Results 51 to 60 of about 96,194 (242)

Quantitative Systems Pharmacology Model of a Masked, Tumor‐Activated Antibody

CPT: Pharmacometrics & Systems Pharmacology, 2019
PROBODY therapeutics (Pb‐Tx) are protease‐activatable prodrugs of monoclonal antibodies (mAbs) designed to target tumors where protease activity is elevated while avoiding normal tissue.
Mark Stroh, Jason Sagert, John M. Burke, Joshua F. Apgar, Lin Lin, Bjorn L. Millard, W. Michael Kavanaugh   +6 more
doaj   +1 more source

Discerning protein pools by selective staining with self‐labeling tags

FEBS Letters, EarlyView.
Cell surface proteins have an intra‐ and extracellular pool. Combining genetic fusion to self‐labeling tags that can be addressed with small molecule fluorophores allows separating these pools. We highlight recent developments and techniques for state‐of‐the‐art interrogation of cell surface proteins in the complex tissue setting.
Kati Fischermanns, Johannes Broichhagen
wiley   +1 more source

Frequency‐Domain Response Analysis for Quantitative Systems Pharmacology Models [PDF]

CPT: Pharmacometrics & Systems Pharmacology, 2017
Drug dosing regimen can significantly impact drug effect and, thus, the success of treatments. Nevertheless, trial and error is still the most commonly used method by conventional pharmacometric approaches to optimize dosing regimen. In this tutorial, we utilize four distinct classes of quantitative systems pharmacology models to introduce frequency ...
Schulthess, P., Post, T.M., Yates, J.W.T., Graaf, P.H. van der   +3 more
openaire   +3 more sources

Autophagy and mitophagy in pancreatic β‐cell homeostasis and their involvement in diabetes pathophysiology

FEBS Letters, EarlyView.
This review focuses on the role of autophagy and mitophagy in maintaining pancreatic β‐cell function and homeostasis. We discuss how genetic defects affecting these pathways contribute to the development of type 1, type 2, monogenic, and gestational diabetes. We further explore their potential as therapeutic targets. Created in BioRender.
Yunkyeong Lee, Mingming Tong, Anna L. Gloyn   +2 more
wiley   +1 more source

Partial depletion of plasminogen activator inhibitor‐1 decreases subcutaneous fat cell hypertrophy and liver cholesterol in high‐fat‐fed female mice

FEBS Letters, EarlyView.
Obesity raises blood levels of PAI‐1, a protein linked to metabolic dysfunction‐associated steatotic liver disease in people with obesity. In female mice fed a high‐fat diet, partially lowering PAI‐1 led to smaller subcutaneous fat cells and lower liver cholesterol, without changing body weight or insulin sensitivity.
Claudia E. Ramirez Bustamante, Robert Sharp, Pradip K. Saha, Elizabeth S. Anaya, Elizabeth L. Lieu, Evelyn L. de Groot, Pooja Patel, Mi Jeong Heo, Aaron R. Cox, Kang Ho Kim, Sean M. Hartig   +10 more
wiley   +1 more source

Quantitative Systems Toxicology Modeling of Acetaminophen Pharmacokinetics and Hepatic Biomarkers After Overdoses of Extended‐Release and Immediate‐Release Formulations in Adults With Chronic Alcohol Use or Low Glutathione

CPT: Pharmacometrics & Systems Pharmacology
Acetaminophen (APAP), an over‐the‐counter analgesic and antipyretic, can cause hepatotoxicity when ingested in large overdoses. APAP has multiple formulations including immediate‐release (IR) and extended‐release (ER) preparations.
Kyunghee Yang, James J. Beaudoin, Brett A. Howell, James Mullin, Elham Amini, John C. K. Lai, Cathy K. Gelotte, Sury Sista, Evren Atillasoy   +8 more
doaj   +1 more source

Dimethyl fumarate combined with cisplatin at subcytotoxic doses sensitizes cervical cancer toward ferroptosis and apoptosis through GSH restriction and p53 (re)activation

Molecular Oncology, EarlyView.
Dimethyl fumarate (DMF) reduces growth of HPV‐positive cervical cancer spheroids and induces ferroptosis in cervical cancer cells via blocking SLC7A11/Glutathione (GSH) axis. Combination of subcytotoxic doses of DMF and cisplatin (CDDP) further suppresses spheroid growth and drives cell death in 2D culture models.
Carolina Punziano, Giuseppina Minopoli, Simona Romano, Laura Marrone, Katia Aquilano, Maria Lina Tornesello, Raffaella Faraonio   +6 more
wiley   +1 more source

A novel quinazolinone insulin receptor inhibitor and its synergy with an EGFR inhibitor in glucose‐driven glioblastoma

Molecular Oncology, EarlyView.
The novel styrylquinazolinone‐based molecule W1B effectively suppresses glioblastoma by inhibiting IGF1R and EGFR. In high‐glucose microenvironments driving tumor resistance, W1B acts synergistically with the EGFR inhibitor dacomitinib. This combination safely blocks compensatory survival signaling in zebrafish xenograft models. Showcasing promising in
Patryk Rurka, Wioleta Cieślik, Wojciech Płaziński, Katarzyna Stępnik, Anna Boguszewska‐Czubara, Elżbieta Kot, Robert Musioł, Mateusz Jasica, Anna Mrozek‐Wilczkiewicz, Katarzyna Malarz   +9 more
wiley   +1 more source

Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization

Molecular Oncology, EarlyView.
In the current study, we demonstrate that the oncogene DMTF1β regulates ULK1 stability by reducing its proteasomal degradation in cancer cells. This stabilization enables ULK1 to induce autophagy, which in turn facilitates cancer cell migration. Consequently, reduced DMTF1β levels lead to decreased autophagy and impaired cancer cell migration.
Jun Xu, Nicolas J. Niklaus, Anna M. Schläfli, Igor Tokarchuk, Magali Humbert, Federico La Manna, Bich Vu, David Maul, Ramin Radpour, Marianna Kruithof‐de Julio, Inti Zlobec, Jörn Dengjel, Bruce E. Torbett, Mario P. Tschan   +13 more
wiley   +1 more source

Quantitative systems pharmacology of interferon alpha administration: A multi-scale approach.

PLoS ONE, 2019
The therapeutic effect of a drug is governed by its pharmacokinetics which determine the downstream pharmacodynamic response within the cellular network. A complete understanding of the drug-effect relationship therefore requires multi-scale models which
Priyata Kalra, Julian Brandl, Thomas Gaub, Christoph Niederalt, Jörg Lippert, Sven Sahle, Lars Küpfer, Ursula Kummer   +7 more
doaj   +1 more source