Article
Chemistry, Multidisciplinary
Benjamin Neuditschko, A. Paden King, Zhouyang Huang, Lukas Janker, Andrea Bileck, Yasmin Borutzki, Sierra C. Marker, Christopher Gerner, Justin J. Wilson, Samuel M. Meier-Menches
Summary: This study presents an improved approach for prioritizing candidate protein targets in inorganic drug discovery. It identifies TRIP as a first-in-class modulator of the scaffold protein NUBP2, disrupting Fe-S cluster biogenesis at sub-cytotoxic concentrations in ovarian cancer cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Medicine, Research & Experimental
Nathalia D. de Moura Sperotto, Rodrigo Braccini Madeira Silva, Marcia Alberton Perello, Ana Flavia Borsoi, Adilio da Silva Dadda, Candida Deves Roth, Raquel Dal Sasso Freitas, Ana Paula Duarte de Souza, Deise do Nascimento de Freitas, Jaqueline Nascimento Picada, Jayne Torres de Sousa, Debora Dreher Nabinger, Stefani Altenhofen, Carla Denise Bonan, Valnes S. Rodrigues-Junior, Cristiano Valim Bizarro, Luiz Augusto Basso, Pablo Machado
Summary: The study investigated the effects of the hTP inhibitor CPBMF-223 in a xenograft tumor model induced by human colorectal carcinoma cells, showing significant inhibition of tumor growth, reduction in vessel number, and decrease in cell migration. Additionally, CPBMF-223 demonstrated a favorable toxicity profile and pharmacokinetic characteristics, highlighting its potential as a promising drug candidate for colorectal cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Tatiana Hernandez Guerrero, Natalia Banos, Laura del Puerto Nevado, Ignacio Mahillo-Fernandez, Bernard Doger De-Speville, Emiliano Calvo, Michael Wick, Jesus Garcia-Foncillas, Victor Moreno
Summary: This study aimed to determine the factors that may predict better engraftment rates in patient-derived xenografts (PDXs). The use of systemic antibiotics and steroids by patients prior to sampling were found to impact the likelihood of success in PDX development. Furthermore, certain clinical, pathological, and molecular factors such as lactate dehydrogenase levels, grade of differentiation, Ki67 levels, presence of lymphovascular invasion, and mismatch repair status were correlated with engraftment success in PDXs.
Article
Pharmacology & Pharmacy
Javad Garousi, Tianqi Xu, Yongsheng Liu, Olga Vorontsova, Sophia Hober, Anna Orlova, Vladimir Tolmachev, Torbjorn Graslund, Anzhelika Vorobyeva
Summary: The developed drug conjugate, ADAPT6-ABD-mcDM1, showed significant therapeutic efficacy in mice bearing HER2-expressing ovarian cancer xenografts by delaying tumor growth and increasing median survival without inducing toxicity. The evaluation of imaging probes demonstrated the suitability of small scaffold proteins as diagnostic companions for potential therapy stratification.
Article
Oncology
F. Guffanti, M. F. Alvisi, A. Anastasia, F. Ricci, M. Chiappa, A. Llop-Guevara, V Serra, R. Fruscio, A. Degasperi, S. Nik-Zainal, M. R. Bani, M. Lupia, R. Giavazzi, E. Rulli, G. Damia
Summary: This study demonstrates that the RAD51 foci score can predict the response to olaparib in ovarian cancer patients, providing a simple and feasible biomarker for clinical application. Furthermore, the findings emphasize the importance of ovarian cancer patient-derived xenografts (PDXs) as a reliable tool for identifying and validating biomarkers of response to therapy.
BRITISH JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Hanlin Lu, Peidong Yuan, Xiaoping Ma, Xiuxin Jiang, Shaozhuang Liu, Chang Ma, Sjaak Philipsen, Qunye Zhang, Jianmin Yang, Feng Xu, Cheng Zhang, Yun Zhang, Wencheng Zhang
Summary: ACE inhibitors are commonly used to treat cardiovascular diseases and promote angiogenesis. This study reveals that endothelial USP7-Sp1/Sp3-Notch1 signaling plays a central role in pathophysiological angiogenesis in response to ACE inhibitor treatment.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
E. Fang, He Zhang, Wanli Yin, Chongyang Wang, Yuanli Liu, Yanze Li, Linlin Wang, Yue Wu, Runze Zhang, Chendan Zou, Tianjun Song, Cedric Matunda, Chaoxia Zou, Xu Gao
Summary: This study reveals the essential role of CPEB3 in ovarian follicle development and female fertility, as it regulates the expression of Gdf9 in oocytes. Cpeb3-mutant mice exhibit a phenotype similar to POI, providing new insights for the understanding and treatment of POI.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Chantale Farah, Marie-Aline Neveu, Caroline Bouzin, Zorica Knezevic, Bernard Gallez, Eleonora Leucci, Jean-Francois Baurain, Lionel Mignion, Benedicte F. Jordan
Summary: There is currently a lack of consensus in determining the beneficial patients for immunotherapy in advanced melanoma, thus necessitating the identification of early-response biomarkers. This study aimed to evaluate the use of in vivo metabolic spectroscopy with HP C-13-pyruvate and C-13-glucose in assessing the early response to anti-PD1 therapy in a melanoma model. The results suggest that hyperpolarized C-13-pyruvate could be used as an early response marker for immune checkpoint inhibitors in melanoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Magdalena Cybula, Lin Wang, Luyao Wang, Ana Luiza Drumond-Bock, Katherine M. Moxley, Doris M. Benbrook, Camille Gunderson-Jackson, Maria J. Ruiz-Echevarria, Resham Bhattacharya, Priyabrata Mukherjee, Magdalena Bieniasz
Summary: Patient-derived xenografts (PDXs) have been shown to faithfully recapitulate patients' tumors and therapeutic responses, with minimal genetic drift during passages in mice. These models hold potential clinical applications and can serve as valuable pre-clinical tools for translational research.
Article
Multidisciplinary Sciences
Alicia Traughber, Gauravi M. Deshpande, Kalash Neupane, Nilam Bhandari, Mariam R. Khan, Megan R. McMullen, Shadi Swaidani, Emmanuel Opoku, Santoshi Muppala, Jonathan D. Smith, Laura E. Nagy, Kailash Gulshan
Summary: The roles of NLRP3, AIM2 inflammasomes, and Gasdermin D (GsdmD) in lung cancer progression are unclear. Using a metastatic LLC cell model, this study found that GsdmD knockout mice exhibited significantly fewer lung cancer foci, decreased metastasis, and increased median survival rate. GsdmD and IL-1 beta were detected in lung tumor tissue, indicating inflammasome activity. Conditioned media from wild-type macrophages enhanced migration and growth of LLC cells, while GsdmD(-/-) macrophages did not. Bone marrow transplantations confirmed the myeloid-specific role of GsdmD in lung cancer metastasis.
Article
Nanoscience & Nanotechnology
Jia Ouyang, Yu Jiang, Chao Deng, Zhiyuan Zhong, Qing Lan
Summary: The study demonstrated that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice, effectively inhibiting glioblastoma invasion with minimal side effects.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Multidisciplinary Sciences
Bridget S. Gosis, Shogo Wada, Chelsea Thorsheim, Kristina Li, Sunhee Jung, Joshua H. Rhoades, Yifan Yang, Jeffrey Brandimarto, Li Li, Kahealani Uehara, Cholsoon Jang, Matthew Lanza, Nathan B. Sanford, Marc R. Bornstein, Sunhye Jeong, Paul M. Titchenell, Sudha B. Biddinger, Zoltan Arany
Summary: Selective inhibition of mTORC1 signaling in mice promotes activation of transcription factor E3 (TFE3) in the liver, protecting against NAFLD and NASH. TFE3 induces lipid consumption and suppresses anabolic lipogenesis, inhibiting lipogenesis by interacting with SREBP-1c on chromatin.
Article
Multidisciplinary Sciences
Anne Rodallec, Cristina Vaghi, Joseph Ciccolini, Raphaelle Fanciullino, Sebastien Benzekry
Summary: This study identified the most accurate formula for estimating tumor volume in xenografted mice with human breast cancer cells. The formula 1/6 π x L x W x (L + W)/2 is recommended for tumors under 1500mm(3).
Article
Medicine, Research & Experimental
Yuyi Wang, Ombretta Salvucci, Hidetaka Ohnuki, Andy D. Tran, Taekyu Ha, Jing-Xin Feng, Michael DiPrima, Hyeongil Kwak, Dunrui Wang, Yanlin Yu, Michael Kruhlak, Giovanna Tosato
Summary: SHP2 is essential for promoting endothelial cell survival and growth in tumor vasculature remodeling. Inhibiting SHP2 activity leads to reduced tumor growth and degeneration of tumor vasculature. Combination of SHP2 inhibitors with Ang2/TIE2 inhibitors shows promise in effectively targeting the tumor endothelium.
EMBO MOLECULAR MEDICINE
(2021)
Article
Dermatology
Gagan Chhabra, Chandra K. Singh, Glorimar Guzman-Perez, Mary A. Ndiaye, Kenneth A. Iczkowski, Nihal Ahmad
Summary: In this study, the antimelanoma efficacy of 4'-bromo-resveratrol (4'-BR) was demonstrated in a mouse model of metastatic melanoma. The treatment significantly reduced the size and volume of primary melanoma tumors, as well as lung metastasis. Mechanistic studies showed modulation in markers of proliferation, survival, and melanoma progression. The treatment also downregulated genes related to metastasis promotion, chemokine/cytokine regulation, and immune functions.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Chemistry, Inorganic & Nuclear
Joshua J. Woods, Jesse A. Spivey, Justin J. Wilson
Summary: The synthesis and characterization of the N-15-labeled analogue of the mitochondrial calcium uptake inhibitor Ru265 was reported. The reactivity of Ru265 towards biologically relevant small molecules was assessed, revealing its ability to form coordination bonds. Time-based studies suggest that hydrogen-bonding interactions may play a more significant role in mediating the inhibitory properties of this complex.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Joshua J. Woods, Ryan Unnerstall, Abbie Hasson, Diane S. Abou, Valery Radchenko, Daniel L. J. Thorek, Justin J. Wilson
Summary: This study investigated four equatorial-spanning ligands as uranium chelators. The results showed that the complexes formed by these ligands with UO22+ were highly stable and exhibited good stability in vivo. The hox ligand demonstrated higher thermodynamic stability, likely due to its lower strain energy. The ligands remained >95% stable in human plasma and >80% intact in the presence of hydroxyapatite (HAP). In vivo experiments in mice showed that the uranium complexes of these ligands did not accumulate in the skeletal system. Overall, these equatorial-spanning ligands hold great promise for 230U TAT.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Aohan Hu, Victoria Brown, Samantha N. MacMillan, Valery Radchenko, Hua Yang, Luke Wharton, Caterina F. Ramogida, Justin J. Wilson
Summary: The study evaluated two 18-membered macrocyclic chelators for their ability to complex Ac-225(3+) and Bi-213(3+), with py-macrodipa showing efficient incorporation of both radionuclides that may surpass well-known chelators. The Bi3+-py-macrodipa complex demonstrated remarkable kinetic inertness, highlighting its potential in targeted alpha therapy.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chilaluck Konkankit, S. Rackovsky
Summary: This study compares the sequences of folded and intrinsically disordered proteins and finds that they have opposite long-length-scale dynamic properties. The results suggest that the long-length-scale properties are crucial in protein folding and contribute to the understanding of protein physics.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Review
Chemistry, Multidisciplinary
Aohan Hu, Justin J. Wilson
Summary: This article provides an overview of recent advances in the development of ligands for large radiometal chelation in nuclear medicine. It discusses the coordination chemistry, radiolabeling properties, and covalent conjugation to biological targeting vectors of ligands such as macropa and macrodipa. The article also highlights the importance of ligand design for novel emerging radiometal ions with unusual coordination chemistry properties.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Zhouyang Huang, Samantha N. N. MacMillan, Justin J. J. Wilson
Summary: In this study, a new fluorogenic mitochondrial calcium uniporter (MCU) inhibitor, RuOCou, is introduced. This compound exhibits both increased MCU-inhibitory activity and fluorescence intensity after aquation. By monitoring its fluorescence response, the aquation of RuOCou can be observed in HeLa cell lysates and live HeLa cells. This fluorogenic prodrug shows potential as a theranostic MCU inhibitor for the treatment of human diseases associated with MCU activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Nicholas P. Bigham, Justin J. Wilson
Summary: This study evaluated the inhibitory effects of six Co3+ cage compounds with sarcophagine-like ligands on mitochondrial Ca2+ uptake mediated by the mitochondrial calcium uniporter (MCU). Among them, [Co(sen)](3+) showed potent MCU inhibitor activity, with IC50 values of 160 and 180 nM in permeabilized HeLa and HEK293T cells, respectively. Moreover, compound 3 moderately accumulated in cells and operated as an MCU inhibitor in intact cells. This work demonstrates the potential of using cobalt coordination complexes as MCU inhibitors.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Zhouyang Huang, Jesse A. A. Spivey, Samantha N. N. MacMillan, Justin J. J. Wilson
Summary: This study reports two potent inhibitors of the mitochondrial calcium uniporter, RuOFc and RuOBz, which could be used as tools to study the role of mCa(2+) uptake on cellular function. RuOFc exhibits higher cellular uptake but also higher cytotoxicity, potentially making it a promising anticancer agent targeting the MCU.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Joshua J. Woods, Robyn J. Novorolsky, Nicholas P. Bigham, George S. Robertson, Justin J. Wilson
Summary: This study reports the synthesis and characterization of Os245 and its aqua-capped analogue Os245' as effective inhibitors of MCU. The inhibition of MCU by these complexes protects neurons against lethal oxygen-glucose deprivation and induces seizure-like behaviors in mice.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Zhouyang Huang, Justin J. Wilson
Summary: The mitochondrial calcium uniporter (MCU) is a transmembrane protein responsible for mediating mitochondrial calcium uptake and has been identified as a potential target for treating various human diseases. Metal coordination complexes, particularly multinuclear ruthenium complexes, have been extensively studied as MCU inhibitors due to their potent inhibitory activities and established use. Recent research has expanded the metal-based toolkit for MCU inhibition. This concept paper summarizes the development of new metal-based inhibitors and their structure-activity relationships in improving therapeutic potential for managing human diseases related to calcium dysregulation in mitochondria.
Article
Radiology, Nuclear Medicine & Medical Imaging
Stanley Fayn, A. Paden King, Nicholas T. Gutsche, Zhijian Duan, Jesse Buffington, Colleen P. Olkowski, Ying Fu, Jessica Hong, Deepak Sail, Kwamena E. Baidoo, Rolf E. Swenson, Ross W. Cheloha, Mitchell Ho, Peter L. Choyke, Freddy E. Escorcia
Summary: Primary liver cancer, particularly hepatocellular carcinoma (HCC), is a major cause of cancer-related deaths globally. Glypican-3 (GPC3) has been identified as a specific marker for HCC and holds potential for radiopharmaceutical imaging and therapy. In this study, we engineered GPC3-specific single-domain antibodies as PET probes using both conventional and site-specific conjugation methods. The results demonstrated that the site-specific conjugate showed more favorable biodistribution and pharmacokinetic properties, making it a promising candidate for PET imaging of GPC3-positive liver cancers.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Review
Chemistry, Multidisciplinary
Nicholas P. Bigham, Justin J. Wilson
Summary: Ischemia-reperfusion injury (IRI) is a significant factor in the mortality rates of heart disease and stroke patients, leading to cell damage and death after blood and oxygen are restored to ischemic or hypoxic tissue. Current therapeutic options for IRI are limited, but metal-containing coordination and organometallic complexes show potential in treating this condition by delivering gasotransmitters, inhibiting mCa2+ uptake, and decomposing ROS. Inorganic chemistry approaches offer opportunities and challenges for managing IRI.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Inorganic & Nuclear
Aohan Hu, Kirsten E. Martin, Dariusz Smilowicz, Eduardo Aluicio-Sarduy, Shelbie J. Cingoranelli, Suzanne E. Lapi, Jonathan W. Engle, Eszter Boros, Justin J. Wilson
Summary: This study describes the synthesis of a bifunctional chelator, py-macrodipa-NCS, and its conjugation to a prostate-specific membrane antigen (PSMA)-binding moiety for radiolabeling complex preparation. In vivo experiments using mice showed that the resulting complex effectively delivered the radiometals to PSMA-positive tumor sites, but partial radiometal dissociation was observed, indicating the need for further optimization.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2023)
Editorial Material
Chemistry, Inorganic & Nuclear
Justin J. Wilson, James M. Hodges
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Chilaluck C. C. Konkankit, S. Rackovsky
Summary: Using tools developed for studying protein dynamics, we can analyze the dynamic characteristics of a large number of protein sequences simultaneously. In this study, we investigate the distribution of protein sequences in a space defined by sequence mobility. The results reveal statistically significant differences in mobility distribution between folded sequences of different structural classes and sequences of intrinsically disordered proteins. Moreover, different regions of the mobility space exhibit considerable variations in structural composition. Helical proteins exhibit distinct dynamic properties at both ends of the mobility spectrum.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)