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  1. Article ; Online: Differences in clinicopathological characteristics between lipohypertrophy and localized insulin-derived amyloidosis: A scoping review.

    Mukai, Kanae / Tanno, Hiromasa / Sugama, Junko / Yanagita, Toshihiko / Kanno, Emi

    Chronic diseases and translational medicine

    2023  Volume 10, Issue 1, Page(s) 22–30

    Abstract: Insulin is used as a therapeutic agent in patients with diabetes, and cutaneous lipohypertrophy (LH) and localized insulin-derived amyloidosis (LIDA) are well-known adverse effects associated with insulin injections. The clinical implications, management, ...

    Abstract Insulin is used as a therapeutic agent in patients with diabetes, and cutaneous lipohypertrophy (LH) and localized insulin-derived amyloidosis (LIDA) are well-known adverse effects associated with insulin injections. The clinical implications, management, assessment methods, and pathological differentiation of LH and LIDA have been recently updated. This review was to update our knowledge of the pathological differentiation, effects of insulin absorption, hypoglycemic events, and recent assessment methods for LH and LIDA. A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews guidelines. Original studies and case reports in English were also included. PubMed and Scopus databases were searched for keywords to identify papers published up to January 2022. A total of 113 studies were identified through a database search, and 31 were eligible for inclusion in this scoping review. In the 31 studies included in this review, patients with type 2 diabetes had high frequencies of LH and LIDA. LH outcome parameters were assessed using pathological findings and imaging. LIDA is mainly determined by pathological methods, such as hematoxylin and eosin and Congo red staining. Several in vitro and in vivo LIDA models of LIDA have been developed. These results suggest that pathological analysis is required to identify LH and LIDA. It is important to consider LIDA, as it likely influences insulin adsorption and glycemic control. Although several studies have evaluated the LIDA process, little is known about the mechanisms underlying the development of adverse effects associated with insulin injections.
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2831148-6
    ISSN 2589-0514 ; 2589-0514
    ISSN (online) 2589-0514
    ISSN 2589-0514
    DOI 10.1002/cdt3.98
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A novel aptamer-based small RNA delivery platform and its application to cancer therapy

    Toshihiko Tanno / Peng Zhang / Christopher Bailey / Yin Wang / Wannaporn Ittiprasert / Martin Devenport / Pan Zheng / Yang Liu

    Genes and Diseases, Vol 10, Iss 3, Pp 1075-

    2023  Volume 1089

    Abstract: Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we ... ...

    Abstract Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we designed a novel targeting small RNA delivery platform comprising of three oligonucleotides: (1) a guide RNA sequence, (2) part of a passenger sequence linked to a DNA aptamer via a PEG linker, and (3) another passenger sequence conjugated to cholesterol, which assemble through complementary base pair annealing. Remarkably, in the presence of magnesium, this molecule self-assembled into a nanoparticle with a hydrophobic cholesterol core, hydrophilic RNA oligonucleotide shell and PEG-linked DNA aptamer flare. The nanoparticles conferred protection to the RNA oligonucleotides against nuclease degradation, which increased bioavailability, and reduced systemic inflammatory responses. The aptamer allowed targeted delivery of RNA therapeutics through cell-specific surface markers, and once inside the cell, the nanoparticles induced lysosomal leakage that released the RNA oligonucleotides into the cytosol to achieve gene silencing. We created a c-Kit-targeting miR-26a delivery particle that specifically accumulated in c-Kit+ breast cancer, significantly increased T cell recruitment, and inhibited tumor growth. Regression of large established tumors were achieved when the nanoparticle was used in combination with anti-CTLA-4 monoclonal antibody.
    Keywords Aptamer ; Cancer ; Micellar nanoparticle ; miRNA ; Target delivery ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Subject code 616
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A novel aptamer-based small RNA delivery platform and its application to cancer therapy.

    Tanno, Toshihiko / Zhang, Peng / Bailey, Christopher / Wang, Yin / Ittiprasert, Wannaporn / Devenport, Martin / Zheng, Pan / Liu, Yang

    Genes & diseases

    2022  Volume 10, Issue 3, Page(s) 1075–1089

    Abstract: Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we ... ...

    Abstract Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we designed a novel targeting small RNA delivery platform comprising of three oligonucleotides: (1) a guide RNA sequence, (2) part of a passenger sequence linked to a DNA aptamer via a PEG linker, and (3) another passenger sequence conjugated to cholesterol, which assemble through complementary base pair annealing. Remarkably, in the presence of magnesium, this molecule self-assembled into a nanoparticle with a hydrophobic cholesterol core, hydrophilic RNA oligonucleotide shell and PEG-linked DNA aptamer flare. The nanoparticles conferred protection to the RNA oligonucleotides against nuclease degradation, which increased bioavailability, and reduced systemic inflammatory responses
    Language English
    Publishing date 2022-05-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2821806-1
    ISSN 2352-3042 ; 2352-3042
    ISSN (online) 2352-3042
    ISSN 2352-3042
    DOI 10.1016/j.gendis.2022.05.004
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  4. Article ; Online: Cancer therapeutic implications of microRNAs in the regulation of immune checkpoint blockade

    Yan Zhang / Toshihiko Tanno / Chrysi Kanellopoulou

    ExRNA, Vol 1, Iss 1, Pp 1-

    2019  Volume 6

    Abstract: Abstract Dampening of patients’ immune response to tumor-specific antigens is a major reason for tumor development and progression. Within tumor microenvironment, aberrant expression of immune checkpoints changes T lymphocyte activity, and induces immune ...

    Abstract Abstract Dampening of patients’ immune response to tumor-specific antigens is a major reason for tumor development and progression. Within tumor microenvironment, aberrant expression of immune checkpoints changes T lymphocyte activity, and induces immune tolerance or escape. Inhibiting these checkpoints, called immune-checkpoint blockade, causes the re-activation of the immune response to suppress tumor progression. microRNAs (miRNAs) are small non-coding RNAs that regulate multiple biological processes including carcinogenesis. miRNAs directly and indirectly control the expression of checkpoint receptors and can benefit the immune checkpoint blockade. In this review, we summarize what is known about miRNAs that regulate the expression of various immune checkpoints in cancer therapy and discuss the clinical implications that miRNAs could be useful therapeutic partners assisting the immune checkpoint therapy.
    Keywords Immune checkpoint blockade ; CTLA-4 ; PD-1 ; PD-L1 ; microRNA ; Therapeutics. Pharmacology ; RM1-950 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: [GDF15 expression and iron overload in ineffective erythropoiesis].

    Tanno, Toshihiko / Miller, Jeffery L

    Rinsho ketsueki] The Japanese journal of clinical hematology

    2011  Volume 52, Issue 6, Page(s) 387–398

    MeSH term(s) Antimicrobial Cationic Peptides/metabolism ; Erythroblasts/secretion ; Erythropoiesis/physiology ; Gene Expression ; Growth Differentiation Factor 15/metabolism ; Growth Differentiation Factor 15/physiology ; Hematologic Diseases/blood ; Hematologic Diseases/genetics ; Hepcidins ; Humans ; Iron/metabolism ; Iron Overload/blood ; Iron Overload/genetics ; Liver/metabolism ; Proteins/physiology ; Proteins/secretion
    Chemical Substances Antimicrobial Cationic Peptides ; GDF15 protein, human ; Growth Differentiation Factor 15 ; Hepcidins ; Proteins ; twisted gastrulation protein, mouse ; Iron (E1UOL152H7)
    Language English
    Publishing date 2011-06
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 390900-1
    ISSN 0485-1439
    ISSN 0485-1439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 535: Show issues

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  6. Article ; Online: Development and maintenance of cancer stem cells under chronic inflammation.

    Tanno, Toshihiko / Matsui, William

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi

    2011  Volume 78, Issue 3, Page(s) 138–145

    Abstract: In many human cancers, tumorigenic potential is not equally shared by all cells but is restricted to phenotypically distinct subpopulations termed cancer stem cells. Cancer stem cells are also capable of both self-renewal and differentiation, and these ... ...

    Abstract In many human cancers, tumorigenic potential is not equally shared by all cells but is restricted to phenotypically distinct subpopulations termed cancer stem cells. Cancer stem cells are also capable of both self-renewal and differentiation, and these functional properties have been suggested to play major roles in tumor initiation and progression. The factors responsible for the development of cancer stem cells and their subsequent regulation are unclear, but several chronic inflammatory states have been associated with an increased risk of malignancy. Therefore, it is possible that specific processes associated with chronic inflammation, as well as the adaptation to cellular stress, regulate cancer stem cells. Several factors associated with chronic inflammation, including cytokines, oxidative stress, and hypoxia, induce the activation of specific cellular response programs that can affect the survival, proliferation, metabolism, and differentiation of cancer cells, as well as the self-renewal and quiescence of normal stem cells. In this review, we discuss how these adaptive processes potentially become subverted to enhance the development and function of cancer stem cells.
    MeSH term(s) Chronic Disease ; Humans ; Inflammation/pathology ; Neoplastic Stem Cells/pathology ; Oxidative Stress ; Regeneration ; Wound Healing
    Language English
    Publishing date 2011-06-30
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2091563-9
    ISSN 1347-3409 ; 1345-4676
    ISSN (online) 1347-3409
    ISSN 1345-4676
    DOI 10.1272/jnms.78.138
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.B 620: Show issues Location:
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  7. Article: An aptamer-based targeted delivery of miR-26a protects mice against chemotherapy toxicity while suppressing tumor growth.

    Tanno, Toshihiko / Zhang, Peng / Lazarski, Christopher A / Liu, Yang / Zheng, Pan

    Blood advances

    2017  Volume 1, Issue 15, Page(s) 1107–1119

    Abstract: The efficacy of traditional chemotherapy is limited by its toxicity, especially with regard to hematopoiesis. Here we show that miR-26a plays a critical role in protecting mice against chemotherapy-induced myeloid suppression by targeting a proapoptotic ... ...

    Abstract The efficacy of traditional chemotherapy is limited by its toxicity, especially with regard to hematopoiesis. Here we show that miR-26a plays a critical role in protecting mice against chemotherapy-induced myeloid suppression by targeting a proapoptotic protein (Bak1) in hematopoietic stem/progenitor cells (HSPCs). Because c-Kit is expressed at high levels in HSPCs, we designed a microRNA-aptamer chimera that contains miR-26a mimic and c-Kit-targeting aptamer and successfully delivered miR-26a into HSPCs to attenuate toxicity of 5' fluorouracil (5-FU) and carboplatin. Meanwhile, our in silico analysis revealed widespread and prognosis-associated downregulation of
    Language English
    Publishing date 2017-06-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2876449-3
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2017004705
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  8. Article ; Online: Iron Loading and Overloading due to Ineffective Erythropoiesis.

    Tanno, Toshihiko / Miller, Jeffery L

    Advances in hematology

    2010  Volume 2010, Page(s) 358283

    Abstract: Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron ... ...

    Abstract Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.
    Language English
    Publishing date 2010-05-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2494501-8
    ISSN 1687-9112 ; 1687-9104
    ISSN (online) 1687-9112
    ISSN 1687-9104
    DOI 10.1155/2010/358283
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  9. Article ; Online: Iron Loading and Overloading due to Ineffective Erythropoiesis

    Jeffery L. Miller / Toshihiko Tanno

    Advances in Hematology , Vol

    2010  Volume 2010

    Keywords Diseases of the blood and blood-forming organs ; RC633-647.5 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.

    Arunsan, Patpicha / Chaidee, Apisit / Cochran, Christina J / Mann, Victoria H / Tanno, Toshihiko / Kumkhaek, Chutima / Smout, Michael J / Karinshak, Shannon E / Rodpai, Rutchanee / Sotillo, Javier / Loukas, Alex / Laha, Thewarach / Brindley, Paul J / Ittiprasert, Wannaporn

    Neoplasia (New York, N.Y.)

    2020  Volume 22, Issue 5, Page(s) 203–216

    Abstract: Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver ... ...

    Abstract Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity. Here, extracellular vesicle (EV)-mediated transfer of mRNAs from human cholangiocytes to naïve recipient cells was investigated following exposure to liver fluke granulin. To minimize the influence of endogenous progranulin, its cognate gene was inactivated using CRISPR/Cas9-based gene knock-out. Several progranulin-depleted cell lines, termed ΔhuPGRN-H69, were established. These lines exhibited >80% reductions in levels of specific transcript and progranulin, both in gene-edited cells and within EVs released by these cells. Profiles of extracellular vesicle RNAs (evRNA) from ΔhuPGRN-H69 for CCA-associated characteristics revealed a paucity of transcripts for estrogen- and Wnt-signaling pathways, peptidase inhibitors and tyrosine phosphatase related to cellular processes including oncogenic transformation. Several CCA-specific evRNAs including MAPK/AKT pathway members were induced by exposure to liver fluke granulin. By comparison, estrogen, Wnt/PI3K and TGF signaling and other CCA pathway mRNAs were upregulated in wild type H69 cells exposed to liver fluke granulin. Of these, CCA-associated evRNAs modified the CCA microenvironment in naïve cells co-cultured with EVs from ΔhuPGRN-H69 cells exposed to liver fluke granulin, and induced translation of MAPK phosphorylation related-protein in naïve recipient cells in comparison with control recipient cells. Exosome-mediated crosstalk in response to liver fluke granulin promoted a CCA-specific program through MAPK pathway which, in turn, established a CCA-conducive disposition.
    MeSH term(s) Animals ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; Bile Ducts/cytology ; Cell Line ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/pathology ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Clustered Regularly Interspaced Short Palindromic Repeats ; Extracellular Vesicles/metabolism ; Gene Expression Regulation, Neoplastic ; Granulins/metabolism ; Granulins/toxicity ; Mutation ; Opisthorchis/metabolism ; Opisthorchis/pathogenicity ; Progranulins/genetics ; Progranulins/metabolism ; Progranulins/pharmacology ; RNA, Messenger/metabolism ; Tumor Microenvironment
    Chemical Substances GRN protein, human ; Granulins ; Progranulins ; RNA, Messenger
    Language English
    Publishing date 2020-03-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2020.02.004
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