In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade.

Introduction: CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade.

Methods: Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation.

Electron vs proton FLASH radiation on murine skin toxicity.

Background And Purpose: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons.

Clonal driver neoantigen loss under EGFR TKI and immune selection pressures.

Neoantigen vaccines are under investigation for various cancers, including epidermal growth factor receptor (EGFR)-driven lung cancers. We tracked the phylogenetic history of an EGFR mutant lung cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, including EGFR exon 19 deletion (ex19del). The ex19del mutation was clonal, but is likely to have appeared after a whole-genome doubling (WGD) event.

The fractionation effect on proton RBE in a late normal tissue damage model in vivo.

Background And Purpose: A constant relative biological effectiveness (RBE) of 1.1 is used in clinical proton therapy (PT) to convert prescribed photon doses into isoeffective proton doses. However, the RBE is not constant; it is a dynamic parameter highly influenced by factors such as linear energy transfer, tissue type, biological endpoint, and dose/fraction.

Development and validation of an LC-MS/MS method for quantification of Osimertinib and its two metabolites AZ7550 and AZ5104 in human plasma including long-time storage.

Osimertinib (AZD9291) is a widely used tyrosine kinase inhibitor for the treatment of non-small cell lung cancer patients with activating EGFR mutations. However, the correlation between dose and efficacy has been debated for several years. For this reason, there is a need for standardized methods for routine analysis, clinical studies on pharmacokinetics and dose-response relationships, and greater understanding of preanalytical conditions, such as sample storage stability.