Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Evaluation of Central Venous Access with Accelerated Seldinger Technique Versus Modified Seldinger Technique

Background

Central vein catheter (CVC) placement using the modified Seldinger technique is a common procedure in the emergency department, but can be time consuming due to the multiple pieces of equipment included in central line kits and the number of steps in the procedure. Preassembled devices combine a needle, guidewire, dilator, and sheath into one unit and potentially simplify the process and reduce time required for CVC placement using the accelerated Seldinger technique.

Erythema ab igne with features resembling keratosis lichenoides chronica

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low‐grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.     

The nature and extent of emotion recognition and empathy impairments in children showing disruptive behaviour referred into a crime prevention programme

Childhood disruptive behaviour has been linked to later antisocial and criminal behaviour. Emotion recognition and empathy impairments, thought to be caused by inattention to the eye region, are hypothesised to contribute to antisocial and criminal behaviour. This is the first study to simultaneously examine emotion recognition and empathy impairments, their relationship, and the mechanism behind these impairments, in children with disruptive behaviour. We hypothesised that children with disruptive behaviour would exhibit negative emotion recognition and cognitive and affective empathy impairments, but that these impairments would not be due to reduced attention to the eye region. We expected these emotion impairments to be driven by disruptive behaviour. We also expected a relationship between emotion recognition and cognitive empathy only. Ninety-two children with disruptive behaviour, who were participating in a police crime prevention programme and rated by their schoolteacher using the Strengths and Difficulties Questionnaire (DB; mean age 8.8 years, 80% male), took part. There was a comparison group of 58 typically developing children (TD; mean age 9.7 years, 78% male). All children completed emotion recognition and empathy tasks, both with concurrent eye tracking to assess social attention. Not only were DB children significantly impaired in negative emotion and neutral emotion recognition, and in cognitive and affective empathy compared to the TD children, but severity of disruptive behaviour also predicted intensity of emotion impairments. There were no differences in social attention to the eye region. Negative emotion recognition and empathy impairments are already present in an identifiable group of children displaying disruptive behaviour. These findings provide evidence to encourage the use of targeted interventions.     

Enhanced NADPH oxidases and reactive oxygen species in the mechanism of methanol-initiated protein oxidation and embryopathies in vivo and in embryo culture

Methanol (MeOH) teratogenicity in rodents may be mediated in part by reactive oxygen species (ROS), the source of which is unknown. To determine if MeOH enhances embryonic ROS-producing NADPH oxidases (NOXs), p22phox mRNA and protein and oxidatively damaged protein were measured in gestational day 12 MeOH-exposed CD-1 mouse embryos with or without pretreatment with the free radical spin trap phenylbutylnitrone (PBN) or the NOX inhibitor diphenyleneiodonium chloride (DPI). MeOH exposure upregulated p22phox mRNA and protein expression, and enhanced protein oxidation, within 3–6 h. Compared to embryos exposed to MeOH alone, PBN and DPI pretreatment decreased MeOH-enhanced p22phox mRNA expression, DPI but not PBN blocked p22phox protein expression, and both blocked protein oxidation. To assess developmental relevance, mouse embryos were exposed in culture for 24 h to MeOH or vehicle with or without pretreatment with PBN, DPI, or the prostaglandin H synthase (PHS) inhibitor eicosatetraynoic acid (ETYA), and evaluated for abnormalities. ETYA did not prevent MeOH embryopathies, despite blocking phenytoin embryopathies (ROS-initiating positive control), precluding bioactivation of MeOH or its metabolites by PHS. Concentration-dependent MeOH embryopathies were blocked by both DPI and PBN pretreatment, suggesting that enhanced embryonic NOX-catalyzed ROS formation and oxidative stress may contribute to the mechanism of MeOH embryopathies.