The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care.

Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies.

Application of non-inferiority testing in microhardness and its relationship to erosion: Relevance for hard tissue safety evaluations.

Purpose: To use non-inferiority statistical testing with simple microhardness measurements (SMH) as a prediction of potential erosive hard tissue damage of topical treatments on enamel.

Methods: Three independent experiments of a simple acid cycling demineralization (ACD) model were used to screen softening effects of various commercial beverages on dental enamel. The cycling model consists of six repeated exposures of enamel slabs with alternating treatments of artificial saliva over the course of 6 hours.

Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma.

Purpose: Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL.

Patients And Methods: Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2.

Observation of two-dimensional Anderson localisation of ultracold atoms.

Anderson localisation -the inhibition of wave propagation in disordered media- is a surprising interference phenomenon which is particularly intriguing in two-dimensional (2D) systems. While an ideal, non-interacting 2D system of infinite size is always localised, the localisation length-scale may be too large to be unambiguously observed in an experiment. In this sense, 2D is a marginal dimension between one-dimension, where all states are strongly localised, and three-dimensions, where a well-defined phase transition between localisation and delocalisation exists as the energy is increased.

Laboratory screening evaluation of the safety of low pH oral care rinse products to dental enamel.

Purpose: To assess the hard tissue safety of a variety of low pH oral care rinses to dental enamel in a newly developed screening method.

Methods: Bovine enamel specimens were subjected to a cycling model that consisted of commercial mouthrinse product exposures and artificial saliva soaks based on a previously published screening method. The effect of test products on the surface of treated specimens was measured using surface microhardness (SMH).

Cavity Dark Mode of Distant Coupled Atom-Cavity Systems.

We report on a combined experimental and theoretical investigation into the normal modes of an all-fiber coupled cavity-quantum-electrodynamics system. The interaction between atomic ensembles and photons in the same cavities, and that between the photons in these cavities and the photons in the fiber connecting these cavities, generates five nondegenerate normal modes. We demonstrate our ability to excite each normal mode individually.

Development of a Screening Method to Establish if pH of Oral Care Products Affects Hard Tissues.

Objectives: To develop a transferable, simple screening method to evaluate the effect of pH of oral care products on oral hard tissues.

Methods: The method reported here is based on the assessment of oral hard surface changes produced by oral care products measured via Vickers Surface Microhardness (SMH). Two variations of this screening test method were developed, one including the use of salivary pellicle and human teeth and a second using bovine substrates with artificial saliva.

Clinical effects of stannous fluoride dentifrice in reducing plaque microbial virulence III: Lipopolysaccharide and TLR2 reporter cell gene activation.

Purpose: This study expanded the analysis of subgingival dental plaques from previous research to include the evaluation of cohort, site and treatment effects on chemically measured endotoxin and activation of Toll-like receptor (TLR) based gene expression in two additional reporter cell lines: a TLR2 specific cell line and a THP-1 (multi TLR reporter) cell line.

Methods: Participants from high and low bleeding cohorts were sampled at baseline for both supra and subgingival dental plaque at both healthy as well as clinically diseased sites and then provided with intervention hygiene products including a stabilized SnF₂ dentifrice and a new soft bristle manual toothbrush. Following 2 and 4 weeks of assigned dentifrice use, participants returned for a re-evaluation of gingival inflammation and bleeding and repeat samplings of dental plaque.

Subgingival uptake and retention of stannous fluoride from dentifrice: Gingival crevicular fluid concentrations in sulci post-brushing.

Purpose: To examine the delivery of stannous fluoride to subgingival sulci following toothpaste use in a clinical population.

Methods: This was a controlled, single-site study. 23 subjects with at least 20 dental pockets, 2-4 mm with bleeding, who had not used a stannous fluoride dentifrice in the last 3 months were enrolled.

Clinical Effects of Stabilized Stannous Fluoride Dentifrice in Reducing Plaque Microbial Virulence II: Metabonomic Changes.

Objectives: The clinical effects of stannous fluoride (SnF2) dentifrice in reducing symptoms of gingivitis and reducing the virulence of subgingival plaque through suppression of activation of gene expression in toll receptor based reporter cells were previously reported. This study expanded analysis of the clinical study to include evaluation of dentifrice effects on salivary metabolites using 1H Nuclear Magnetic Resonance (1H NMR) systems biology-based metabonomics.

Methods: The clinical design was reported previously (J Clin Dent2017;28:16-26).

Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases.

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed.

Simultaneous Pancreas and Kidney Transplantation is Associated With Inferior Long-Term Outcomes in African Americans.

Objectives: Simultaneous pancreas and kidney transplant (SPK) is the most effective treatment for patients with type 1 diabetes mellitus and renal failure. However, the effect of ethnicity on SPK outcomes is not well understood.

Methods: We studied the influence of recipient ethnicity on SPK using the United Network for Organ Sharing database.

A Profilometry-Based Dentifrice Abrasion Method for V8 Brushing Machines Part III: Multi-Laboratory Validation Testing of RDA-PE.

Objectives: We have previously reported on progress toward the refinement of profilometry-based abrasivity testing of dentifrices using a V8 brushing machine and tactile or optical measurement of dentin wear. The general application of this technique may be advanced by demonstration of successful inter-laboratory confirmation of the method. The objective of this study was to explore the capability of different laboratories in the assessment of dentifrice abrasivity using a profilometry-based evaluation technique developed in our Mason laboratories.

Lipopolysaccharide and lipoteichoic acid binding by antimicrobials used in oral care formulations.

Purpose: To study the reactivity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) with the cationically charged agents cetylpyridinium chloride, stannous fluoride, and the non-cationic agent triclosan. We also assessed the effect of these agents to inhibit LPS and LTA binding to cellular Toll-like Receptors (TLRs) in vitro.

Methods: The ability of these antimicrobials to bind with LPS and/or LTA was assessed in both the Limulus amebocyte lysate and BODIPY-TR-cadaverine dye assays.

Quantitation of endotoxin and lipoteichoic acid virulence using toll receptor reporter gene.

Purpose: To apply quantitative Toll-like receptors (TLR) cell assays to compare lipopolysaccharides (LPSs) and lipoteichoic acids (LTAs) from different oral bacterial strains for potential pathogenicity in vitro.

Methods: The potency of LPS and LTA from different bacteria on activation of TLR reporter genes in HEK-tlr cell lines was examined. P.

Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II-Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3.

Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8 T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4 T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3).

Clinical Effects of Stabilized Stannous Fluoride Dentifrice in Reducing Plaque Microbial Virulence I: Microbiological and Receptor Cell Findings.

Objectives: Lipopolysaccharides (LPSs) and lipoteichoic acids (LTAs), or bacterial endotoxins, bind with Toll-like receptors (TLRs) that are expressed on host cells of the periodontium, thereby contributing to the periodontal pathogenicity of oral bacteria. Stannous fluoride (SnF2), an antibacterial fluoride that treats and controls gingivitis, has been shown to react with lipophilic domains/anionic charges in LPS and LTA. The effects of bacterial species and dental plaque on toll receptors can be studied using genetically engineered cell lines containing linked toll receptors on their surfaces.

Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study.

Background: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours.

Lipopolysaccharide and Lipoteichoic Acid Virulence Deactivation by Stannous Fluoride.

Objectives: Oral bacterial pathogens promote gingivitis and periodontal disease. Bacterial endotoxins, also known as lipopolysaccharides (LPSs) and lipoteichoic acids (LTAs), are known to enhance bacterial pathogenicity through binding with Toll-like receptors (TLRs), a group of pattern recognition receptors critical to the activation of innate immunity, that are expressed on host cells. Both LPS and LTA contain lipophilic domains and anionic charges that may be susceptible to reactivity with stannous fluoride, a commonly used ingredient clinically proven for the treatment and prevention of gingivitis.

Salivary protein changes in response to acute stress in medical residents performing advanced clinical simulations: a pilot proteomics study.

Context: Quantitative changes of salivary proteins due to acute stress were detected.

Objective: To explore protein markers of stress in saliva of eight medical residents who performed emergency medicine simulations.

Materials And Methods: Saliva was collected before the simulations, after the simulations, and following morning upon waking.

Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma.

Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion.

A Profilometry-Based Dentifrice Abrasion Method for V8 Brushing Machines Part II: Comparison of RDA-PE and Radiotracer RDA Measures.

Objective: The purpose of this study was to compare the abrasivity of commercial dentifrices by two techniques: the conventional gold standard radiotracer-based Radioactive Dentin Abrasivity (RDA) method; and a newly validated technique based on V8 brushing that included a profilometry-based evaluation of dentin wear. This profilometry-based method is referred to as RDA-Profilometry Equivalent, or RDA-PE.

Methods: A total of 36 dentifrices were sourced from four global dentifrice markets (Asia Pacific [including China], Europe, Latin America, and North America) and tested blindly using both the standard radiotracer (RDA) method and the new profilometry method (RDA-PE), taking care to follow specific details related to specimen preparation and treatment.

Response of chronic gingivitis to hygiene therapy and experimental gingivitis. Clinical, microbiological and metabonomic changes.

Purpose: To compare the clinical, microbiological and metabonomic profiles of subjects with high and low levels of chronic gingival bleeding during a controlled oral hygiene regimen intervention including sequential phases of rigorous therapeutic oral hygiene followed by experimental gingivitis (EG).

Methods: Two cohorts of qualified study subjects with differences in gingival bleeding on probing levels at their baseline clinical examination were entered into the study. These two cohorts were followed through three separate study phases including a 1-week baseline phase, a 2-week phase of rigorous oral hygiene including dental prophylaxis, and a 3-week EG phase of no oral hygiene to encourage relapse of gingivitis.