Results 131 to 140 of about 87,604,756 (316)

Loss of IGF‐1R impairs DNA‐PKcs recruitment to chromatin leading to defective end‐joining

Molecular Oncology, EarlyView.
IGF‐1R promotes radioresistance by facilitating DNA‐PKcs recruitment to chromatin, enabling non‐homologous end‐joining (NHEJ) repair of double‐strand breaks. Inhibition or loss of IGF‐1R disrupts this recruitment to damage sites, driving compensatory reliance on microhomology‐mediated end‐joining (MMEJ) repair.
Matthew O. Ellis, Jack V. Mills, Wojciech Niedzwiedz, Valentine M. Macaulay   +3 more
wiley   +1 more source

Cigarette smoke and cigarette smoke condensate induce cell injury and early biomarkers of inflammation in human and rodent Precision-Cut Lung Slices

, 2022
S.173The use of high animal numbers and the suffering of animals in experiments such as repeated dose toxicity studies (RDT)demand for alternative test approaches. This can be done by grouping of chemicals to reduce in vivo studies.
Braubach, Peter, Sewald, Katherina, Braun, Armin, Knebel, Jan W., Ritter, Detlef, Obernolte, Helena, Jonigk, Danny   +6 more
core   +1 more source

USP29‐regulated noncanonical stabilization of the hypoxia‐inducible factor‐α in aggressive prostate cancer

Molecular Oncology, EarlyView.
We identify USP29 as the only DUB mirroring CA9 expression, a marker of hypoxia and HIF pathway activation associated with PCA aggressiveness. USP29 stabilizes HIF‐1α and HIF‐2α via a noncanonical mechanism that is independent of PHD/pVHL activity yet relies on proteasomal regulation, establishing USP29 as a previously unrecognized regulator of hypoxic
Amelie S Schober, Leire Moreno‐Cugnon, Laura Martínez‐Pérez, Amaia Ercilla, Amaia Zabala‐Letona, Adrián Vicente‐Barrueco, Maider Fagoaga‐Eugui, Saioa Garcia‐Longarte, Blanca Calle‐Ciborro, Encarnación Pérez‐Andrés, Onintza Carlevaris, Sara Pozo, Isabel Mendizabal, Ugo Mayor, Arkaitz Carracedo, Violaine Sée, Edurne Berra   +16 more
wiley   +1 more source

Mission and accomplishments of ZEBET, the national centre for alternatives in Germany at the BfR (Federal Institute for Risk Assessment)

, 2008
Replacement of the rabbit Draize skin irritation test or the animal photo-irritation test is in course in Europeunder the REACH chemical strategy and the Cosmetics Directive. Various in vitro protocols, including3D skin models, have been assessed.
Seiler,A., Liebsch,M., Spielmann,H., Grune,B., Vogel,R.   +4 more
core  

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 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

Mechanistic read-across comes of age: a comparative appraisal of EFSA 2025 guidance, ECHA’s RAAF, and good read-across practice

Frontiers in Toxicology
Read-across has matured from an expert-driven extrapolation based largely on structural analogy into a rigorously documented, mechanistically informed cornerstone of next-generation risk assessment.
Thomas Hartung, Thomas Hartung, Thomas Hartung, Thomas Hartung, Costanza Rovida, Costanza Rovida   +5 more
doaj   +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

Assigning Ethical Weights to Clinical Signs Observed During Toxicity Testing

, 2017
Reducing the number of laboratory animals used and refining experimental procedures to enhance animal welfare are fundamental questions to be considered in connection with animal experimentation.
Ringblom, Joakim, Hansson, Sven Ove, Öberg, Mattias, Öberg, M., Törnqvist, Elin, Hansson, Sven Ove,, Rudén, C., Rudén, Christina,, Ringblom, J., Törnqvist, E.   +9 more
core   +1 more source

Advancing next-generation brain organoid platforms for investigating traumatic brain injury from repeated blast exposures

Frontiers in Bioengineering and Biotechnology
Service members and law enforcement personnel are frequently exposed to blast overpressure during training and combat due to the use of heavy weaponry such as large-caliber rifles, explosives, and ordnance.
Eyal Bar-Kochba, Catherine M. Carneal, Vanessa D. Alphonse, Andrea C. Timm, Amanda W. Ernlund, Carissa L. Rodriguez, Itzy E. Morales Pantoja, Lena Smirnova, Thomas Hartung, Thomas Hartung, Andrew C. Merkle   +10 more
doaj   +1 more source