1. Quantitative mass spectrometry methods for pharmaceutical analysis
Glenn Loos, Ann Van Schepdael, Deirdre Cabooter Philos Trans A Math Phys Eng Sci. 2016 Oct 28;374(2079):20150366. doi: 10.1098/rsta.2015.0366.
Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage.This article is part of the themed issue 'Quantitative mass spectrometry'.
2. Palmitic acid: Enabling the tumor's nerves
H Furkan Alkan, Patricia Altea-Manzano, Sarah-Maria Fendt Cell Metab. 2022 Jan 4;34(1):7-9. doi: 10.1016/j.cmet.2021.12.015.
Diet can influence tumor aggressiveness. Recently in Nature, a study by Pascual et al. provided evidence that dietary palmitic acid induces an epigenetic memory by modulating particular histone methylation marks in cancer cells. This allows cancer cells to activate extracellular matrix secretion from Schwann cells of the tumor microenvironment, which ultimately potentiates metastasis initiation.
3. Tumor vessel co-option probed by single-cell analysis
Laure-Anne Teuwen, et al. Cell Rep. 2021 Jun 15;35(11):109253. doi: 10.1016/j.celrep.2021.109253.
Tumor vessel co-option is poorly understood, yet it is a resistance mechanism against anti-angiogenic therapy (AAT). The heterogeneity of co-opted endothelial cells (ECs) and pericytes, co-opting cancer and myeloid cells in tumors growing via vessel co-option, has not been investigated at the single-cell level. Here, we use a murine AAT-resistant lung tumor model, in which VEGF-targeting induces vessel co-option for continued growth. Single-cell RNA sequencing (scRNA-seq) of 31,964 cells reveals, unexpectedly, a largely similar transcriptome of co-opted tumor ECs (TECs) and pericytes as their healthy counterparts. Notably, we identify cell types that might contribute to vessel co-option, i.e., an invasive cancer-cell subtype, possibly assisted by a matrix-remodeling macrophage population, and another M1-like macrophage subtype, possibly involved in keeping or rendering vascular cells quiescent.
