Review
Neurosciences
Sridhar Goud Nerella, Michael Michaelides, Takafumi Minamimoto, Robert B. Innis, Victor W. Pike, Mark A. G. Eldridge
Summary: Positron emission tomography (PET) can be used as a noninvasive method to monitor and quantify protein expression in the brain over time. It is useful for tracking changes in biomarkers of mental health disorders and evaluating therapeutic interventions like stem cell and molecular genetic therapies. The effectiveness of PET monitoring relies on the availability of radiotracers that have good central nervous system penetration and high selectivity for the target protein.
TRENDS IN NEUROSCIENCES
(2023)
Article
Pharmacology & Pharmacy
Etienne E. Muller, Dumisile Maseko, Ranmini S. Kularatne
Summary: This study conducted phenotypic and genotypic surveillance on ACV resistance in HSV-2 derived from genital ulcer samples collected in a primary healthcare facility in South Africa. The results revealed no resistance-associated mutations, but identified several known natural polymorphisms and amino acid changes of unknown significance. All cultivable HSV-2 isolates showed susceptibility to ACV.
ANTIVIRAL RESEARCH
(2022)
Review
Immunology
Mingming Hu, Xuliang Liao, Yi Tao, Yaohui Chen
Summary: The treatment of recurrent glioma is challenging due to its molecular heterogeneity and resistance to commonly used treatments. Oncolytic viruses, which selectively replicate within tumor cells and stimulate the immune system, have emerged as a promising therapeutic option. Genetic modifications have been important in optimizing the efficacy of oncolytic herpes simplex virus and oncolytic adenovirus for recurrent gliomas. This review article summarizes these genetic modifications and aims to identify strategies to enhance the therapeutic benefits of oncolytic viruses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Saeed Oraee-Yazdani, Mohammadhosein Akhlaghpasand, Fatemeh Rostami, Maryam Golmohammadi, Roozbeh Tavanaei, Gelareh Shokri, Maryam Hafizi, Maryam Oraee-Yazdani, Ali-Reza Zali, Masoud Soleimani
Summary: This study reported a case of a patient with malignant brain tumor who underwent bone marrow-derived MSCs carrying the HSV-TK gene therapy. MRI observation revealed partial recurrence and enlargement of the tumor after injection. The results of this study suggest that gene therapy using the HSV-TK gene may have some effect on the treatment of brain tumors.
FRONTIERS IN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Narayan Bashyal, Tae-Young Lee, Da-Young Chang, Jin-Hwa Jung, Min Gyeong Kim, Rakshya Acharya, Sung-Soo Kim, Il-Hoan Oh, Haeyoung Suh-Kim
Summary: Research has shown that MSC-TK(A168H) cells modified with the HSV-TK(A168H) gene exhibit safety in pre-clinical trials, making them suitable for therapeutic use. This genetic modification makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.
MOLECULES AND CELLS
(2022)
Article
Multidisciplinary Sciences
Magali Saez-Ayala, Laurent Hoffer, Sebastien Abel, Khaoula Ben Yaala, Benoit Sicard, Guillaume P. Andrieu, Mehdi Latiri, Emma K. Davison, Marco A. Ciufolini, Paul Bremond, Etienne Rebuffet, Philippe Roche, Carine Derviaux, Edwige Voisset, Camille Montersino, Remy Castellano, Yves Collette, Vahid Asnafi, Stephane Betzi, Patrice Dubreuil, Sebastien Combes, Xavier Morelli
Summary: Cancer cells rely on two pathways, the de novo pathway and the salvage pathway, for nucleotide synthesis. In this study, we developed a potent inhibitor for the salvage pathway by using a multidisciplinary approach combining computational design and experimental evaluations. Our lead compound, OR0642, showed significantly higher potency compared to the original compound, masitinib, identified through drug repositioning. In a xenograft mouse model of T-cell acute lymphoblastic leukemia, OR0642 in combination with a physiological inhibitor of the de novo pathway doubled the survival rate, demonstrating the proof-of-concept of this drug design strategy.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Fatemeh Tirgar, Zahra Azizi, Saereh Hosseindoost, Mahmoudreza Hadjighassem
Summary: This study demonstrates that olfactory ensheathing cells (OECs) can be used as a novel carrier for gene therapy in glioblastoma multiforme (GBM) animal models. OECs have high migration capability and can effectively suppress tumor progression.
Article
Biochemistry & Molecular Biology
Changdong Wang, Yanxi Shen, Yongping Ma
Summary: This study comprehensively identified and quantified protein expression profiling in gastric cancer cells treated with BF-TK/GCV for the first time. The results showed that BF-TK/GCV inhibited tumor metastasis and downregulated the expression of metastasis-related proteins, as demonstrated by immunohistochemistry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Katharina Woess, Yuchen Sun, Hanae Morio, Anna Stierschneider, Anna Kaufmann, Stefan Hainzl, Lisa Trattner, Thomas Kocher, Birgit Tockner, Victoria Leb-Reichl, Markus Steiner, Gabriele Brachtl, Andrew P. South, Johann W. Bauer, Julia Reichelt, Tomomi Furihata, Verena Wally, Ulrich Koller, Josefina Pinon Hofbauer, Christina Guttmann-Gruber
Summary: Conventional anti-cancer therapies lack tumor specificity and can result in iatrogenic effects. Spliceosome-mediated RNA trans-splicing (SMaRT) is a promising approach that can target tumor cells while sparing normal cells. This study demonstrates the potential of SMaRT using the RNA trans-splicing molecule RTM44 to target the cancer gene Ct-SLCO1B3 in aggressive skin cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Tianxin Gao, Pei Wang, Teng Gong, Ying Zhou, Ancong Wang, Xiaoying Tang, Xiaolei Song, Yingwei Fan
Summary: The use of molecular imaging technologies in brain imaging is not only important for disease diagnosis and treatment, but also for in-depth study of brain functions. Reporter gene technology based on optical imaging has made breakthroughs in molecular-level brain function studies. The applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies in brain imaging are discussed, with a focus on cell therapies and gene therapies. These methods have shown potential for preclinical and clinical research, providing deeper imaging depths and wider imaging ranges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Dermatology
Shinichi Imafuku
Summary: Herpes simplex is a common infection caused by the herpes simplex virus, which is transmitted through contact of the skin/mucous membrane and establishes latency in the sensory ganglia. It occasionally reactivates and forms blisters around the lips or genitalia. Diagnosis of typical herpes simplex is not difficult, but definitive tests are limited. Safe and effective oral antiviral drugs are available for treatment, and a new patient-initiated therapy method has been introduced in Japan.
JOURNAL OF DERMATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xinling Li, Xiaochun Yang, Zhijian Li, Xiaobin Zheng, Yong-Jian Peng, Wenjie Lin, Ling Zhou, Dehai Cao, Minyi Situ, Qingqiang Tu, Huiqiang Huang, Wei Fan, Guokai Feng, Xiaofei Zhang
Summary: Cell therapies have achieved cures for hematopoietic disorders, neurodegenerative diseases, and cancer, but not all patients can benefit from them. The clinical methods for monitoring the therapeutic functions of transferred cells over time are limited, resulting in uncertain prognosis. Positron emission tomography (PET) cell tracking provides comprehensive information on the proliferation status and distribution of therapeutic cells. This study developed the first SNAP-tagged PET radiotracer, which can selectively target SNAP-tagged cells for in vivo cell tracking, with promising results in vitro and in vivo.
Article
Biotechnology & Applied Microbiology
Hyla Allouche-Arnon, Olga Khersonsky, Nishanth D. Tirukoti, Yoav Peleg, Orly Dym, Shira Albeck, Alexander Brandis, Tevie Mehlman, Liat Avram, Talia Harris, Nirbhay N. Yadav, Sarel J. Fleishman, Amnon Bar-Shir
Summary: This research utilizes the MRI system GeneREFORM for two-color imaging, improving the detection of transgene expression in live animals. By designing orthogonal reporter genes and reporter probes, dynamic proton exchange MRI imaging is achieved, paving the way for future deep-tissue multiplexed imaging of gene expression in live animals.
NATURE BIOTECHNOLOGY
(2022)
Review
Oncology
Nikhil I. Khushalani, Kevin J. Harrington, Alan Melcher, Praveen K. Bommareddy, Dmitriy Zamarin
Summary: The field of oncolytic immunotherapy (OI) has rapidly evolved since the approval of talimogene laherparepvec for melanoma treatment. Numerous clinical studies are evaluating the efficacy of OIs in different tumor types. Advances in understanding the anti-tumor immune response have led to the development of next-generation OIs, involving modifications to the viral genome and incorporation of transgenes. This review explores these approaches, along with the advantages and disadvantages of intratumoral versus intravenous administration, the use of OIs in overcoming resistance to immune checkpoint blockade, and potential strategies for improving OI efficacy in combination therapies.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Biochemistry & Molecular Biology
Carly Boye, Sezgi Arpag, Michael Francis, Scott DeClemente, Aislin West, Richard Heller, Anna Bulysheva
Summary: Gene therapy has a wide range of applications but viral delivery methods have safety concerns. By using smaller plasmid DNA backbones, gene expression levels can be significantly increased using non-viral methods, as shown in rat tenocytes and myocardium. Delivery to the skin showed more moderate improvements.
BIOELECTROCHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Soumya Poddar, Edmund Capparelli, Ethan W. Rosser, Raymond M. Gipson, Liu Wei, Thuc Le, Michael E. Jung, Caius Radu, Mina Nikanjam
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Oncology
Kyle Current, Catherine Meyer, Clara E. Magyar, Christine E. Mona, Joel Almajano, Roger Slavik, Andreea D. Stuparu, Chloe Cheng, David W. Dawson, Caius G. Radu, Johannes Czernin, Katharina Lueckerath
CLINICAL CANCER RESEARCH
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Johannes Czernin, Kyle Current, Christine E. Mona, Lea Nyiranshuti, Firas Hikmat, Caius G. Radu, Katharina Luckerath
Summary: PSMA RNT and PD-1 blockade showed synergistic effects in improving therapeutic outcomes in a mouse model of prostate cancer, extending time to progression and survival compared to monotherapies.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Johannes Czernin, Caius Radu
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Andreea D. Stuparu, Joseph R. Capri, Catherine A. L. Meyer, Thuc M. Le, Susan L. Evans-Axelsson, Kyle Current, Mark Lennox, Christine E. Mona, Wolfgang P. Fendler, Jeremie Calais, Matthias Eiber, Magnus Dahlbom, Johannes Czernin, Caius G. Radu, Katharina Lueckerath, Roger Slavik
Summary: The study found that PSMA-targeted radioligand therapy significantly improved disease control in a dose-dependent manner in a mouse model of PCa. Analysis of the proteome and phosphoproteome data revealed activation of genotoxic stress response pathways, and supported a role for TP53 in mediating RLT responsiveness.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Alexandra M. Moore, Lei Zhou, Jing Cui, Luyi Li, Nanping Wu, Alice Yu, Soumya Poddar, Keke Liang, Evan R. Abt, Stephanie Kim, Razmik Ghukasyan, Nooneh Khachatourian, Kristina Pagano, Irmina Elliott, Amanda M. Dann, Rana Riahi, Thuc Le, David W. Dawson, Caius G. Radu, Timothy R. Donahue
Summary: Emerging evidence suggests that intratumoral interferon signaling can trigger targetable vulnerabilities in PDAC by reducing NAD levels through up-regulating NAD-consuming enzymes. This sensitizes PDAC cells to NAMPT inhibition, leading to decreased cell proliferation and invasion in vitro, as well as suppression of tumor growth and metastases in vivo.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Keke Liang, Evan R. Abt, Thuc M. Le, Arthur Cho, Amanda M. Dann, Jing Cui, Luyi Li, Khalid Rashid, Amanda L. Creech, Liu Wei, Razmik Ghukasyan, Ethan W. Rosser, Nanping Wu, Giuseppe Carlucci, Johannes Czernin, Timothy R. Donahue, Caius G. Radu
Summary: Type I interferons play a critical role in cancer immunotherapies by activating pattern recognition receptors. Lack of noninvasive pharmacodynamic biomarkers has been a challenge in clinical translation of these therapies. This study found that IFN signaling enhances tumor cell nucleotide metabolism and can be detected using [F-18]FLT PET imaging, making it a potential biomarker for STING agonist-based therapies in pancreatic ductal adenocarcinoma.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Evan R. Abt, Thuc M. Le, Amanda M. Dann, Joseph R. Capri, Soumya Poddar, Vincent Lok, Luyi Li, Keke Liang, Amanda L. Creech, Khalid Rashid, Woosuk Kim, Nanping Wu, Jing Cui, Arthur Cho, Hailey Rose Lee, Ethan W. Rosser, Jason M. Link, Johannes Czernin, Ting-Ting Wu, Robert Damoiseaux, David W. Dawson, Timothy R. Donahue, Caius G. Radu
Summary: Type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors. IFN activates the ATR kinase, leading to cell-cycle arrest in S-phase, nucleotide pool insufficiency, and nucleoside efflux in PDAC cells. ATR inhibitors, combined with IFN, induce lethal DNA damage and downregulate nucleotide biosynthesis. This study reveals the interaction between IFN, DNA replication stress response networks, and nucleotide metabolism, providing a rationale for targeted therapeutic interventions leveraging IFN signaling in tumors.
Article
Oncology
Kristina Y. Aguilera, Thuc Le, Rana Riahi, Anna R. Lay, Stefan Hinz, Edris A. Saadat, Ajay A. Vashisht, James Wohlschlegel, Timothy R. Donahue, Caius G. Radu, David W. Dawson
Summary: This study found that autophagy and lysosomal activity are enhanced in RNF43-mutant PDAC in response to PORCNi LGK974, which disrupts mitochondrial function and alters transcriptional activity. These findings reveal potential therapeutic targets for combining PORCNi with other drugs for the treatment of PDAC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Immunology
Bao Ying Chen, Jessica R. Salas, Alyssa O. Trias, Arely Perez Rodriguez, Jonathan E. Tsang, Miriam Guemes, Thuc M. Le, Zoran Galic, H. Michael Shepard, Lawrence Steinman, David A. Nathanson, Johannes Czernin, Owen N. Witte, Caius G. Radu, Kenneth A. Schultz, Peter M. Clark
Summary: Research on multiple sclerosis and autoimmune diseases has found that targeting deoxycytidine kinase (dCK) can limit the progression of symptoms, and dCK activity is essential for activation-induced proliferation in specific lymphocytes.
Article
Oncology
Samantha B. Kemp, Noah Cheng, Nune Markosyan, Rina Sor, Il-Kyu Kim, Jill Hallin, Jason Shoush, Liz Quinones, Natalie V. Brown, Jared B. Bassett, Nikhil Joshi, Salina Yuan, Molly Smith, William P. Vostrejs, Kia Z. Perez-Vale, Benjamin Kahn, Feiyan Mo, Timothy R. Donahue, Caius G. Radu, Cynthia Clendenin, James G. Christensen, Robert H. Vanderheide, Ben Z. Stanger
Summary: This study evaluated the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in PDAC models with an intact immune system. The results showed that MRTX1133 can induce deep tumor regressions and alter the tumor microenvironment, demonstrating its potential as a novel therapy for PDAC patients. Further clinical testing is warranted.
Article
Virology
Alex K. Lam, Romin Roshan, Wendell Miley, Nazzarena Labo, James Zhen, Andrew P. Kurland, Celine Cheng, Haigen Huang, Pu-Lin Teng, Claire Harelson, Danyang Gong, Ying K. Tam, Caius G. Radu, Marta Epeldegui, Jeffrey R. Johnson, Z. Hong Zhou, Denise Whitby, Ting-Ting Wu
Summary: KSHV is a virus that can cause cancer and a vaccine to prevent its infection would be beneficial in preventing cancer development.
JOURNAL OF VIROLOGY
(2023)
Meeting Abstract
Oncology
Amanda L. Creech, Thuc M. Le, Evan R. Abt, Joseph R. Capri, Timothy R. Donahue, Caius G. Radu
Article
Medicine, Research & Experimental
Evan R. Abt, Khalid Rashid, Thuc M. Le, Suwen Li, Hailey R. Lee, Vincent Lok, Luyi Li, Amanda L. Creech, Amanda N. Labora, Hanna K. Mandl, Alex K. Lam, Arthur Cho, Valerie Rezek, Nanping Wu, Gabriel Abril-Rodriguez, Ethan W. Rosser, Steven D. Mittelman, Willy Hugo, Thomas Mehrling, Shanta Bantia, Antoni Ribas, Timothy R. Donahue, Gay M. Crooks, Ting-Ting Wu, Caius G. Radu
Summary: The deficiency of PNP can lead to both immunodeficiency and autoimmunity. The mechanisms behind this paradoxical association are not fully understood. This study reveals that the inactivation of PNP can affect T cell development and B cell signaling, resulting in immune abnormalities and autoimmune diseases.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Shen Li, Tomohiro Yokota, Ping Wang, Johanna ten Hoeve, Feiyang Ma, Thuc M. Le, Evan R. Abt, Yonggang Zhou, Rimao Wu, Maxine Nanthavongdouangsy, Abraham Rodriguez, Yijie Wang, Yen-Ju Lin, Hayato Muranaka, Mark Sharpley, Demetrios T. Braddock, Vicky E. MacRae, Utpal Banerjee, Pei-Yu Chiou, Marcus Seldin, Dian Huang, Michael Teitell, Ilya Gertsman, Michael Jung, Steven J. Bensinger, Robert Damoiseaux, Kym Faull, Matteo Pellegrini, Aldons J. Lusis, Thomas G. Graeber, Caius G. Radu, Arjun Deb
Summary: Cardiomyocytes play a pivotal role in heart repair by regulating nucleotide metabolism and fates of nonmyocytes through the release of specific substances.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
