Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates by Yangyang Gao, Yuwei Xia, Yixin Chen, Shiqi Zhou, Yingying Fang, Jieru Yu, Leyin Zhang, Leyin Zhang, Leitao Sun, Leitao Sun, Leitao Sun

“…From the ADC’s PK/PD property while coming into play in vivo and the PK/PD study strategy, to specific ADC optimization methods and recommendations based on PK/PD, it has been study-approved that the PK/PD properties exert a subtle role in the development of ADC, whether in preclinical trials or clinical promotion.ConclusionThe study of PK/PD unfolds the detailed mechanism of ADC action, making it easier to control related parameters in the process of designing ADC, limited efficacy and inevitable off-target toxicity remain a challenging bottleneck.…”
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Chemotherapy in synergy with innate immune agonists enhances T cell priming for checkpoint inhibitor treatment in pancreatic cancer by Nan Niu, Keyu Li, Junke Wang, Vanessa Funes, Birginia Espinoza, Pan Li, Jianxin Wang, Melissa Lyman, Mengni He, Brian Herbst, Michael Wichroski, Ruslan Novosiadly, Sami Shoucair, Yiping Mou, Lei Zheng

“…Methods We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy. …”
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A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome by Kathleen Campbell, Jeffrey L. Neul, David N. Lieberman, Elizabeth Berry-Kravis, Tim A. Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L. Carpenter, Eric D. Marsh, Jana von Hehn

“…Abstract Background Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy. …”
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A1, an innovative fluorinated CXCR4 inhibitor, redefines the therapeutic landscape in colorectal cancer by Hossein Khorramdelazad, Kowsar Bagherzadeh, Ali Rahimi, Ali Darehkordi, Alireza Najafi, Milad Karimi, Majid Khoshmirsafa, Gholamhossein Hassanshahi, Elaheh Safari, Reza Falak

“…Further validation through rigorous preclinical and clinical studies may position A1 as a promising alternative to AMD3100 in human cancers.…”
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Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 by Lieven Declercq Pharmacist, Sofie Celen PhD, Joan Lecina PhD, Muneer Ahamed PhD, Thomas Tousseyn Prof, MD, PhD, Diederik Moechars PhD, Jesus Alcazar PhD, Manuela Ariza PhD, Katleen Fierens PhD, Astrid Bottelbergs PhD, Jonas Mariën PhD, Rik Vandenberghe Prof, MD, PhD, Ignacio Jose Andres PhD, Koen Van Laere Prof, MD, PhD, Alfons Verbruggen Prof, PhD, Guy Bormans Prof, PhD

“…In the present study, the biodistribution, radiometabolite quantification, and competition-binding studies were performed in order to acquire comparative preclinical data as well as to establish the value of T808 and T807 as benchmark compounds for assessment of binding affinities of eight new/other tau tracers. …”
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Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study by Kotaro Noda, Yorito Hattori, Tatsuya Nishii, Hiroki Horinouchi, Yuriko Nakaoku, Soshiro Ogata, Yasunobu Inagaki, Ryotaro Asano, Takeshi Yoshimoto, Kunihiro Nishimura, Takeshi Ogo, Yoshikazu Nakaoka, Masafumi Ihara

“…Conclusions A longer right ventricular outflow tract acceleration time may reflect an increased pulmonary vascular bed induced by abnormal vascular collateral networks and dilation of capillary vessels in peripheral pulmonary arteries in the preclinical stage of RNF213‐related pulmonary hypertension. …”
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Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer by Sara M Tolaney, Tianyu Li, Edward T Richardson, Judith Agudo, Elizabeth A Mittendorf, Beth Overmoyer, Eric P Winer, Adrienne G Waks, Tanya E Keenan, Nabihah Tayob, Gerburg M Wulf, Victoria Attaya, Leilani Anderson, Ian E Krop, Eliezer M Van Allen

“…Background Preclinical and clinical data support potential synergy between anti-HER2 therapy plus immune checkpoint blockade. …”
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Agathisflavone Inhibits Viability and Modulates the Expression of miR-125b, miR-155, IL-6, and Arginase in Glioblastoma Cells and Microglia/Macrophage Activation by Karina Costa da Silva, Irlã Santos Lima, Cleonice Creusa dos Santos, Carolina Kymie Vasques Nonaka, Bruno Solano de Freitas Souza, Jorge Mauricio David, Henning Ulrich, Ravena Pereira do Nascimento, Maria de Fátima Dias Costa, Balbino Lino dos Santos, Silvia Lima Costa

“…These results demonstrate the effect of flavonoids on the growth of GBM cells, which impacts cells in the microenvironment and can be considered for preclinical studies for adjuvant treatments.…”
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Advancements in Hyaluronic Acid Effect in Alveolar Ridge Preservation: A Narrative Review by Paul Andrei Nistor, Andreea Cândea, Iulia Cristina Micu, Andrada Soancă, Carmen Silvia Caloian, Alina Bârdea, Alexandra Roman

“…This study aims to assess current clinical and preclinical evidence regarding the biological effects of HYA and its application in ARP. …”
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PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies by Neysha Martinez-Orengo, Swati Shah, Jianhao Lai, Falguni Basuli, Anna Lyndaker, Mitchell L. Turner, Morteza Peiravi, Suman Sourabh, Kevon Sampson, Peng Zhang, Rolf E. Swenson, Paolo Lusso, Frank Maldarelli, Avindra Nath, Chuen-Yen Lau, Dima A. Hammoud

“…These results establish an Env+ imaging method that will enable next stage testing in an HIV-1 preclinical infection model and potentially in PWH.…”
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Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization by Ruofei Zhang, Yanfang Shen, Xiaoying Zhou, Jianru Li, Hanqing Zhao, Zixia Zhang, Jun Zhao, Hongjun Jin, Shuanshuan Guo, Hui Ding, Guohui Nie, Zhe Zhang, Ying Wang, Xiyun Yan, Kelong Fan

“…Human heavy-chain ferritin, a specific ligand of TfR1, selectively recognizes hypoxic NPC lesions in preclinical models. Based on these findings, we design a hypoxia-targeted nanozyme by loading platinum nanoparticles into ferritin. …”
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Distinct sex differences in ethanol consumption and operant self-administration in C57BL/6J mice with uniform regulation by glutamate AMPAR activity by Sara Faccidomo, Sara Faccidomo, Vallari R. Eastman, Taruni S. Santanam, Katarina S. Swaim, Seth M. Taylor, Clyde W. Hodge, Clyde W. Hodge

“…IntroductionConsidering sex as a biological variable (SABV) in preclinical research can enhance understanding of the neurobiology of alcohol use disorder (AUD). …”
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Overexpression of MMP13 Is Associated with Clinical Outcomes and Poor Prognosis in Oral Squamous Cell Carcinoma by Vui King Vincent-Chong, Iman Salahshourifar, Lee Peng Karen-Ng, Ming Yhong Siow, Thomas George Kallarakkal, Anand Ramanathan, Yi-Hsin Yang, Goot Heah Khor, Zainal Ariff Abdul Rahman, Siti Mazlipah Ismail, Narayanan Prepageran, Wan Mahadzir Wan Mustafa, Mannil Thomas Abraham, Keng Kiong Tay, Sok Ching Cheong, Rosnah Binti Zain

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Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2 by Brigitta Buttari, Antonella Tramutola, Ana I. Rojo, Niki Chondrogianni, Sarmistha Saha, Alessandra Berry, Letizia Giona, Joana P. Miranda, Elisabetta Profumo, Sergio Davinelli, Andreas Daiber, Antonio Cuadrado, Fabio Di Domenico

“…Given NRF2’s role in mitigating proteotoxic stress, the pharmacological modulation of NRF2 has emerged as a promising therapeutic strategy, even in aged preclinical models. By inducing NRF2, it is possible to mitigate the damaging effects of oxidative stress, metabolic dysfunction, and inflammation, thus reducing protein misfolding. …”
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Electrochemotherapy with bleomycin, oxaliplatin, or cisplatin in mouse tumor models, from tumor ablation to in situ vaccination by Katja Uršič Valentinuzzi, Katja Uršič Valentinuzzi, Urška Kamenšek, Urška Kamenšek, Simona Kranjc Brezar, Chloe Heranney, Chloe Heranney, Tilen Komel, Tilen Komel, Simon Buček, Simon Buček, Maja Čemažar, Maja Čemažar, Gregor Serša, Gregor Serša

“…Collectively, ECT demonstrated effectiveness in inducing in situ vaccination in both tumor models; however, an abscopal effect was observed in the 4T1 tumor model only.ConclusionsThis is the first preclinical study systematically comparing the immune involvement in intratumoral ECT’s efficiency using three distinct chemotherapeutic drugs in mouse tumor models. …”
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Evaluation of host immune responses to Mycobacteriophage Fionnbharth by route of delivery by Thomas Smytheman, Tiffany Pecor, Dana E. Miller, Debora Ferede, Suhavi Kaur, Matthew H. Harband, Hazem F. M. Abdelaal, Carlos A. Guerrero-Bustamante, Krista G. Freeman, Whitney E. Harrington, Lisa M. Frenkel, Graham F. Hatfull, Rhea N. Coler, Sasha E. Larsen

“…We aimed to determine the impact of repeated mucosal or intravenous (IV) delivery of representative anti-M.tb phage FionnbharthΔ45Δ47 (Fionnbharth) in a preclinical mouse model. In addition, we specifically sought to understand which route induced anti-phage antibodies, which may reduce the long-term impact of phage therapy. …”
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Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition by Mie K. Jakobsen, Sofie Traynor, Aaraby Y. Nielsen, Christina Dahl, Mette Staehr, Simon T. Jakobsen, Maria S. Madsen, Rasmus Siersbaek, Mikkel G. Terp, Josefine B. Jensen, Christina B. Pedersen, Anup Shrestha, Jonathan R. Brewer, Pascal H. G. Duijf, Odd L. Gammelgaard, Henrik J. Ditzel, Alexei F. Kirkin, Per Guldberg, Morten F. Gjerstorff

“…Abstract Background Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. …”
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The Croton genera (Euphorbiaceae) and its richness in chemical constituents with potential range of applications by Carlos Andrés Coy-Barrera, Laura Galvis, Maria Juliana Rueda, Sergio Alejandro Torres-Cortés

“…An important aspect to consider is that the present review of herbal medicines provides an alternative for developing new therapeutic objectives supported by preclinical studies and promotes new treatment options against the diseases that affect us in the current situation. …”
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Machine learning models for dementia screening to classify brain amyloid positivity on positron emission tomography using blood markers and demographic characteristics: a retrospec... by Noriyuki Kimura, Kotaro Sasaki, Teruaki Masuda, Takuya Ataka, Mariko Matsumoto, Mika Kitamura, Yosuke Nakamura, Etsuro Matsubara

“…This study developed machine learning models to classify positron emission tomography (PET) Aβ-positivity in participants with preclinical and prodromal AD using data accessible to primary care physicians. …”
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Immunotherapeutic Potential of Mollusk Hemocyanins in Combination with Human Vaccine Adjuvants in Murine Models of Oral Cancer by Juan José Mora Román, Miguel Del Campo, Javiera Villar, Francesca Paolini, Gianfranca Curzio, Aldo Venuti, Lilian Jara, Jorge Ferreira, Paola Murgas, Alvaro Lladser, Augusto Manubens, María Inés Becker

“…Here, we analyzed the preclinical therapeutic potential of the traditional keyhole limpet hemocyanin (KLH) and two new hemocyanins from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH) in mouse models of oral squamous cell carcinoma. …”
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