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Yu, Di
Publications (10 of 36) Show all publications
Kang, N., Shen, W., Gao, H., Feng, Y., Zhu, W., Yang, S., . . . Yu, D. (2018). Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis. Molecules, 23(6), Article ID 1431.
Open this publication in new window or tab >>Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis
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2018 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, no 6, article id 1431Article in journal (Refereed) Published
Abstract [en]

Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds.

Methods: The antischistosomal activity of hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro.

Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA.

Conclusions: HSA may have great potential to be an antischistosomal agent for further research.

Place, publisher, year, edition, pages
MDPI, 2018
Keywords
hederacolchiside A1, Schistosoma japonicum, Schistosoma mansoni, antischistosomal
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-360492 (URN)10.3390/molecules23061431 (DOI)000435875400192 ()29899232 (PubMedID)
Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2018-09-17Bibliographically approved
Fotaki, G., Jin, C., Kerzeli, I. K., Ramachandran, M., Martikainen, M.-M., Karlsson-Parra, A., . . . Essand, M. (2018). Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models. Oncoimmunology, 7(3), Article ID e1397250.
Open this publication in new window or tab >>Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models
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2018 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 7, no 3, article id e1397250Article in journal (Refereed) Published
Abstract [en]

Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens (TAAs) are frequently used as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidence indicate that ex vivo engineered DCs are poor in migration and in fact do not directly present TAA epitopes to naïve T cells in vivo. Instead, it is proposed that bystander host DCs take up material from vaccine-DCs, migrate and subsequently initiate antitumor T-cell responses. We used mouse models to examine the possibility of using pro-inflammatory allogeneic DCs (alloDCs) to activate host DCs and enable them to promote antigen-specific T-cell immunity. We found that alloDCs were able to initiate host DC activation and migration to draining lymph node leading to T-cell activation. The pro-inflammatory milieu created by alloDCs also led to recruitment of NK cells and neutrophils at the site of injection. Vaccination with alloDCs combined with Ad5M(gp100), an infection-enhanced adenovirus encoding the human melanoma-associated antigen gp100 resulted in generation of CD8+ T cells with a T-cell receptor (TCR) specific for the gp10025-33 epitope (gp100-TCR+). Ad5M(gp100)-alloDC vaccination in combination with transfer of gp100-specific pmel-1 T cells resulted in prolonged survival of B16-F10 melanoma-bearing mice and altered the composition of the tumor microenvironment (TME). We hereby propose that alloDCs together with TAA- or neoepitope-encoding Ad5M can become an “off-the-shelf” cancer vaccine, which can reverse the TME-induced immunosuppression and induce host cellular anti-tumor immune responses in patients without the need of a time-consuming preparation step of autologous DCs.

Keywords
adjuvants, Allogeneic dendritic cells, cell-based immunotherapy, tumor microenvironment, tumor-associated antigen
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346362 (URN)10.1080/2162402X.2017.1397250 (DOI)000423567000013 ()29399398 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/373; CAN 2016/318Swedish Childhood Cancer Foundation, PR2015-0049Swedish Research Council, 2015-03688
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2019-02-21Bibliographically approved
Lugano, R., Vemuri, K., Yu, D., Bergqvist, M., Smits, A., Essand, M., . . . Dimberg, A. (2018). CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis.. Journal of Clinical Investigation, 128(8), 3280-3297
Open this publication in new window or tab >>CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis.
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2018 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 128, no 8, p. 3280-3297Article in journal (Refereed) Published
Abstract [en]

Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytical cleavage. The CD93-MMRN2 complex was required for activation of integrin-β1, phosphorylation of focal adhesion kinase (FAK) and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of integrin-β1 and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for therapy.

Keywords
Brain cancer, Fibronectin, Oncology, Vascular Biology, endothelial cells
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-350902 (URN)10.1172/JCI97459 (DOI)000440461500015 ()29763414 (PubMedID)
Funder
Swedish Cancer Society, CAN 2014/832Swedish Cancer Society, CAN 2017/502Swedish Cancer Society, CAN 2015/1216Swedish Childhood Cancer Foundation, PR2015-0133Swedish Childhood Cancer Foundation, NCP2015-0075Swedish Research Council, 2016-02495
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-11-08Bibliographically approved
Shridhar, N., Ruotsalainen, J., van der Sluis, T., Rogava, M., Yu, D., Essand, M., . . . Tueting, T. (2018). Modifying melanoma immune microenvironment by heterologous prime-boost vaccination with adenovirus and Modified Vaccinia Ankara virus vectors. Paper presented at 45th Annual Meeting of the Arbeitsgemeinscha-Dermatologische-Forschung (ADF), MAR 07-10, 2018, Zurich, SWITZERLAND. Experimental dermatology, 27(3), E54-E55
Open this publication in new window or tab >>Modifying melanoma immune microenvironment by heterologous prime-boost vaccination with adenovirus and Modified Vaccinia Ankara virus vectors
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2018 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 27, no 3, p. E54-E55Article in journal, Meeting abstract (Other academic) Published
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-361438 (URN)000427009500127 ()
Conference
45th Annual Meeting of the Arbeitsgemeinscha-Dermatologische-Forschung (ADF), MAR 07-10, 2018, Zurich, SWITZERLAND
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-02-07Bibliographically approved
Younis, S., Kamel, W., Falkeborn, T., Wang, H., Yu, D., Daniels, R., . . . Andersson, L. (2018). Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth. Proceedings of the National Academy of Sciences of the United States of America, 115(16), E3808-E3816
Open this publication in new window or tab >>Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth
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2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 16, p. E3808-E3816Article in journal (Refereed) Published
Abstract [en]

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.

Keywords
ZC3H11A, mRNA export, stress response, virus infection
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-354118 (URN)10.1073/pnas.1722333115 (DOI)000430191900026 ()29610341 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
Fotaki, G., Jin, C., Ramachandran, M., Kerzeli, I. K., Karlsson-Parra, A., Yu, D. & Essand, M. (2018). Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses. Oncoimmunology, 7(3), Article ID e1395126.
Open this publication in new window or tab >>Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses
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2018 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 7, no 3, article id e1395126Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.

Keywords
Allogeneic dendritic cells, cell-based immunotherapy, innate immune cells, cell activation
National Category
Immunology in the medical area Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346363 (URN)10.1080/2162402X.2017.1395126 (DOI)000423567000006 ()
Funder
Swedish Cancer Society, CAN 2013/373; CAN 2016/318Swedish Childhood Cancer Foundation, PR2015-0049Swedish Research Council, 2015-03688
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2019-02-21Bibliographically approved
Ma, J., Ramachandran, M., Jin, C., Essand, M. & Yu, D. (2017). Adenovirus, Semliki Forest virus and vaccinia virus-induced immunogenic cell death augments oncolytic virus immunotherapy. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 341-341
Open this publication in new window or tab >>Adenovirus, Semliki Forest virus and vaccinia virus-induced immunogenic cell death augments oncolytic virus immunotherapy
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 341-341Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-346971 (URN)000411865200218 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Essand, M., Ma, J., Jin, C., Ramachandran, M. & Yu, D. (2017). CAR T-Cells with Induced Secretion of Helicobacter Pylori Neutrophil-Activating Protein (HP-NAP) Yields Improved Anti-Tumor Activity and Reduced Immunosuppression. Paper presented at 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 10-13, 2017, Washington, DC. Molecular Therapy, 25(5 S1), 288-288
Open this publication in new window or tab >>CAR T-Cells with Induced Secretion of Helicobacter Pylori Neutrophil-Activating Protein (HP-NAP) Yields Improved Anti-Tumor Activity and Reduced Immunosuppression
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2017 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 25, no 5 S1, p. 288-288Article in journal, Meeting abstract (Other academic) Published
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-331372 (URN)000401083600621 ()
Conference
20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 10-13, 2017, Washington, DC
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Spyrou, A., Kundu, S., Haseeb, L., Yu, D., Olofsson, T., Dredge, K., . . . Forsling, K. (2017). Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth. Molecular Cancer Therapeutics, 16(8), 1705-1716
Open this publication in new window or tab >>Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth
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2017 (English)In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 16, no 8, p. 1705-1716Article in journal (Refereed) Published
Abstract [en]

Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM. Here, we report that the levels of HPSE in pediatric brain tumors are higher than in healthy brain tissue and that treatment of pediatric brain tumor cells with HPSE stimulated their growth. In addition, the latent, 65 kDa form of HPSE (that requires intracellular enzymatic processing for activation) enhanced cell viability and rapidly activated the ERK and AKT signaling pathways, before enzymatically active HPSE was detected. The HPSE inhibitor PG545 efficiently killed pediatric brain tumor cells, but not normal human astrocytes, and this compound also reduced tumor cell invasion in vitro and potently reduced the size of flank tumors in vivo. Our findings indicate that HPSE in malignant brain tumors affects both the tumor cells themselves and their ECM. In conclusion, HPSE plays a substantial role in childhood brain tumors, by contributing to tumor aggressiveness and thereby represents a potential therapeutic target.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-333701 (URN)10.1158/1535-7163.MCT-16-0900 (DOI)000406929200023 ()28716813 (PubMedID)
Funder
Swedish Cancer Society, 130500Swedish Research Council, 521-2013-3356Swedish Childhood Cancer Foundation, PROJ12/093, NCp2015-0077EU, Horizon 2020, 645756
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-11-23Bibliographically approved
Sarén, T., Ramachandran, M., Martikainen, M. & Yu, D. (2017). Insertion of the Type-I IFN Decoy Receptor B18R in a miRNA-Tagged Semliki Forest Virus Improves Oncolytic Capacity but Results in Neurotoxicity. Paper presented at 10th International Conference on Replicating Oncolytic Virus Therapeutics, OCT 01-04, 2016, Vancouver, CANADA. MOLECULAR THERAPY-ONCOLYTICS, 7, 67-75
Open this publication in new window or tab >>Insertion of the Type-I IFN Decoy Receptor B18R in a miRNA-Tagged Semliki Forest Virus Improves Oncolytic Capacity but Results in Neurotoxicity
2017 (English)In: MOLECULAR THERAPY-ONCOLYTICS, ISSN 2372-7705, Vol. 7, p. 67-75Article in journal (Refereed) Published
Abstract [en]

Oncolytic Semliki Forest virus (SFV) has been suggested as a potential candidate for the treatment of glioblastoma and neuroblastoma. However, the oncolytic capacity of SFV is restricted by the anti-viral type-I interferon (IFN) response. The aim of this study was to increase the oncolytic capacity of a microRNA target tagged SFV against glioblastoma by arming it with the Vaccinia-virus-encoded type-I IFN decoy receptor B18R (SFV4B18RmiRT) to neutralize type-I IFN response. Expression of B18R by SFV4B18RmiRT aided neutralization of IFN-b, which was shown by reduced STAT-1 phosphorylation and improved virus spread in plaque assays. B18R expression by SFV4 increased its oncolytic capacity in vitro against murine glioblastoma (CT-2A), regardless of the presence of exogenous IFN-b. Both SFV4B18RmiRT and SFV4miRT treatments controlled tumor growth in mice with syngeneic orthotopic gliomablastoma (CT-2A). However, treatment with SFV4B18RmiRT induced severe neurological symptoms in some mice because of virus replication in the healthy brain. Neither neurotoxicity nor virus replication in the brain was observed when SFV4miRT was administered. In summary, our results indicate that the oncolytic capacity of SFV4 was improved in vitro and in vivo by incorporation of B18R, but neurotoxicity of the virus was increased, possibly due to loss of microRNA targets.

Place, publisher, year, edition, pages
CELL PRESS, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-341813 (URN)10.1016/j.omto.2017.10.001 (DOI)000419677400008 ()29159280 (PubMedID)
Conference
10th International Conference on Replicating Oncolytic Virus Therapeutics, OCT 01-04, 2016, Vancouver, CANADA
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-20Bibliographically approved
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