Finding novel vulnerabilities of hypomorphic BRCA1 alleles
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 +10 more
wiley +1 more source
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 +9 more
wiley +1 more source
Tackling regulated cell death yields enhanced protection in lung grafts. [PDF]
Chen Q +14 more
europepmc +1 more source
Enhancing Fundamental Rights Protection
The EU should ensure fundamental rights’ compatibility of EU legislation before its adoption. To that effect, we propose three distinct paths to improve the EU control mechanisms. Whilst mechanisms to ensure quality control do exist, primarily in the form of impact assessments, these mostly remain a merely formal exercise.
Gambardella, Ilaria +6 more
openaire +2 more sources
Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization
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 +13 more
wiley +1 more source
Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine. [PDF]
Hawman DW +21 more
europepmc +2 more sources
Self-Adjuvanting TLR7/8 Agonist and Fentanyl Hapten Co-Conjugate Achieves Enhanced Protection against Fentanyl Challenge. [PDF]
Powers N +8 more
europepmc +1 more source
Loss of proton‐sensing TDAG8 increases tumor progression in mouse models of colon cancer
Loss of the pH‐sensing receptor TDAG8 accelerates colorectal cancer progression in mice. Animals lacking TDAG8 expression had increased tumor growth, DNA damage, and recruitment of tumor‐associated immune cells, including macrophages, neutrophils, and monocytes.
Ermanno Malagola +11 more
wiley +1 more source
Intravenous BCG Vaccination of Diversity Outbred Mice Results in Moderately Enhanced Protection against Challenge with Mycobacterium tuberculosis Compared to Intradermal Vaccination. [PDF]
Kurtz SL +5 more
europepmc +1 more source
Breast cancer remains a major cause of cancer death in women, frequently developing endocrine therapy resistance. This study demonstrates that upregulated p21‐activated kinase 1 (PAK1) activity drives resistance to tamoxifen and long‐term estrogen deprivation in ER+ breast cancer models.
Luisa Schwarzmüller +10 more
wiley +1 more source

