Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)

Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin-binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment-by-marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild-type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild-type (WT) patients (chemo HR = 0.98, 95% CI = 0.74-1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05-2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02-2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67-1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68-13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31-2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88-1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32-1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab

Blood�based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)

Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin�binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment�by�marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild�type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild�type (WT) patients (chemo HR = 0.98, 95% CI = 0.74–1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05–2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02–2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67–1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68–13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31–2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88–1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32–1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab

Functional disulfide-stabilized polymer-protein particles

Polymer-protein hybrid particles (PPHPs) have a significant potential in drug delivery, diagnosis and biomedical imaging applications Herein, we describe a Simple route to disulfide cross-linked, poly(ethylene glycol)-streptavidin hybrid particles with tunable diameters. These particles have great versatility and potential for it number of reasons. First, they possess free biotin binding sites oil their streptavidin (SAv) coated surface, enabling the conjugation of any biotinylated-molecule such as biotinylated antibodies. Second, core-stabilization call easily be controlled using reversible disulfide cross-links, and third, thiol- and ene-reactive functionalities in the core ate available for the conjugation of drugs and labels In detail, micelles having a biotinylated poly(ethylene glycol) corona and a disulfide cross-linked. reactive core were formed using alpha-biotin PEG-b-pol y(pyridyldisulfide ethylmethacrylate) block copolymers synthesized via RAFT polymerization Functionalization of the micelle core was performed in a one-pot reaction concurrent with the micellization and cross-linking processes by using a thiol-reactive model compound (a maleimide derivative of a green fluorophore). The resultant micelles displayed spherical morphology with a diameter of 54 +/- 4 nm. Biotin functionality was largely exposed on the micelle corona (75 mol % ability), as determined by a streptavidin/HABA assay. The micelles were subsequently decorated with (red avail, fluorophore-labeled) streptavidin (SAv) through the accessible biotins on the surface, yielding SM-linked micelle aggregates with tunable dimensions (in the range between 350 rim and 2 pin), as determined by transmission electron microscopy. Fluorescent-labels oil the particles were monitored using confocal microscopy, revealing that the SAv coats the periphery of the PPHPs

An approach to biodegradable star polymeric architectures using disulfide coupling

The straightforward synthesis of biodegradable star polymers via both in situ polymerization from a trifunctional RAFT agent and post-polymerization conjugation of pyridyldisulfide-ended linear polymers to a trithiol precursor is described

RAFT controlled synthesis of six-armed biodegradable star polymeric architectures via a 'core-first' methodology

Six-armed biodegradable star polymers made from polystyrene (polySt), poly(polyethylene glycol) acrylate (polyPEG-A) and the block copolymer, polySt-b-polyPEG-A were synthesized using a 'core-first' methodology via RAFT polymerization. Disulfide linkages between the core and the arms conferred biodegradability on the stars. The star architectures were found to degrade rapidly on treatment with DL-dithiothreitol (DTT) and degrade more slowly in the presence of glutathione (GSH), the most abundant intracellular thiol tethered peptide. These star polymers were well characterized using gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), electrospray ionization mass spectroscopy (ESI-MS) and dynamic light scattering (DLS). (C) 2009 Elsevier Ltd. All rights reserved

Hierarchical NiCo-LDH core/shell homostructural electrodes with MOF-derived shell for electrochemical energy storage

Constructing hierarchical structure is an effective strategy to boost the electrochemical performance of layered double hydroxide (LDH) materials, but the rational design of such delicate architectures is still challenging. Herein, a unique hierarchical core/shell homostructure with NiCo-LDH nanorods (NCNRs) as core and NiCo-LDH nanosheets (NCNSs) as shell is constructed via in-situ ZIF shell growth and subsequent ion exchange-coprecipitation process. Such novel hierarchical structure provides a large accessible surface area and more exposed electrochemical active sites. The in-situ growth and conversion process contribute to the formation of robust adhesion between the core and the shell, which could facilitate the effective charge and ion diffusion, as well as improve the mechanical stability. Benefiting from the unique structure, the NCNRs@NCNSs electrode exhibits a high capacitance of 2640.2 F g-1, along with the good rate performance and cyclic stability. Furthermore, the as-assembled asymmetric supercapacitor of NCNRs@NCNSs//AC device displays a high energy density of 22.81 Wh kg-1 at the power density of 374.95 W kg-1. This work demonstrates a new strategy for designing hierarchical LDH with core/shell structure as electrode materials for superior electrochemical energy storage.The authors are thankful to funds from the National Natural Science Foundation of China (52002194 and 51802168), Natural Science Foundation of Shandong Province (ZR2020QE065), the China Postdoctoral Science Foundation (2019M652317), the Shandong Postdoctoral Innovation Project, the Qingdao Postdoctoral Application Research Project and Shandong Double Hundred Foreign Experts program

Electrochemical synthesis of NiCo layered double hydroxide nanosheets decorated on moderately oxidized graphene films for energy storage

The introduction of oxygenous functional groups onto graphene can provide additional pseudocapacitance for supercapacitors. However, how to balance the amount of introduced oxygenous functional groups and the reduced electrical conductivity arising from the disruption of the conjugated system remains a big challenge. Here, a controllable strategy is reported to prepare moderately oxidized reduced graphene oxide (MORGO) via an electrochemical oxidation process. The MORGO not only has oxygenous groups with appropriate quantities, but also preserves the highly crystalline structure of the π-π conjugated carbon framework. As a result, the MORGO films showed superior electrochemical properties to the pristine RGO films and other previously reported RGO films. Furthermore, the oxygenous groups and the conductivity of MORGO films can be easily adjusted by controlling the oxidation time. A hierarchical composite of NiCo-layered double hydroxide nanosheet arrays on MORGO films (MORGO/NiCo-LDH) was also constructed via electrochemical deposition to combine the advantages of electric double-layer electrode materials and faradaic electrode materials. The flexible solid-state supercapacitor fabricated with MORGO/NiCo-LDH film electrodes exhibits a high energy density (0.51 mW h cm⁻³), as well as a long cycle life (88.2% capacitance retention after 10 000 cycles).This work was supported by the Qingdao Innovation Leading Talent Program and the Taishan Scholars Program