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Berkovska, O.

Publications and source records attributed to Berkovska, O..

2 recordsLinked to original sources

Mass spectrometry-based proteomics delivers in-depth proteome profiling of FFPE lung cancer biopsies from single glass slides

Clinical proteomics has the potential to add a valuable data layer to genomic and histopathological analyses in precision oncology, but its application to limited clinical material remains challenging. Here, we demonstrate that state-of-the-art mass spectrometry-based proteomics enables in-depth proteomic profiling of formalin-fixed paraffin-embedded (FFPE), including small biopsies and single tissue sections mounted on glass slides. Despite minimal input material, single-slide analyses of clinical lung tumor specimens yielded biologically and clinically informative data, supporting detection of actionable proteins, immune-related signatures, and multivariate biomarkers. These results establish the feasibility of proteomics for retrospective FFPE studies and routine clinical practice, expanding opportunities for biomarker discovery and precision medicine from scarce tissue material.

cancer biology↗

A microparticulate based formulation to protect therapeutic enzymes from proteolytic digestion: phenylalanine ammonia lyase as case study

Phenylketonuria is a genetic disorder affecting the metabolism of phenylalanine (phe) due to a deficiency in the enzyme phenylalanine hydroxylase. This disorder is characterized by an elevated phe blood level, which can lead to severe intellectual disabilities in newborns. The current strategy to prevent these devastating consequences is limited to a life-long phe-free diet, which implies major lifestyle changes and restrictions. Recently, an injectable enzyme replacement therapy, Pegvaliase, has been approved for treating phenylketonuria, but is associated with significant side-effects. In this study a phe-metabolizing system suitable for oral delivery is designed to overcome the need for daily injections. Active phenylalanine ammonia-lyase (PAL), an enzyme that catalyzes phe metabolism, is loaded into mesoporous silica microparticles (MSPs) with pore sizes ranging from 10 to 35 nm. The surface of the MSPs is lined with a semipermeable barrier to allow permeation of phe while blocking digestive enzymes that degrade PAL. The enzymatic activity can be partially preserved in vitro by coating the MSPs with poly(allylamine) and poly(acrylic acid)-bowman birk (protease inhibitor) conjugate. The carrier system presented herein may provide a general approach to overcome gastro-intestinal proteolytic digestion and to deliver active enzymes to the intestinal lumen for prolonged local action.

bioengineering↗