=== Generating (published_papers) ===
=== Generating (research_interests) ===
=== Generating (teaching_experience) ===
=== Generating (education) ===
=== Generating (research_experience) ===
=== Generating (misc) ===
=== Generating (research_projects) ===
=== Generating (books_etc) ===
=== Generating (industrial_property_rights) ===
=== Generating (awards) ===
=== Generating (association_memberships) ===
=== Generating (presentations) ===
==== begin registerFile(/WWW/pub2/data/ERD/person/60644/researchmap/published_papers-propagate.jsonl) ====
line:1, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/42244377","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105040961381","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=464873","label":"url"}],"paper_title":{"en":"Three-dimensional cell-culture systems using nanofibrillated bacterial cellulose restores drug metabolism activity in HepG2 hepatocellular carcinoma cells","ja":"Three-dimensional cell-culture systems using nanofibrillated bacterial cellulose restores drug metabolism activity in HepG2 hepatocellular carcinoma cells"},"authors":{"en":[{"name":"ANDO Hidenori"},{"name":"Amorim Matsuo Cristina Nana"},{"name":"Akagi Shunsuke"},{"name":"Tajima Kenji"},{"name":"Takata Haruka"},{"name":"Serizawa Ryo"},{"name":"Matsushima Tokuo"},{"name":"Kusano Takatomo"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"安藤 英紀"},{"name":"松尾 アモリムクリスティーナ菜々"},{"name":"赤木 俊介"},{"name":"Tajima Kenji"},{"name":"髙田 春風"},{"name":"Serizawa Ryo"},{"name":"Matsushima Tokuo"},{"name":"Kusano Takatomo"},{"name":"石田 竜弘"}]},"description":{"en":"Three-dimensional (3D) culture more faithfully reproducesin vivo-like cell interactions and functions than conventional two-dimensional (2D) monolayers. Although HepG2 cells are widely used in drug discovery, their 2D cultures exhibit low expression of drug-metabolizing enzymes such as cytochrome P450s (CYPs), limiting utility for toxicity and pharmacokinetic studies. Nano-fibrillated bacterial cellulose (NFBC) is a unique biomaterial that features exceptional homogeneity, high purity, and excellent biocompatibility. We recently employed two NFBC-based 3D culture systems: the Suspension and the OnGel methods. However, the capacity of NFBC to improve hepatocyte-specific functions has yet to be systematically explored. In this study, we aimed to establish a 3D culture platform for HepG2 cells using NFBC to restore hepatic functionality, and drug-metabolizing activity in particular, via comparison with conventional 2D monolayers. Both of these 3D culture systems produced viable HepG2 spheroids with good proliferation. Exploratory microarray profiling suggested broad upregulation of multiple absorption, distribution, metabolism and excretion (ADME) genes in the HepG2 spheroids. Among these, the enzyme Cytochrome P450 3A4 (CYP3A4) showed a significant increase in protein expression and in enzymatic activity in the HepG2 spheroids, which was functionally confirmed by acetaminophen (APAP) toxicity via its bioactivation into toxic metabolite. In addition, the HepG2 spheroids displayed reduced sensitivity to the anticancer drug doxorubicin compared to 2D monolayer. Collectively, these findings demonstrate that NFBC-based 3D culture systems effectively restore liver-specific functions in HepG2 cells, which results in HepG2 spheroids with metabolic competence and physiologically relevant drug responses, and could offer a promising tool for high-throughputin vitrodrug screening.","ja":"Three-dimensional (3D) culture more faithfully reproducesin vivo-like cell interactions and functions than conventional two-dimensional (2D) monolayers. Although HepG2 cells are widely used in drug discovery, their 2D cultures exhibit low expression of drug-metabolizing enzymes such as cytochrome P450s (CYPs), limiting utility for toxicity and pharmacokinetic studies. Nano-fibrillated bacterial cellulose (NFBC) is a unique biomaterial that features exceptional homogeneity, high purity, and excellent biocompatibility. We recently employed two NFBC-based 3D culture systems: the Suspension and the OnGel methods. However, the capacity of NFBC to improve hepatocyte-specific functions has yet to be systematically explored. In this study, we aimed to establish a 3D culture platform for HepG2 cells using NFBC to restore hepatic functionality, and drug-metabolizing activity in particular, via comparison with conventional 2D monolayers. Both of these 3D culture systems produced viable HepG2 spheroids with good proliferation. Exploratory microarray profiling suggested broad upregulation of multiple absorption, distribution, metabolism and excretion (ADME) genes in the HepG2 spheroids. Among these, the enzyme Cytochrome P450 3A4 (CYP3A4) showed a significant increase in protein expression and in enzymatic activity in the HepG2 spheroids, which was functionally confirmed by acetaminophen (APAP) toxicity via its bioactivation into toxic metabolite. In addition, the HepG2 spheroids displayed reduced sensitivity to the anticancer drug doxorubicin compared to 2D monolayer. Collectively, these findings demonstrate that NFBC-based 3D culture systems effectively restore liver-specific functions in HepG2 cells, which results in HepG2 spheroids with metabolic competence and physiologically relevant drug responses, and could offer a promising tool for high-throughputin vitrodrug screening."},"publication_date":"2026-06-05","publication_name":{"en":"Biomedical Materials","ja":"Biomedical Materials"},"volume":"21","number":"3","starting_page":"035025","ending_page":"035025","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1088/1748-605X/ae7243"],"issn":["1748-6041"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"1000300291","type":"published_papers","id":"54848250"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/41818855","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105035584530","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=462607","label":"url"}],"paper_title":{"en":"A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics","ja":"A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics"},"authors":{"en":[{"name":"Denda Masaya"},{"name":"Kohmura Yutaka"},{"name":"Kobayashi Daishiro"},{"name":"Yoshimaru Tetsuro"},{"name":"Fukuda Shoichiro"},{"name":"ANDO Hidenori"},{"name":"Ishida Tatsuhiro"},{"name":"Katagiri Toyomasa"},{"name":"Otaka Akira"}],"ja":[{"name":"傳田 将也"},{"name":"Kohmura Yutaka"},{"name":"Kobayashi Daishiro"},{"name":"吉丸 哲郎"},{"name":"福田 翔一郎"},{"name":"安藤 英紀"},{"name":"石田 竜弘"},{"name":"片桐 豊雅"},{"name":"大髙 章"}]},"description":{"en":"Protein-protein interactions (PPIs) are attractive yet challenging drug targets, motivating the development of conformationally constrained peptides such as stapled α-helices. Here we report a one-pot cysteine-tryptophan (Cys-Trp) cross-linking strategy that enables direct formation of Trp-indole CH sulfenylation staples concomitant with global side-chain deprotection and resin cleavage. Application of this approach afforded a Cys-Trp-stapled analogue of estrogen receptor-α (ERα) activity regulator synthetic peptide (ERAP), designed to disrupt a pathogenic PPI implicated in breast cancer. The resulting stapled ERAP, stERAP(C-W), exhibited potent and sustained antiproliferative activity comparable to that of the original stERAP. Moreover, stereochemical modification at the stapling residues was readily achieved, and circular dichroism (CD) analyses revealed a systematic decrease in α-helicity upon D-amino acid substitution. Overall, this study establishes Cys-Trp stapling as a concise and versatile platform for generating bioactive stapled peptides with tunable conformational properties.","ja":"Protein-protein interactions (PPIs) are attractive yet challenging drug targets, motivating the development of conformationally constrained peptides such as stapled α-helices. Here we report a one-pot cysteine-tryptophan (Cys-Trp) cross-linking strategy that enables direct formation of Trp-indole CH sulfenylation staples concomitant with global side-chain deprotection and resin cleavage. Application of this approach afforded a Cys-Trp-stapled analogue of estrogen receptor-α (ERα) activity regulator synthetic peptide (ERAP), designed to disrupt a pathogenic PPI implicated in breast cancer. The resulting stapled ERAP, stERAP(C-W), exhibited potent and sustained antiproliferative activity comparable to that of the original stERAP. Moreover, stereochemical modification at the stapling residues was readily achieved, and circular dichroism (CD) analyses revealed a systematic decrease in α-helicity upon D-amino acid substitution. Overall, this study establishes Cys-Trp stapling as a concise and versatile platform for generating bioactive stapled peptides with tunable conformational properties."},"publication_date":"2026-03-07","publication_name":{"en":"Bioorganic & Medicinal Chemistry","ja":"Bioorganic & Medicinal Chemistry"},"volume":"137","starting_page":"118622","ending_page":"118622","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bmc.2026.118622"],"issn":["0968-0896"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:3, {"insert":{"user_id":"1000300291","type":"published_papers","id":"51438166"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/40525653","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105008442030","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=444657","label":"url"}],"paper_title":{"en":"Imiquimod-Loaded Phospholipid-Free Small Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases","ja":"Imiquimod-Loaded Phospholipid-Free Small Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases"},"authors":{"en":[{"name":"Chan Vanessa"},{"name":"Lee Hsin Mei"},{"name":"Takata Haruka"},{"name":"Cheng Sheng Liang"},{"name":"Yen Yu Ting"},{"name":"Pfeifer Lisa"},{"name":"Rushton Luke"},{"name":"Chao Po Han"},{"name":"Zhao Feng"},{"name":"Ong Chun Yat"},{"name":"Al-Fayez Nojoud"},{"name":"Ishida Tatsuhiro"},{"name":"Chen Yunching"},{"name":"Li Shyh Dar"}],"ja":[{"name":"Chan Vanessa"},{"name":"Lee Hsin Mei"},{"name":"髙田 春風"},{"name":"Cheng Sheng Liang"},{"name":"Yen Yu Ting"},{"name":"Pfeifer Lisa"},{"name":"Rushton Luke"},{"name":"Chao Po Han"},{"name":"Zhao Feng"},{"name":"Ong Chun Yat"},{"name":"Al-Fayez Nojoud"},{"name":"石田 竜弘"},{"name":"Chen Yunching"},{"name":"Li Shyh Dar"}]},"description":{"en":"Liver cancers are often diagnosed at advanced stages and are the fourth leading cause of cancer death globally. Liver metastases, particularly from colorectal cancer, occur in 66% of patients. Immunotherapies for these cancers are limited by immunosuppressive tumor microenvironments. To address this, phospholipid-free small unilamellar vesicles (PFSUV) are developed to deliver the toll-like receptor 7 agonist Imiquimod (IMQ) to hepatocytes. PFSUV consists of 83 mol% cholesterol and 17 mol% Tween80, with IMQ encapsulated in these 75-nm particles. Intravenous administration of PFSUV-IMQ sustained liver IFN-α levels over 24 h while reducing systemic exposure. In a CT26 liver metastasis model, PFSUV-IMQ combined with Oxaliplatin reduced tumor size, increased CD8+ T cell infiltration, and enhanced tumor apoptosis. In an HCA-1 liver cancer model, the same treatment decreased tumor burden, increased apoptosis, and reduced lung metastases. Flow cytometry revealed increased CD86+/MHC-II+ dendritic cells and IFN-γ+ CD8+ T cells in treated tumors. RNA-seq shows enrichment of innate immune activation genes after a single dose. These findings suggest that targeted IMQ delivery activates the tumor immune microenvironment, leading to reduced tumor burden in liver cancer and metastasis models.","ja":"Liver cancers are often diagnosed at advanced stages and are the fourth leading cause of cancer death globally. Liver metastases, particularly from colorectal cancer, occur in 66% of patients. Immunotherapies for these cancers are limited by immunosuppressive tumor microenvironments. To address this, phospholipid-free small unilamellar vesicles (PFSUV) are developed to deliver the toll-like receptor 7 agonist Imiquimod (IMQ) to hepatocytes. PFSUV consists of 83 mol% cholesterol and 17 mol% Tween80, with IMQ encapsulated in these 75-nm particles. Intravenous administration of PFSUV-IMQ sustained liver IFN-α levels over 24 h while reducing systemic exposure. In a CT26 liver metastasis model, PFSUV-IMQ combined with Oxaliplatin reduced tumor size, increased CD8+ T cell infiltration, and enhanced tumor apoptosis. In an HCA-1 liver cancer model, the same treatment decreased tumor burden, increased apoptosis, and reduced lung metastases. Flow cytometry revealed increased CD86+/MHC-II+ dendritic cells and IFN-γ+ CD8+ T cells in treated tumors. RNA-seq shows enrichment of innate immune activation genes after a single dose. These findings suggest that targeted IMQ delivery activates the tumor immune microenvironment, leading to reduced tumor burden in liver cancer and metastasis models."},"publication_date":"2025-06-17","publication_name":{"en":"Advanced Healthcare Materials","ja":"Advanced Healthcare Materials"},"volume":"14","number":"22","starting_page":"e2501691","ending_page":"e2501691","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/adhm.202501691"],"issn":["2192-2640"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:4, {"insert":{"user_id":"1000300291","type":"published_papers","id":"51438167"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/40553724","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105008439387","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=444656","label":"url"}],"paper_title":{"en":"Protein-bound cisplatin could exhibit an efficient antitumor effect in vivo","ja":"Protein-bound cisplatin could exhibit an efficient antitumor effect in vivo"},"authors":{"en":[{"name":"Matsuo Nana Cristina Amorim"},{"name":"ANDO Hidenori"},{"name":"Takata Haruka"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"松尾 アモリムクリスティーナ菜々"},{"name":"安藤 英紀"},{"name":"髙田 春風"},{"name":"石田 竜弘"}]},"description":{"en":"Cisplatin has been a mainstay in the treatment of various cancers, and continues to be one of the most effective and essential drugs for cancer treatment. However, the severe nephrotoxicity induced by cisplatin continues to be problematic in clinical settings. Following intravenous (i.v.) injection, cisplatin binds to serum proteins in blood circulation. Also, the contributions that protein-bound cisplatin confers to both the antitumor and adverse effects remain uncertain. In this study, therefore, we performed pharmacokinetic and pharmacological studies of protein-bound cisplatin. Following i.v. injection, protein-bound cisplatin was retained in blood circulation much longer than free-form cisplatin. The protein-bound cisplatin caused no renal toxicities, while equivalent doses of free-form cisplatin did produce this negative effect. In antitumor studies, surprisingly, sequential i.v. treatments with protein-bound cisplatin clearly suppressed tumor growth to an extent that was comparable to the same doses of free-form cisplatin both in the treatment of murine B16F10 melanoma as well as in that for human A2780 ovarian tumor-bearing mice. These results suggest that the protein-bound form partially contributes to the therapeutic outcome of i.v.-injected cisplatin for cancer treatments. Also, protein-bound cisplatin could become a novel anticancer agent to suppress tumor growth with less renal toxicity.","ja":"Cisplatin has been a mainstay in the treatment of various cancers, and continues to be one of the most effective and essential drugs for cancer treatment. However, the severe nephrotoxicity induced by cisplatin continues to be problematic in clinical settings. Following intravenous (i.v.) injection, cisplatin binds to serum proteins in blood circulation. Also, the contributions that protein-bound cisplatin confers to both the antitumor and adverse effects remain uncertain. In this study, therefore, we performed pharmacokinetic and pharmacological studies of protein-bound cisplatin. Following i.v. injection, protein-bound cisplatin was retained in blood circulation much longer than free-form cisplatin. The protein-bound cisplatin caused no renal toxicities, while equivalent doses of free-form cisplatin did produce this negative effect. In antitumor studies, surprisingly, sequential i.v. treatments with protein-bound cisplatin clearly suppressed tumor growth to an extent that was comparable to the same doses of free-form cisplatin both in the treatment of murine B16F10 melanoma as well as in that for human A2780 ovarian tumor-bearing mice. These results suggest that the protein-bound form partially contributes to the therapeutic outcome of i.v.-injected cisplatin for cancer treatments. Also, protein-bound cisplatin could become a novel anticancer agent to suppress tumor growth with less renal toxicity."},"publication_date":"2025-06-17","publication_name":{"en":"Journal of Pharmaceutical Sciences","ja":"Journal of Pharmaceutical Sciences"},"volume":"114","number":"8","starting_page":"103881","ending_page":"103881","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.xphs.2025.103881"],"issn":["0022-3549"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:5, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=414763","label":"url"}],"paper_title":{"en":"Application of bacterial-derived long cellulose nanofiber to suspension culture of mammalian cells as a shear protectant","ja":"Application of bacterial-derived long cellulose nanofiber to suspension culture of mammalian cells as a shear protectant"},"authors":{"en":[{"name":"Kaneko Eiichiro"},{"name":"Tsujisaki Haruto"},{"name":"Fujiwara Masashi"},{"name":"ANDO Hidenori"},{"name":"Sato Yasushi"},{"name":"Ishida Tatsuhiro"},{"name":"Tani Hirofumi"},{"name":"Tajima Kenji"}],"ja":[{"name":"Kaneko Eiichiro"},{"name":"Tsujisaki Haruto"},{"name":"Fujiwara Masashi"},{"name":"安藤 英紀"},{"name":"Sato Yasushi"},{"name":"石田 竜弘"},{"name":"Tani Hirofumi"},{"name":"Tajima Kenji"}]},"publication_date":"2024-11","publication_name":{"en":"International Journal of Biological Macromolecules","ja":"International Journal of Biological Macromolecules"},"volume":"280","number":"3","starting_page":"135938","ending_page":"135938","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijbiomac.2024.135938"],"issn":["0141-8130"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:6, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012299","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38813140","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85193252659","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=412140","label":"url"}],"paper_title":{"en":"Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases.","ja":"Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases."},"authors":{"en":[{"name":"Hori Taiki"},{"name":"Shimizu Taro"},{"name":"ANDO Hidenori"},{"name":"Okada Naoto"},{"name":"Yamagami Hiroki"},{"name":"Yasui Saya"},{"name":"Hosoki Minae"},{"name":"Tojima Akihiro"},{"name":"Otoda Toshiki"},{"name":"Yuasa Tomoyuki"},{"name":"Aihara Ken-ichi"},{"name":"Takishita Makoto"},{"name":"Yoshida Sumiko"},{"name":"Abe Masahiro"},{"name":"Ishida Tatsuhiro"},{"name":"Nakamura Shingen"}],"ja":[{"name":"堀 太貴"},{"name":"清水 太郎"},{"name":"安藤 英紀"},{"name":"岡田 直人"},{"name":"山上 紘規"},{"name":"Yasui Saya"},{"name":"Hosoki Minae"},{"name":"Tojima Akihiro"},{"name":"乙田 敏城"},{"name":"湯浅 智之"},{"name":"粟飯原 賢一"},{"name":"Takishita Makoto"},{"name":"吉田 守美子"},{"name":"安倍 正博"},{"name":"石田 竜弘"},{"name":"中村 信元"}]},"description":{"en":"The effects of vaccination are modified by hematological and autoimmune diseases and/or treatment. Anti-SARS-CoV-2 mRNA vaccine contains polyethylene glycol (PEG), it is largely unknown whether PEG influences the effects of vaccination or induces a humoral response. This study examined whether anti-PEG antibodies before vaccination (pre-existing) influenced the acquisition of SARS-CoV-2 antibodies and evaluated the relationship between the development of anti-SARS-CoV-2 antibodies and anti-PEG antibodies after SARS-CoV-2 vaccination in hematological and autoimmune diseases. Anti-SARS-CoV-2 antibody IgG, anti-PEG IgG, and IgM titers were evaluated in patients with hematological and autoimmune diseases after the second dose of BNT162B2. Anti-PEG IgG and IgM titers were also measured before vaccination to examine changes after vaccination and the relationship with vaccine efficacy. In patients with hematological (n = 182) and autoimmune diseases (n = 96), anti-SARS-CoV-2 and anti-PEG antibody titers were evaluated after a median of 33 days from 2nd vaccination. The median anti-SARS-CoV-2 antibody titers were 1901 AU/mL and 3832 AU/mL in patients with hematological and autoimmune disease, respectively. Multiple regression analysis showed that age and days from 2nd vaccination were negatively associated with anti-SARS-CoV-2 antibody titers. Anti-CD20 antibody treatment was negatively correlated with anti-SARS-CoV-2 antibody titers in hematological disease, and C-reactive protein (CRP) was positively correlated with anti-SARS-CoV-2 antibody titers in autoimmune disease. Baseline anti-PEG antibody titers were significantly higher in patients with autoimmune disease but were not correlated with anti-SARS-CoV-2 antibody titers. Patients with increased anti-PEG IgG acquired higher anti-SARS-CoV-2 antibody titers in patients with autoimmune disease. Anti-SARS-CoV-2 antibody acquisition was suboptimal in patients with hematological disease, but both anti-SARS-CoV-2 antibody and anti-PEG IgG were acquired in patients with autoimmune disease, reflecting robust humoral immune response. Pre-existing anti-PEG antibody titers did not affect anti-SARS-CoV-2 antibody acquisition.","ja":"The effects of vaccination are modified by hematological and autoimmune diseases and/or treatment. Anti-SARS-CoV-2 mRNA vaccine contains polyethylene glycol (PEG), it is largely unknown whether PEG influences the effects of vaccination or induces a humoral response. This study examined whether anti-PEG antibodies before vaccination (pre-existing) influenced the acquisition of SARS-CoV-2 antibodies and evaluated the relationship between the development of anti-SARS-CoV-2 antibodies and anti-PEG antibodies after SARS-CoV-2 vaccination in hematological and autoimmune diseases. Anti-SARS-CoV-2 antibody IgG, anti-PEG IgG, and IgM titers were evaluated in patients with hematological and autoimmune diseases after the second dose of BNT162B2. Anti-PEG IgG and IgM titers were also measured before vaccination to examine changes after vaccination and the relationship with vaccine efficacy. In patients with hematological (n = 182) and autoimmune diseases (n = 96), anti-SARS-CoV-2 and anti-PEG antibody titers were evaluated after a median of 33 days from 2nd vaccination. The median anti-SARS-CoV-2 antibody titers were 1901 AU/mL and 3832 AU/mL in patients with hematological and autoimmune disease, respectively. Multiple regression analysis showed that age and days from 2nd vaccination were negatively associated with anti-SARS-CoV-2 antibody titers. Anti-CD20 antibody treatment was negatively correlated with anti-SARS-CoV-2 antibody titers in hematological disease, and C-reactive protein (CRP) was positively correlated with anti-SARS-CoV-2 antibody titers in autoimmune disease. Baseline anti-PEG antibody titers were significantly higher in patients with autoimmune disease but were not correlated with anti-SARS-CoV-2 antibody titers. Patients with increased anti-PEG IgG acquired higher anti-SARS-CoV-2 antibody titers in patients with autoimmune disease. Anti-SARS-CoV-2 antibody acquisition was suboptimal in patients with hematological disease, but both anti-SARS-CoV-2 antibody and anti-PEG IgG were acquired in patients with autoimmune disease, reflecting robust humoral immune response. Pre-existing anti-PEG antibody titers did not affect anti-SARS-CoV-2 antibody acquisition."},"publication_date":"2024-05-17","publication_name":{"en":"Heliyon","ja":"Heliyon"},"volume":"10","number":"10","starting_page":"e31489","ending_page":"e31489","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.heliyon.2024.e31489"],"issn":["2405-8440"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:7, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=405320","label":"url"}],"paper_title":{"en":"Peritoneal B Cells Play a Role in The Production of Anti-Polyethylene Glycol (PEG) IgM Against Intravenously Injected siRNA-PEGylated Liposome Complexes","ja":"Peritoneal B Cells Play a Role in The Production of Anti-Polyethylene Glycol (PEG) IgM Against Intravenously Injected siRNA-PEGylated Liposome Complexes"},"authors":{"en":[{"name":"Shimizu Taro"},{"name":"Amr S Abu Lila"},{"name":"Kitayama Yuka"},{"name":"Abe Ryo"},{"name":"Takata Haruka"},{"name":"ANDO Hidenori"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"清水 太郎"},{"name":"Amr S Abu Lila"},{"name":"北山 由佳"},{"name":"阿部 遼"},{"name":"髙田 春風"},{"name":"安藤 英紀"},{"name":"異島 優"},{"name":"石田 竜弘"}]},"publication_date":"2024-02","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"47","number":"2","starting_page":"469","ending_page":"477","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b23-00733"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:8, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012091","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38256961","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050867133847869696/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=405319","label":"url"}],"paper_title":{"en":"Acute kidney injury caused by rhabdomyolysis is ameliorated by serum albumin-based supersulfides donors through antioxidative pathways","ja":"Acute kidney injury caused by rhabdomyolysis is ameliorated by serum albumin-based supersulfides donors through antioxidative pathways"},"authors":{"en":[{"name":"Ikeda-Imafuku Mayumi"},{"name":"Fukuta Tatsuya"},{"name":"Victor Tuan Giam Chuang"},{"name":"Sawa Tomohiro"},{"name":"Maruyama Toru"},{"name":"Otagiri Masaki"},{"name":"Ishida Tatsuhiro"},{"name":"Ishima Yu"}],"ja":[{"name":"池田 真由美"},{"name":"福田 達也"},{"name":"Victor Tuan Giam Chuang"},{"name":"Sawa Tomohiro"},{"name":"Maruyama Toru"},{"name":"Otagiri Masaki"},{"name":"石田 竜弘"},{"name":"異島 優"}]},"description":{"en":"Oxidative stress is responsible for the onset and progression of various kinds of diseases including rhabdomyolysis-induced acute kidney injury (AKI). Antioxidants are, therefore, thought to aid in the recovery of illnesses linked to oxidative stress. Supersulfide species have been shown to have substantial antioxidative activity; however, due to their limited bioavailability, few supersulfide donors have had their actions evaluated in vivo. In this study, human serum albumin (HSA) and N-acetyl-L-cysteine polysulfides (NACSn), which have polysulfides in an oxidized form, were conjugated to create a supersulfide donor. HSA is chosen to be a carrier of NACSn because of its extended blood circulation and high level of biocompatibility. In contrast to a supersulfide donor containing reduced polysulfide in HSA, the NACSn-conjugated HSAs exhibited stronger antioxidant activity than HSA and free NACSn without being uptaken by the cells in vitro. The supersulfide donor reduced the levels of blood urea nitrogen and serum creatinine significantly in a mouse model of rhabdomyolysis-induced AKI. Supersulfide donors significantly reduced the expression of oxidative stress markers in the kidney. These results indicate that the developed supersulfide donor has the therapeutic effect on rhabdomyolysis-induced AKI.","ja":"Oxidative stress is responsible for the onset and progression of various kinds of diseases including rhabdomyolysis-induced acute kidney injury (AKI). Antioxidants are, therefore, thought to aid in the recovery of illnesses linked to oxidative stress. Supersulfide species have been shown to have substantial antioxidative activity; however, due to their limited bioavailability, few supersulfide donors have had their actions evaluated in vivo. In this study, human serum albumin (HSA) and N-acetyl-L-cysteine polysulfides (NACSn), which have polysulfides in an oxidized form, were conjugated to create a supersulfide donor. HSA is chosen to be a carrier of NACSn because of its extended blood circulation and high level of biocompatibility. In contrast to a supersulfide donor containing reduced polysulfide in HSA, the NACSn-conjugated HSAs exhibited stronger antioxidant activity than HSA and free NACSn without being uptaken by the cells in vitro. The supersulfide donor reduced the levels of blood urea nitrogen and serum creatinine significantly in a mouse model of rhabdomyolysis-induced AKI. Supersulfide donors significantly reduced the expression of oxidative stress markers in the kidney. These results indicate that the developed supersulfide donor has the therapeutic effect on rhabdomyolysis-induced AKI."},"publication_date":"2024-01-18","publication_name":{"en":"Pharmaceuticals","ja":"Pharmaceuticals"},"volume":"17","number":"1","starting_page":"128","ending_page":"128","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ph17010128"],"issn":["1424-8247"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:9, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37579503","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85169045394","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402793","label":"url"}],"paper_title":{"en":"Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticle for the Treatment of Hepatitis","ja":"Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticle for the Treatment of Hepatitis"},"authors":{"en":[{"name":"Yasuda Kengo"},{"name":"Maeda Hitoshi"},{"name":"Kinoshita Ryo"},{"name":"Minayoshi Yuki"},{"name":"Mizuta Yuki"},{"name":"Nakamura Yuka"},{"name":"Imoto Shuhei"},{"name":"Nishi Koji"},{"name":"Yamasaki Keishi"},{"name":"Sakuragi Mina"},{"name":"Nakamura Teruya"},{"name":"Ikeda-Imafuku Mayumi"},{"name":"Iwao Yasunori"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"},{"name":"Iwakiri Yasuko"},{"name":"Otagiri Masaki"},{"name":"Watanabe Hiroshi"},{"name":"Maruyama Toru"}],"ja":[{"name":"Yasuda Kengo"},{"name":"Maeda Hitoshi"},{"name":"木下 遼"},{"name":"Minayoshi Yuki"},{"name":"Mizuta Yuki"},{"name":"Nakamura Yuka"},{"name":"Imoto Shuhei"},{"name":"Nishi Koji"},{"name":"Yamasaki Keishi"},{"name":"Sakuragi Mina"},{"name":"Nakamura Teruya"},{"name":"池田 真由美"},{"name":"Iwao Yasunori"},{"name":"異島 優"},{"name":"石田 竜弘"},{"name":"Iwakiri Yasuko"},{"name":"Otagiri Masaki"},{"name":"Watanabe Hiroshi"},{"name":"Maruyama Toru"}]},"description":{"en":"Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics.","ja":"Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics."},"publication_date":"2023-08-14","publication_name":{"en":"ACS Nano","ja":"ACS Nano"},"volume":"17","number":"17","starting_page":"16668","ending_page":"16681","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1021/acsnano.3c02877"],"issn":["1936-086X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:10, {"insert":{"user_id":"1000300291","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37355210","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402792","label":"url"}],"paper_title":{"en":"Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route","ja":"Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route"},"authors":{"en":[{"name":"Takata Haruka"},{"name":"Shimizu Taro"},{"name":"Yamade Rina"},{"name":"Elhewan Ali Emam Elsadek Emam Nehal"},{"name":"Emam Abdallah Emam Sherif"},{"name":"ANDO Hidenori"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"髙田 春風"},{"name":"清水 太郎"},{"name":"山出 莉奈"},{"name":"Nehal Emam Elsadek Emam Ali Elhewan"},{"name":"Sherif Emam Abdallah Emam"},{"name":"安藤 英紀"},{"name":"異島 優"},{"name":"石田 竜弘"}]},"description":{"en":"Modifying the surface of nanoparticles with polyethylene glycol (PEG) is a commonly used approach for improving the in vitro stability of nanoparticles such as liposomes and increasing their circulation half-lives. We have demonstrated that, in certain conditions, an intravenous (i.v.) injection of PEGylated liposomes (PEG-Lip) induced anti-PEG IgM antibodies, which led to rapid clearance of second doses in mice. SARS-CoV-2 vaccines, composed of mRNA-containing PEGylated lipid nanoparticles, have been widely administered as intramuscular (i.m.) injections, so it is important to determine if PEGylated formulations can induce anti-PEG antibodies. If the favorable properties that PEGylation imparts to therapeutic nanoparticles are to be widely applicable this should apply to various routes of administration. However, there are few reports on the effect of different administration routes on the in vivo production of anti-PEG IgM. In this study, we investigated anti-PEG IgM production in mice following i.m., intraperitoneal (i.p.) and subcutaneous (s.c.) administration of PEG-Lip. PEG-Lip appeared to induce anti-PEG IgM by all the tested routes of administration, although the lipid dose causing maximum responses varied. Splenectomy attenuated the anti-PEG IgM production for all routes of administration, suggesting that splenic immune cells may have contributed to anti-PEG IgM production. Interestingly, in vitro experiments indicated that not only splenic cells but also cells in the peritoneal cavity induced anti-PEG IgM following incubation with PEG-Lip. These observations confirm previous experiments that have shown that measurable amounts of PEG-Lip administered i.p., i.m. or s.c. are absorbed to some extent into the blood circulation, where they can be distributed to the spleen and/or peritoneal cavity, and are recognized by B cells, triggering anti-PEG IgM production. The results obtained in this study have important implications for developing efficient PEGylated nanoparticular delivery system.","ja":"Modifying the surface of nanoparticles with polyethylene glycol (PEG) is a commonly used approach for improving the in vitro stability of nanoparticles such as liposomes and increasing their circulation half-lives. We have demonstrated that, in certain conditions, an intravenous (i.v.) injection of PEGylated liposomes (PEG-Lip) induced anti-PEG IgM antibodies, which led to rapid clearance of second doses in mice. SARS-CoV-2 vaccines, composed of mRNA-containing PEGylated lipid nanoparticles, have been widely administered as intramuscular (i.m.) injections, so it is important to determine if PEGylated formulations can induce anti-PEG antibodies. If the favorable properties that PEGylation imparts to therapeutic nanoparticles are to be widely applicable this should apply to various routes of administration. However, there are few reports on the effect of different administration routes on the in vivo production of anti-PEG IgM. In this study, we investigated anti-PEG IgM production in mice following i.m., intraperitoneal (i.p.) and subcutaneous (s.c.) administration of PEG-Lip. PEG-Lip appeared to induce anti-PEG IgM by all the tested routes of administration, although the lipid dose causing maximum responses varied. Splenectomy attenuated the anti-PEG IgM production for all routes of administration, suggesting that splenic immune cells may have contributed to anti-PEG IgM production. Interestingly, in vitro experiments indicated that not only splenic cells but also cells in the peritoneal cavity induced anti-PEG IgM following incubation with PEG-Lip. These observations confirm previous experiments that have shown that measurable amounts of PEG-Lip administered i.p., i.m. or s.c. are absorbed to some extent into the blood circulation, where they can be distributed to the spleen and/or peritoneal cavity, and are recognized by B cells, triggering anti-PEG IgM production. The results obtained in this study have important implications for developing efficient PEGylated nanoparticular delivery system."},"publication_date":"2023-08","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"360","starting_page":"285","ending_page":"292","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2023.06.027"],"issn":["1873-4995"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:11, {"insert":{"user_id":"1000300291","type":"published_papers","id":"41379367"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36805860","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85148357615","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=393938","label":"url"}],"paper_title":{"en":"Ionic liquid-based transcutaneous peptide antitumor vaccine; therapeutic effect in a mouse tumor model","ja":"Ionic liquid-based transcutaneous peptide antitumor vaccine; therapeutic effect in a mouse tumor model"},"authors":{"en":[{"name":"Shimizu Taro"},{"name":"Matsuzaki Takaaki"},{"name":"Fukuda Shoichiro"},{"name":"Yoshioka Chihiro"},{"name":"Shimazaki Yuna"},{"name":"Takese Shunsuke"},{"name":"Yamanaka Katsuhiro"},{"name":"Nakae Takashi"},{"name":"Ishibashi Masaki"},{"name":"Hamamoto Hidetoshi"},{"name":"ANDO Hidenori"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"清水 太郎"},{"name":"松﨑 隆朗"},{"name":"福田 翔一郎"},{"name":"吉岡 千尋"},{"name":"島﨑 優奈"},{"name":"竹瀬 俊輔"},{"name":"Yamanaka Katsuhiro"},{"name":"Nakae Takashi"},{"name":"Ishibashi Masaki"},{"name":"Hamamoto Hidetoshi"},{"name":"安藤 英紀"},{"name":"異島 優"},{"name":"石田 竜弘"}]},"description":{"en":"Traditional vaccinations need to be injected with needles, and since some people have a strong aversion to needles, a needle-free alternative delivery system is important. In this study, we employed ionic liquids (ILs) for transcutaneous delivery of cancer antigen-derived peptides to obtain anticancer therapeutic effects in a needle-free manner. ILs successfully increased the in vitro skin permeability of a peptide from Wilms tumor 1 (WT1), one of the more promising cancer antigens, plus or minus an adjuvant, resiquimod (R848), a toll-like receptor 7 agonist. In vivo studies demonstrated that concomitant transcutaneous delivery of WT1 peptide and R848 by ILs induced WT1-specific cytotoxic T lymphocyte (CTL) in mice, resulting in tumor growth inhibition in Lewis lung carcinoma-bearing mice. Interestingly, administrating R848 in ILs before WT1 peptides in ILs increased tumor growth inhibition effects compared to co-administration of both. We found that the prior application of R848 increased the infiltration of leukocytes in the skin and that subsequent delivery of WT1 peptides was more likely to induce WT1-specific CTL. Furthermore, sequential immunization with IL-based formulations was applicable to different types of peptides and cancer models without induction of skin irritation. IL-based transcutaneous delivery of cancer antigen-derived peptides and adjuvants, either alone or together, could be a novel approach to needle-free cancer therapeutic vaccines.","ja":"Traditional vaccinations need to be injected with needles, and since some people have a strong aversion to needles, a needle-free alternative delivery system is important. In this study, we employed ionic liquids (ILs) for transcutaneous delivery of cancer antigen-derived peptides to obtain anticancer therapeutic effects in a needle-free manner. ILs successfully increased the in vitro skin permeability of a peptide from Wilms tumor 1 (WT1), one of the more promising cancer antigens, plus or minus an adjuvant, resiquimod (R848), a toll-like receptor 7 agonist. In vivo studies demonstrated that concomitant transcutaneous delivery of WT1 peptide and R848 by ILs induced WT1-specific cytotoxic T lymphocyte (CTL) in mice, resulting in tumor growth inhibition in Lewis lung carcinoma-bearing mice. Interestingly, administrating R848 in ILs before WT1 peptides in ILs increased tumor growth inhibition effects compared to co-administration of both. We found that the prior application of R848 increased the infiltration of leukocytes in the skin and that subsequent delivery of WT1 peptides was more likely to induce WT1-specific CTL. Furthermore, sequential immunization with IL-based formulations was applicable to different types of peptides and cancer models without induction of skin irritation. IL-based transcutaneous delivery of cancer antigen-derived peptides and adjuvants, either alone or together, could be a novel approach to needle-free cancer therapeutic vaccines."},"publication_date":"2023-03","publication_name":{"en":"The AAPS Journal","ja":"The AAPS Journal"},"volume":"25","number":"2","starting_page":"27","ending_page":"27","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1208/s12248-023-00790-w"],"issn":["1550-7416"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:12, {"insert":{"user_id":"1000300291","type":"published_papers","id":"40510324"},"force":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010807","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=392886","label":"url"}],"paper_title":{"en":"FTY720 reduces lipid accumulation by upregulating ABCA1 through liver X receptor and sphingosine kinase 2 signaling in macrophages","ja":"FTY720 reduces lipid accumulation by upregulating ABCA1 through liver X receptor and sphingosine kinase 2 signaling in macrophages"},"authors":{"en":[{"name":"Tachibana Kohki"},{"name":"Kusumoto Kohshi"},{"name":"Ogawa Mai"},{"name":"ANDO Hidenori"},{"name":"Shimizu Taro"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"},{"name":"Okuhira Keiichiro"}],"ja":[{"name":"立花 洸季"},{"name":"楠本 嵩志"},{"name":"小川 真依"},{"name":"安藤 英紀"},{"name":"清水 太郎"},{"name":"異島 優"},{"name":"石田 竜弘"},{"name":"奥平 桂一郎"}]},"publication_date":"2022-11-23","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"23","starting_page":"14617","ending_page":"14617","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms232314617"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:13, {"insert":{"user_id":"1000300291","type":"published_papers","id":"36217199"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35370275","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=383795","label":"url"}],"paper_title":{"en":"Importance of process parameters influencing the mean diameters of siRNA-containing lipid nanoparticles (LNPs) on the in vitro activity of prepared LNPs","ja":"Importance of process parameters influencing the mean diameters of siRNA-containing lipid nanoparticles (LNPs) on the in vitro activity of prepared LNPs"},"authors":{"en":[{"name":"Nakamura Kazuya"},{"name":"Aihara Keisuke"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"中村 和也"},{"name":"Aihara Keisuke"},{"name":"石田 竜弘"}]},"description":{"en":"Genetic drugs have the potential to treat a variety of diseases. Recently, lipid nanoparticles (LNPs) have attracted much attention among drug delivery systems for genetic drugs. LNPs have been practically used in small interfering RNA (siRNA) drugs and mRNA vaccines. Although LNPs are generally prepared by mixing nucleic acids in acidic aqueous buffer and lipid excipients in alcohol (i.e., ethanol), it is not well understood which process parameters in the LNPs formation affect the physicochemical properties and the functionality of LNPs. In this study, we used siRNA-containing LNPs as a model, and evaluated the effect that aqueous solution parameters (buffering agent type, salt concentration, and pH) and mixing parameters (ratio, speed, and temperature) exert on the physicochemical properties and in vitro gene-knockdown activity of LNPs. Among such parameters, the type of buffering agent, salt concentration (ionic strength), pH in acidic aqueous buffer, as well as the mixing ratio and speed significantly affected the mean particle diameter and in vitro gene-knockdown activity of LNPs. A strong correlation between the mean particle diameters and their in vitro gene-knockdown activities was observed. These observations suggest that the process parameters influencing the mean LNPs diameter are likely to be important in the formation of LNPs and also that these correlate with in vitro gene-knockdown activity. Because LNP systems are being further developed for future clinical applications of genetic drugs, information regarding the LNPs manufacturing process is of utmost importance. The results observed in this study will be useful for the manufacturing of optimal LNPs.","ja":"Genetic drugs have the potential to treat a variety of diseases. Recently, lipid nanoparticles (LNPs) have attracted much attention among drug delivery systems for genetic drugs. LNPs have been practically used in small interfering RNA (siRNA) drugs and mRNA vaccines. Although LNPs are generally prepared by mixing nucleic acids in acidic aqueous buffer and lipid excipients in alcohol (i.e., ethanol), it is not well understood which process parameters in the LNPs formation affect the physicochemical properties and the functionality of LNPs. In this study, we used siRNA-containing LNPs as a model, and evaluated the effect that aqueous solution parameters (buffering agent type, salt concentration, and pH) and mixing parameters (ratio, speed, and temperature) exert on the physicochemical properties and in vitro gene-knockdown activity of LNPs. Among such parameters, the type of buffering agent, salt concentration (ionic strength), pH in acidic aqueous buffer, as well as the mixing ratio and speed significantly affected the mean particle diameter and in vitro gene-knockdown activity of LNPs. A strong correlation between the mean particle diameters and their in vitro gene-knockdown activities was observed. These observations suggest that the process parameters influencing the mean LNPs diameter are likely to be important in the formation of LNPs and also that these correlate with in vitro gene-knockdown activity. Because LNP systems are being further developed for future clinical applications of genetic drugs, information regarding the LNPs manufacturing process is of utmost importance. The results observed in this study will be useful for the manufacturing of optimal LNPs."},"publication_date":"2022-04-01","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"45","number":"4","starting_page":"497","ending_page":"507","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b21-01016"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:14, {"insert":{"user_id":"1000300291","type":"published_papers","id":"33006581"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=376679","label":"url"}],"paper_title":{"en":"Liposomalization of oxaliplatin exacerbates the non-liposomal formulation-induced decrease of sweet taste sensitivity in rats","ja":"Liposomalization of oxaliplatin exacerbates the non-liposomal formulation-induced decrease of sweet taste sensitivity in rats"},"authors":{"en":[{"name":"Mogi Keisuke"},{"name":"Kamiya Ikumi"},{"name":"Makino Aimi"},{"name":"Hirao Ayaka"},{"name":"Abe Reina"},{"name":"Doi Yusuke"},{"name":"Shimizu Taro"},{"name":"ANDO Hidenori"},{"name":"Morito Katsuya"},{"name":"Takayama Kentaro"},{"name":"Ishida Tatsuhiro"},{"name":"Nagasawa Kazuki"}],"ja":[{"name":"Mogi Keisuke"},{"name":"Kamiya Ikumi"},{"name":"Makino Aimi"},{"name":"Hirao Ayaka"},{"name":"Abe Reina"},{"name":"土井 祐輔"},{"name":"清水 太郎"},{"name":"安藤 英紀"},{"name":"Morito Katsuya"},{"name":"Takayama Kentaro"},{"name":"石田 竜弘"},{"name":"Nagasawa Kazuki"}]},"publication_date":"2021-12","publication_name":{"en":"Journal of Pharmaceutical Sciences","ja":"Journal of Pharmaceutical Sciences"},"volume":"110","number":"12","starting_page":"3937","ending_page":"3945","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.xphs.2021.07.004"],"issn":["0022-3549"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:15, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507453"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=368803","label":"url"}],"paper_title":{"en":"PEG shedding-rate-dependent blood clearance of PEGylated lipid nanoparticles in mice: faster PEG shedding attenuates anti-PEG IgM production","ja":"PEG shedding-rate-dependent blood clearance of PEGylated lipid nanoparticles in mice: faster PEG shedding attenuates anti-PEG IgM production"},"authors":{"en":[{"name":"Suzuki Takuya"},{"name":"Suzuki Yuta"},{"name":"Hihara Taro"},{"name":"Kubara Kenji"},{"name":"Kondo Keita"},{"name":"Hyodo Kenji"},{"name":"Yamazaki Kazuto"},{"name":"Ishida Tatsuhiro"},{"name":"Ishihara Hiroshi"}],"ja":[{"name":"Suzuki Takuya"},{"name":"Suzuki Yuta"},{"name":"Hihara Taro"},{"name":"Kubara Kenji"},{"name":"Kondo Keita"},{"name":"Hyodo Kenji"},{"name":"Yamazaki Kazuto"},{"name":"石田 竜弘"},{"name":"Ishihara Hiroshi"}]},"publication_date":"2020-10-15","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"588","starting_page":"119792","ending_page":"119792","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2020.119792"],"issn":["0378-5173"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:16, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507469"},"force":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007966","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31609087","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359929","label":"url"}],"paper_title":{"en":"A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in peritoneally disseminated xenograft model","ja":"A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in peritoneally disseminated xenograft model"},"authors":{"en":[{"name":"ANDO Hidenori"},{"name":"Fukushima M"},{"name":"Eshima K"},{"name":"Hasui Taichi"},{"name":"Shimizu Taro"},{"name":"Ishima Yu"},{"name":"Huang C"},{"name":"Wada H"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"安藤 英紀"},{"name":"Fukushima M"},{"name":"Eshima K"},{"name":"蓮井 太一"},{"name":"清水 太郎"},{"name":"異島 優"},{"name":"Huang C"},{"name":"Wada H"},{"name":"石田 竜弘"}]},"description":{"en":"In advanced gastric cancer, peritoneal dissemination is a life-threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP-10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP-10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer-bearing mice via intraperitoneal administration. In this study, we expanded DFP-10825 to the treatment of peritoneally disseminated gastric cancer. DFP-10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI-N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence-labeled DFP-10825 was monitored in this MKN45 peritoneally disseminated mouse model. Intraperitoneal injection of DFP-10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI-N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP-10825. Interestingly, after intraperitoneal injection, fluorescence-labeled DFP-10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors. Intraperitoneal injection of DFP-10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP-10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer.","ja":"In advanced gastric cancer, peritoneal dissemination is a life-threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP-10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP-10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer-bearing mice via intraperitoneal administration. In this study, we expanded DFP-10825 to the treatment of peritoneally disseminated gastric cancer. DFP-10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI-N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence-labeled DFP-10825 was monitored in this MKN45 peritoneally disseminated mouse model. Intraperitoneal injection of DFP-10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI-N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP-10825. Interestingly, after intraperitoneal injection, fluorescence-labeled DFP-10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors. Intraperitoneal injection of DFP-10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP-10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer."},"publication_date":"2019-12","publication_name":{"en":"Cancer Medicine","ja":"Cancer Medicine"},"volume":"8","number":"17","starting_page":"7313","ending_page":"7321","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/cam4.2598"],"issn":["2045-7634"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:17, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507474"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31155576","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85067107514","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=352535","label":"url"}],"paper_title":{"en":"A photo-activatable peptide mimicking functions of apolipoprotein A-I","ja":"A photo-activatable peptide mimicking functions of apolipoprotein A-I"},"authors":{"en":[{"name":"Kawahara Haruka"},{"name":"Miyashita Naoki"},{"name":"Tachibana Kohki"},{"name":"Tsuda Yusuke"},{"name":"Morimoto Kyohei"},{"name":"Tsuji Kouhei"},{"name":"Shigenaga Akira"},{"name":"Otaka Akira"},{"name":"Ishida Tatsuhiro"},{"name":"Okuhira Keiichiro"}],"ja":[{"name":"川原 遥華"},{"name":"宮下 直樹"},{"name":"立花 洸季"},{"name":"津田 雄介"},{"name":"森本 恭平"},{"name":"辻 耕平"},{"name":"重永 章"},{"name":"大髙 章"},{"name":"石田 竜弘"},{"name":"奥平 桂一郎"}]},"description":{"en":"Apolipoprotein A-I (apoA-I) plays a critical role in high-density lipoprotein (HDL) biogenesis, function and structural dynamics. Peptides that mimic apoA-I have a short amphipathic α-helical structure that can functionally recapitulate many of the same biologic properties of full-length apoA-I in HDL. Hence, they might be expected to have clinical applications in the reduction of atherosclerosis. However, nonspecific cellular efflux of cholesterol induced by apoA-I mimetic peptides might cause side effects that are, as yet, unidentified. In this study, we developed a photo-activatable peptide, 2F*, which is an 18 amino acid peptide mimicking apoA-I bearing an internal photocleavable caging group that is designed to assume an α-helical structure in response to a light stimulus and trigger efflux of cholesterol from cells. Without light irradiation, 2F* peptide showed a low tendency for the formation of α-helices, and therefore did not associate with lipids and failed to induce efflux of cholesterol. In addition, 2F* did not cause hemolysis under our experimental condition. Mass spectrometry indicated that, after light exposure, the caging group detached from 2F* and it assumed the α-helical structure in the presence of lipids, and enhanced cholesterol efflux from cells. Photo-activatable peptides such as 2F* that control cholesterol efflux following light stimulus may be useful for future atherosclerosis-reducing therapies.","ja":"Apolipoprotein A-I (apoA-I) plays a critical role in high-density lipoprotein (HDL) biogenesis, function and structural dynamics. Peptides that mimic apoA-I have a short amphipathic α-helical structure that can functionally recapitulate many of the same biologic properties of full-length apoA-I in HDL. Hence, they might be expected to have clinical applications in the reduction of atherosclerosis. However, nonspecific cellular efflux of cholesterol induced by apoA-I mimetic peptides might cause side effects that are, as yet, unidentified. In this study, we developed a photo-activatable peptide, 2F*, which is an 18 amino acid peptide mimicking apoA-I bearing an internal photocleavable caging group that is designed to assume an α-helical structure in response to a light stimulus and trigger efflux of cholesterol from cells. Without light irradiation, 2F* peptide showed a low tendency for the formation of α-helices, and therefore did not associate with lipids and failed to induce efflux of cholesterol. In addition, 2F* did not cause hemolysis under our experimental condition. Mass spectrometry indicated that, after light exposure, the caging group detached from 2F* and it assumed the α-helical structure in the presence of lipids, and enhanced cholesterol efflux from cells. Photo-activatable peptides such as 2F* that control cholesterol efflux following light stimulus may be useful for future atherosclerosis-reducing therapies."},"publication_date":"2019-06-01","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"42","number":"6","starting_page":"1019","ending_page":"1024","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b19-00114"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:18, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507483"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29462689","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85042257067","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=336344","label":"url"}],"paper_title":{"en":"A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM induction and on the accelerated clearance of PEGylated liposomes","ja":"A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM induction and on the accelerated clearance of PEGylated liposomes"},"authors":{"en":[{"name":"Shimizu Taro"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"Fujita Risako"},{"name":"Awata Mizuki"},{"name":"Kawanishi Munehira"},{"name":"Hashimoto Yosuke"},{"name":"Okuhira Keiichiro"},{"name":"Ishima Yu"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"清水 太郎"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"藤田 理紗子"},{"name":"粟田 瑞月"},{"name":"川西 宗平"},{"name":"橋本 洋佑"},{"name":"奥平 桂一郎"},{"name":"異島 優"},{"name":"石田 竜弘"}]},"description":{"en":"Surface decoration of liposomes with polyethylene glycol (PEG), PEGylation, is recognized as a method to bestow liposomes with a prolonged circulation time following intravenous administration. However, many reports have emphasized that a first dose of PEGylated liposomes (PL) elicits an anti-PEG IgM antibody response that can trigger a rapid systemic clearance of a second dose of PL via a phenomenon that is referred to as \"accelerated blood clearance (ABC).\" Such a phenomenon is usually observed with PL that has been modified with methoxy-PEG. In the current study, we introduced various functional groups, methoxy (OCH), amino (NH), carboxyl (COOH), and hydroxyl (OH), at the chain ends of PEG to investigate the effect on anti-PEG IgM induction. Among different PEG-modified liposomes, hydroxyl PEG-modified liposomes (PL-OH) efficiently attenuated the anti-PEG IgM response in vitro. In addition, PL-OH was less recognizable by anti-PEG IgM compared with other PLs. These findings raised the possibility that PL-OH could attenuate/abrogate elicitation of the ABC phenomenon. Nonetheless, upon repeated intravenous injection, PL-OH triggered the enhanced clearance of a subsequently injected second dose. Furthermore, in vitro studies have demonstrated that, as a complement activator, PL-OH is stronger than PL-OCH and induces further complement activation in the presence of anti-PEG IgM, which was the predominant contributor to the rapid clearance of a second dose of PL-OH. Our results suggest that the screening of complement activation by polymer-modified products in tandem with anti-polymer antibody production should be a prerequisite in the development of polymers that might enhance the therapeutic efficacy of nanocarriers.","ja":"Surface decoration of liposomes with polyethylene glycol (PEG), PEGylation, is recognized as a method to bestow liposomes with a prolonged circulation time following intravenous administration. However, many reports have emphasized that a first dose of PEGylated liposomes (PL) elicits an anti-PEG IgM antibody response that can trigger a rapid systemic clearance of a second dose of PL via a phenomenon that is referred to as \"accelerated blood clearance (ABC).\" Such a phenomenon is usually observed with PL that has been modified with methoxy-PEG. In the current study, we introduced various functional groups, methoxy (OCH), amino (NH), carboxyl (COOH), and hydroxyl (OH), at the chain ends of PEG to investigate the effect on anti-PEG IgM induction. Among different PEG-modified liposomes, hydroxyl PEG-modified liposomes (PL-OH) efficiently attenuated the anti-PEG IgM response in vitro. In addition, PL-OH was less recognizable by anti-PEG IgM compared with other PLs. These findings raised the possibility that PL-OH could attenuate/abrogate elicitation of the ABC phenomenon. Nonetheless, upon repeated intravenous injection, PL-OH triggered the enhanced clearance of a subsequently injected second dose. Furthermore, in vitro studies have demonstrated that, as a complement activator, PL-OH is stronger than PL-OCH and induces further complement activation in the presence of anti-PEG IgM, which was the predominant contributor to the rapid clearance of a second dose of PL-OH. Our results suggest that the screening of complement activation by polymer-modified products in tandem with anti-polymer antibody production should be a prerequisite in the development of polymers that might enhance the therapeutic efficacy of nanocarriers."},"publication_date":"2018-06","publication_name":{"en":"European Journal of Pharmaceutics and Biopharmaceutics","ja":"European Journal of Pharmaceutics and Biopharmaceutics"},"volume":"127","starting_page":"142","ending_page":"149","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ejpb.2018.02.019"],"issn":["1873-3441"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:19, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507512"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26476173","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84944717805","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=304996","label":"url"}],"paper_title":{"en":"Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed","ja":"Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed"},"authors":{"en":[{"name":"ANDO Hidenori"},{"name":"Kobayashi Sakiko"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"Essam Eldin N"},{"name":"Katoh Chihiro"},{"name":"Shimizu Taro"},{"name":"Ukawa Masami"},{"name":"Kawazoe Kazuyoshi"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"安藤 英紀"},{"name":"小林 早紀子"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"Essam Eldin N"},{"name":"加藤 千尋"},{"name":"清水 太郎"},{"name":"鵜川 真実"},{"name":"川添 和義"},{"name":"石田 竜弘"}]},"description":{"en":"Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the \"fluid\" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM.","ja":"Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the \"fluid\" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM."},"publication_date":"2015-12-28","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"220","starting_page":"29","ending_page":"36","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2015.10.019"],"issn":["1873-4995"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:20, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507513"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26095176","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84937974851","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=295059","label":"url"}],"paper_title":{"en":"Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells","ja":"Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells"},"authors":{"en":[{"name":"Shimizu Taro"},{"name":"Mima Yu"},{"name":"Hashimoto Yosuke"},{"name":"Ukawa Masami"},{"name":"ANDO Hidenori"},{"name":"Kiwada Hiroshi"},{"name":"Ishida Tatsuhiro"}],"ja":[{"name":"清水 太郎"},{"name":"美馬 優"},{"name":"橋本 洋佑"},{"name":"鵜川 真実"},{"name":"安藤 英紀"},{"name":"際田 弘志"},{"name":"石田 竜弘"}]},"description":{"en":"The accelerated blood clearance (ABC) phenomenon makes it crucial to use PEGylated liposomes and micelles to deliver drugs. The ABC phenomenon is an immune response against an initial dose of PEGylated liposome, which causes subsequent doses to be rapidly cleared by macrophages in the liver. We recently found that in the early phase of the ABC phenomenon, subsequent doses of PEGylated liposomes were associated with splenic marginal zone (MZ)-B cells and were transported from the MZ to the follicle (FO). In this study, we investigated the underlying mechanisms behind the association of subsequent doses of PEGylated liposomes with MZ-B cells in the spleen. Serum factors, anti-PEG IgM and complement system, were crucial to the association of PEGylated liposomes with MZ-B cells, while the sensitization of MZ-B cells by the first dose of PEGylated liposomes was not significant. It was the complement receptors (CRs) on the MZ-B cells, rather than either the PEG-specific B-cell receptors or the IgM Fc receptors, that were the main contributors to the association between PEGylated liposomes and MZ-B cells. It appeared that anti-PEG IgM would bind to PEGylated liposomes and causes subsequent complement activation, resulting in the formation of immune complexes of PEGylated liposome-anti-PEG IgM-complement. The MZ-B cells then recognized these immune complexes via their CRs. Such an association via CRs might have triggered the transport of the immune complex by MZ-B cells to the FO in the spleen. The information obtained in this study might be useful in the development of an efficient antigen delivery system to usher PEGylated nanoparticles into FO dendritic cells.","ja":"The accelerated blood clearance (ABC) phenomenon makes it crucial to use PEGylated liposomes and micelles to deliver drugs. The ABC phenomenon is an immune response against an initial dose of PEGylated liposome, which causes subsequent doses to be rapidly cleared by macrophages in the liver. We recently found that in the early phase of the ABC phenomenon, subsequent doses of PEGylated liposomes were associated with splenic marginal zone (MZ)-B cells and were transported from the MZ to the follicle (FO). In this study, we investigated the underlying mechanisms behind the association of subsequent doses of PEGylated liposomes with MZ-B cells in the spleen. Serum factors, anti-PEG IgM and complement system, were crucial to the association of PEGylated liposomes with MZ-B cells, while the sensitization of MZ-B cells by the first dose of PEGylated liposomes was not significant. It was the complement receptors (CRs) on the MZ-B cells, rather than either the PEG-specific B-cell receptors or the IgM Fc receptors, that were the main contributors to the association between PEGylated liposomes and MZ-B cells. It appeared that anti-PEG IgM would bind to PEGylated liposomes and causes subsequent complement activation, resulting in the formation of immune complexes of PEGylated liposome-anti-PEG IgM-complement. The MZ-B cells then recognized these immune complexes via their CRs. Such an association via CRs might have triggered the transport of the immune complex by MZ-B cells to the FO in the spleen. The information obtained in this study might be useful in the development of an efficient antigen delivery system to usher PEGylated nanoparticles into FO dendritic cells."},"publication_date":"2015-10","publication_name":{"en":"Immunobiology","ja":"Immunobiology"},"volume":"220","number":"10","starting_page":"1151","ending_page":"1160","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.imbio.2015.06.005"],"issn":["1878-3279"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:21, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507536"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22850293","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=250266","label":"url"}],"paper_title":{"en":"Accelerated blood clearance of PEGylated liposomes containing doxorubicin upon repeated administration to dogs.","ja":"Accelerated blood clearance of PEGylated liposomes containing doxorubicin upon repeated administration to dogs."},"authors":{"en":[{"name":"Suzuki Takuya"},{"name":"Ichihara Masako"},{"name":"Hyodo Kenji"},{"name":"Yamamoto Eiichi"},{"name":"Ishida Tatsuhiro"},{"name":"Kiwada Hiroshi"},{"name":"Ishihara Hiroshi"},{"name":"Kikuchi Hiroshi"}],"ja":[{"name":"鈴木 卓也"},{"name":"市原 理子"},{"name":"Hyodo Kenji"},{"name":"Yamamoto Eiichi"},{"name":"石田 竜弘"},{"name":"際田 弘志"},{"name":"Ishihara Hiroshi"},{"name":"Kikuchi Hiroshi"}]},"description":{"en":"The accelerated blood clearance phenomenon involving anti-PEG IgM production has been recognized as an important issue for the design and development of PEGylated liposomes. Here, we show that empty PEGylated liposomes and Doxil, PEGylated liposomes containing doxorubicin, both caused anti-PEG IgM production and thereby a rapid clearance of the second and/or third dose of Doxil in Beagle dogs in a lipid-dose, inverse-dependent manner. It appears that the pharmacokinetic profile of the second and third administration of Doxil reflected the presence of anti-PEG IgM circulating in the blood. Doxil plus an excess amount of empty PEGylated liposomes rather enhanced the production of anti-PEG IgM compared to Doxil of the same doxorubicin dose. During sequential administration, increasing the lipid dose of Doxil in each dose by the addition of empty PEGylated liposomes strongly attenuated the magnitude of the ABC phenomenon during the effectuation phase of a second and third dose of Doxil. Our results suggest that the pre-clinical study of anti-cancer drug-containing PEGylated liposomes with dogs must be carefully designed and performed with monitoring of the anti-PEG IgM and liposomal drugs circulating in the blood.","ja":"The accelerated blood clearance phenomenon involving anti-PEG IgM production has been recognized as an important issue for the design and development of PEGylated liposomes. Here, we show that empty PEGylated liposomes and Doxil, PEGylated liposomes containing doxorubicin, both caused anti-PEG IgM production and thereby a rapid clearance of the second and/or third dose of Doxil in Beagle dogs in a lipid-dose, inverse-dependent manner. It appears that the pharmacokinetic profile of the second and third administration of Doxil reflected the presence of anti-PEG IgM circulating in the blood. Doxil plus an excess amount of empty PEGylated liposomes rather enhanced the production of anti-PEG IgM compared to Doxil of the same doxorubicin dose. During sequential administration, increasing the lipid dose of Doxil in each dose by the addition of empty PEGylated liposomes strongly attenuated the magnitude of the ABC phenomenon during the effectuation phase of a second and third dose of Doxil. Our results suggest that the pre-clinical study of anti-cancer drug-containing PEGylated liposomes with dogs must be carefully designed and performed with monitoring of the anti-PEG IgM and liposomal drugs circulating in the blood."},"publication_date":"2012-10-15","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"436","number":"1-2","starting_page":"636","ending_page":"643","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2012.07.049"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:22, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507543"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21878904","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=231566","label":"url"}],"paper_title":{"en":"A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA.","ja":"A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA."},"authors":{"en":[{"name":"Nakamura Kazuya"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"Matsunaga Mariko"},{"name":"Doi Yusuke"},{"name":"Ishida Tatsuhiro"},{"name":"Kiwada Hiroshi"}],"ja":[{"name":"中村 和也"},{"name":"Amr Selim Ahmed Ali Abu Lila"},{"name":"松永 真理子"},{"name":"土井 祐輔"},{"name":"石田 竜弘"},{"name":"際田 弘志"}]},"description":{"en":"5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors.","ja":"5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors."},"publication_date":"2011-08-30","publication_name":{"en":"Molecular Therapy","ja":"Molecular Therapy"},"volume":"19","number":"11","starting_page":"2040","ending_page":"2047","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/mt.2011.174"],"issn":["1525-0024"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:23, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507553"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20227473","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=208434","label":"url"}],"paper_title":{"en":"T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes.","ja":"T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes."},"authors":{"en":[{"name":"Koide H"},{"name":"Asai T"},{"name":"Hatanaka K"},{"name":"Akai S"},{"name":"Ishii T"},{"name":"Kenjo E"},{"name":"Ishida Tatsuhiro"},{"name":"Kiwada Hiroshi"},{"name":"Tsukada H"},{"name":"Oku N"}],"ja":[{"name":"Koide H"},{"name":"Asai T"},{"name":"Hatanaka K"},{"name":"Akai S"},{"name":"Ishii T"},{"name":"Kenjo E"},{"name":"石田 竜弘"},{"name":"際田 弘志"},{"name":"Tsukada H"},{"name":"Oku N"}]},"description":{"en":"Repeated injection of polyethyleneglycol-modified (PEGylated) liposomes causes a rapid clearance of them from the bloodstream, this phenomenon is called accelerated blood clearance (ABC). In the present study, we focused on the immune system responsible for the ABC phenomenon. PEGylated liposomes were preadministered to BALB/c mice and [(3)H]-labeled ones were then administered to them 3 days after the preadministration. Consistent with our previous results, the preadministration with PEGylated liposomes triggered the rapid clearance of [(3)H]-labeled PEGylated liposomes from the bloodstream, but that with PEGylated liposomes encapsulating doxorubicin (Dox) did not. In addition, we found that the ABC phenomenon was observed when a mixture of free Dox and PEGylated liposomes was preadministered. These data indicate that immune cells responsible for the ABC phenomenon might be selectively damaged by the Dox encapsulated in PEGylated liposomes. The ABC phenomenon was also observed in BALB/c nu/nu mice, but not in BALB/c SCID mice. The amount of anti-PEG IgM antibody induced by the stimulation with the PEGylated liposomes was significantly increased in the BALB/c nu/nu mice, but not in the BALB/c SCID ones. These data indicate that a T cell-independent B cell response would play a significant role in the ABC phenomenon. Furthermore, the present study suggests that PEGylated liposomes might be recognized by B cells as a thymus-independent type 2 (TI-2) antigen. The present study provides important information for the future development of liposomal medicines.","ja":"Repeated injection of polyethyleneglycol-modified (PEGylated) liposomes causes a rapid clearance of them from the bloodstream, this phenomenon is called accelerated blood clearance (ABC). In the present study, we focused on the immune system responsible for the ABC phenomenon. PEGylated liposomes were preadministered to BALB/c mice and [(3)H]-labeled ones were then administered to them 3 days after the preadministration. Consistent with our previous results, the preadministration with PEGylated liposomes triggered the rapid clearance of [(3)H]-labeled PEGylated liposomes from the bloodstream, but that with PEGylated liposomes encapsulating doxorubicin (Dox) did not. In addition, we found that the ABC phenomenon was observed when a mixture of free Dox and PEGylated liposomes was preadministered. These data indicate that immune cells responsible for the ABC phenomenon might be selectively damaged by the Dox encapsulated in PEGylated liposomes. The ABC phenomenon was also observed in BALB/c nu/nu mice, but not in BALB/c SCID mice. The amount of anti-PEG IgM antibody induced by the stimulation with the PEGylated liposomes was significantly increased in the BALB/c nu/nu mice, but not in the BALB/c SCID ones. These data indicate that a T cell-independent B cell response would play a significant role in the ABC phenomenon. Furthermore, the present study suggests that PEGylated liposomes might be recognized by B cells as a thymus-independent type 2 (TI-2) antigen. The present study provides important information for the future development of liposomal medicines."},"publication_date":"2010-03-21","publication_name":{"en":"International Journal of Pharmaceutics","ja":"International Journal of Pharmaceutics"},"volume":"392","number":"1-2","starting_page":"218","ending_page":"223","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ijpharm.2010.03.022"],"issn":["1873-3476"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:24, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507588"},"force":{"see_also":[{"@id":"http://ajpheart.physiology.org/cgi/content/abstract/288/5/H2163","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15626692","label":"url"},{"@id":"https://www.scopus.com/pages/publications/20944449213","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=131097","label":"url"}],"paper_title":{"en":"Nitrite is an alternative source of NO in vivo","ja":"Nitrite is an alternative source of NO in vivo"},"authors":{"en":[{"name":"Tsuchiya Koichiro"},{"name":"Kanematsu Yasuhisa"},{"name":"Yoshizumi Masanori"},{"name":"Ohnishi Hideki"},{"name":"Kirima Kazuyoshi"},{"name":"Izawa Yuki"},{"name":"Shikishima Michiyo"},{"name":"Ishida Tatsuhiro"},{"name":"Kondo Shuji"},{"name":"Kagami Shoji"},{"name":"Takiguchi Yoshiharu"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"土屋 浩一郎"},{"name":"兼松 康久"},{"name":"Yoshizumi Masanori"},{"name":"Ohnishi Hideki"},{"name":"Kirima Kazuyoshi"},{"name":"井澤 有紀"},{"name":"Shikishima Michiyo"},{"name":"石田 竜弘"},{"name":"Kondo Shuji"},{"name":"香美 祥二"},{"name":"滝口 祥令"},{"name":"玉置 俊晃"}]},"description":{"en":"In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.","ja":"In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects."},"publication_date":"2005-05","publication_name":{"en":"American Journal of Physiology, Heart and Circulatory Physiology","ja":"American Journal of Physiology, Heart and Circulatory Physiology"},"volume":"288","number":"5","starting_page":"H2163","ending_page":"H2170","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpheart.00525.2004"],"issn":["0363-6135"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
line:25, {"insert":{"user_id":"1000300291","type":"published_papers","id":"30507591"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15023452","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=91837","label":"url"}],"paper_title":{"en":"Effect of the physicochemical properties of initially injected liposomes on the clearance of subsequently injected PEGylated liposomes in mice.","ja":"Effect of the physicochemical properties of initially injected liposomes on the clearance of subsequently injected PEGylated liposomes in mice."},"authors":{"en":[{"name":"Ishida Tatsuhiro"},{"name":"Ichikawa Takako"},{"name":"Ichihara Masako"},{"name":"Sadzuka Yasuyuki"},{"name":"Kiwada Hiroshi"}],"ja":[{"name":"石田 竜弘"},{"name":"市川 高子"},{"name":"市原 理子"},{"name":"佐塚 泰之"},{"name":"際田 弘志"}]},"description":{"en":"Using mice as a model, we recently reported that the long-circulating properties of polyethylene glycol (PEG) (M.W. 2000)-modified liposomes (mPEG(2000)-liposomes) disappeared when they were intravenously injected at certain intervals [referred to as the \"accelerated blood clearance (ABC) phenomenon\"]. Herein, we report on a study of issue of whether physicochemical properties of a prior dose of liposomes such as degree of PEGylation, PEG chain length, lipid dose, surface charge, size, play a role in inducing this phenomenon. The injection of conventional liposomes (without a PEG-coating) significantly induced the phenomenon. The PEGylation of conventional liposomes attenuated the induction of the phenomenon somewhat with increasing molar content of PEG derivative and PEG chain length. These findings clearly suggest that the PEGylation of liposomes are not the major cause of the ABC phenomenon but, rather, played a role in preventing it. In addition, increasing the lipid dose in a prior dose of mPEG(2000)-liposomes (0-25 micromol/kg) increased the induction of the phenomenon in a sigmoid manner. The surface charge and size of the liposomes were not critical for the induction of the phenomenon, although generally these serve as determinants in the biodistribution of liposomes. The results reported here clearly indicate that the physicochemical properties of a prior dose of liposomes strongly affect the pharmacokinetic behavior of a subsequent injection of mPEG(2000)-liposomes: The extent of PEGylation and the lipid dose had an effect, but the surface charge and size did not. The results reported herein have a considerable impact on the design and engineering of liposomal formulations for use in multiple drug therapy as well as in therapy that involves the use of liposomal drugs.","ja":"Using mice as a model, we recently reported that the long-circulating properties of polyethylene glycol (PEG) (M.W. 2000)-modified liposomes (mPEG(2000)-liposomes) disappeared when they were intravenously injected at certain intervals [referred to as the \"accelerated blood clearance (ABC) phenomenon\"]. Herein, we report on a study of issue of whether physicochemical properties of a prior dose of liposomes such as degree of PEGylation, PEG chain length, lipid dose, surface charge, size, play a role in inducing this phenomenon. The injection of conventional liposomes (without a PEG-coating) significantly induced the phenomenon. The PEGylation of conventional liposomes attenuated the induction of the phenomenon somewhat with increasing molar content of PEG derivative and PEG chain length. These findings clearly suggest that the PEGylation of liposomes are not the major cause of the ABC phenomenon but, rather, played a role in preventing it. In addition, increasing the lipid dose in a prior dose of mPEG(2000)-liposomes (0-25 micromol/kg) increased the induction of the phenomenon in a sigmoid manner. The surface charge and size of the liposomes were not critical for the induction of the phenomenon, although generally these serve as determinants in the biodistribution of liposomes. The results reported here clearly indicate that the physicochemical properties of a prior dose of liposomes strongly affect the pharmacokinetic behavior of a subsequent injection of mPEG(2000)-liposomes: The extent of PEGylation and the lipid dose had an effect, but the surface charge and size did not. The results reported herein have a considerable impact on the design and engineering of liposomal formulations for use in multiple drug therapy as well as in therapy that involves the use of liposomal drugs."},"publication_date":"2004-03-24","publication_name":{"en":"Journal of Controlled Release","ja":"Journal of Controlled Release"},"volume":"95","number":"3","starting_page":"403","ending_page":"412","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jconrel.2003.12.011"],"issn":["0168-3659"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
==== end registerFile(/WWW/pub2/data/ERD/person/60644/researchmap/published_papers-propagate.jsonl, R8UOrKABRJbN-uhaIOYM) ====
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line:1, {"insert":{"user_id":"1000300291","type":"misc","id":"30512986"},"force":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1050287462784741632/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=359930","label":"url"}],"paper_title":{"en":"フルーツ由来新奇酢酸菌によるナノセルロースの合成とその応用","ja":"フルーツ由来新奇酢酸菌によるナノセルロースの合成とその応用"},"authors":{"en":[{"name":"田島 健次"},{"name":"小瀬 亮太"},{"name":"松島 得雄"},{"name":"Ishida Tatsuhiro"},{"name":"ANDO Hidenori"}],"ja":[{"name":"田島 健次"},{"name":"小瀬 亮太"},{"name":"松島 得雄"},{"name":"石田 竜弘"},{"name":"安藤 英紀"}]},"publication_date":"2019-09","publication_name":{"en":"Journal of The Brewing Society of Japan","ja":"日本醸造協会誌"},"volume":"114","number":"9","starting_page":"540","ending_page":"549","languages":["jpn"],"identifiers":{"issn":["0914-7314"]},"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
line:2, {"insert":{"user_id":"1000300291","type":"misc","id":"30513008"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=190456","label":"url"}],"paper_title":{"en":"siRNA を利用したArgonaute2 遺伝子knockdown によるがん治療法の開発","ja":"siRNA を利用したArgonaute2 遺伝子knockdown によるがん治療法の開発"},"authors":{"en":[{"name":"Ishida Tatsuhiro"},{"name":"Tagami Tatsuaki"},{"name":"Kiwada Hiroshi"}],"ja":[{"name":"石田 竜弘"},{"name":"田上 辰秋"},{"name":"際田 弘志"}]},"publication_date":"2009-04-15","publication_name":{"en":"和光純薬時報","ja":"和光純薬時報"},"volume":"77","number":"2","starting_page":"8","ending_page":"11","languages":["jpn"],"misc_type":"introduction_scientific_journal"},"priority":"input_data"}
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