Results 121 to 130 of about 1,354,013 (264)

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

Molecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer   +8 more
wiley   +1 more source

ZW4864‐mediated inhibition of the β‐catenin/BCL9/BCL9L complex reveals therapeutic potential in bladder cancer

Molecular Oncology, EarlyView.
BCL9 and BCL9L drive bladder cancer progression by enhancing β‐catenin signaling, promoting proliferation, migration, invasion, and organoid growth. Genetic depletion of BCL9(L) suppresses malignant phenotypes, while pharmacological disruption of the β‐catenin/BCL9(L) complex with ZW4864 inhibits canonical Wnt signaling and tumor‐associated cellular ...
Roland Kotolloshi, Mandy Berndt‐Paetz, Eileen Lerner, Gregoire Najjar, Anca Azoitei, Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer, Cagatay Günes, Otmar Huber, Marc‐Oliver Grimm, Daniel Steinbach   +11 more
wiley   +1 more source

Circulating microRNA signatures of cachexia and cancer in Canis familiaris as a comparative oncology model for human disease

Molecular Oncology, EarlyView.
Circulating microRNAs as biomarkers of cachexia and sex‐specific cancer in senior dogs. In 25 client‐owned dogs, four circulating miRNAs (miR‐15a, miR‐15b, miR‐16, miR‐140) were downregulated in cachexia, with miR‐16 the strongest individual biomarker (AUC = 0.899).
Soon‐Seok Park, Kyongman An, Gyeonghwa Kim, Soo‐Nyun Choi, Hong‐Ki Lee, Keun Hur, Kyu‐Shik Jeong   +6 more
wiley   +1 more source

Translating whole‐genome doubling into precision medicine in cancer

Molecular Oncology, EarlyView.
Whole‐genome doubling creates a WGD‐positive tumor state characterized by persistent chromosomal instability, karyotypic diversification, and cellular stress. These same biological pressures drive aggressive tumor evolution while exposing therapeutic vulnerabilities, providing a rationale for WGD‐informed precision medicine. Whole‐genome doubling (WGD)
Sejung Lee, Junghyeok Lim, Jinhyuk Bhin
wiley   +1 more source

Interferon beta drives therapy resistance in a patient‐derived model of high‐grade serous ovarian cancer

Molecular Oncology, EarlyView.
Interferon type 1 (IFN‐1) production and signaling is associated with the acquisition of therapy resistance, following chronic DNA damage, via Interferon‐related DNA damage resistance signature (IRDS) gene expression. An alternative, DNA damage‐independent role of sustained IFN‐1 mediated resistance was identified and characterized by the emergence of ...
Ashlyn Conant, Tise Suzuki, Kiera McGivney, V. S. S. Abhinav Ayyadevara, Sharon Asariah, Jay Deng, Ethan Nyein, Jacqueline Coats, Gary Yu, Yevgeniya J. Ioffe, Christian Hurtz, Juli J. Unternaehrer   +11 more
wiley   +1 more source

Pharmacological chromatin remodeling enhances response to estrogen therapy in ER+ breast cancer

Molecular Oncology, EarlyView.
Estrogen therapy elicits clinical benefit in ~ 30% of patients with endocrine‐resistant estrogen receptor (ER)‐positive breast cancer. Based on findings that ER transcriptional activation underlies response to estrogen therapy, we tested the effects of epigenetic dysregulation via pharmacological inhibition of histone deacetylases (HDACi).
Anneka L. Johnson Thomas, Barbara Karakyriakou, Patricia C. Muskus, Alyssa M. Roberts, Justin Rendleman, Alexa Warren, Hanxu Lu, Kimberly A. Birmingham, Malone K. Friedman, Abigail E. Goen, Huijuan Yang, Owen M. Wilkins, Fred W. Kolling, Eugene Demidenko, Julie M. Jorns, Brock C. Christensen, Todd W. Miller   +16 more
wiley   +1 more source

A light‐triggered Time‐Resolved X‐ray Solution Scattering (TR‐XSS) workflow with application to protein conformational dynamics

FEBS Open Bio, EarlyView.
Time‐resolved X‐ray solution scattering captures how proteins change shape in real time under near‐native conditions. This article presents a practical workflow for light‐triggered TR‐XSS experiments, from data collection to structural refinement. Using a calcium‐transporting membrane protein as an example, the approach can be broadly applied to study ...
Fatemeh Sabzian‐Molaei, Fredrik Orädd, Konstantinos Magkakis, Magnus Andersson   +3 more
wiley   +1 more source

Single‐molecule DNA flow‐stretch assays for high‐throughput DNA–protein interaction studies

FEBS Open Bio, EarlyView.
We describe an optimised single‐molecule DNA flow‐stretch assay that visualises DNA–protein interactions in real time. Linear DNA fragments are tethered to a surface and stretched by buffer flow for fluorescence imaging. Using λ and φX174 DNA, this protocol enhances reproducibility and accessibility, providing a versatile approach for studying diverse ...
Ayush Kumar Ganguli, Mohammad Nour Alsamsam, Ugnė Bagdonaitė, Van Truc Vu, Chun‐Jen Huang, Polina Kuzhir, Mindaugas Zaremba, Aurimas Kopūstas, Marijonas Tutkus   +8 more
wiley   +1 more source

Analysing the significance of small conformational changes and low occupancy states in serial crystallographic data

FEBS Open Bio, EarlyView.
This protocol paper outlines methods to establish the success of a time‐resolved serial crystallographic experiment, by means of statistical analysis of timepoint data in reciprocal space and models in real space. We show how to amplify the signal from excited states to visualise structural changes in successful experiments.
Jake Hill, Yelyzaveta Pulnova, Elke De Zitter, Helen M. Ginn, Briony A. Yorke   +4 more
wiley   +1 more source