 Laget: 2022-10-06 Sist oppdatert: 2022-11-29bibliografisk kontrollert
Mallikarjuna, P., Zhou, Y. & Landström, M. (2022). The Synergistic Cooperation between TGF-Cancer and Fibrosis. Biomolecules, 12(5), Article ID 635.
Åpne denne publikasjonen i ny fane eller vindu >>The Synergistic Cooperation between TGF-Cancer and Fibrosis
2022 (engelsk)Inngår i: Biomolecules, E-ISSN 2218-273X, Vol. 12, nr 5, artikkel-id 635Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

Transforming growth factor β (TGF-β) is a multifunctional cytokine regulating homeostasis and immune responses in adult animals and humans. Aberrant and overactive TGF-β signaling promotes cancer initiation and fibrosis through epithelial–mesenchymal transition (EMT), as well as the invasion and metastatic growth of cancer cells. TGF-β is a key factor that is active during hypoxic conditions in cancer and is thereby capable of contributing to angiogenesis in various types of cancer. Another potent role of TGF-β is suppressing immune responses in cancer patients. The strong tumor-promoting effects of TGF-β and its profibrotic effects make it a focus for the development of novel therapeutic strategies against cancer and fibrosis as well as an attractive drug target in combination with immune regulatory checkpoint inhibitors. TGF-β belongs to a family of cytokines that exert their function through signaling via serine/threonine kinase transmembrane receptors to intracellular Smad proteins via the canonical pathway and in combination with co-regulators such as the adaptor protein and E3 ubiquitin ligases TRAF4 and TRAF6 to promote non-canonical pathways. Finally, the outcome of gene transcription initiated by TGF-β is context-dependent and controlled by signals exerted by other growth factors such as EGF and Wnt. Here, we discuss the synergistic cooperation between TGF-β and hypoxia in development, fibrosis and cancer.

sted, utgiver, år, opplag, sider
MDPI, 2022
Emneord
cancer, fibrosis, HIF-1α/2α, hypoxia, Smad, TGF-β, TRAF6
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-194472 (URN)10.3390/biom12050635 (DOI)000802711300001 ()2-s2.0-85128728480 (Scopus ID)
Forskningsfinansiär
Swedish Cancer Society, 20 0964 PjFProstatacancerförbundet, 2019The Kempe Foundations, SMK-1866Novo Nordisk, NNF19OC0059307
Tilgjengelig fra: 2022-05-06 Laget: 2022-05-06 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Yakymovych, I., Yakymovych, M., Hamidi, A., Landström, M. & Heldin, C.-H. (2022). The type II TGF-β receptor phosphorylates Tyr182 in the type I receptor to activate downstream Src signaling. Science Signaling, 15(760), Article ID eabp9521.
Åpne denne publikasjonen i ny fane eller vindu >>The type II TGF-β receptor phosphorylates Tyr182 in the type I receptor to activate downstream Src signaling
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2022 (engelsk)Inngår i: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 15, nr 760, artikkel-id eabp9521Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Transforming growth factor–β (TGF-β) signaling has important roles during embryonic development and in tissue homeostasis. TGF-β ligands exert cellular effects by binding to type I (TβRI) and type II (TβRII) receptors and inducing both SMAD-dependent and SMAD-independent intracellular signaling pathways, the latter of which includes the activation of the tyrosine kinase Src. We investigated the mechanism by which TGF-β stimulation activates Src in human and mouse cells. Before TGF-β stimulation, inactive Src was complexed with TβRII. Upon TGF-β1 stimulation, TβRII associated with and phosphorylated TβRI at Tyr182. Binding of Src to TβRI involved the interaction of the Src SH2 domain with phosphorylated Tyr182 and the interaction of the Src SH3 domain with a proline-rich region in TβRI and led to the activation of Src kinase activity and Src autophosphorylation. TGF-β1–induced Src activation required the kinase activities of TβRII and Src but not that of TβRI. Activated Src also phosphorylated TβRI on several tyrosine residues, which may stabilize the binding of Src to the receptor. Src activation was required for the ability of TGF-β to induce fibronectin production and migration in human breast carcinoma cells and to induce α–smooth muscle actin and actin reorganization in mouse fibroblasts. Thus, TGF-β induces Src activation by stimulating a direct interaction with TβRI that depends on tyrosine phosphorylation of TβRI by TβRII.

sted, utgiver, år, opplag, sider
American Association for the Advancement of Science, 2022
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-201358 (URN)10.1126/scisignal.abp9521 (DOI)000909193200002 ()36378749 (PubMedID)2-s2.0-85141940300 (Scopus ID)
Forskningsfinansiär
EU, European Research Council, 787472Swedish Research Council, K2019-01598Swedish Research Council, 2015-02757Swedish Cancer Society, 18 0491Knut and Alice Wallenberg Foundation, 2012.0090ProstatacancerförbundetKonung Gustaf V:s och Drottning Victorias FrimurarestiftelseRegion Västerbotten, ALF; 7003284
Tilgjengelig fra: 2022-12-07 Laget: 2022-12-07 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Song, J., Zhou, Y., Yakymovych, I., Schmidt, A., Li, C., Heldin, C.-H. & Landström, M. (2022). The ubiquitin-ligase TRAF6 and TGFβ type I receptor form a complex with Aurora kinase B contributing to mitotic progression and cytokinesis in cancer cells. EBioMedicine, 82, Article ID 104155.
Åpne denne publikasjonen i ny fane eller vindu >>The ubiquitin-ligase TRAF6 and TGFβ type I receptor form a complex with Aurora kinase B contributing to mitotic progression and cytokinesis in cancer cells
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2022 (engelsk)Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 82, artikkel-id 104155Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Transforming growth factor β (TGFβ) is overexpressed in several advanced cancer types and promotes tumor progression. We have reported that the intracellular domain (ICD) of TGFβ receptor (TβR) I is cleaved by proteolytic enzymes in cancer cells, and then translocated to the nucleus in a manner dependent on the endosomal adaptor proteins APPL1/2, driving an invasiveness program. How cancer cells evade TGFβ-induced growth inhibition is unclear.

Methods: We performed microarray analysis to search for genes regulated by APPL1/2 proteins in castration-resistant prostate cancer (CRPC) cells. We investigated the role of TβRI and TRAF6 in mitosis in cancer cell lines cultured in 10% FBS in the absence of exogenous TGFβ. The molecular mechanism of the ubiquitination of AURKB by TRAF6 in mitosis and the formation of AURKB–TβRI complex in cancer cell lines and tissue microarrays was also studied.

Findings: During mitosis and cytokinesis, AURKB–TβRI complexes formed in midbodies in CRPC and KELLY neuroblastoma cells. TRAF6 induced polyubiquitination of AURKB on K85 and K87, protruding on the surface of AURKB to facilitate its activation. AURKB–TβRI complexes in patient's tumor tissue sections correlated with the malignancy of prostate cancer.

Interpretation: The AURKB–TβRI complex may become a prognostic biomarker for patients with risk of developing aggressive PC.

sted, utgiver, år, opplag, sider
Elsevier, 2022
Emneord
APPL1, AURKB, Cancer, Mitosis, TRAF6, TβRI
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-198907 (URN)10.1016/j.ebiom.2022.104155 (DOI)000888297800004 ()35853811 (PubMedID)2-s2.0-85135890887 (Scopus ID)
Forskningsfinansiär
Swedish Society for Medical Research (SSMF), 2019-01598Swedish Society for Medical Research (SSMF), 2015-02757Swedish Society for Medical Research (SSMF), 2020-01291Swedish Cancer Society, 20 0964Region Västerbotten, RV-939377Region Västerbotten, RV-967041Region Västerbotten, RV-970057EU, European Research Council, 787472Knut and Alice Wallenberg Foundation, 2019.0345Stiftelsen Seth M. Kempes Minnes Stipendiefond, SMK-1866
Tilgjengelig fra: 2022-09-05 Laget: 2022-09-05 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Tumkur Sitaram, R., Landström, M., Roos, G. & Ljungberg, B. (2021). Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status. Journal of Clinical Pathology, 74(4), 216-222
Åpne denne publikasjonen i ny fane eller vindu >>Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status
2021 (engelsk)Inngår i: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 74, nr 4, s. 216-222Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

Renal cell carcinoma (RCC) includes diverse tumor types characterized by various genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, play a crucial role in the modification of signaling networks, tumor pathogenesis, and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe typesRCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of VHL gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including PTEN/PI3K/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signaling pathways directly or indirectly involved in ccRCC tumor progression, metastasis, angiogenesis, and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumor cells utilize alternate signaling pathways. This review compiles the state of knowledge about the PI3K/AKT signaling pathway confined to ccRCC and their cross-talks with VHL/HIF pathways.

sted, utgiver, år, opplag, sider
BMJ Publishing Group Ltd, 2021
Emneord
ccRCC, PTEN, PI3K, VHL/HIF, signaling pathway
HSV kategori
Forskningsprogram
medicinsk cellbiologi
Identifikatorer
urn:nbn:se:umu:diva-170709 (URN)10.1136/jclinpath-2020-206693 (DOI)000631874000007 ()32467322 (PubMedID)2-s2.0-85085755245 (Scopus ID)
Forskningsfinansiär
Cancerforskningsfonden i Norrland, AMP20- 1009
Tilgjengelig fra: 2020-05-13 Laget: 2020-05-13 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Rakhimova, O., Schmidt, A., Landström, M., Johansson, A., Kelk, P. & Romani Vestman, N. (2020). Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria. Frontiers in Cellular and Infection Microbiology, 10, Article ID 620801.
Åpne denne publikasjonen i ny fane eller vindu >>Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria
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2020 (engelsk)Inngår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 10, artikkel-id 620801Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The use of stem cells from the apical papilla (SCAPs) has been proposed as a means of promoting root maturation in permanent immature teeth, and plays a significant role in regenerative dental procedures. However, the role of SCAPs may be compromised by microenvironmental factors, such as hypoxic conditions and the presence of bacteria from infected dental root canals. We aim to investigate oral bacterial modulation of SCAP in terms of binding capacity using flow cytometry and imaging, real-time cell proliferation monitoring, and cytokine secretion (IL-6, IL-8, and TGF-β isoforms) under anaerobic conditions. SCAPs were exposed to key species in dental root canal infection, namely Actinomyces gerensceriae, Slackia exigua, Fusobacterium nucleatum, and Enterococcus faecalis, as well as two probiotic strains, Lactobacillus gasseri strain B6 and Lactobacillus reuteri (DSM 17938). We found that A. gerensceriae, S. exigua, F. nucleatum, and E. faecalis, but not the Lactobacillus probiotic strains bind to SCAPs on anaerobic conditions. Enterococcus faecalis and F. nucleatum exhibited the strongest binding capacity, resulting in significantly reduced SCAP proliferation. Notably, F. nucleatum, but not E. faecalis, induce production of the proinflammatory chemokine IL-8 and IL-10 from SCAPs. Production of TGF-β1 and TGF-β2 by SCAPs was dependent on species, cell line, and time, but secretion of TGF-β3 did not vary significantly over time. In conclusion, SCAP response is compromised when exposed to bacterial stimuli from infected dental root canals in anaerobic conditions. Thus, stem cell-mediated endodontic regenerative studies need to include microenvironmental conditions, such as the presence of microorganisms to promote further advantage in the field.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2020
Emneord
SCAP, cytokines-metabolism, endodontics, regeneration, root maturation
HSV kategori
Forskningsprogram
biomedicinsk laboratorievetenskap
Identifikatorer
urn:nbn:se:umu:diva-181522 (URN)10.3389/fcimb.2020.620801 (DOI)000627053500001 ()33718256 (PubMedID)2-s2.0-85102478862 (Scopus ID)
Forskningsfinansiär
Knut and Alice Wallenberg Foundation, 396168403Region Västerbotten, 396168402Region Västerbotten, 7003459Region Västerbotten, 700589
Tilgjengelig fra: 2021-03-16 Laget: 2021-03-16 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Hollandsworth, H. M., Schmitt, V., Amirfakhri, S., Filemoni, F., Schmidt, A., Landström, M., . . . Bouvet, M. (2020). Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules. Translational Oncology, 13(12), Article ID 100857.
Åpne denne publikasjonen i ny fane eller vindu >>Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules
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2020 (engelsk)Inngår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 13, nr 12, artikkel-id 100857Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ-IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 μg or 50 μg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 μg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ± 1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.

sted, utgiver, år, opplag, sider
Elsevier, 2020
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-176551 (URN)10.1016/j.tranon.2020.100857 (DOI)000577515200008 ()32866936 (PubMedID)2-s2.0-85089836490 (Scopus ID)
Tilgjengelig fra: 2020-11-11 Laget: 2020-11-11 Sist oppdatert: 2023-03-23bibliografisk kontrollert
Prosjekter
Molekylära mekanismer för migration och invasivitet av prostatacancerceller [2009-04405_VR]; Umeå universitetNYA MOLEKYLÄRA SIGNALERINGSVÄGAR SOM LEDER TILL INVASIV CANCER STYRS AV TRANSFORMING GROWTH FACTOR BETA OCH UBIQUITIN-LIGASET TRAF6 [2012-02781_VR]; Umeå universitetUtforskande av signalvägar som regleras av Transforming Groth Factor Beta och TRAF6 i prostatacancer [2016-02513_VR]; Umeå universitetUTVÄRDERING AV NYA CANCERSPECIFIKA LÄKEMEDEL [2016-06125_VR]; Umeå universitetUndersökning av nya funktioner för nyckelproteiner i onkogen TGFbeta och Wnt-signalering [2019-01598_VR]; Umeå universitet
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-6737-7230