ABSTRACT
Receptor tyrosine kinase erythroblastic oncogene B2 (ERBB2), also known as human epidermal growth factor receptor 2 (HER2), represents an oncogenic driver and has been effectively targeted in breast and gastric cancer. Recently, next-generation sequencing (NGS) discovered ERBB2 as a promising therapeutic target in metastatic colorectal cancer (mCRC), where it is altered in 3-5% of patients, but no therapies are currently approved for this use. Herein, we present the experience of a single center in diagnosing actionable genetic ERBB2 alterations using NGS and utilizing the latest therapeutic options. Between October 2019 and December 2022, a total of 107 patients with advanced CRC underwent molecular analysis, revealing actionable ERBB2 mutations in two patients and ERBB2 amplifications in two other patients. These findings correlated with immunohistochemical (IHC) staining. Of these four patients, two were treated with trastuzumab-deruxtecan (T-DXd). We present two exemplary cases of patients with actionable ERBB2 alterations to demonstrate the effectiveness of T-DXd in heavily pretreated ERBB2-positive mCRC patients and the need for early molecular profiling. To fully exploit the potential of this promising treatment, earlier molecular profiling and the initiation of targeted therapies are essential.
ABSTRACT
BACKGROUND: Cell characteristics, including cell type, size, shape, packing, cell-to-cell-adhesion, intercellular space, and cell wall thickness, influence the physical characteristics of plant tissues. Genotypic differences were found concerning damage susceptibility related to beet texture for sugar beet (Beta vulgaris). Sugar beet storage roots are characterized by heterogeneous tissue with several cambium rings surrounded by small-celled vascular tissue and big-celled sugar-storing parenchyma between the rings. This study presents a procedure for phenotyping heterogeneous tissues like beetroots by imaging. RESULTS: Ten Beta genotypes (nine sugar beet and one fodder beet) were included to establish a pipeline for the automated histologic evaluation of cell characteristics and tissue arrangement using digital image processing written in the programming language R. The identification of cells has been validated by comparison with manual cell identification. Cells are reliably discriminated from intercellular spaces, and cells with similar morphological features are assigned to biological tissue types. CONCLUSIONS: Genotypic differences in cell diameter and cell arrangement can straightforwardly be phenotyped by the presented workflow. The presented routine can further identify genotypic differences in cell diameter and cell arrangement during early growth stages and between sugar storage capabilities.
ABSTRACT
BACKGROUND: The assessment of the environmental risks for pesticides is a current topic of the European Union (EU) strategy 'Farm to Fork'. Therefore, an analysis of the status quo of pesticide use from 2010 to 2015 and the associated environmental risks was performed for sugar beet cultivation in Germany. Based on this assessment, crop protection strategies should be developed that contribute to risk reduction. RESULTS: Pesticide use data from 2314 randomly chosen sugar beet growing farms were available from annual farm surveys from 2010 until 2015. Possible environmental risks from pesticide applications were calculated with the model SYNOPS-GIS. Each pesticide application pattern was combined with several model fields. The concentrations of active ingredients in the non-target compartments, namely soil, neighboring surface waters and field margins, were used to determined risk indices (exposure toxicity ratios, ETRs) for different terrestrial and aquatic reference species. ETRs were mainly lower than a risk threshold used throughout this study (ETR = 1). The risks caused by herbicide use were studied in more detail since herbicides are applied on nearly all fields. The aquatic risks posed by herbicides were independent of specific active ingredients or application patterns. Instead, certain combinations of active ingredients, application dates and field-specific environmental conditions provoked higher risks. The aquatic risks were strongly influenced by the distance of the fields to surface waters. CONCLUSIONS: Further risk mitigation seems possible by combining field-specific measures and technical options. © 2021 Society of Chemical Industry.
