Article
Pharmacology & Pharmacy
Yunzhou Fan, Haoxun Wang, Zhou Yu, Zhengxuan Liang, Yufan Li, Guofeng You
Summary: Organic anion transporter 3 (OAT3) is a crucial transporter in the kidney proximal tubules that plays a key role in the systemic clearance of various substances. This study found that inhibiting the proteasome, but not the lysosome, increased the ubiquitination and transport activity of OAT3. Two anticancer drugs, bortezomib and carfilzomib, were used to further investigate the role of proteasome inhibition in OAT3 regulation. The results showed that inhibiting the proteasome enhanced OAT3 function by increasing its surface expression and transport activity. In vivo studies in rats confirmed these findings. These findings suggest that the proteasome could be a potential target for regulating OAT3 and could be used to treat OAT3-related conditions and ensure drug efficacy and safety.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ladislav Sivak, Vladimir Subr, Jirina Kovarova, Barbora Dvorakova, Milada Sirova, Blanka Sihova, Eva Randarova, Michal Kraus, Jakub Tomala, Martin Studenovsky, Michaela Vondrackova, Radislav Sedlacek, Petr Makovicky, Jitka Fucikova, Sarka Vosahlikova, Radek Spisek, Libor Kostka, Tomas Etrych, Marek Kovar
Summary: Repurposing drug strategy using P-RD nanomedicine has successfully identified the anticancer effects of RD on cancer cells, which has been validated in mice experiments and human cancer cell lines, making it a promising therapeutic candidate with great potential for deep preclinical investigation.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Merry Gunawan, Choonbing Low, Kurt Neo, Siawey Yeo, Candice Ho, Veluchamy A. Barathi, Anita Sookyee Chan, Najam A. Sharif, Masaaki Kageyama
Summary: This study showed that autophagy may not be an effective intrinsic protective mechanism for retinal damage induced by insults, including impaired proteasomal activity. Activation of autophagy beyond normal levels is required to alleviate the cytotoxic effect of proteasomal inhibition, suggesting the need for further research on the precise roles of different forms of autophagy in rescuing retinal neurons under various pathological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Surgery
Amy P. Rossi, Simon Tremblay, Cyd M. Castro-Rojas, Ashley A. Burg, Krishna M. Roskin, Jenna M. Gehman, Adele Rike-Shields, Rita R. Alloway, Paul Brailey, David Allman, David A. Hildeman, E. Steve Woodle
Summary: This study suggests that the limited effectiveness of plasma cell-targeted therapies may be due to the protective bone marrow microenvironments. The CXCR4 antagonist, plerixafor, has shown potential in altering plasma cell residence in the bone marrow, thereby enhancing treatment outcomes. The study also explores the transcriptional effects of plerixafor in combination with the proteasome inhibitor, bortezomib, in HLA-sensitized kidney transplant candidates.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Toxicology
Gregory Hamm, Gareth Maglennon, Beth Williamson, Ruth Macdonald, Ann Doherty, Stewart Jones, Jayne Harris, James Blades, Alexander R. Harmer, Peter Barton, Philip B. Rawlins, Paul Smith, Jon Winter-Holt, Lindsay McMurray, Julia Johansson, Paul Fitzpatrick, William McCoull, Muireann Coen
Summary: The study evaluated the in vivo effects of pharmacological inhibition of MERTK in mice, demonstrating potential toxic effects on the retina. These findings suggest that MERTK inhibitors may result in retinal damage.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emily M. Huntsman, Rachel M. Cho, Helen V. Kogan, Nora K. McNamara-Bordewick, Robert J. Tomko, Jonathan W. Snow
Summary: Nosema ceranae, a microsporidian parasite, is sensitive to pharmacological disruption of proteasome function, making proteasome inhibition a potential novel treatment strategy for infection in honey bees.
Article
Chemistry, Medicinal
Yusaku Sadahiro, Yuki Hitora, Ichiro Kimura, Natsuko Hitora-Imamura, Risako Onodera, Keiichi Motoyama, Sachiko Tsukamoto
Summary: Mutant p53 loses its tumor suppressor function and gains new abilities for oncogenic progression. A compound called CF isolated from a fungus was found to decrease mutant p53 levels and inhibit tumor cell growth.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vasudha Tandon, Rita Moreno, Kira Allmeroth, Jean Quinn, Sandra E. Wiley, Lynden G. Nicely, Martin S. Denzel, Joanne Edwards, Laureano de la Vega, Sourav Banerjee
Summary: Preserving proteostasis is a crucial survival mechanism for cancer, and targeting the kinase DYRK2 and its substrate HSF1 can induce apoptosis faster than individual targeting. This study suggests that cotargeting DYRK2 and HSF1 could be a promising strategy in suppressing cancer.
BIOSCIENCE REPORTS
(2023)
Article
Cell Biology
Mala Rao, Sandipkumar Darji, Philip H. Stavrides, Chris N. Goulbourne, Asok Kumar, Dun-Sheng Yang, Lang Yoo, James Peddy, Ju-Hyun Lee, Aidong Yuan, Ralph A. Nixon
Summary: This study reveals the important role of autophagy in the degradation of neurofilament proteins in neurons, which may regulate the size of axon cytoskeleton and the responses of the neurofilament cytoskeleton to injury and disease.
Article
Biochemistry & Molecular Biology
Hong-Jae Lee, Dong-Min Lee, Min-Ji Seo, Ho-Chul Kang, Seok-Kyu Kwon, Kyeong-Sook Choi
Summary: PSMD14 is a potential prognostic marker and therapeutic target in cancer, and inducing paraptosis by targeting PSMD14 could overcome resistance to proteasome inhibitors or pro-apoptotic drugs in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Jinkyung Kim, Anthony J. Ricci
Summary: This study tracks the entry and targeting process of a commonly used antibiotic, aminoglycosides (AGs), in the cochlea. The authors found that AGs enter the cochlea through the stria vascularis and selectively target cochlear sensory hair cells (HCs). They also identified the mechanotransducer channel and megalin as key factors in AG uptake. Blocking megalin prevented AG accumulation in HCs and reduced HC degeneration and hearing loss.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Ruiyi Yuan, Younghee Hahn, Max H. Stempel, David K. Sidibe, Olivia Laxton, Jessica Chen, Aditi Kulkarni, Sandra Maday
Summary: Neurons and astrocytes have unique requirements for quality control pathways, such as autophagy and the UPS, to maintain proper function and survival. This study investigated the relationship between autophagy and the proteasome in primary astrocytes and neurons, and found that proteasome inhibition did not robustly upregulate autophagy. Instead, astrocytes formed Ub-positive aggregates in response to UPS inhibition, but these structures were not efficiently degraded by autophagy. Additionally, neurons were more vulnerable to proteotoxic stress compared to astrocytes.
Article
Agriculture, Dairy & Animal Science
Jiaxin Bao, Zhiyong Wu, Muhammad Ishfaq, Jian Wang, Yusong Miao, Dong Niu, Rui Li, Jichang Li, Chunli Chen
Summary: This study aimed to determine the relationship between the PK/PD index and efficacy of baicalin in the M. gallisepticum infection model in chickens. The results showed that baicalin concentration in lung tissues was higher than in plasma, and its ratios of AUC(24h)/MIC against bacteriostatic, bactericidal, and eradication were 0.62, 1.33, and 1.49 h, respectively. These findings provide potential reference for future clinical dose selection and evaluation of susceptibility breakpoints.
Article
Cardiac & Cardiovascular Systems
Nikolaos Makris, Georgios Georgiopoulos, Aggeliki Laina, Maria-Eirini Tselegkidi, Despoina Fotiou, Nikolaos Kanellias, Evaggelos Eleftherakis-Papaiakovou, Magda Migkou, Eleni Dimitra Papanagnou, Konstantinos Katogiannis, Ioannis Petropoulos, Hector Anninos, Dimitrios Bampatsias, Eleni Maneta, Elisabeth Samouilidou, Dimitris Nikas, Giorgia Ciliberti, Konstantinos Stellos, Evaggelos Terpos, Maria Gavriatopoulou, Ioannis P. Trougakos, Ignatios Ikonomidis, Meletios-Athanasios Dimopoulos, Efstathios Kastritis, Kimon Stamatelopoulos
Summary: This study aimed to investigate the effect of proteasome inhibition on myocardial mechanics and found that inhibition of the ubiquitin-proteasome system led to global deterioration of cardiac function, which was also associated with cardiotoxicity.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2023)
Article
Hematology
Oriana Miltiadous, Kseniya Petrova-Drus, Shipra Kaicker, Susan Mathew, Michael Kluk, Julia T. Geyer, Irene Rodriguez-Sanchez, Nancy Bouvier, Giorgio Inghirami, Elliot Stieglitz, Nafa Khedoudja, Ryma Benayed, Michelle Richardson, Wade Anderson, Jamal Benhamida, Daoqi You, Dory Londono, Andrew L. Kung, Susan E. Prockop, Mikhail Roshal, Yanming Zhang, Neerav Shukla
Summary: FIP1L1-RARA-associated neoplasm is a rare and aggressive disease. This study presents a pediatric case with successful long-term outcome using a combination of chemotherapy, differentiating agents, and allogeneic hematopoietic stem cell transplant.
Article
Oncology
Barbara Spitzer, Kayleigh D. Rutherford, Gunes Gundem, Erin M. McGovern, Nathan E. Millard, Juan E. Arango Ossa, Irene Y. Cheung, Teng Gao, Max F. Levine, Yanming Zhang, Juan S. Medina-Martinez, Yi Feng, Ryan N. Ptashkin, Kelly L. Bolton, Noushin Farnoud, Yangyu Zhou, Minal A. Patel, Georgios Asimomitis, Cassidy C. Cobbs, Neeman Mohibullah, Kety H. Huberman, Maria E. Arcilla, Brian H. Kushner, Shakeel Modak, Andrew L. Kung, Ahmet Zehir, Ross L. Levine, Scott A. Armstrong, Nai Kong Cheung, Elli Papaemmanuil
Summary: This study aimed to explore the relationship between the development of t-MDS/AL and molecular abnormalities in pediatric patients with high-risk neuroblastoma. The study found that at least one disease-defining alteration was detected in all cases at t-MDS/AL diagnosis, with TP53 gene mutations and KMT2A gene rearrangements being the most common. Compared to the transient and control groups, t-MDS/AL patients had acquired mutations at an earlier stage before the onset of the disease. Additionally, the study revealed that only a small number of pediatric patients with solid tumors had clonal hematopoiesis involving myeloid genes.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Andrew D. Woods, Noah E. Berlow, Michael Ortiz, Filemon Dela Cruz, Armaan Siddiquee, Diego F. Coutinho, Reshma Purohit, Katherine E. Tranbarger Freier, Joel E. Michalek, Melvin Lathara, Kevin Matlock, Ganapati Srivivasa, Brigitte Royer-Pokora, Renata Veselska, Andrew L. Kung, Charles Keller
Summary: In this study, it was found that MYCN overexpression can be reduced by inhibiting BRD4, leading to growth suppression in Wilms tumor cells and reduced tumor volumes in mouse models. These findings provide a new therapeutic strategy for treating Wilms tumor.
PEDIATRIC BLOOD & CANCER
(2022)
Review
Cardiac & Cardiovascular Systems
Thiago L. Scudeler, Lucas C. Godoy, Tedi Hoxha, Andrew Kung, Pedro R. Moreno, Michael E. Farkouh
Summary: In patients with diabetes mellitus and acute coronary syndrome, coronary artery bypass graft surgery has been shown to be superior to percutaneous coronary intervention in long-term follow-up. PCI remains the most frequently performed procedure in ACS patients, but CABG may be preferred in certain cases.
CURRENT CARDIOLOGY REPORTS
(2022)
Article
Hematology
Madhavi Lakkaraja, Michael Scordo, Audrey Mauguen, Christina Cho, Sean Devlin, Josel D. Ruiz, Elizabeth Klein, Scott T. Avecilla, Farid Boulad, Maria Cancio, Kevin J. Curran, Ann A. Jakubowski, Nancy A. Kernan, Andrew L. Kung, Richard J. O'Reilly, Esperanza B. Papadopoulos, Susan Prockop, Ichelle van Roessel, Andromachi Scaradavou, Brian C. Shaffer, Gunjan Shah, Barbara Spitzer, Roni Tamari, Sergio A. Giralt, Miguel-Angel Perales, Jaap Jan Boelens
Summary: The traditional weight-based dosing in rabbit antithymocyte globulin (rATG) treatment leads to variable clearance and higher mortality. A personalized pharmacokinetic-guided rATG dosing strategy can improve patient survival.
Article
Multidisciplinary Sciences
N. Shukla, M. F. Levine, G. Gundem, D. Domenico, B. Spitzer, N. Bouvier, J. E. Arango-Ossa, D. Glodzik, J. S. Medina-Martinez, U. Bhanot, J. Gutierrez-Abril, Y. Zhou, E. Fiala, E. Stockfisch, S. Li, M. Rodriguez-Sanchez, T. O'Donohue, C. Cobbs, M. H. A. Roehrl, J. Benhamida, F. Iglesias Cardenas, M. Ortiz, M. Kinnaman, S. Roberts, M. Ladanyi, S. Modak, S. Farouk-Sait, E. Slotkin, M. A. Karajannis, F. Dela Cruz, J. Glade Bender, A. Zehir, A. Viale, M. F. Walsh, A. L. Kung, E. Papaemmanuil
Summary: The authors developed a workflow to deliver comprehensive cWGTS results within clinically-relevant timeframes. Compared to other diagnostic methods, cWGTS has the potential to capture all clinically reported mutations with comparable sensitivity. These findings provide important technical considerations for implementing cWGTS in clinical oncology.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Gunes Gundem, Max F. Levine, Stephen S. Roberts, Irene Y. Cheung, Juan S. Medina-Martinez, Yi Feng, Juan E. Arango-Ossa, Loic Chadoutaud, Mathieu Rita, Georgios Asimomitis, Joe Zhou, Daoqi You, Nancy Bouvier, Barbara Spitzer, David B. Solit, Filemon Dela Cruz, Michael P. LaQuaglia, Brian H. Kushner, Shakeel Modak, Neerav Shukla, Christine A. Iacobuzio-Donahue, Andrew L. Kung, Nai-Kong V. Cheung, Elli Papaemmanuil
Summary: Patients with high-risk neuroblastoma often experience widely metastatic disease and relapse despite intensive therapy. Understanding the genetic and clonal dynamics of metastatic spread and disease progression has been limited. In this study, genomic profiling of sequential and spatially separated samples from 283 patients revealed subtype-specific genetic evolutionary trajectories and the clonal dynamics of metastases. Convergent evolution of mutations targeting shared pathways emerged as a predominant feature of disease progression.
Article
Oncology
Prabhjot S. Mundi, Filemon S. Dela Cruz, Adina Grunn, Daniel Diolaiti, Audrey Mauguen, Allison R. Rainey, Kristina Guillan, Armaan Siddiquee, Daoqi You, Ronald Realubit, Charles Karan, Michael Ortiz, Eugene F. Douglass, Melissa Accordino, Suzanne Mistretta, Frances Brogan, Jeffrey N. Bruce, Cristina I. Caescu, Richard D. Carvajal, Katherine D. Crew, Guarionex Decastro, Mark Heaney, Brian S. Henick, Dawn L. Hershman, June Y. Hou, Fabio M. Iwamoto, Joseph G. Jurcic, Ravi P. Kiran, Michael D. Kluger, Teri Kreisl, Nicole Lamanna, Andrew B. Lassman, Emerson A. Lim, Gulam A. Manji, Guy M. McKhann, James M. McKiernan, Alfred I. Neugut, Kenneth P. Olive, Todd Rosenblat Rosenblatsenblat, Gary K. Schwartz, Catherine A. Shu, Michael B. Sisti, Ana Tergas, Reena M. Vattakalam, Mary Welch, Sven Wenske, Jason D. Wright, Peter Canoll, Hanina Hibshoosh, Kevin Kalinsky, Mahalaxmi Aburi, Peter A. Sims, Mariano J. Alvarez, Andrew L. Kung, Andrea Califano
Summary: We evaluated two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to oncology drugs. The predicted drugs showed significantly higher disease control rates compared to unpredicted controls, suggesting these methods have potential for complementing existing precision cancer medicine approaches. This study introduces scalable systems biology tools for predicting drug response in vivo.
Letter
Allergy
Binni Kunvarjee, Alan Bidgoli, Rebecca Pellett Madan, Esther Vidal, Devin McAvoy, Kinga K. Hosszu, Andromachi Scaradavou, Barbara G. Spitzer, Kevin J. Curran, Maria Cancio, Andrew C. Harris, Richard J. O'Reilly, Andrew L. Kung, Susan Prockop, Jaap Jan Boelens, Joseph H. Oved
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Hematology
Roni Tamari, Michael Scordo, Binni M. Kunvarjee, Anthony Proli, Andrew Lin, Jessica Flynn, Christina Cho, Sean Devlin, Elizabeth Klein, Farid Boulad, Maria I. Cancio, Kevin J. Curran, Ann A. Jakubowski, Nancy A. Kernan, Andrew L. Kung, Richard J. O'Reilly, Esperanza B. Papadopoulos, Susan Prockop, Andromachi Scaradavou, Brian C. Shaffer, Gunjan Shah, Barbara Spitzer, Boglarka Gyurkocza, Sergio A. Giralt, Miguel-Angel Perales, Jaap Jan Boelens
Summary: This study retrospectively analyzed the pharmacokinetic exposure of busulfan in T-cell depleted (TCD) allo-HCT and found a significant association with 5-year overall survival. Optimizing the exposure using a published population pharmacokinetic model may significantly improve survival outcomes.
Meeting Abstract
Oncology
Somnath Tagore, Jovana Pavisic, Aaron T. Griffin, Katherine Janeway, Andrew L. Kung, Filemon Dela Cruz, Alejandro Sweet-Cordero, Inge Behroozfard, Stanley Leung, Alex Lee, Darrell Yamashiro, Julia Glade Bender, Andrea Califano
Meeting Abstract
Oncology
Filemon S. Dela Cruz, Joseph G. McCarter, Daoqi You, Nancy Bouvier, Xinyi Wang, Kristina C. Guillan, Armaan H. Siddiquee, Katie B. Souto, Hongyan Li, Teng Gao, Dominik Glodzik, Daniel Diolaiti, Neerav N. Shukla, Joachim Silber, Umeshkumar K. Bhanot, Faruk Erdem Kombak, Diego F. Coutinho, Shanita Li, Juan E. Arango Ossa, Juan S. Medina-Martinez, Michael V. Ortiz, Emily K. Slotkin, Michael D. Kinnaman, Sameer F. Sait, Tara J. O'Donohue, Marissa Mattar, Maximiliano Meneses, Michael P. LaQuaglia, Todd E. Heaton, Justin T. Gerstle, Nicola Fabbri, Chelsey M. Burke, Irene M. Rodriquez-Sanchez, Christine A. Iacobuzio-Donahue, Julia L. Glade Bender, Ryan D. Roberts, Jason T. Yustein, Nino C. Rainusso, Brian D. Crompton, Elizabeth Stewart, Alejandro Sweet-Cordero, Leanne C. Sayles, Andrika D. Thomas, Michael H. Roehrl, Elisa de Stanchina, Elli Papaemmanuil, Andrew L. Kung
Meeting Abstract
Oncology
Diego F. Coutinho, Chelsey Burke, Prabhjot Mundi, Michael V. Ortiz, Kelly L. Vallance, Matthew Long, Nestor Rosales, Glorymar Ibanez, Lianna J. Marks, Daniel Diolaiti, Andoyo Ndengu, Daoqi You, Armaan Siddiquee, Ervin S. Gaviria, Allison R. Rainey, Andrea Califano, Andrew L. Kung, Filemon S. Dela Cruz
Article
Medicine, Research & Experimental
Diego F. Coutinho, Prabhjot S. Mundi, Lianna J. Marks, Chelsey Burke, Michael V. Ortiz, Daniel Diolaiti, Lauren Bird, Kelly L. Vallance, Glorymar Ibanez, Daoqi You, Matthew Long, Nestor Rosales, Adina Grunn, Andoyo Ndengu, Armaan Siddiquee, Ervin S. Gaviria, Allison R. Rainey, Ladan Fazlollahi, Hajime Hosoi, Andrea Califano, Andrew L. Kung, Filemon S. Dela Cruz
Summary: This study identified elevated activity of exportin 1 (XPO1) in malignant rhabdoid tumors and Wilms' tumors and demonstrated the inhibitory effects of XPO1 inhibitor selinexor on tumor growth in vitro and in vivo.
Meeting Abstract
Oncology
Michael David Kinnaman, Simone Zaccaria, Alvin Makohon-Moore, Gunes Gundem, Juan E. Arango Ossa, Nancy Bouvier, Filemon S. Dela Cruz, Meera Hameed, Julia Lynne Glade Bender, William D. Tap, Paul A. Meyers, Elli Papaemmanuil, Andrew Kung, Christine A. Iacobuzio-Donahue
JOURNAL OF CLINICAL ONCOLOGY
(2022)