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7. Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System.

Author

Sunwoo, Yongjun, Eom, Sae Hyun, Yun, Ji Seong, Kim, Yujin, Lee, Jeongmin, Lee, Soo Hyeon, Shin, Sooyoung, and Choi, Yeo Jin

Subjects
DRUG side effects, COGNITION disorders, COGNITIVE aging, ANTIPARKINSONIAN agents, ODDS ratio
Abstract

Background and Objectives: Despite high incidences of cognitive impairment with aging, evidence on the prevalence and the seriousness of drug-induced cognitive impairment is limited. This study aims to evaluate the prevalence and the severity of drug-induced cognitive impairment and to investigate the clinical predictors of increased hospitalization risk from serious drug-induced cognitive impairment. Materials and Methods: Adverse drug events (ADEs) regarding drug-induced cognitive impairment reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were included (KIDS KAERS DB 2212A0073). The association between the etiologic classes and the reporting serious adverse events (SAEs) was evaluated using disproportionality analysis, and the effect was estimated with reporting odds ratio (ROR). Clinical predictors associated with increased risk of hospitalization from SAEs were identified via multivariate logistic analysis, and the effect was estimated with odds ratio (OR). Results: The most etiologic medication class for drug-induced cognitive impairment ADEs was analgesics, followed by sedative-hypnotics. Anticancer (ROR 57.105, 95% CI 15.174–214.909) and anti-Parkinson agents (ROR 4.057, 95% CI 1.121–14.688) were more likely to report serious drug-induced cognitive impairments. Male sex (OR 19.540, 95% CI 2.440–156.647) and cancer diagnosis (OR 18.115, 95% CI 3.246–101.101) are the major clinical predictors for increased risk of hospitalizations due to serious drug-induced cognitive impairment. Conclusions: This study highlights the significant prevalence and severity of drug-induced cognitive impairment with cancer diagnosis and anticancer agents. However, further large-scaled studies are required because of the potential underreporting of drug-induced cognitive impairments in real practice settings, which is further contributed to by the complexity of multiple contributing factors such as comorbidities. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome

Author

Park, Yeon Hee, Lal, Samir, Lee, Jeong Eon, Choi, Yoon-La, Wen, Ji, Ram, Sripad, Ding, Ying, Lee, Soo-Hyeon, Powell, Eric, Lee, Se Kyung, Yu, Jong Han, Ching, Keith A., Nam, Jae-Yong, Kim, Seok Won, Nam, Seok Jin, Kim, Ji-Yeon, Cho, Soo Youn, Park, Seri, Kim, Jinho, Hwang, Soohyn, Kim, Yu Jin, Bonato, Vinicius, Fernandez, Diane, Deng, Shibing, Wang, Shuoguo, Shin, Hyuntae, Kang, Eun-Suk, Park, Woong-Yang, Rejto, Paul A., Bienkowska, Jadwiga, and Kan, Zhengyan

Published
2020
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14. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Koroveshi, Dhurata, Bouzid, Kamel, Casalnuovo, Monica, Cascallar, Diana, Korbenfeld, Ernesto Pablo, Bastick, Patricia, Beith, Jane, Colosimo, Maree, Friedlander, Michael, Ganju, Vinod, Green, Michael, Patterson, Kevin, Redfern, Andrew, Richardson, Gary, Ceric, Timur, Gordana, Kecman, Beato, Carlos Augusto, Ferrari, Marcela, Hegg, Roberto, Helena, Vanessa, Ismael, Gustavo Fernando, Lessa, Alvaro Edson, Mano, Max, Morelle, Alessandra, Nogueira, Jose Alberto, Timcheva, Konstanta, Tomova, Antoaneta, Tsakova, Maya, Zlatareva-Petrova, Ani, Asselah, Jamil, Assi, Hazem, Brezden-Masley, Christine, Chia, Stephen, Freedman, Ori, Harb, Mohammed, Joy, Anil Abraham, Kulkarni, Swati, Prady, Catherine, Gaete, Alejandro Andres Acevedo, Matamala, Luis, Torres, Roberto, Yanez, Eduardo, Franco, Sandra, Urrego, Marcela, Gugić, Damir, Vrbanec, Damir, Melichar, Bohuslav, Prausová, Jana, Vyzula, Rostislav, Pilarte, Rafael Gutierrez, León, María Isabel, Muñoz, Rene, Ramos, Glenda, Azeem, Hamdy Abdel, Aziz, Amr Abdel, El Zawahry, Heba, Osegueda, Finlander Rosales, Alexandre, Jerome, Artignan, Xavier, Barletta, Hugues, Beguier, Emmanuel, Berdah, Jean-François, Marty, Chantal Bernard, Bollet, Marc, Bourgeois, Hugues, Bressac, Claude, Burki, Franck, Campone, Mario, Coeffic, David, Cojocarasu, Oana Zveltlana, Dagada, Corinne, Dalenc, Florence, Del Piano, Francesco, Desauw, Christophe, Desmoulins, Isabelle, Dohollou, Nadine, Egreteau, Joelle, Ferrero, Jean-Marc, Foa, Cyril, Garidi, Reda, Gasnault, Laurent, Gligorov, Joseph, Guardiola, Emmanuel, Hamizi, Salima, Jarcau, Rosana, Jacquin, Jean-Philippe, Jaubert, Dominique, Jolimoy, Geneviève, Mineur, Hortense Laharie, Largillier, Remy, Leduc, Bernard, Martin, Philippe, Melis, Adrien, Monge, Jeremy, Moullet, Isabelle, Mousseau, Mireille, Nguyen, Suzanne, Orfeuvre, Hubert, Petit, Thierry, Pivot, Xavier, Priou, Frank, Bach, Isabelle Sillet, Simon, Helene, Stefani, Laetitia, Uwer, Lionel, Youssef, Ali, Aktas, Bahriye, von der Assen, Albert, Augustin, Doris, Balser, Christina, Bauer, Lelia-Eveline, Bechtner, Christina, Beyer, Greta, Brucker, Cosima, Bückner, Ute, Busch, Steffi, Christensen, Bernd, Deryal, Mustafa, Farrokh, Andre, Faust, Elke, Friedrichs, Kay, Graf, Heiko, Griesshammer, Martin, Grischke, Eva-Maria, Hänle, Claudia, Heider, Andrea, Henschen, Stephan, Hesse, Tobias, Jackisch, Christian, Kisro, Jens, Köhler, Andreas, Kuemmel, Sherko, Lampe, Dieter, Lantzsch, Tilmann, Latos, Kunibert, Lex, Benno, Liedtke, Cornelia, Luedders, Doerte, Maintz, Christoph, Müller, Volkmar, Overkamp, Friedrich, Park-Simon, Tjoung-won, Paul, Marion, Prechtl, Anita, Ringsdorf, Uta, Runnebaum, Ingo, Ruth, Sylvia, Salat, Christoph, Scheffen, Iris, Schilling, Jörg, Schmatloch, Sabine, Schmidt, Marcus, Schneeweiss, Andreas, Schrader, Iris, Seipelt, Gernot, Simon, Elke, Stefek, Andrea, Stickeler, Elmar, Thill, Marc, Tio, Joke, Tuczek, Anna, Warm, Mathias, Weigel, Michael, Wischnik, Arthur, Wojcinski, Sebastian, Ziegler-Löhr, Katja, Aravantinos, Gerasimos, Ardavanis, Alexandros, Fountzilas, George, Gogas, Helen, Kakolyris, Stylianos, Mavroudis, Dimitris, Papadimitriou, Christos, Papandreou, Christos, Papazisis, Konstantinos, Castro, Hugo, Hernandez-Monroy, Cesar Estuardo, Ngan, Roger, Yeo, Winnie, Bittner, Nora, Boer, Katalin, Csejtei, Andras, Horvath, Zsolt, Kocsis, Judit, Mangel, László Csaba, Mezei, Klara, Nagy, Zsuzsanna, Szanto, Janos, Atmakusuma, Djumhana, Fadjari, Heri, Kurnianda, Djohan, Prayogo, Nugroho, Tanggo, Eddie Herman, Coate, Linda, Hennessy, Bryan, Kelly, Cathy, Martin, Michael, Nasim, Saira, O'Connor, Miriam, Aieta, Michele, Allegrini, Giacomo, Amadori, Dino, Bidoli, Paolo, Biti, Giampaolo, Bordonaro, Roberto, Bottini, Alberto, Carterni, Giacomo, Cavanna, Luigi, Cazzaniga, Marina, Cognetti, Francesco, Contu, Antonio, Cruciani, Giorgio, Donadio, Michela, Falcone, Alfredo, Farci, Daniele, Forcignanò, R. Chiara, Frassoldati, Antonio, Gaion, Fernando, Gamucci, Teresa, Giotta, Francesco, de Laurentiis, Michele, Livi, Lorenzo, Lorusso, Vito, Maiello, Evaristo, Marchetti, Paolo, Mariani, Gabriella, Mion, Marta, Moscetti, Luca, Musolino, Antonino, Pazzola, Antonio, Pedrazzoli, Paolo, Pigi, Andrea, de Placido, Sabino, Caremoli, Elena Rota, Santoro, Armando, Tienghi, Amelia, Ahn, Jin-Seok, Jung, Kyung Hae, Lee, Keun Seok, Lee, Soo Hyeon, Seo, Jae Hong, Sohn, Joo-Hyuk, Cesas, Alvydas, Juozaityte, Elona, Cheah, Nellie Lay Chin, Chong, Flora Li Tze, Devi, Beena C.R., Phua, Vincent, Teoh, Darren, Ching, Lee Wei, Yusof, Mastura, Corona, Jorge, Dominguez, Adriana, Mendoza, René Lazaro González, Hernandez, Carlos Alberto, Ramiro, Alejandro Juarez, Santos, Juan Matos, Espinosa, Paola Morales, Villarreal Garza, Cynthia Mayte, Errihani, Hassan, Bakker, Sandra, van den Berkmortel, Franchette, Blaisse, R.J.B., Huinink, Daan ten Bokkel, van den Bosch, J., Braun, J.J., Dercksen, M.W., Droogendijk, Helga, Erdkamp, Frans, Haringhuizen, Annebeth, de Jongh, F.E., Kok, T.C., Los, Maartje, Madretsma, Stanley, Terwogt, Jetske M. Meerum, van der Padt, Annemieke, van Rossum-Schornagel, Quirine Clementine, Smilde, T.J., de Valk, Bart, van der Velden, Annette, van Warmerdam, Laurence, van de Wouw, A.J., North, Richard, Kersten, Christian, Mjaaland, Ingvild, Wist, Erik, Aziz, Zeba, Masood, Nehal, Rashid, Kamran, Shah, Mazhar, Alcedo, Juan Carlos, Aleman, Diana, Neciosup, Silvia, Reategui, Rocio, Valdiviezo, Natalia, Vera, Luis, Fernando, Gracieux, Roque, Fernando, Strebel, Heinrik Martin, Krzemieniecki, Krzysztof, Litwiniuk, Maria, Mruk, Andrzej, Pienkowski, Tadeusz, Sawrycki, Piotr, Slomian, Grzegorz, Tomczak, Piotr, Afonso, Noemia, Cardoso, Fátima, Damasceno, Margarida, Nave, Monica, Badulescu, Florinel, Ciule, Larisa, Curescu, Stefan, Eniu, Alexandru, Filip, Dumitru, Grecea, Daniela, Jinga, Dan-Corneliu, Lungulescu, Dan, Oprean, Cristina Marinela, Stanculeanu, Dana Lucia, Turdean, Maria, Dvornichenko, Viktoria, Emelyanov, Sergey, Lichinitser, Mikhail, Manikhas, Alexey, Sakaeva, Dina, Shirinkin, Vadim, Stroyakovskiy, Daniil, Abulkhair, Omalkhair, Zekri, Jamal, Filipovic, Sladjana, Kovcin, Vladimir, Nedovic, Jasmina, Pesic, Jasna, Vasovic, Suzana, Ng, Raymond, Bystricky, Branislav, Leskova, Jaroslava, Mardiak, Jozef, Mišurová, Etela, Wagnerova, Maria, Takač, Iztok, Demetriou, Georgia Savva, Dreosti, Lydia, Govender, Poovandren, Jordaan, Johannes Petrus, Veersamy, Petrosian, Romero, Jose Luis Alonso, Lopez, Norberto Batista, Arias, Carmen Cañabate, Chacon, Jose, Aramburo, Antonio Fernandez, Morales, Luis Antonio Fernandez, Garcia, Mirta, Estevez, Laura Garcia, Garcia-Palomo Perez, Andres, Garcia Saenz, Jose Angel, Garcia Sanchis, Laura, Cubells, Laia Garrigos, Cortijo, Lucia Gonzalez, Santiago, Santiago Gonzalez, De Aranguiz, Blanca Hernando Fernandez, Mañas, José Juan Illarramendi, Gallego, Pedro Jimenez, Cussac, Antonio Llombart, Ferrandiz, Cristina Llorca, Garrido, Maria Lomas, Alvarez, Pilar Lopez, Vega, Jose Manuel Lopez, Del Prado, Purificacion Martinez, Jañez, Noelia Martinez, Murillo, Serafin Morales, Rosales, Adolfo Murias, Jaso, Laura Murillo, Fernandez, Ignacio Pelaez, Martorell, Antonia Perello, Carrion, Ramon Perez, Simon, Sonia Pernas, Alcibar, Arrate Plazaola, Lorenzo, Jose Ponce, Garcia, Vanesa Quiroga, Asensio, Teresa Ramon y Cajal, Maicas, Maria Dolores Torregrosa, Villanueva Silva, Maria Jose, Killander, Fredrika, Svensson, Jan Henry, Fehr, Mathias, Hauser, Nik, Müller, Andreas, Pagani, Olivia, Passmann-Kegel, Heike, Popescu, Razvan, Rabaglio, Manuela, Rauch, Daniel, Schlatter, Christina, Zaman, Khalil, Chang, Tsai-Wang, Huang, Chiun-Sheng, Wang, Hwei-Chung, Yu, Jyh-Cherng, Bandidwattanawong, Chanyoot, Maneechavakajorn, Jedzada, Seetalarom, Kasan, Dejthevaporn, Thitiya (Sirisinha), Somwangprasert, Areewan, Vongsaisuwon, Mawin, Akbulut, Hakan, Altundag, Kadri, Arican, Ali, Bozcuk, Hakan, Eralp, Yesim, Idris, Mohamed, Isikdogan, Abdurrahman, Senol, Coskun Hasan, Sevinc, Alper, Uygun, Kazim, Yucel, Eftal, Yucel, Idris, Yumuk, Fulden, Shparyk, Yaroslav, Voitko, Nataliia, Jaloudi, Mohammed, Adams, Jocelyn, Agrawal, Rajiv, Ahmed, Samreen, Alhasso, Abdulla, Allerton, Rozenn, Anwar, Suhail, Archer, Caroline, Ashford, Richard, Barraclough, Lisa, Bertelli, Gianfilippo, Bishop, Jill, Branson, Tony, Butt, Mohammed, Chakrabarti, Amit, Chakraborti, Prabir, Churn, Mark, Crowley, Clare, Davis, Ruth, Dhadda, Amandeep, Eldeeb, Hany, Fraser, Judith, Hall, Julia, Hickish, Tamas, Hogg, Martin, Howe, Theresa, Joffe, Jonathan, Kelleher, Muireann, Kelly, Stephen, Kendall, Anne, Kristeleit, Hartmut, Lumsden, Graeme, Macmillan, Craig, MacPherson, Iain, Malik, Zafar, Mithal, Natasha, Neal, Anthony, Panwar, Udaiveer, Proctor, Andrew, Proctor, Steven John, Raj, Sanjay, Rehman, Shazza, Sandri, Ines, Scatchard, Kate, Sherwin, Elizabeth, Sims, Eliot, Singer, Julian, Smith, Sarah, Tahir, Saad, Taylor, Wendy, Tsalic, Medy, Verrill, Mark, Wardley, Andrew, Waters, Simon, Wheatley, Duncan, Wright, Kathryn, Yuille, Frances, Alonso, Isabel, Artagaveytia, Nora, Rodriguez, Robinson, Arbona, Esther, Garcia, Yuraima, Lion, Lorena, Marcano, Dalila, Van Thuan, Tran, Gligorov, J., Ataseven, B., Verrill, M., De Laurentiis, M., Jung, K.H., Azim, H.A., Al-Sakaff, N., Lauer, S., Shing, M., and Pivot, X.

Published
2017
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16. REXO5 promotes genomic integrity through regulating R-loop using its exonuclease activity

Author

Lee, Ye Jin, Lee, Seo Yun, Kim, Soomi, Kim, Soo-Hyun, Lee, Soo Hyeon, Park, Sungho, Kim, Jae Jin, Kim, Dong-Wook, and Kim, Hongtae

Abstract

Chronic myeloid leukemia (CML), caused by BCR::ABL1 fusion gene, is known to regulate disease progression by altering the expression of genes. However, the molecular mechanisms underlying these changes are largely unknown. In this study, we identified RNA Exonuclease 5 (REXO5/LOC81691) as a novel gene with elevated mRNA expression levels in chronic myeloid leukemia (CML) patients. Additionally, using the REXO5knockout (KO) K562 cell lines, we revealed a novel role for REXO5 in the DNA damage response (DDR). Compared to wild-type (WT) cells, REXO5KO cells showed an accumulation of R-loops and increased DNA damage. We demonstrated that REXO5 translocates to sites of DNA damage through its RNA recognition motif (RRM) and selectively binds to R loops. Interestingly, we identified that REXO5 regulates R-loop levels by degrading mRNA within R-loop using its exonuclease domain. REXO5KO showed ATR-CHK1 activation. Collectively, we demonstrated that REXO5 plays a key role in the physiological control of R-loops using its exonuclease domain. These findings may provide novel insights into how REXO5expression changes contribute to CML pathogenesis.

Published
2024
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24. A protocol to inject ocular drug implants into mouse eyes

Author

Lin, Cheng-Hui, primary, Sun, Young Joo, additional, Lee, Soo Hyeon, additional, Mujica, Elena M., additional, Kunchur, Caitlin R., additional, Wu, Man-Ru, additional, Yang, Jing, additional, Jung, Youn Soo, additional, Chiang, Bryce, additional, Wang, Sui, additional, and Mahajan, Vinit B., additional

Published
2022
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32. Substrate-dependent modulation of the leukotriene A4 hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation.

Author

Lee, Kyung Hyeon, Ali, Nadia Fazal, Lee, Soo Hyeon, Zhang, Zhimin, Burdick, Marie, Beaulac, Zachary J., Petruncio, Greg, Li, Linxia, Xiang, Jiangdong, Chung, Ezra M., Foreman, Kenneth W., Noble, Schroeder M., Shim, Yun M., and Paige, Mikell

Subjects
PNEUMONIA, PEPTIDASE, X-ray crystallography, LIGAND binding (Biochemistry), PEPTIDES
Abstract

The aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Safety analysis of ex vivo‐expanded canine natural killer cells in a xenogeneic mouse model of graft‐versus‐host disease.

Author

Kim, Cheol‐Jung, Park, Se‐Cheol, Lee, Soo‐Hyeon, Lim, Yu‐Jin, Yoon, Meesun, Park, Jun‐Gyu, Baek, Yeong‐Bin, Cho, Kyoung‐Oh, Hong, Jeong Won, Shin, Dong‐Jun, and Kim, Sang‐Ki

Subjects
KILLER cells, MONONUCLEAR leukocytes, GRAFT versus host disease, LABORATORY mice, B cells, NECROSIS
Abstract

Canine natural killer (NK) cells are large, granular lymphocytes that are neither B lymphocytes nor T lymphocytes. However, it has been reported that canine NK cells share some of the phenotypic characteristics of T lymphocytes, such as CD3 and CD5. Studies are needed to assess the safety of canine NK cells for immunotherapy, especially because the safety of using allogeneic NK cells as an immunotherapy for dogs has yet to be shown. In this study, the safety of cultured canine NK cells was assessed using a xenogeneic mouse model of graft‐versus‐host disease (GVHD). Mice were injected with either canine peripheral blood mononuclear cells (PBMCs) or cultured NK cells for 2 or 3 weeks. Data were then collected on changes in mice body weights, disease severity scores, and survival rates. Histopathological and immunohistochemical evaluations were also performed. All mice injected with canine PBMCs died within 45 days after injection. Severe clinical signs were caused by GVHD. The histopathological and immunohistochemical evaluations showed that mice injected with canine PBMCs had multiple lesions, including necrosis in their lungs, livers, kidneys, and stomachs, and the injected cells were present around the lesions. By contrast, no mice injected with cultured NK cells without removing the CD3+TCR– cells exhibited any clinical abnormalities. Moreover, they all survived the 90‐day experimental period without exhibiting any histopathological changes. Accordingly, the results of this study suggest that canine NK cells do not cause significant side effects such as GVHD and allogeneic NK cells can safely be used for cancer immunotherapy in dogs. [ABSTRACT FROM AUTHOR]

Published
2022
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45. A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy

Author

Oh, Sooyeon, primary, Park, YoungJoon, additional, Lee, Hyun-Jung, additional, Lee, Jooho, additional, Lee, Soo-Hyeon, additional, Baek, Young-Seok, additional, Chun, Su-Kyung, additional, Lee, Seung-Min, additional, Kim, Mina, additional, Chon, Young-Eun, additional, Ha, Yeonjung, additional, Cho, Yuri, additional, Kim, Gi Jin, additional, Hwang, Seong-Gyu, additional, and Kwack, KyuBum, additional

Published
2020
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