Prognostic relevance of glycosylation-associated genes in breast cancer

Glycosylation of cellular proteins has important impact on their stability and functional properties, and glycan structures strongly influence cell adhesion. Many enzymes are involved in glycoconjugate synthesis and degradation, but there is only limited information about their role in breast cancer progression. Therefore, we retrieved RNA expression data of 202 glycosylation genes generated by microarray analysis (Affymetrix HG-U133A) in a cohort of 194 mammary carcinomas with long-term follow-up information. After univariate and multivariate Cox regression analysis, genes with independent prognostic value were identified. These were further analysed by Kaplan–Meier analysis and log-rank tests, and their prognostic value was validated in a second cohort of 200 tumour samples from patients without systemic therapy. In our first cohort, we identified 24 genes with independent prognostic value, coding for sixteen anabolic and eight catabolic enzymes. Functionally, these genes are involved in all important glycosylation pathways, namely O-glycosylation, N-glycosylation, O-fucosylation, synthesis of glycosaminoglycans and glycolipids. Eighteen genes also showed prognostic significance in chemotherapy-treated patients. In the second cohort, six of the 24 relevant genes were of prognostic significance (FUT1, FUCA1, POFUT1, MAN1A1, RPN1 and DPM1), whereas a trend was observed for three additional probesets (GCNT4, ST3GAL6 and UGCG). In a stratified analysis of molecular subtypes combining both cohorts, great differences appeared suggesting a predominant role of N-glycosylation in luminal cancers and O-glycosylation in triple-negative ones. Correlations of gene expression with metastases of various localizations point to a role of glycan structures in organ-specific metastatic spread. Our results indicate that various glycosylation reactions influence progression and metastasis of breast cancer and might thus represent potential therapeutic targets.     

Karyotyping mouse chromosomes by multiplex-FISH (M-FISH)

Karyotyping of mouse chromosomes is a skillful art, which is laborious work even for experienced cytogeneticists. With the growing number of mouse models for human diseases, there is an increasing demand for automated mouse karyotyping systems. Here, such a karyotyping system for mouse chromosomes based on the multiplex-fluorescence in-situ hybridization (M-FISH) technology is shown. The system was tested on a number of individual mice with numerical and structural aberrations and its reproducibility and robustness verified. Mouse M-FISH should be a valuable tool for the analysis of chromosomal rearrangements in mice.     

Embracing bioethics in neonatal intensive care, part I: evolving toward neonatal evidence-based ethics

Ethical treatment dilemmas are not new to the NICU. With technologic advances over the past 20 years, NICU care has developed rapidly, and survival rates have improved for some of the tiniest and most critically ill infants. In guiding clinical practice, however, standards in evidenced-based medicine have often superseded standards in evidence-based ethics. Part I of this article presents a historical review of neonatal care and an overview of cases that have set precedents in neonatal ethical debate. It also includes recommendations for enhancing the skills of neonatal nurses as patient advocates in NICU ethical issues, an area that is, at times, controversial and baffling to clinicians.     

Update Breast Cancer 2022 Part 4 – Advanced-Stage Breast Cancer

For the treatment of patients with advanced HER2-negative hormone receptor-positive breast cancer, several substances have been introduced into practice in recent years. In addition, other drugs are under development. A number of studies have been published over the past year which have shown either an advantage for progression-free survival or for overall survival. This review summarizes the latest results, which have been published at current congresses or in specialist journals, and classifies them in the clinical treatment context. In particular, the importance of therapy with CDK4/6 inhibitors – trastuzumab deruxtecan, sacituzumab govitecan and capivasertib – is discussed. For trastuzumab deruxtecan, an overall survival benefit in HER2-negative breast cancer with low HER2 expression (HER2-low expression) was reported in the Destiny-Breast-04 study. Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. The lack of overall survival benefit for palbociclib in the first line of therapy raises the question of clinical classification.Key words: advanced breast cancer, chemotherapy, endocrine therapy, antibody drug conjugates     

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.Key words: breast cancer, surgery, chemotherapy, therapy standard