Article
Chemistry, Medicinal
Aleksei E. Machulkin, Anastasia A. Uspenskaya, Nikolay Y. Zyk, Ekaterina A. Nimenko, Anton P. Ber, Stanislav A. Petrov, Radik R. Shafikov, Dmitry A. Skvortsov, Galina B. Smirnova, Yulia A. Borisova, Vadim S. Pokrovsky, Vasilii S. Kolmogorov, Alexander N. Vaneev, Yan A. Ivanenkov, Alexander D. Khudyakov, Sergei Kovalev, Alexander S. Erofeev, Petr Gorelkin, Elena K. Beloglazkina, Nikolay Zyk, Elena S. Khazanova, Alexander G. Majouga
Summary: The study focused on developing docetaxel conjugates for prostate cancer treatment, showing promising cytotoxicity and increased solubility compared to the drug itself. In vivo evaluation demonstrated strong inhibitory effects on tumor growth and lower toxicity compared to free docetaxel. The PSMA-targeted docetaxel conjugate is considered a good candidate for further preclinical trials due to its high antitumor activity, reduced side effects, and improved solubility.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Ayako Nakayama, Takeyuki Nagashima, Yoshihiro Nishizono, Kazuyuki Kuramoto, Kenichi Mori, Kazuya Homboh, Masatoshi Yuri, Masashi Shimazaki
Summary: ASP2453 is a potential therapeutic agent for KRAS G12C-mutated cancer, showing improved anti-tumour effects of targeted agents and immune checkpoint inhibitors, with faster binding kinetics and stronger inhibitory effects on KRAS activation and cell proliferation compared to AMG 510.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Gaowei Li, Zongliang Zhang, Linjun Cai, Xin Tang, Jianhan Huang, Lingyu Yu, Guoqing Wang, Kunhong Zhong, Yi Cao, Chang Liu, Yuelong Wang, Aiping Tong, Liangxue Zhou
Summary: Fn14, a specific antigen highly expressed in GBM tissues and cell lines, serves as a promising target for immunotherapy. Fn14x CD3 BiTE and Fn14-specific CAR-T cells demonstrated potent antitumor activity in vitro and in vivo, suggesting their potential as immunotherapeutic options for malignant brain cancer.
Review
Oncology
Asta Juzeniene, Vilde Yuli Stenberg, Oyvind Sverre Bruland, Roy Hartvig Larsen
Summary: There is currently no cure for late stage metastatic prostate cancer, but targeted alpha therapy focusing on the overexpressed protein PSMA may offer a promising treatment option. This therapy utilizes radionuclides emitting alpha-particles to target PSMA, potentially providing a more effective and selective treatment option for patients.
Article
Multidisciplinary Sciences
Kris M. White, Romel Rosales, Soner Yildiz, Thomas Kehrer, Lisa Miorin, Elena Moreno, Sonia Jangra, Melissa B. Uccellini, Raveen Rathnasinghe, Lynda Coughlan, Carles Martinez-Romero, Jyoti Batra, Ajda Rojc, Mehdi Bouhaddou, Jacqueline M. Fabius, Kirsten Obernier, Marion Dejosez, Maria Jose Guillen, Alejandro Losada, Pablo Aviles, Michael Schotsaert, Thomas Zwaka, Marco Vignuzzi, Kevan M. Shokat, Nevan J. Krogan, Adolfo Garcia-Sastre
Summary: The study revealed that plitidepsin possesses potent antiviral activity against SARS-CoV-2, more effective than the approved drug remdesivir. By inhibiting the eukaryotic translation elongation factor 1A, plitidepsin can significantly reduce viral replication of SARS-CoV-2 in the lungs of mice, making it a promising candidate for COVID-19 treatment.
Article
Multidisciplinary Sciences
Morten P. Oksvold, Ulrika Warpman Berglund, Helge Gad, Baoyan Bai, Trond Stokke, Idun Dale Rein, Therese Pham, Kumar Sanjiv, Geir Frode Oy, Jens Henrik Norum, Erlend B. Smeland, June H. Myklebust, Thomas Helleday, Thea Kristin Vatsveen
Summary: The drug karonudib, designed to inhibit the enzyme MTH1, showed promising efficacy in preclinical B-cell lymphoma models by reducing viability, increasing DNA insertion, inducing apoptosis, and displaying high potency as a single agent in two different lymphoma xenograft models.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Liangyin Lv, Hui Wang, Wenqiang Shi, Yang Wang, Wen Zhu, Zexin Liu, Xiaoqu Chen, Chen Zheng, Wencheng Kong, Wei Li, Jianwei Zhu, Huili Lu
Summary: This study successfully designed a novel IL-15 superagonist F4RLI with improved manufacturing processes and biopharmaceutical applications. F4RLI showed enhanced stability and prolonged half-life of IL-15, and demonstrated potential in tumor immunotherapy.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Immunology
Kamel Chettab, Chantel Fitzsimmons, Alexey Novikov, Morgane Denis, Capucine Phelip, Doriane Mathe, Pierre Antoine Choffour, Sabine Beaumel, Eric Fourmaux, Patrick Norca, David Kryza, Anne Evesque, Lars Petter Jordheim, Emeline Perrial, Eva-Laure Matera, Martine Caroff, Jerome Kerzerho, Charles Dumontet
Summary: Bacterial lipopolysaccharides (LPS) have potent anti-tumor activity but their toxicity prevents effective systemic administration in humans. This study demonstrates that liposomal encapsulation of LPS preserves its anti-tumor activity and enhances the efficacy of rituximab, an anti-CD20 antibody, in lymphoma models. Liposomal encapsulation also reduces cytokine induction and toxicity while maintaining immunoadjuvant effects, making it a promising systemically active anticancer agent.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Sonia Infante-Tadeo, Vanessa Rodriguez-Fanjul, Cintia C. Vequi-Suplicy, Ana M. Pizarro
Summary: The passage describes the rapid hydrolysis and high basicity of complexes [Os(eta 6-arene)(C,N-phenylpyridine)Z] with chlorido or tethered oxygen as the ligand. It also reveals the structure-activity relationship between Os-CN and Os-NN complexes.
INORGANIC CHEMISTRY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Nahid Yusufi, Alexander Wurzer, Michael Herz, Calogero D'Alessandria, Benedikt Feuerecker, Wolfgang Weber, Hans-Juergen Wester, Stephan Nekolla, Matthias Eiber
Summary: The study evaluated the biodistribution, dosimetry, and therapeutic efficacy of F-19/Lu-177-rhPSMA-7.3 compared to Lu-177-PSMA I&T, showing superior tumor uptake and retention for F-19/Lu-177-rhPSMA-7.3. Preliminary treatment experiments demonstrated a favorable antitumor response for F-19/Lu-177-rhPSMA-7.3 compared to Lu-177-PSMA I&T.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Chemistry, Medicinal
Jun Liang, Jason R. Zbieg, Robert A. Blake, Jae H. Chang, Stephen Daly, Antonio G. DiPasquale, Lori S. Friedman, Thomas Gelzleichter, Matthew Gill, Jennifer M. Giltnane, Simon Goodacre, Jane Guan, Steven J. Hartman, Ellen Rei Ingalla, Lorn Kategaya, James R. Kiefer, Tracy Kleinheinz, Sharada S. Labadie, Tommy Lai, Jun Li, Jiangpeng Liao, Zhiguo Liu, Vidhi Mody, Neville McLean, Ciara Metcalfe, Michelle A. Nannini, Jason Oeh, Martin G. O'Rourke, Daniel F. Ortwine, Yingqing Ran, Nicholas C. Ray, Fabien Roussel, Amy Sambrone, Deepak Sampath, Leah K. Schutt, Maia Vinogradova, John Wai, Tao Wang, Ingrid E. Wertz, Jonathan R. White, Siew Kuen Yeap, Amy Young, Birong Zhang, Xiaoping Zheng, Wei Zhou, Yu Zhong, Xiaojing Wang
Summary: The discovery of clinical candidate 35 (GDC-9545 or giredestrant) as an efficient and potent selective estrogen receptor degrader (SERD) and full antagonist has shown promising results in preclinical studies, demonstrating low drug-drug interaction liability and excellent safety profiles. This compound is currently undergoing Phase III clinical trials for the treatment of breast cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medical Laboratory Technology
Famke Aeffner, Crystal Faelan, Steven A. Moore, Alexander Moody, Joshua C. Black, Jay S. Charleston, Diane E. Frank, Johannes Dworzak, I. Kris Piper, Manish Ranjitkar, Kristin Wilson, Suzanne Kanaly, Daniel G. Rudmann, Holger Lange, G. David Young, Anthony Milici
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2019)
Article
Medical Laboratory Technology
Mark D. Zarella, Douglas Bowman, Farnke Aeffner, Navid Farahani, Albert Xthona, Syeda Fatima Absar, Anil Parwani, Marilyn Bui, Douglas Hartman
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2019)
Review
Oncology
Esther Abels, Liron Pantanowitz, Famke Aeffner, Mark D. Zarella, Jeroen van der Laak, Marilyn M. Bui, Venkata N. P. Vemuri, Anil V. Parwani, Jeff Gibbs, Emmanuel Agosto-Arroyo, Andrew H. Beck, Cleopatra Kozlowski
JOURNAL OF PATHOLOGY
(2019)
Review
Pathology
Saravanan Kaliyaperumal, Kristin Wilson, Famke Aeffner, Charles Dean
TOXICOLOGIC PATHOLOGY
(2020)
Article
Pathology
Oliver C. Turner, Famke Aeffner, Dinesh S. Bangari, Wanda High, Brian Knight, Tom Forest, Brieuc Cossic, Lauren E. Himmel, Daniel G. Rudmann, Bhupinder Bawa, Anantharaman Muthuswamy, Olulanu H. Aina, Elijah F. Edmondson, Chandrassegar Saravanan, Danielle L. Brown, Tobias Sing, Manu M. Sebastian
TOXICOLOGIC PATHOLOGY
(2020)
Article
Pathology
Aleksandra Zuraw, Michael Staup, Robert Klopfleisch, Famke Aeffner, Danielle Brown, Thomas Westerling-Bui, Daniel Rudmann
Summary: Digital tissue image analysis requires a well-designed quality control system to ensure accuracy, with toxicologic pathologists playing a crucial role in reporting data accurately. The manuscript outlines common end points and approaches for quality assurance, drawing from a proposed FDA regulatory framework for AI/ML-based software modifications.
TOXICOLOGIC PATHOLOGY
(2021)
Article
Pathology
Vanessa L. Schumacher, Famke Aeffner, Erio Barale-Thomas, Catherine Botteron, Jonathan Carter, Laetitia Elies, Jeffery A. Engelhardt, Pierluigi Fant, Thomas Forest, Peter Hall, Deon Hildebrand, Robert Klopfleisch, Thomas Lucotte, Heike Marxfeld, LuAnn Mckinney, Pierre Moulin, Elizabeth Neyens, Xavier Palazzi, Alain Piton, Elena Riccardi, Daniel R. Roth, Serge Rousselle, Justin D. Vidal, Bethany Williams
Summary: Advancements in digital pathology have led to increased adoption in human medical pathology, but challenges remain in toxicologic pathology, particularly in regulatory studies. International workshops are being held to assess current applications, challenges, and outline minimal requirements for gaining regulatory acceptance in toxicologic pathology workflows.
TOXICOLOGIC PATHOLOGY
(2021)
Article
Oncology
Elizabeth Pham, Matthias Friedrich, Famke Aeffner, Michael Lutteropp, Natalie F. Mariano, Petra Deegen, Christoph Dahlhoff, Franziska Vogel, Claudia Bluemel, John M. Harrold, Christian Brandl, Natalia Grinberg, Benno Rattel, Angela Coxon, Julie M. Bailis
Summary: MUC12, highly expressed in colorectal tumors but restricted in normal tissues, is a potential therapeutic target for BiTE molecules. However, high doses of BiTE targeting MUC12 may lead to on-target toxicity, as shown in current studies.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Cell Biology
Brian Belmontes, Deepali Sawant, Wendy Zhong, Hong Tan, Anupurna Kaul, Famke Aeffner, Sarah A. O'Brien, Matthew Chun, Rajkumar Noubade, Jason Eng, Hayley Ma, Markus Muenz, Peng Li, Benjamin M. Alba, Melissa Thomas, Kevin Cook, Xiaoting Wang, Jason DeVoss, Jackson G. Egen, Olivier Nolan-Stevaux
Summary: Our study in immunocompetent mouse models revealed that pretreatment tumor-associated T cell density is a critical factor in determining response to BiTE therapy. CD8+ T cells were identified as important targets and mediators of BiTE activity, while CD4(+) T cells played an antagonistic role in BiTE efficacy. In addition, therapeutic combinations such as ICB and 4-1BB agonism were found to synergize with BiTE treatment in poorly T cell-infiltrated, immunotherapy-refractory tumors.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Pathology
Thomas Forest, Famke Aeffner, Dinesh S. Bangari, Bhupinder Bawa, Jonathan Carter, James Fikes, Wanda B. High, Shim-Mo Hayashi, Matthew Jacobsen, LuAnn McKinney, Daniel Rudmann, Thomas Steinbach, Vanessa Schumacher, Oliver C. Turner, Jerrold M. Ward, Cynthia J. Willson
Summary: This article presents the results of a survey on the use of digital pathology in nonclinical toxicology studies before the COVID-19 pandemic. The survey showed that digital histopathology was not widely used for routine GLP histopathology assessment. However, many institutions started investigating or adopting digital WSI systems during the pandemic to reduce employee exposure to COVID-19.
TOXICOLOGIC PATHOLOGY
(2022)
Article
Oncology
Ye Shen, Jason S. Eng, Flordeliza Fajardo, Lingming Liang, Cong Li, Patrick Collins, Donato Tedesco, Olivier Nolan-Stevaux
Summary: This study reveals that genetic alterations in cancer cells have a significant impact on the antitumor activity of bispecific T-cell engagers (BiTEs). The T-cell costimulation pathway and the apoptosis pathway are identified as key modifiers of BiTE activity. Loss of genes such as CD58, CD80/CD86, CFLAR, BCL2L1, and BID can alter the responsiveness to BiTE therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Pathology
Thomas Forest, Famke Aeffner, Dinesh S. Bangari, Bhupinder Bawa, Jonathan Carter, James Fikes, Wanda High, Shim-Mo Hayashi, Matthew Jacobsen, LuAnn McKinney, Daniel Rudmann, Thomas Steinbach, Vanessa Schumacher, Oliver Turner, Jerrold M. Ward, Cynthia J. Willson
Summary: The use of digital pathology in toxicologic pathology has the potential to enhance evaluation and collaboration, but comes with significant resource requirements. This article provides a comprehensive perspective on digital whole-slide imaging and offers points to consider for organizations implementing digital pathology workflows.
TOXICOLOGIC PATHOLOGY
(2022)