The radiation survival response of asynchronously-dividing populations of the cell line V79-WNRE indicates substructure in the low dose region that can be better characterized by separately fitting the data within the low and high dose regions to the linear-quadratic (LQ) equation. Flow cytometry and cell sorting techniques have been used to determine the response of both asynchronous populations and synchronous populations obtained by mitotic selection with or without an additional drug block. The statistically significant substructure which is present in the radiation response of asynchronous cells is absent in G1/S cells synchronized by mitotic selection followed by hydroxyurea (or aphidicolin) accumulation at the G1/S boundary. Such G1/S populations have a radiation response that is well characterized by a single LQ expression over 3 logs of cell inactivation. In contrast, the radiation response of cells synchronized by mitotic selection alone and irradiated in early G1 shows substantial substructure when fitted to the LQ equation, reflecting some radioresistance at high dose. While this response is well described by a single hit plus multitarget equation, it is possible that the small proportion (< 5%) of interphase cells in such mitotically-selected populations may be responsible for the resistance observed at higher doses.

Download full-text PDF

Source
http://dx.doi.org/10.1080/09553009314551821DOI Listing

Publication Analysis

Top Keywords

mitotic selection
12
radiation response
12
substructure radiation
8
radiation survival
8
survival response
8
low dose
8
high dose
8
response asynchronous
8
cells synchronized
8
synchronized mitotic
8

Similar Publications

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt's lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7).

View Article and Find Full Text PDF

Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies and immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available p38α inhibitors only allow for insufficient target inhibition. Here we describe a unique class of p38α inhibitors with ultralong target residence times (designated ULTR-p38i) that robustly inhibit p38α downstream signaling and induce distinct biological phenotypes.

View Article and Find Full Text PDF

Histone mutations (H3 K27M, H3 G34R/V) are molecular features defining subtypes of paediatric-type diffuse high-grade gliomas (HGG) (diffuse midline glioma (DMG), H3 K27-altered, diffuse hemispheric glioma (DHG), H3 G34-mutant). The WHO classification recognises in exceptional cases, these mutations co-occur. We report one such case of a 2-year-old female presenting with neurological symptoms; MRI imaging identified a brainstem lesion which was biopsied.

View Article and Find Full Text PDF

Canine oral melanoma (OM) exhibits poor prognosis and limited treatment options. The success of immune checkpoint inhibitors (ICIs) in human melanoma has driven interest in similar therapeutic approaches in the dog, although the immunosuppressive mechanisms adopted by canine OM remain unclear. This study aimed to evaluate the expression of the immune checkpoints PD-1/PD-L1 and CTLA-4 by RNAscope in situ hybridization (ISH) in canine OM, to investigate their expression pattern and explore their potential role in melanoma progression.

View Article and Find Full Text PDF

In-silico-based lead optimization of hit compounds targeting mitotic kinesin Eg5 for cancer management.

In Silico Pharmacol

January 2025

Phyto-medicine and Computational Biology Laboratory, Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State Nigeria.

Unlabelled: Lead optimization is vital for turning hit compounds into therapeutic drugs. This study builds upon a prior in silico research, where the hit compounds had better binding affinity and stability compared to a reference drug. Using a genetic algorithm, 12,500 analogs of the top compounds from the prior study were generated.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!