Augmenting Prognostication: Utilizing Activity Trackers to Enhance Survival Prediction in Metastatic Non-Small Cell Lung Cancer.

Introduction/background: Prognostication by performance status (PS) assessment is a fundamental element of treatment decisions and clinical trial design in oncology, but it is limited by subjectivity and potential miscommunication between patient, physician, and family. Activity tracker offers the potential to collect a broad range of patient-generated data to supplement the assessment of PS.

Patients And Methods: Patients with metastatic NSCLC (mNSCLC) participated in a single institute, prospective, observational feasibility study conducted at Huntsman Cancer Institute.

A phase I open-label study of the safety and efficacy of apatinib (rivoceranib) administered to patients with advanced malignancies to improve sensitivity to pembrolizumab in the second- or later-line setting (APPEASE).

Objective: APPEASE is a phase I study to assess the safety, dosing, and efficacy of rivoceranib (a selective, small-molecule inhibitor of VEGFR2) in combination with pembrolizumab. We aimed to treat patients with metastatic malignancies who have progressed through at least first-line therapy, with pembrolizumab 200 mg every 3 weeks, as well as escalating doses of rivoceranib until disease progression or unacceptable toxicity.

Results: Five patients were enrolled on the starting dose of rivoceranib 300 mg once daily.

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds.

The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is an increasing clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here, we report a novel class of naturally occurring and semisynthetic epoxy-tiglianes, derived from the Queensland blushwood tree (, and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens.

Caveolin-1, a Key Mediator Across Multiple Pathways in Glioblastoma and an Independent Negative Biomarker of Patient Survival.

Glioblastoma (GB) remains an aggressive malignancy with an extremely poor prognosis. Discovering new candidate drug targets for GB remains an unmet medical need. Caveolin-1 (Cav-1) has been shown to act variously as both a tumour suppressor and tumour promoter in many cancers.

Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and is associated with a very poor prognosis. The standard treatment for newly diagnosed patients involves total tumor surgical resection (if possible), plus irradiation and adjuvant chemotherapy. Despite treatment, the prognosis is still poor, and the tumor often recurs within two centimeters of the original tumor.

Quantifying the effects of antibiotic treatment on the extracellular polymer network of antimicrobial resistant and sensitive biofilms using multiple particle tracking.

Novel therapeutics designed to target the polymeric matrix of biofilms requires innovative techniques to accurately assess their efficacy. Here, multiple particle tracking (MPT) was developed to characterize the physical and mechanical properties of antimicrobial resistant (AMR) bacterial biofilms and to quantify the effects of antibiotic treatment. Studies employed nanoparticles (NPs) of varying charge and size (40-500 nm) in Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus (MRSA) biofilms and also in polymyxin B (PMB) treated Escherichia coli biofilms of PMB-sensitive (PMB) IR57 and PMB-resistant (PMB) PN47 strains.

Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment.

The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting to Plasmodium falciparum-infected vs.

Humidified Warmed CO Treatment Therapy Strategies Can Save Lives With Mitigation and Suppression of SARS-CoV-2 Infection: An Evidence Review.

The coronavirus disease (COVID-19) outbreak has presented enormous challenges for healthcare, societal, and economic systems worldwide. There is an urgent global need for a universal vaccine to cover all SARS-CoV-2 mutant strains to stop the current COVID-19 pandemic and the threat of an inevitable second wave of coronavirus. Carbon dioxide is safe and superior antimicrobial, which suggests it should be effective against coronaviruses and mutants thereof.

, a Crosstalk between Neurons, Vascular Structures and Neoplastic Cells in Brain Tumours; Early Manifestation of Invasive Behaviour.

The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognised as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow-Robin spaces. In this review, we provide an overview of emerging knowledge regarding how interactions between neurons and glioma cells can modulate tumour evolution and how neurons play a key role in glioma growth and progression, as well as the role of perivascular satellitosis into mechanisms of glioma cells spread.

Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain.

Interleukin-13 (IL-13) drives cells of myeloid origin towards a more anti-inflammatory phenotype, but delivery to the brain remains problematic. Herein, we show that heparin-based cryogel microcarriers load high amounts of IL-13, releasing it slowly. Intra-striatal injection of loaded microcarriers caused local up-regulation of ARG1 in myeloid cells for pro-regenerative immunomodulation in the brain.

Poly(ethylene glycol) based nanotubes for tuneable drug delivery to glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumour, which is associated with a poor two-year survival rate and a high rate of fatal recurrence near the original tumour. Focal/local drug delivery devices hold promise for improving therapeutic outcomes for GBM by increasing drug concentrations locally at the tumour site, or by facilitating the use of potent anti-cancer drugs that are poorly permeable across the blood brain barrier (BBB). For inoperable tumours, stereotactic delivery to the tumour necessitates the development of nanoscale/microscale injectable drug delivery devices.

Auto-fluorescent PAMAM-based dendritic molecules and their potential application in pharmaceutical sciences.

The epithelial permeation of water-soluble fluorescent PAMAM dendrons based on 7H-benz[de] benzimidazo [2,1-a] isoquinoline-7-one as a fluorescent core across epithelial cell models MDCK I and MDCK II has been quantified. Hydrodynamic radii have been derived from self-diffusion coefficients obtained via pulsed-gradient spin-echo Nuclear Magnetic Resonance (PGSE-NMR). Results indicate that these dendritic molecules are molecularly disperse, non-aggregating, and only slightly larger than their parent homologues.

A human co-culture cell model incorporating microglia supports glioblastoma growth and migration, and confers resistance to cytotoxics.

Despite the importance of the tumor microenvironment in regulating tumor progression, few in vitro models have been developed to understand the effects of non-neoplastic cells and extracellular matrix (ECM) on drug resistance in glioblastoma (GBM) cells. Using CellTrace-labeled human GBM and microglial (MG) cells, we established a 2D co-culture including various ratios of the two cell types. Viability, proliferation, migration, and drug response assays were carried out to assess the role of MG.

Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows.

Modulation of the fate of zein nanoparticles by their coating with a Gantrez® AN-thiamine polymer conjugate.

The aim of this work was to evaluate the mucus-permeating properties of nanocarriers using zein nanoparticles (NPZ) coated with a Gantrez® AN-thiamine conjugate (GT). NPZ were coated by incubation at different GT-to-zein ratios: 2.5% coating with GT (GT-NPZ1), 5% (GT-NPZ2) and 10% (GT-NPZ3).

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies.

Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions.

Mannosylated Nanoparticles for Oral Immunotherapy in a Murine Model of Peanut Allergy.

Peanut allergy is one of the most prevalent and severe of food allergies with no available cure. The aim of this work was to evaluate the potential of an oral immunotherapy based on the use of a roasted peanut extract encapsulated in nanoparticles with immunoadjuvant properties. For this, a polymer conjugate formed by the covalent binding of mannosamine to the copolymer of methyl vinyl ether and maleic anhydride was first synthetized and characterized.

A Systematic Review and Meta-Analysis Reveals Altered Drug Pharmacokinetics in Humans During Acute Exposure to Terrestrial High Altitude-Clinical Justification for Dose Adjustment?

Unlabelled: Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure to terrestrial high altitude-clinical justification for dose adjustment? High Alt Med Biol.

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide.

Background: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy.

Methods: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP).

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs.

Unlabelled: The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5mg/ml.

Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival.

The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells.

Evaluation of nanoparticles as oral vehicles for immunotherapy against experimental peanut allergy.

The aim of this work was to evaluate the potential application of an original oral immunotherapy, based on the use of nanoparticles, against an experimentally induced peanut allergy. In this context, a roasted peanut extract, containing the main allergenic proteins, were encapsulated into poly(anhydride) nanoparticles. The resulting peanut-loaded nanoparticles (PE-NP) displayed a mean size of about 150nm and a significantly lower surface hydrophobicity than empty nanoparticles (NP).

INSIDIA: A FIJI Macro Delivering High-Throughput and High-Content Spheroid Invasion Analysis.

Time-series image capture of in vitro 3D spheroidal cancer models embedded within an extracellular matrix affords examination of spheroid growth and cancer cell invasion. However, a customizable, comprehensive and open source solution for the quantitative analysis of such spheroid images is lacking. Here, the authors describe INSIDIA (INvasion SpheroID ImageJ Analysis), an open-source macro implemented as a customizable software algorithm running on the FIJI platform, that enables high-throughput high-content quantitative analysis of spheroid images (both bright-field gray and fluorescent images) with the output of a range of parameters defining the spheroid "tumor" core and its invasive characteristics.