Spatial competition constrains resistance to targeted cancer therapy

Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden and resistance in tumour spheroids, but not in monolayer culture. Mathematical modelling indicates that tumour spatial structure amplifies the fitness penalty of resistant cells, and identifies their relative fitness as a critical determinant of the clinical benefit of AT. Our results justify further investigation of AT with kinase inhibitors

<em>Adenium obesum</em> flowers extract mitigates testicular injury and oxidative stress in streptozotocin-induced diabetic rats.

Background and Objective: Diabetes Mellitus (DM) is a major healthcare problem worldwide and considerable evidence proved its negative impact on the male reproductive system. Adenium obesum is an interesting medicinal plant with a wide range of bioactivities. The current study examined the protective effects of A. obesum flower extract (AOE) on testicular injury in streptozotocin (STZ)-induced type I diabetic rats. Materials and Methods: Diabetes was induced by a single injection of 50 mg kg(-1) STZ. Diabetic rats received 250 and 500 mg kg(-1) AOE for 21 days and samples were collected for analysis. Results: As compared to the diabetic control rats, treatment with AOE increased serum testosterone, Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels, decreased testicular thiobarbituric acid reactive substances (TBARS) content, effectively enhanced reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Additionally, AGE effectively inhibited diabetes-induced testicular tissue injuryand prevented inflammatoryand apoptotic responses manifested by decreased TNF-alpha, IL-6 and Bax and increased Bcl-2. Conclusion: These results demonstrated that AGE mitigates testicular injury, oxidative stress, inflammatory response and apoptotic cell death in STZ-induced diabetic rats

Does the timing of oral feeding affect the fistulization risk among head and neck cancer patients undergoing free flap reconstruction?

No abstract available