Activity

To evaluate the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing, cost, and clinical implications of enfortumab vedotin-ejfv (EV) in the treatment of locally advanced or metastatic urothelial carcinoma (UC).

A literature search of PubMed (inception to August 2020) was conducted using the terms

, and

. Data were also obtained from package inserts, meeting abstracts, and ongoing studies from ClinicalTrials.gov.

All relevant published articles, package inserts, and meeting abstracts evaluating EV for the treatment of UC were analyzed.

Antibody-drug conjugates (ADCs) deliver potent cytotoxic agents using highly selective monoclonal antibodies. Targeting the near-universal expression of Nectin-4 on UC cells is a viable therapeutic strategy. In a pivotal phase II trial, EV demonstrated an overall response rate of 44%, and a median duration of response of 7.6 months. Pyrroltinib dimaleate Estimated overall survival was 11.7 months with a median estimated progression-free survival of 5.6 months. Results were similar among difficult-to-treat patients, including those with liver metastases. Unique toxicity concerns with EV require careful consideration and monitoring.

EV, a first-in-class anti-Nectin-4 ADC, provides impressive response rates with manageable toxicities, making it a promising treatment option for patients with multiply relapsed or refractory UC.

The US Food and Drug Administration-approved EV demonstrates antitumor activity in heavily pretreated patients with UC but harbors important adverse effects and financial concerns. Additional studies are required to identify the optimal sequencing, patient population, and place in therapy for EV.

The US Food and Drug Administration-approved EV demonstrates antitumor activity in heavily pretreated patients with UC but harbors important adverse effects and financial concerns. Additional studies are required to identify the optimal sequencing, patient population, and place in therapy for EV.Numerous sophisticated diagnostic techniques have been designed to monitor electrode-electrolyte interfaces that mainly govern the lifetime and reliability of batteries. Among them is the electrochemical quartz crystal microbalance (EQCM) that offers valuable insights of the interfaces once the required conditions of the deposited film in terms of viscoelastic and hydrodynamic properties are fulfilled. Herein, we propose a friendly protocol that includes the elaboration of a homogeneous deposit by spray coating followed by QCM measurements at multiharmonic frequencies to ensure the film flatness and rigidity for collecting meaningful data. Moreover, for easiness of the measurements, we report the design of a versatile and airtight EQCM cell setup that can be used either with aqueous or non-aqueous electrolytes. We also present, using a model battery material, LiFePO4, how dual frequency and motional resistance monitoring during electrochemical cycling can be used as a well-suitable indicator for achieving reliable and reproducible electrogravimetric measurements. We demonstrate through this study the essential role of the solvent assisting lithium-ion insertion at the LiFePO4 interface with a major outcome of solvent-dependent interfacial behavior. Namely, in aqueous media, we prove a near-surface desolvation of lithium ions from their water solvation shell as compared with organic molecules. This spatial dissimilarity leads to a smoother Li-ion transport across the LFP-H2O interface, hence accounting for the difference in rate capability of LFP in the respective electrolytes. Overall, we hope our analytical insights on interfacial mechanisms will help in gaining a wider acceptance of EQCM-based methods from the battery community.Immunoglobulin G (IgG) glycosylation is a key post-translational modification in regulating IgG function. It is therefore a prominent target for biomarker discovery and a critical quality attribute of antibody-based biopharmaceuticals. A common approach for IgG glycosylation analysis is the measurement of tryptic glycopeptides. Glycosylation stability during sample processing is a key prerequisite for an accurate and robust analysis yet has hitherto hardly been studied. Especially, acid hydrolysis of sialic acids may be a source for instability. Therefore, we investigated acid denaturation, centrifugal vacuum concentration, and glycopeptide storage regarding changes in the IgG glycosylation profile. Intravenous IgG was analyzed employing imaginable deviations from a reference method and stress conditions. All glycosylation features -sialylation, galactosylation, bisection, and fucosylation-remained unchanged for most conditions. Only with prolonged exposure to acidic conditions at 37 °C, sialylation decreased significantly and subtle changes occurred for galactosylation. Consequently, provided that long or intense heating in acidic solutions is avoided, sample preparation for bottom-up glycoproteomics does not introduce conceivable biases.Hybridization of DNA probes immobilized on a solid support is a key process for DNA biosensors and microarrays. Although the surface environment is known to influence the kinetics of DNA hybridization, so far it has not been possible to quantitatively predict how hybridization kinetics is influenced by the complex interactions of the surface environment. Using spatial statistical analysis of probes and hybridized target molecules on a few electrochemical DNA (E-DNA) sensors, functioning through hybridization-induced conformational change of redox-tagged hairpin probes, we developed a phenomenological model that describes how the hybridization rates for single probe molecules are determined by the local environment. The predicted single-molecule rate constants, upon incorporation into numerical simulation, reproduced the overall kinetics of E-DNA sensor surfaces at different probe densities and different degrees of probe clustering. Our study showed that the nanoscale spatial organization is a major factor behind the counterintuitive trends in hybridization kinetics. It also highlights the importance of models that can account for heterogeneity in surface hybridization. The molecular level understanding of hybridization at surfaces and accurate prediction of hybridization kinetics may lead to new opportunities in development of more sensitive and reproducible DNA biosensors and microarrays.