Imaging PD-L1 in the brain-Journey from the lab to the clinic.

Background: Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy.

Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRAS with Demonstrable CNS Penetration.

The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of , AZD4747, a clinical development candidate for the treatment of KRAS-positive tumors, including the treatment of central nervous system (CNS) metastases. Building on our earlier discovery of C5-tethered quinazoline AZD4625, excision of a usually critical pyrimidine ring yielded a weak but brain-penetrant start point which was optimized for potency and DMPK.

Type I atlanto-occipital dislocation complicated by non-communicating hydrocephalus - A case report.

Hydrocephalus, an extremely rare complication of craniocervical junction injuries, is postulated to result from compression of the fourth ventricular cerebrospinal fluid (CSF) outlets by fractured and displaced bone fragments, a swollen upper spinal cord or adhesions formed after a traumatic subarachnoid haemorrhage. We present the case of a 21-year-old woman for whom an injury to the cervical spine complicated by a type I atlanto-occipital dislocation contributed to the development of non-communicating hydrocephalus. The hydrocephalus was probably a consequence of impaired CSF circulation at the fourth ventricular outlets (the foramina of Luschka and Magendie), caused by post-haemorrhagic adhesions formed after severe injury to the craniocervical junction.

External validation of the Chicago Chiari Outcome Scale in adults with Chiari malformation type I.

Objective: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients.

Preservation of the Hypoxic Transcriptome in Glioblastoma Patient-Derived Cell Lines Maintained at Lowered Oxygen Tension.

Despite numerous efforts aiming to characterise glioblastoma pathology (GBM) and discover new therapeutic strategies, GBM remains one of the most challenging tumours to treat. Here we propose the optimisation of in vitro culturing of GBM patient-derived cells, namely the establishment of GBM-derived cultures and their maintenance at oxygen tension mimicking oxygenation conditions occurring within the tumour. To globally analyse cell states, we performed the transcriptome analysis of GBM patient-derived cells kept as spheroids in serum-free conditions at the reduced oxygen tension (5% O), cells cultured at atmospheric oxygen (20% O), and parental tumour.