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3,279 results on '"MATSUMOTO, Hiroshi"'

6. Infantile Epileptic Spasms Syndrome Complicated by Leigh Syndrome and Leigh-Like Syndrome: A Retrospective, Nationwide, Multicenter Case Series

Author

Sasaki, Michiru, Okanishi, Tohru, Matsuoka, Tsuyoshi, Yoshimura, Ayumi, Maruyama, Shinsuke, Shiohama, Tadashi, Hoshino, Hiroki, Mori, Tatsuo, Majima, Hisakazu, Matsumoto, Hiroshi, Kobayashi, Satoru, Chiyonobu, Tomohiro, Matsushige, Takeshi, Nakamura, Kazuyuki, Kubota, Kazuo, Tanaka, Ryuta, Fujita, Takako, Enoki, Hideo, Suzuki, Yasuhiro, Nakamura, Sadao, Fujimoto, Ayataka, and Maegaki, Yoshihiro

Published
2024
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17. Characteristics of Mucosa-Associated Microbiota in Ulcerative Colitis Patients with 5-Aminosalicylic Acid Intolerance.

Author

Matsumoto, Hiroshi, Sasahira, Momoyo, Go, Tei Tei, Yo, Shogen, Ninomiya, Takehiro, Osawa, Motoyasu, Handa, Osamu, Umegami, Eiji, Inoue, Ryo, and Shiotani, Akiko

Subjects
ULCERATIVE colitis, SIGMOID colon, GUT microbiome, DYSBIOSIS, ILEUM
Abstract

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks

Author

Lui, Kei, Marshall, Peter, Schmidt, Peter, Dhawan, Anjali, Korostenski, Larissa, Travadi, Javeed Travadi, Sharp, Mary, Gill, Andy, Pillow, Jane, Stack, Jacqueline, Birch, Pita, Nothdurft, Karen, Cooke, Lucy, Casalaz, Dan, Holberton, Jim, Stewart, Alice, Downe, Lyn, Stewart, Michael, Berry, Andrew, Hunt, Rod, Morris, Peter, Paoli, Tony De, Bolisetty, Srinivas, Paradisis, Mary, Greenhalgh, Mark, Koorts, Pieter, Kuschel, Carl, Jacobs, Sue, Doyle, Lex, Craven, John, Numa, Andrew, Carlisle, Hazel, Badawi, Nadia, Popat, Himanshu, Koh, Guan, Davis, Jonathan, Luig, Melissa, Headley, Bevan, Andersen, Chad, Ng, Linda, Chambers, Georgina, Austin, Nicola, Lynn, Adrienne, Darlow, Brian, Edmonds, Liza, Mildenhall, Lindsay, Buksh, Mariam, Battin, Malcolm, Boom, Jutta van den, Richardson, Vaughan, Barker, David, Hammond, Barbara, Rajadurai, Victor Samuel, Lam, Simon, Fung, Genevieve, Shah, Prakesh S., Beltempo, Marc, Kanungo, Jaideep, Ting, Joseph, Cieslak, Zenon, Sherlock, Rebecca, Mehrem, Ayman Abou, Toye, Jennifer, Aziz, Khalid, Fajardo, Carlos, Bodani, Jaya, Strueby, Lannae, Seshia, Mary, Louis, Deepak, Alvaro, Ruben, Mukerji, Amit, Da Silva, Orlando, Adie, Mohammad, Lee, Kyong-Soon, Ng, Eugene, Lemyre, Brigitte, Daboval, Thierry, Khurshid, Faiza, Pelausa, Ermelinda, Barrington, Keith, Lapoint, Anie, Ethier, Guillaume, Drolet, Christine, Piedboeuf, Bruno, Claveau, Martine, St-Hilaire, Marie, Bertelle, Valerie, Masse, Edith, Canning, Roderick, Makary, Hala, Ojah, Cecil, Monterrosa, Luis, Emberley, Julie, Afifi, Jehier, Kajetanowicz, Andrzej, Lee, Shoo K., Metsäranta, Marjo, Lehtonen, Liisa, Tammela, Outi, Sankilampi, Ulla, Saarela, Timo, Morag, Iris, Zangen, Shmuel, Smolkin, Tatyana, Mimouni, Francis, Bader, David, Rothschild, Avi, Strauss, Zipora, Felszer, Clari, Omari, Hussam, Tov-Friedman, Smadar Even, Bar-Oz, Benjamin, Feldman, Michael, Saad, Nizar, Flidel-Rimon, Orna, Weisbrod, Meir, Lubin, Daniel, Litmanovitz, Ita, Kugelman, Amir, Shinwell, Eric, Klinger, Gil, Nijim, Yousif, Bin-Nun, Alona, Golan, Agneta, Mandel, Dror, Fleisher-Sheffer, Vered, Oron, Anat, Bakhrakh, Lev, Hattori, Satoshi, Shirai, Masaru, Ishioka, Toru, Mori, Toshihiko, Amizuka, Takasuke, Huchimukai, Toru, Yoshida, Hiroshi, Sasaki, Ayako, Shimizu, Junichi, Nakamura, Toshihiko, Maruyama, Mami, Matsumoto, Hiroshi, Hosokawa, Shinichi, Taki, Atsuko, Nakagawa, Machiko, Ko, Kyone, Uozumi, Azusa, Nakata, Setsuko, Shimazaki, Akira, Yoda, Tatsuya, Numata, Osamu, Imamura, Hiroaki, Kobayashi, Azusa, Tokuriki, Shuko, Uchida, Yasushi, Arai, Takahiro, Ito, Mitsuhiro, Ieda, Kuniko, Ono, Toshiyuki, Hayashi, Masashi, Maki, Kanemasa, Yamakawa, MieToru, Kawai, Masahiko, Fujii, Noriko, Shiomi, Kozue, Nozaki, Koji, Wada, Hiroshi, Kim, Taho, Tokunaga, Yasuyuki, Takatera, Akihiro, Oshima, Toshio, Sumida, Hiroshi, Michinomae, Yae, Kusumoto, Yoshio, Yoshimoto, Seiji, Morisawa, Takeshi, Ohashi, Tamaki, Takahashi, Yukihiro, Sugimoto, Moriharu, Ono, Noriaki, Miyagawa, Shinichiro, Saijo, Takahiko, Yamagami, Takashi, Koyano, Kosuke, Kobayashi, Shoko, Kanda, Takeshi, Sakemi, Yoshihiro, Aoki, Mikio, Iida, Koichi, Goshi, Mitsushi, Maruyama, Yuko, Avila-Alvarez, Alejandro, Fernandez-Trisac, José Luis, Pico, M<ce:sup loc='post">a</ce:sup> Luz Couce, Fernández Seara, María José, Gutiérrez, Andrés Martínez, Vizcaíno, Carolina, Iglesias, Miriam Salvador, Zaplana, Honorio Sánchez, Colomer, Belén Fernández, García López, José Enrique, Mozo, Rafael García, González Martínez, M. Teresa, Sebastián, M<ce:sup loc='post">a</ce:sup> Dolores Muro, Carbonell, Marta Balart, Barnusell, Joan Badia, Puiggròs, Mònica Domingo, Aloy, Josep Figueras, Mussons, Francesc Botet, Sanz, Israel Anquela, Galiana, Gemma Ginovart, Coroleu, W., Iriondo, Martin, Vilella, Laura Castells, Porta, Roser, Demestre, Xavier, Nadal, Silvia Martínez, de Frutos Martínez, Cristina, López Cuesta, María Jesús, Mora, Dolores Esquivel, Tardío, Joaquín Ortiz, Benavente, Isabel, Alonso, Almudena, Olmos, Ramón Aguilera, García Cabezas, Miguel A., Jiménez, M<ce:sup loc='post">a</ce:sup> Dolores Martínez, Caballero, M<ce:sup loc='post">a</ce:sup> Pilar Jaraba, Díaz, M<ce:sup loc='post">a</ce:sup> Dolores Ordoñez, Fagundo, Alberto Trujillo, Canals, Lluis Mayol, García-Muñoz Rodrigo, Fermín, Martí, Lourdes Urquía, Moreno Galdo, María Fernanda, Suazo, José Antonio Hurtado, López, Eduardo Narbona, Fernández, José Uberos, Cortajarena Altuna, Miguel A., Zuriarrain, Oihana Muga, Navarro, David Mora, Domínguez, María Teresa, Ruiz del Prado, M<ce:sup loc='post">a</ce:sup> Yolanda, Díez, Inés Esteban, Palau Benavides, María Teresa, Lapeña, Santiago, Prada, Teresa, Mir, Eduard Soler, Sánchez, Araceli Corredera, Vega, Enrique Criado, Prado, Náyade del, Fernández, Cristina, Vilaplana, Lucía Cabanillas, Pérez, Irene Cuadrado, Gómez, Luisa López, Comeche, Laura Domingo, Martín, Isabel Llana, Armengod, Carmen González, Labián, Carmen Muñoz, Muñoz, M<ce:sup loc='post">a</ce:sup> José Santos, Bravo, Dorotea Blanco, Pérez, Vicente, Fernández, M<ce:sup loc='post">a</ce:sup> Dolores Elorza, González, Celia Díaz, Segura, Susana Ares, Azorín, Manuela López, Jimenez, Ana Belén, Sánchez-Tamayo, Tomás, Moreno, Elías Tapia, González, María, Sánchez Martínez, José Enrique, Lloreda García, José María, Orayen, Concepción Goñi, González, Javier Vilas, Albo, María Suárez, Colmenero, Eva González, Gutiérrez González, Elena Pilar, Vacas del Arco, Beatriz, Fernández, Josefina Márquez, Gordillo, Laura Acosta, Asensio, Mercedes Granero, Díaz, Carmen Macías, Albújar, Mar, Jorge, Pedro Fuster, Romero, Sabina, Falero, Mónica Rivero, Escobar Izquierdo, Ana Belén, Capell, Javier Estañ, Macián, M<ce:sup loc='post">a</ce:sup> Isabel Izquierdo, Vicente, M<ce:sup loc='post">a</ce:sup> Mar Montejo, Caballero, Raquel Izquierdo, Martínez, M<ce:sup loc='post">a</ce:sup> Mercedes, Euba, Aintzane, Serna, Amaya Rodríguez, López de Heredia Goya, Juan María, Legorburu, Alberto Pérez, Amorós, Ana Gutiérrez, Marugán Isabel, Víctor Manuel, González, Natalio Hernández, Gracia, Segundo Rite, Faci, M<ce:sup loc='post">a</ce:sup> Purificación Ventura, Villagrasa, M<ce:sup loc='post">a</ce:sup> Pilar Samper, Kofron, Jiri, Brodd, Katarina Strand, Odlind, Andreas, Alberg, Lars, Arwehed, Sofia, Hafström, Ola, Kasemo, Anna, Nederman, Karin, Åhman, Lars, Ingemarsson, Fredrik, Petersson, Henrik, Thurn, Pernilla, Albinsson, Eva, Selander, Bo, Abrahamsson, Thomas, Heimdahl, Ingela, Sveinsdottir, Kristbjorg, Wejryd, Erik, Hedlund, Anna, Söderberg, Maria Katarina, Navér, Lars, Brune, Thomas, Bäckström, Jens, Robinson, Johan, Farooqi, Aijaz, Normann, Erik, Fredriksson, Magnus, Palm, Anders, Rosenqvist, Urban, Walde, Bengt, Hagman, Cecilia, Ohlin, Andreas, Florell, Rein, Smedsaas-Löfvenberg, Agneta, Adams, Mark, Meyer, Philipp, Kusche, Rachel, Schulzke, Sven, Nelle, Mathias, Wagner, Bendicht, Riedel, Thomas, Kaczala, Grégoire, Pfister, Riccardo E., Tolsa, Jean-François, Roth, Matthias, Stocker, Martin, Laubscher, Bernhard, Malzacher, Andreas, Micallef, John P., Hegi, Lukas, Bassler, Dirk, Arlettaz, Romaine, Bernet, Vera, Dani, Carlo, Fiorini, Patrizio, Ghirri, Paolo, Tomasini, Barbara, Mittal, Anita, Kefas, Jonathan, Kamalanathan, Anand, Grosdenier, Michael, Dewhurst, Christopher, Bontea, Andreea, Webb, Delyth, Garr, Ross, Hassan, Ahmed, Ambadkar, Priyadarshan, Dyke, Mark, McDevitt, Katharine, Rewitzky, Glynis, D'Amore, Angela, Kamath, P., Settle, Paul, Maddock, Natasha, Edi-Osagie, Ngozi, Zipitis, Christos, Heal, Carrie, Birch, Jacqeline, Hasib, Abdul, Soe, Aung, Abdul-Malik, Bushra, Kisat, Hamudi, Vasu, Vimal, Sivashankar, Savi, Gupta, Richa, Rawlingson, Chris, Wickham, Tim, Theron, Marice, Kendall, Giles, Gupta, Aashish, Aladangady, Narendra, Ali, Imdad, Jain, Neeraj, Mannan, Khalid, Murthy, Vadivelam, Sullivan, Caroline, Chuang, Shu-Ling, Bate, Tristan, Tyszcuzk, Lidia, Lee, Geraint, Obi, Ozioma, Chang, John, Pai, Vinay, Huddy, Charlotte, Yasin, Salim, Nicholl, Richard, Pandey, Poornima, Cusack, Jonathan, Kairamkonda, Venkatesh, Muogbo, Dominic, Harry, Liza, Surana, Pinki, Broggio, Penny, Pillay, Tilly, Deshpande, Sanjeev, Mahadevan, Moore, Alison, Bastani, Porus, Garbash, Mehdi, Lal, Mithilesh, Abu-Harb, Majd, Allwood, Alex, Selter, Michael, Munyard, Paul, Bartle, David, Paul, Siba, Whincup, Graham, Rekha, Sanghavi, Amess, Philip, Obi, Ben, Reynolds, Peter, Misra, Indranil, De Halpert, Peter, Salgia, Sanjay, Sanghavi, Rekha, Paul, Nicola, Deketelaere, Abby, Khashu, Minesh, Johnson, Mark, Groves, Charlotte, Baird, Jim, Brennan, Nick, Vamvakiti, Katia, McIntyre, John, Holman, Jennifer, Jones, Stephen, Pike, Alison, Cairns, Pamela, Eaton, Megan, Schwarz, Karin, Gibson, David, Miall, Lawrence, Krishnamurthy, Dr, Narayanan, Sankara, Seaton, Sarah E., Draper, Elizabeth S., Kusuda, Satoshi, Håkansson, Stellan, Helenius, Kjell, Reichman, Brian, Vento, Maximo, Darlow, Brian A., Rusconi, Franca, Isayama, Tetsuya, Norman, Mikael, Yang, Junmin, and Modi, Neena

Published
2021
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29. Glossary and Tutorial of Xenobiotic Metabolism Terms Used During Small-Molecule Drug Discovery and Development

Author

Erhardt, Paul, primary, Bachmann, Kenneth, additional, Birkett, Donald, additional, Boberg, Michael, additional, Bodor, Nicholas, additional, Gibson, Gordon, additional, Hawkins, David, additional, Hawksworth, Gabrielle, additional, Hinson, Jack, additional, Koehler, Daniel, additional, Kress, Brian, additional, Luniwal, Amarjit, additional, Matsumoto, Hiroshi, additional, Novak, Raymond, additional, Portoghese, Phillip, additional, Sarver, Jeffrey, additional, Serafini, M. Teresa, additional, Trabbic, Christopher, additional, Vermeulen, Nico, additional, and Wrighton, Steven, additional

Published
2021
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31. Retroviral replicating vector–mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity

Author

Hiraoka, Kei, Inagaki, Akihito, Kato, Yuki, Huang, Tiffany T, Mitchell, Leah A, Kamijima, Shuichi, Takahashi, Masamichi, Matsumoto, Hiroshi, Hacke, Katrin, Kruse, Carol A, Ostertag, Derek, Robbins, Joan M, Gruber, Harry E, Jolly, Douglas J, and Kasahara, Noriyuki

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Neurosciences, Biotechnology, Brain Cancer, Gene Therapy, Cancer, Brain Disorders, Genetics, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Animals, Brain Neoplasms, Cell Line, Tumor, Cell Survival, Cytosine Deaminase, Female, Genetic Therapy, Genetic Vectors, Glioma, Humans, Mice, Neoplasm Recurrence, Local, Retroviridae, Survival Analysis, antitumor immunity, prodrug activator gene therapy, retroviral replicating vector, Toca 511, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundProdrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.MethodsHere we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.ResultsIn both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.ConclusionThese results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity.

Published
2017

36. Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy

Author

Goda, Kyosuke, Murao, Takahisa, Handa, Yukiko, Katsumata, Ryo, Fukushima, Shinya, Nakato, Rui, Osawa, Motoyasu, Ishii, Manabu, Fujita, Minoru, Handa, Osamu, Matsumoto, Hiroshi, Fujita, Yoshihiko, Nishio, Kazuto, Wallace, Timothy M., Gomez-Esquivel, Rene, Berzosa, Manuel, Wolfsen, Herbert C., Wallace, Michael B., Umegaki, Eiji, and Shiotani, Akiko

Published
2021
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37. Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study.

Author

Oshima, Naoki, Hiraoka, Sakiko, Hayashi, Ryohei, Takahashi, Sakuma, Ishii, Manabu, Hashimoto, Shinichi, Yashima, Kazuo, Igawa, Shoko, Inokuchi, Toshihiro, Ueno, Yoshitaka, Inaba, Tomoki, Matsumoto, Hiroshi, Kawashima, Kousaku, Takami, Taro, Isomoto, Hajime, Shiotani, Akiko, Tanaka, Shinji, and Ishihara, Shunji

Published
2024
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38. Current and Future Treatment of Helicobacter pylori Infections

Author

Matsumoto, Hiroshi, Shiotani, Akiko, Graham, David Y., Donelli, Gianfranco, Series editor, Akova, Murat, Editorial board member, Andreoni, Massimo, Editorial board member, Averhoff, Beate, Editorial board member, Azeredo, Joana, Editorial board member, Baquero, Fernando, Editorial board member, Belibasakis, George, Editorial board member, Bouza, Emilio, Editorial board member, Capobianchi, Maria Rosaria, Editorial board member, Coenye, Tom, Editorial board member, Collignon, Anne, Editorial board member, Colwell, Rita, Editorial board member, Ghannoum, Mahmoud, Editorial board member, Greco, Donato, Editorial board member, Kaplan, Jeffrey B., Editorial board member, Katalinic-Jankovic, Vera, Editorial board member, Krogfelt, Karen, Editorial board member, Landini, Maria Paola, Editorial board member, Mastrantonio, Paola, Editorial board member, Mazzei, Teresita, Editorial board member, Mylonakis, Eleftherios, Editorial board member, Nakayama, Jiro, Editorial board member, Peixe, Luisa, Editorial board member, Percival, Steven, Editorial board member, Poljak, Mario, Editorial board member, Pozio, Edoardo, Editorial board member, Raad, Issam, Editorial board member, Sagnelli, Evangelista, Editorial board member, Stefani, Stefania, Editorial board member, Stoodley, Paul, Editorial board member, Vila, Jordi, Editorial board member, Kamiya, Shigeru, editor, and Backert, Steffen, editor

Published
2019
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40. Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm

Author

Harrison, Adele, Synnes, Anne, Ting, Joseph, Cieslak, Zenon, Sherlock, Rebecca, Yee, Wendy, Aziz, Khalid, Toye, Jennifer, Fajardo, Carlos, Kalapesi, Zarin, Sankaran, Koravangattu, Daspal, Sibasis, Seshia, Mary, Alvaro, Ruben, Mukerji, Amit, Da Silva, Orlando, Nwaesei, Chuks, Lee, Kyong-Soon, Dunn, Michael, Lemyre, Brigitte, Dow, Kimberly, Pelausa, Ermelinda, Barrington, Keith, Drolet, Christine, Piedboeuf, Bruno, Claveau, Martine, Beltempo, Marc, Bertelle, Valerie, Masse, Edith, Canning, Roderick, Makary, Hala, Ojah, Cecil, Monterrosa, Luis, Deshpandey, Akhil, Afifi, Jehier, Kajetanowicz, Andrzej, Andersson, Sture, Tammela, Outi, Sankilampi, Ulla, Saarela, Timo, Heymann, Eli, Zangen, Shmuel, Smolkin, Tatyana, Mimouni, Francis, Bader, David, Rothschild, Avi, Strauss, Zipora, Felszer, Clari, Omari, Hussam, Tov-Friedman, Smadar Even, Bar-Oz, Benjamin, Feldman, Michael, Saad, Nizar, Flidel-Rimon, Orna, Weisbrod, Meir, Lubin, Daniel, Litmanovitz, Ita, Kugelman, Amir, Shinwell, Eric, Klinger, Gil, Nijim, Yousif, Bin-Nun, Alona, Golan, Agneta, Mandel, Dror, Fleisher-Sheffer, Vered, Kohelet, David, Bakhrakh, Lev, Hattori, Satoshi, Shirai, Masaru, Ishioka, Toru, Mori, Toshihiko, Amizuka, Takasuke, Huchimukai, Toru, Yoshida, Hiroshi, Sasaki, Ayako, Shimizu, Junichi, Nakamura, Toshihiko, Maruyama, Mami, Matsumoto, Hiroshi, Hosokawa, Shinichi, Taki, Atsuko, Nakagawa, Machiko, Ko, Kyone, Uozumi, Azusa, Nakata, Setsuko, Shimazaki, Akira, Yoda, Tatsuya, Numata, Osamu, Imamura, Hiroaki, Kobayashi, Azusa, Tokuriki, Shuko, Uchida, Yasushi, Arai, Takahiro, Ito, Mitsuhiro, Ieda, Kuniko, Ono, Toshiyuki, Hayashi, Masashi, Maki, Kanemasa, Yamakawa, Mie- Toru, Kawai, Masahiko, Fujii, Noriko, Shiomi, Kozue, Nozaki, Koji, Wada, Hiroshi, Kim, Taho, Tokunaga, Yasuyuki, Takatera, Akihiro, Oshima, Toshio, Sumida, Hiroshi, Michinomae, Yae, Kusumoto, Yoshio, Yoshimoto, Seiji, Morisawa, Takeshi, Ohashi, Tamaki, Takahashi, Yukihiro, Sugimoto, Moriharu, Ono, Noriaki, Miyagawa, Shinichiro, Saijo, Takahiko, Yamagami, Takashi, Koyano, Kosuke, Kobayashi, Shoko, Kanda, Takeshi, Sakemi, Yoshihiro, Aoki, Mikio, Iida, Koichi, Goshi, Mitsushi, Maruyama, Yuko, Kofron, Jiri, Brodd, Katarina Strand, Odlind, Andreas, Alberg, Lars, Arwehed, Sofia, Hafström, Ola, Kasemo, Anna, Nederman, Karin, Åhman, Lars, Ingemarsson, Fredrik, Petersson, Henrik, Thurn, Pernilla, Albinsson, Eva, Selander, Bo, Abrahamsson, Thomas, Heimdahl, Ingela, Sveinsdottir, Kristbjorg, Wejryd, Erik, Hedlund, Anna, Söderberg, Maria Katarina, Navér, Lars, Brune, Thomas, Bäckström, Jens, Robinson, Johan, Farooqi, Aijaz, Normann, Erik, Fredriksson, Magnus, Palm, Anders, Rosenqvist, Urban, Walde, Bengt, Hagman, Cecilia, Ohlin, Andreas, Florell, Rein, Löfvenberg, Agneta Smedsaas, Meyer, Philipp, Kusche, Rachel, Schulzke, Sven, Nelle, Mathias, Wagner, Bendicht, Riedel, Thomas, Kaczala, Grégoire, Pfister, Riccardo E., Tolsa, Jean-François, Roth, Matthias, Stocker, Martin, Laubscher, Bernhard, Malzacher, Andreas, Micallef, John P., Hegi, Lukas, Arlettaz, Romaine, Bernet, Vera, Isayama, Tetsuya, Kusuda, Satoshi, Reichman, Brian, Lee, Shoo K., Lehtonen, Liisa, Norman, Mikael, Adams, Mark, Bassler, Dirk, Helenius, Kjell, Hakansson, Stellan, Yang, Junmin, Jain, Amish, and Shah, Prakesh S.

Published
2020
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49. Mucosal gene therapy using a pseudotyped lentivirus vector encoding murine interleukin-10 (mIL-10) suppresses the development and relapse of experimental murine colitis

Author

Matsumoto, Hiroshi, Haga, Kazunori, Ohno, Izumi, Hiraoka, Kei, Kimura, Takahiro, Hermann, Kip, Kasahara, Noriyuki, Anton, Peter, and McGowan, Ian

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Digestive Diseases, Gene Therapy, Biotechnology, Autoimmune Disease, Inflammatory Bowel Disease, Genetics, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Administration, Mucosal, Administration, Rectal, Animals, Colitis, Dextran Sulfate, Disease Models, Animal, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Interleukin-10, Lentivirus, Mice, Mice, Inbred BALB C, Recurrence, Gene therapy, Lentivirus vector, Clinical Sciences, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract

BackgroundTherapeutic gene transfer is currently being evaluated as a potential therapy for inflammatory bowel disease. This study investigates the safety and therapeutic benefit of a locally administered lentiviral vector encoding murine interleukin-10 in altering the onset and relapse of dextran sodium sulfate induced murine colitis.MethodsLentiviral vectors encoding the reporter genes firefly-luciferase and murine interleukin-10 were administered by intrarectal instillation, either once or twice following an ethanol enema to facilitate mucosal uptake, on Days 3 and 20 in Balb/c mice with acute and relapsing colitis induced with dextran sulfate sodium (DSS). DSS colitis was characterized using clinical disease activity, macroscopic, and microscopic scores. Bioluminescence optical imaging analysis was employed to examine mucosal lentiviral vector uptake and transgene expression. Levels of tumor necrosis factor-α and interleukin-6 in homogenates of rectal tissue were measured by ELISA. Biodistribution of the lentiviral vector to other organs was evaluated by real time quantitative PCR.ResultsMucosal delivery of lentiviral vector resulted in significant transduction of colorectal mucosa, as shown by bioluminescence imaging analysis. Lentiviral vector-mediated local expression of interleukin-10 resulted in significantly increased levels of this cytokine, as well as reduced levels of tumor necrosis factor-α and interleukin-6, and significantly reduced the clinical disease activity, macroscopic, and microscopic scores of DSS colitis. Systemic biodistribution of locally instilled lentiviral vector to other organs was not detected.ConclusionsTopically-delivered lentiviral vectors encoding interleukin-10 safely penetrated local mucosal tissue and had therapeutic benefit in this DSS model of murine colitis.

Published
2014

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