Implementation of MALDI Mass Spectrometry Imaging in Cancer Proteomics Research: Applications and Challenges.

Studying the proteome-the entire set of proteins in cells, tissues, organs and body fluids-is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may lead to a better understanding of tumor biology and to a more effective diagnosis, prognosis, recurrence and response to therapy. Moreover, proteins can act as a biomarker or potential drug targets.

Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients.

(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC.

MALDI Mass Spectrometry Imaging Linked with Top-Down Proteomics as a Tool to Study the Non-Small-Cell Lung Cancer Tumor Microenvironment.

Advanced non-small-cell lung cancer (NSCLC) is generally linked with a poor prognosis and is one of the leading causes of cancer-related deaths worldwide. Since only a minority of the patients respond well to chemotherapy and/or targeted therapies, immunotherapy might be a valid alternative in the lung cancer treatment field, as immunotherapy attempts to strengthen the body's own immune response to recognize and eliminate malignant tumor cells. However, positive response patterns to immunotherapy remain unclear.

Diagnostic considerations regarding pediatric delirium: a review and a proposal for an algorithm for pediatric intensive care units.

Context: If delirium is not diagnosed, it is unlikely that any effort will be made to reverse it. Given evidence for under-diagnosis, tools that aid recognition are required.

Objective: Relating three presentations of pediatric delirium (PD) to standard criteria and developing a diagnostic algorithm.

Pediatric illness severity measures predict delirium in a pediatric intensive care unit.

Context: Delirium in children is a serious but understudied neuropsychiatric disorder. So there is little to guide the clinician in terms of identifying those at risk.

Objective: To study, in a pediatric intensive care unit (PICU), the predictive power of widely used generic pediatric mortality scoring systems in relation to the occurrence of pediatric delirium (PD).