Otorhinolaryngology
- Cyst of the right lymphatic ductPublication date: Available online 30 September 2019Source: European Annals of Otorhinolaryngology, Head and Neck DiseasesAuthor(s): I. Stárek, R. Salzman, Z. Pokorná, D. SkanderováAbstractIntroductionCysts originating from cervical lymphatic ducts are very rare affections. However, they play an important role in the differential diagnosis of supraclavicular masses. The aetiology remains unclear. Practically all cases arise from the thoracic duct
Journal of Voice
- Chronic Refractory Cough: Objective Improvement With Aerodynamic-FocusedPrevious investigations have reported that a chronic cough that is refractory to medical therapies improves with behavioral therapies. However, the treatment parameters that may account for improvement in cough symptoms have not yet been objectively documented. The purpose of this study was to document changes in chronic refractory cough using a breath training protocol.
Medgadget
- Disc Pump for Less Obtrusive Ambulatory Blood Pressure SystemsTTP Ventus, the UK-based developer of the Disc Pump, has recently begun working on a new application for this technology – ambulatory blood pressure systems. The company claims that the Disc Pump, which is a miniaturized, quiet, and highly efficient pump, could revolutionize ambulatory blood pressure measurements. At present, 24-hour blood pressure monitors are commonly used to monitor blood pressure at regular intervals throughout the da
- Hexoskin Shirt Proving Itself for Lung Function MeasurementA few years ago Hexoskin, a Canadian startup, announced the development of a sensor-packed t-shirt that can measure a number of physiological parameters in real-time. It’s novel because it doesn’t require the wearer to put on individual sensors and attach them to the skin, allowing common daily at-home and athletic activities to be performed. We also got a chance to interview the co-founder of the company. Now, news is out that the Hexoski
- Nanoparticles Inside Samples of Mucus to Measure COPD DevelopmentManagement of chronic obstructive pulmonary disease (COPD) suffers not only from a lack of effective therapies, but also from an inability to track the disease’s progression. Spirometers that measure how much air patients can displace using their lungs are the “gold standard,” but that standard is pretty poor in helping to predict how COPD will develop. Researchers at Johns Hopkins University have now used special nanoparticles to test the
- Nanoparticles for RNA Vaccine Delivery Help Stop Melanoma Tumor GrowthRNA vaccines are a promising way to harness the immune system to fight cancers and infections. Some are currently in clinical trials, but the technology is still in its early stages. A major impediment to the effectiveness of RNA vaccines is the difficulty in getting them into the correct immune cells to produce the desired proteins and guaranteeing that the immune system will respond with sufficient force. To help with this, chemists at M
Angewandte Chemie International Edition
- Defect‐Mediated Ordering of Condensed Water Structures in Microporous ZeolitesThe structure and stability of water clusters in Beta zeolites with diverse defect site types were evaluated by combining ab‐initio molecular dynamics and transmission IR spectroscopy. Sn and SnOH defects nucleate strongly correlated local water clusters, while silanol nests nucleate extended water networks. Abstract Ab‐initio molecular dynamics simulations and transmission infrared spectroscopy are employed to characterize the structure of
- Tuning the Electrochemical Performance of Titanium Carbide MXene by Controllable in situ Anodic OxidationMXenes are a class of two‐dimensional (2D) transition metal carbides, nitrides and carbonitrides that have shown promise for high‐rate pseudocapacitive energy storage. However, the effects that irreversible oxidation have on the surface chemistry and electrochemical properties of MXenes are still not understood. Here we report on a controlled anodic oxidation method which improves the rate performance of titanium carbide MXene (Ti 3 C 2 T x,
- Nickel‐Catalyzed Domino Heck‐Type Reactions using Methyl Esters as Cross‐Coupling ElectrophilesWhile esters are frequently used as traditional electrophiles in substitution chemistry, their application in cross‐coupling chemistry is still in its infancy. In this work, we demonstrate that methyl esters can be used as coupling electrophiles in Ni‐catalyzed Heck‐type reactions via challenging cleavage of the C(acyl)‐O bond under relatively mild conditions at 80 or 100 °C. With the σ‐Ni(II) intermediate generated from the insertion of acyl Ni(
- A 3D Analogue of Phenyllithium: Solution‐Phase, Solid‐State and Computational Study of the Lithiacarborane [Li–CB11H11]–The lithiacarborane [Li–CB11H11]– plays a central role in carborane chemistry, as it is a key intermediate to achieve selective functionalization of the monocarba‐closo‐dodecaborate [CB11H12]– for applications in various fields. Also, it is an organometallic species of fundamental interest because it represents a 3D analogue of phenyllithium featuring an exo C–Li bond in addition to the delocalized negative endo charge of the spherical cluster. F
- Anisotropic Thermal Expansion as the Source of Macroscopic and Molecular Scale Motion in Phosphorescent Amphidynamic CrystalsThe structural origin of multiscale phenomena, with physical manifestations ranging from the molecular to the macroscopic scale, remains largely undocumented. Here we report the discovery of a crystalline molecular rotor with rotationally‐modulated triplet emission that displays macroscopic dynamics in the form of crystal moving and/or jumping, also known as salient effects. Crystals of molecular rotor 2 with a central 1,4‐diethynyl‐2,3‐difluo
- proto‐Urea‐RNA (Wöhler RNA) containing unusually stable urea nucleosidesThe RNA world hypothesis assumes that life on Earth began with nucleotides that formed information carrying RNA oligomers able to self‐replicate. Prebiotic reactions leading to the contemporary nucleosides are now known, but their execution often requires specific starting materials and lengthy reaction sequences. It was therefore proposed that the RNA‐world was likely proceeded by a proto‐RNA world constructed from molecules that were likely pre
- Giant Enhancement of Second Harmonic Generation Accompanied by the Structural Transformation of 7‐fold to 8‐fold Interpenetrated MOFInterpenetration in metal‐organic frameworks (MOFs) is an intriguing phenomenon with significant impacts on the properties, and functional applications of MOFs. Herein, we showed that a 7‐fold interpenetrated MOF is transformed to an 8‐fold interpenetrated MOF by the loss of DMF in a single‐crystal‐to‐single‐crystal manner. This is accompanied by a giant enhancement of the second harmonic generation (SHG ~125 times) and two‐photon photoluminescen
- Efficient Organocatalytic Dehydrogenation of Ammonia‐BoraneThe dehydrogenation of ammonia borane by sterically encumbered pyridones as organocatalysts is reported. With 6‐ tert ‐butyl‐2‐thiopyridone as the catalyst, a turnover frequency (TOF) of 88 h −1 was achieved. Experimental mechanistic investigations, substantiated by DLPNO‐CCSD(T) computations, indicate a mechanistic scenario that commences with the protonation of a B–H bond by the mercaptopyridine form of the catalyst. The reactive intermedia
- Halide Anion Triggered Reactions of Michael Acceptors with Tropylium IonTropylium bromide undergoes non‐catalyzed, regioselective additions to a large variety of Michael acceptors. In this way, acrylic esters are converted into ß‐bromo‐α‐cycloheptatrienyl‐propionic esters. The reactions are interpreted by nucleophilic attack of bromide ions at the electron‐deficient olefins and the approach of the tropylium ion to the incipient carbanion. Quantum chemical calculations were performed to elucidate the analogy to the am
- Supported Catalytically‐Active Supramolecular Hydrogels for Continuous Flow ChemistryInspired from biology, one current goal in supramolecular chemistry is to control the emergence of new functionalities arising from self‐assembly of molecules. In particular, some peptides can self‐assemble and lead to exceptional catalytically‐active fibrous networks able to underpin hydrogels. Unfortunately, the mechanical fragility of these materials is incompatible with process developments relaying this exciting field to academic curiosity.
- [3+2] Fragmentation of a Pentaphosphido Ligand by CyanideThe activation of white phosphorus (P4) by transition metal complexes has been studied for decades, but the functionalization and release of the resulting (organo)phosphorus ligands has rarely been achieved. Herein we describe the formation of rare diphosphan‐1‐ide anions from a P5 ligand by treatment with cyanide. Cobalt diorganopentaphosphido complexes have been synthesized by a stepwise reaction sequence involving a low‐valent diimine cobalt
- Solid/Gas Phase Structures and Energetic Properties of the Dangerous Methyl and Fluoromethyl NitratesAn improved synthesis for the simplest nitric acid ester, methyl nitrate, and a new synthesis of fluoromethyl nitrate use the metathesis of the corresponding iodomethanes with silver nitrate. Both compounds were identified by spectroscopy and structure determination in the solid on in‐situ grown crystals by X‐ray diffraction as well as in the gas phase by electron diffraction. Fluorination leads to structures with shorter C–O and N–O bonds, has
- Metal‐Organic Gels from Silver Nanoclusters with Aggregation‐Induced Emission and Fluorescence‐to‐Phosphorescence SwitchingLuminescent metal nanoclusters (NCs) are emerging as a new class of functional materials which have rich physicochemical properties and wide potential applications. In recent years, it has been found that some metal NCs undergo aggregation‐induced emission (AIE) and an interesting fluorescence‐to‐phosphorescence (F‐P) switching in solutions. However, insights of both the AIE and the F‐P switching remain largely unknown. Herein, we report the gela
- Design parameters of tissue engineering scaffolds at atomic scaleStem cell behaviour is critically regulated by the material properties of the surrounding extracellular matrix, which has important implications for the design of tissue engineering scaffolds that act as biomimetic stem cell substrates and offer fascinating applications in regenerative medicine. However, our understanding of stem cell scaffolds is strongly limited because our knowledge of their material properties is confined to nanoscopic‐to‐mac
- Free Standing CoO‐POM Janus like Ultrathin NanosheetsWe report a single step solution based strategy to obtain 2D janus like free standing ultrathin nanosheets build from two structurally unrelated species i.e. polyoxomolybdate (POM) and CoO. A controlled 2D‐to‐1D morphological transition was achieved by judiciously adjusting the solvent choices. These POM‐CoO heterostructures can behave as an ideal catalyst for the epoxidation of styrene. Benefiting from their amphiphilic nature, these 2D POM‐CoO
- S‐Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C‐AlkylationA tandem enzymatic strategy to enhance the scope of C‐ alkylation of small molecules via the in situ formation of S ‐adenosyl methionine (SAM) cofactor analogues is described. A solvent‐exposed channel present in the SAM‐forming enzyme SalL tolerates 5'‐chloro‐5’‐deoxyadenosine (ClDA) analogues modified at the 2‐position of the adenine nucleobase. Coupling SalL‐catalyzed cofactor production with C‐ (m)ethyl transfer to coumarin substrat
- Fluorine: A Paradoxical Element. By Alain Tressaud.Elsevier, 2019. 259 pp., softcover, € 147.00.—ISBN 978‐0‐128‐12990‐6
- Potassium Ion Assisted Regeneration of Active Cyano Groups in Carbon Nitride Nanoribbons: Visible Light Driven Photocatalytic Nitrogen ReductionActive site: A superior g‐C3N4 photocatalyst for the nitrogen reduction reaction (NRR) is reported. The catalyst features ‐C≡N groups and intercalated K+, and is used as model to investigate the mechanistic pathway of the photocatalytic NRR involving ‐C≡N‐type active sites. Abstract As a metal‐free nitrogen reduction reaction (NRR) photocatalyst, g‐C3N4 is available from a scalable synthesis at low cost. Importantly, it can be readily funct
- Stable Confinement of Black Phosphorus Quantum Dots on Black Tin Oxide Nanotubes: A Robust, Double‐Active Electrocatalyst toward Efficient Nitrogen FixationThrough facile self‐assembly, black phosphorus quantum dots are stably confined on the SnO2−x nanotubes, which serve as an electrocatalytically active and electrically conductive matrix. Benefiting from their synergistic superiority, the two components result in a robust, double‐active electrocatalyst delivering impressively high ammonia yield and Faradaic efficiency. Abstract A conceptually new, metal‐free electrocatalyst, black phosphor
- Unveiling the Neutral Forms of GlutamineThree neutral forms of the proteinogenic glutamine, intimately connected to its biological functions, have been generated by laser ablation and structurally characterized by microwave spectroscopy. Abstract Neutral glutamine has been evaporated by laser ablation of its solid sample to seed a rare gas carrier prior to a supersonic expansion and proved by Fourier transform microwave techniques. We report on three distinct neutral conformers t
- Ring Contraction by NHC‐Induced Pnictogen AbstractionTightening one's belt: The NHC induced pnictogen abstraction proves to be a general method to induce ring contraction reactions of polypnictogen ligands, leading to new and otherwise not accessible compounds. This method can be applied to sandwich complexes containing cyclo‐En end decks as well as triple‐decker complexes (E=P, As) and allows to generate unprecedented anionic compounds [Cp′′′Co(η 3‐P3)]− and [(Cp*M)2(μ, η 5:5‐E5)]− (M=Mo, V; E=P
- Supramolecular photothermal effects: A promising mechanism for efficient thermal conversionSupramolecular assembly has gained great success in regulating the photothermal conversion efficiency of organic photothermal materials with considerable simplicity and flexibility. A typical feature of these materials is that the photothermal performance is controlled by noncovalent intermolecular interactions, which is distinguished from conventional molecular design. Rather than diverse assembly strategies, it is the inherent supramolecular ph
- Tuning the Reactivity of Cyclopropenes from Living ROMP to Single Addition and AROMP via Simple SubstituentsRing‐opening metathesis polymerization (ROMP) has become one of the most important living polymerizations. Despite being the most strained cyclic olefin, cyclopropenes (CPEs) remain underexplored for ROMP. We discovered that the simple swap of 1‐methyl to 1‐phenyl on 1‐(benzoyloxymethyl)‐CPEs elicited strikingly different modes of reactivity, switching from living polymerization to selective single addition and living alternating ROMP, respective
- A Pyrazine‐Based Polymer for Fast‐Charge BatteriesThe lack of high‐power and stable cathodes prohibits the development of rechargeable metal (Na, Mg, Al) batteries. Herein, poly‐hexaazatrinaphthalene (PHATN), an environmentally benign, abundant and sustainable polymer, is employed as a universal cathode material for these metal batteries. In Na‐ion batteries (NIBs), PHATN delivers a reversible capacity of 220 mAh g ‐1 at 50 mA g ‐1 , corresponding to the energy density of 440 Wh kg ‐1 , an
- Coordinative Chain Transfer Polymerization of Butadiene with Functionalized Aluminum ReagentsFunctionalized aluminium alkyls enable an effective coordinative chain transfer polymerization with selective chain initiation by the functionalized alkyl. (ω‐aminoalkyl)diisobutyl aluminum reagents (twelve examples studied) obtained by hydroalumination of α‐amino‐ω‐enes with diisobutyl aluminum hydride promote the stereoselective catalytic chain growth of butadiene on aluminum in presence of Nd(versatate)3, Cp*2Nd(allyl) or Cp*2Gd(allyl) precata
- Production of hydrogen peroxide through photocatalytic processes: a critical review of recent advancesHydrogen peroxide (H 2 O 2 ) has received increasing attention because it is not only a mild and environment‐friendly oxidant for organic synthesis and environmental remediation but also a promising new liquid fuel. The production of H 2 O 2 through photocatalysis is green, sustainable and promising process, considering it uses water and oxygen as the source materials and solar light as the energy. Encouraging processes have been develope
- Understanding the pH Dependence of Underpotential Deposited Hydrogen on PlatinumUnderstanding the pH dependent shift of the oxidation peak of the underpotential deposited hydrogen (Hupd) in cyclic voltammograms on the Pt surface is of significance in terms of both the fundamentals of electrochemistry and the rational design of catalysts for the hydrogen oxidation/evolution reactions (HOR/HER). In this work, we provide compelling evidence that the pH dependent shift in the Hupd peak on Pt surfaces is driven by the structure o
- Accessibility of cortical regions to focal TES: Dependence on spatial position, safety, and practical constraintsPublication date: December 2019Source: NeuroImage, Volume 203Author(s): Guilherme Bicalho Saturnino, Hartwig Roman Siebner, Axel Thielscher, Kristoffer Hougaard MadsenAbstractTranscranial electric stimulation (TES) can modulate intrinsic neural activity in the brain by injecting weak currents through electrodes attached to the scalp. TES has been widely used as a neuroscience tool to investigate how behavioural and physiological variables of brai
- A special role for the right posterior superior temporal sulcus during speech productionPublication date: December 2019Source: NeuroImage, Volume 203Author(s): Adam Kenji Yamamoto, Oiwi Parker Jones, Thomas M.H. Hope, Susan Prejawa, Marion Oberhuber, Philipp Ludersdorfer, Tarek A. Yousry, David W. Green, Cathy J. PriceAbstractThis fMRI study of 24 healthy human participants investigated whether any part of the auditory cortex was more responsive to self-generated speech sounds compared to hearing another person speak. The results de
Clinical Cancer Research current issue
- Comprehensive Genomic Landscapes in Early and Later Onset Colorectal CancerPurpose:The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. Experimental Design:DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genom
- Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver MetastasesPurpose:Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection. Experimental Design:We identified patients who underwent initial CLM resection during 2007–2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recu
- Radiation-Induced Amplification of TGFB1-Induced Mesenchymal Stem Cell-Mediated Sodium Iodide Symporter (NIS) Gene 131I TherapyPurpose:The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery of the theranostic sodium iodide symporter (NIS) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in the enhanced recruitment of NIS-expressing MSCs into human hepatocellular carcinoma (HuH7). In parallel, the tumor-associated cytokine TGFB1 becomes strongly upregulated in HuH7 tumors
- Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic TumorsPurpose:Mutant KRAS is a major driver of pancreatic oncogenesis and therapy resistance, yet KRAS inhibitors are lacking in the clinic. KRAS requires farnesylation for membrane localization and cancer-causing activity prompting the development of farnesyltransferase inhibitors (FTIs) as anticancer agents. However, KRAS becomes geranylgeranylated and active when cancer cells are treated with FTIs. To overcome this geranylgeranylation-dependent resi
- Liver- and Microbiome-derived Bile Acids Accumulate in Human Breast Tumors and Inhibit Growth and Improve Patient SurvivalPurpose:Metabolomics is a discovery tool for novel associations of metabolites with disease. Here, we interrogated the metabolome of human breast tumors to describe metabolites whose accumulation affects tumor biology. Experimental Design:We applied large-scale metabolomics followed by absolute quantification and machine learning-based feature selection using LASSO to identify metabolites that show a robust association with tumor biology and dis
- The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor TherapyPurpose:Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response. Experimental Design:Comprehensive molecular profiling was performed on 317 tumors from patients with MC
- ERK Regulates HIF1{alpha}-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian CancerPurpose:Up to 80% of patients with ovarian cancer develop platinum resistance over time to platinum-based chemotherapy. Increased HIF1α level is an important mechanism governing platinum resistance in platinum-resistant ovarian cancer (PROC). However, the mechanism regulating HIF1α stability in PROC remains largely unknown. Here, we elucidate the mechanism of HIF1α stability regulation in PROC and explore therapeutic approaches to overcome cispla
- Molecular Classification of Epithelial Ovarian Cancer Based on Methylation Profiling: Evidence for Survival HeterogeneityPurpose:Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number variation, RNA expression data, and outcomes. Experimental Design:A total of 162 paraffin-embedded ovarian epithelial tumor tissues, including t
- Unbiased Metabolic Profiling Predicts Sensitivity of High MYC-Expressing Atypical Teratoid/Rhabdoid Tumors to Glutamine Inhibition with 6-Diazo-5-Oxo-L-NorleucinePurpose:Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive infantile brain tumors with poor survival. Recent advancements have highlighted significant molecular heterogeneity in AT/RT with an aggressive subgroup featuring overexpression of the MYC proto-oncogene. We perform the first comprehensive metabolic profiling of patient-derived AT/RT cell lines to identify therapeutic susceptibilities in high MYC-expressing AT/RT. Experimental Desi
- Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based ChemotherapyPurpose:Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1–35 years after CBC and evaluate genetic contributions to these levels. Experimental Design:Eligible TCS given 300 or 400 (±15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questio
- Bispecific Antibodies Enable Synthetic Agonistic Receptor-Transduced T Cells for Tumor ImmunotherapyPurpose:Genetically engineered T cells are powerful anticancer treatments but are limited by safety and specificity issues. We herein describe an MHC-unrestricted modular platform combining autologous T cells, transduced with a targetable synthetic agonistic receptor (SAR), with bispecific antibodies (BiAb) that specifically recruit and activate T cells for tumor killing. Experimental Design:BiAbs of different formats were generated by recombina
- Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating RET Alterations and Oncogenic Signaling Pathway AberrationsPurpose:RET is an emerging oncogenic target showing promise in phase I/II clinical trials. An understudied aspect of RET-driven cancers is the extent to which co-occurring genomic alterations exist and how they may impact prognosis or therapeutic response. Experimental Design:Somatic activating RET alterations were identified among 32,989 consecutive patients with metastatic solid tumors tested with a clinical cell-free circulating tumor DNA (cf
- Activation of JAK/STAT Signaling in Megakaryocytes Sustains Myeloproliferation In VivoPurpose:The myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by the expansion of the erythroid, megakaryocytic, and granulocytic lineages. A common feature of these disorders is the presence of abnormal megakaryocytes, which have been implicated as causative agents in the development of bone marrow fibrosis. However, the specific contributions of megakaryocyte
- ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular CarcinomaPurpose:Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice. Experimental Design:To identify potential bioma
- Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary AdenocarcinomaPurpose:Naturally occurring primary canine lung cancers share clinicopathologic features with human lung cancers in never-smokers, but the genetic underpinnings of canine lung cancer are unknown. We have charted the genomic landscape of canine lung cancer and performed functional characterization of novel, recurrent HER2 (ERBB2) mutations occurring in canine pulmonary adenocarcinoma (cPAC). Experimental Design:We performed multiplatform genomic
- Tumor-Localized Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody-Anticalin Fusion PRS-343Purpose:4-1BB (CD137) is a key costimulatory immunoreceptor and promising therapeutic target in cancer. To overcome limitations of current 4-1BB–targeting antibodies, we have developed PRS-343, a 4-1BB/HER2 bispecific molecule. PRS-343 is designed to facilitate T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation. Experimental Design:PRS-343 was generated by the genetic fusion of 4-1BB–specific Anticalin protei
- Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder CancerPurpose:The CANON [CAVATAK in NON–muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1–targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. Patients and Methods:Fifteen patients enrolled in this "window of opportunity" phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the se
- First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1Purpose:LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1–expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV3
- A Randomized Double-Blind Placebo-Controlled Phase II Trial of Dendritic Cell Vaccine ICT-107 in Newly Diagnosed Patients with GlioblastomaPurpose:To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods:We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1+ and/or -A2+–resected patients with residual tumor ≤1 cm3 recei
- Clinical Response of Live-Attenuated, Listeria monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural MesotheliomaPurpose:Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express mesothelin, a tumor-associated antigen highly expressed in MPM. CRS-207 induces antitumor immune responses and increases susceptibility of neoplastic cells to immune-mediated killing. Patients and Methods:Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and p
- A Phase 0 Trial of Ribociclib in Recurrent Glioblastoma Patients Incorporating a Tumor Pharmacodynamic- and Pharmacokinetic-Guided Expansion CohortPurpose:CDK4/6-dependent cell-cycle regulation is disrupted in most glioblastomas. This study assesses the central nervous system (CNS) pharmacokinetics and tumor pharmacodynamics of ribociclib, a highly selective CDK4/6 inhibitor, in patients with recurrent glioblastoma. Patients and Methods:Patients with recurrent glioblastoma with intact retinoblastoma protein (RB) expression and CDKN2A deletion or CDK4/6 amplification were treated with riboc
- Photodynamic Therapy for the Treatment of Vertebral Metastases: A Phase I Clinical TrialPurpose:Vertebroplasty (VP) and balloon kyphoplasty (KP) are minimally invasive stabilization procedures for pathologic vertebral compression fractures (VCF). Concurrent administration of photodynamic therapy (PDT) as a tumor-ablative modality has yet to be studied in humans as a potential complement to improved mechanical stability that is afforded by vertebral cement augmentation (VCA). Patients and Methods:This first-in-human trial used a sin
- Health-Related Quality of Life Impact from Adding Bevacizumab to Cisplatin-Pemetrexed in Malignant Pleural Mesothelioma in the MAPS IFCT-GFPC-0701 Phase III TrialPurpose:The IFCT-GFPC-0701 MAPS phase III trial highlighted significant improvement in overall survival from adding bevacizumab to the standard first-line chemotherapy regimen [cisplatin plus pemetrexed (PC)] in advanced malignant pleural mesothelioma (MPM). We present the results of health-related quality of life (HRQoL), a secondary endpoint of MAPS. Patients and Methods:HRQoL was assessed using the European Organisation for Research and Treat
- Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma PatientsPurpose:ErbB3 and its ligand neuregulin-1 (NRG1) are widely expressed in head and neck squamous cell carcinoma (HNSCC) and associated with tumor progression. A "window-of-opportunity" study (NCT02473731) was conducted to evaluate the pharmacodynamic effects of CDX-3379, an anti-ErbB3 mAb, in patients with HNSCC. Patients and Methods:Twelve patients with newly diagnosed, operable HNSCC received two infusions of CDX-3379 (1,000 mg) at a 2-week int
- The Promise of Neoadjuvant Immunotherapy and Surgery for Cancer TreatmentCancer immunotherapies utilizing immune checkpoint inhibitors (ICI) have demonstrated durable efficacy in a proportion of patients with advanced/metastatic cancers. More recently, the use of ICIs for the adjuvant treatment of patients with surgically resectable melanoma has also demonstrated efficacy by improving relapse-free survival and in the case of ipilimumab (anti–CTLA-4) also improving overall survival. Although promising, the effective sc
- Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant MelanomaThe characterization of the MAPK signaling pathway has led to the development of multiple promising targeted therapy options for a subset of patients with metastatic melanoma. The combination of BRAF and MEK inhibitors represents an FDA-approved standard of care in patients with metastatic and resected BRAF-mutated melanoma. There are currently three FDA-approved BRAF/MEK inhibitor combinations for the treatment of patients with BRAF-mutated mela
- A Tumor-Localized Approach to Bypass Anti-4-1BB Immuno-Toxicity4-1BB (CD137) is an important costimulatory molecule upregulated on antigen-experienced T cells, however, clinical development of 4-1BB agonists has stalled because of significant liver immuno-toxicity. Using rational protein engineering, a next-generation anticalin-antibody–based therapy achieved localized 4-1BB activation triggered by tumor-expressed antigen, helping to revitalize this pathway in immuno-oncology. See related article by Hinner
- DNA Methylation as a Robust Classifier of Epithelial Ovarian CancerEpithelial ovarian cancers (EOC) can be defined across different histologic subtypes by specific DNA methylation profiles which correlate with outcome. Identification of distinct EOC methylation subgroups emphasizes the role of epigenetic remodeling to establish unique EOC etiology during transformation, and harbors the potential to direct personalized medicine and patient care. See related article by Bodelon et al., p. 5937
Analytical Chemistry
- [ASAP] Wash-Free Multiplexed Mix-and-Read Suspension Array Fluorescence Immunoassay for Anthropogenic Markers in WastewaterAnalytical ChemistryDOI: 10.1021/acs.analchem.9b03040
- [ASAP] Insights from Nitrogen Compounds in Gas Oils Highlighted by High-Resolution Fourier Transform Mass SpectrometryAnalytical ChemistryDOI: 10.1021/acs.analchem.9b01702
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