Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models.

Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis.

Patient-derived xenografts (PDX) are tumor-in-mouse models for cancer. PDX collections, such as the NCI PDXNet, are powerful resources for preclinical therapeutic testing. However, variations in experimental and analysis procedures have limited interpretability.

Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27.

In silico design of small molecule inhibitors of CDK9/cyclin T1 interaction.

In order to design a small molecule which potentially may interfere with CDK9/cyclin T1 complex formation and therefore influence its physiological role, a computational study of dynamics and druggability of CDK9 binding surface was conducted. Druggability estimates and pocket opening analyses indicated binding regions of cyclin T1 residues, Phe 146 and Lys 6, as starting points for the design of small molecules with the potential to inhibit the CDK9/cyclin T1 association. A pharmacophore model was created, based on these two residues and used to select potential inhibitor structures.

Computational study and peptide inhibitors design for the CDK9 - cyclin T1 complex.

Cyclin dependent kinase 9 (CDK9) is a protein that belongs to the cyclin-dependent kinases family, and its main role is in the regulation of the cell transcription processes. Since the increased activity of CDK9 is connected with the development of pathological processes such as tumor growth and survival and HIV-1 replication, inhibition of the CDK9 could be of particular interest for treating such diseases. The activation of CDK9 is initiated by the formation of CDK9/cyclin T1 complex, therefore disruption of its formation could be a promising strategy for the design of CDK9 inhibitors.