Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma.

Purpose: Many patients with locoregionally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.

Experimental Design: We retrospectively evaluated a personalized, commercial ctDNA assay (Signatera, Natera) during clinical care of patients treated for predominantly newly diagnosed human papillomavirus-negative HNSCC.

SWOG 1609 cohort 48: anti-CTLA-4 and anti-PD-1 for advanced gallbladder cancer.

Introduction: Most patients with advanced gallbladder cancer are treated with multiagent chemotherapy. Immune checkpoint inhibitors offer the possibility of a durable response with less toxicity. This prospective, multicenter, open-label study was designed to evaluate the anticancer activity of nivolumab plus ipilimumab in patients with advanced gallbladder cancer.

Germline DNA damage response gene mutations as predictive biomarkers of immune checkpoint inhibitor efficacy.

Background: Impaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity.

Materials And Methods: A retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed.

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in Patients with Gestational Trophoblastic Neoplasia.

Purpose: The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).

Patients And Methods: This prospective, open-label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN.

The impact of substance use on health care utilization, treatment, and outcomes in patients with non-small cell lung cancer.

Background: Mortality from non-small cell lung cancer (NSCLC) has improved with screening and novel treatments. The substance use epidemic has threatened health outcomes in a variety of diseases, but little is known about how it is associated with NSCLC outcomes.

Methods: We performed a retrospective cohort study of 211 patients with NSCLC treated at a safety-net hospital.

A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma.

Objectives: We aimed to test the safety of the CDK4/6 inhibitor palbociclib in combination with the EGFR inhibitor cetuximab and the PD-L1 inhibitor avelumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Materials And Methods: This phase I study enrolled eligible adult patients with R/M HNSCC into three sequential single dose-escalation cohorts of palbociclib (75, 100, and 125 mg) PO daily on days 1 to 21 of a 28-day cycle in combination with avelumab 10 mg/kg IV every 2 weeks and cetuximab 400 mg/mIV on day 1, then 250 mg/mweekly thereafter. The study followed a 3 + 3 design with no intra-patient escalation.

Immune Checkpoint Inhibitor Rechallenge After Prior Immune Toxicity.

Immune checkpoint inhibitors (ICIs) have become an essential part of treatment for many cancer types. These monoclonal antibodies remove a critical negative regulatory signal that allows the immune system to recognize and destroy malignant cells that were previously undetectable. Unfortunately, their use has ushered in a whole new form of drug toxicity whereby the immune system attacks normal tissues in the body, referred to hereafter as immune-related adverse events (irAEs).

Active-Site Tryptophan, the Target of Antineoplastic C-Terminal Binding Protein Inhibitors, Mediates Inhibitor Disruption of CtBP Oligomerization and Transcription Coregulatory Activities.

C-terminal binding proteins (CtBP1/2) are oncogenic transcriptional coregulators and dehydrogenases often overexpressed in multiple solid tumors, including breast, colon, and ovarian cancer, and associated with poor survival. CtBPs act by repressing expression of genes responsible for apoptosis (e.g.

Correction: Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

[This corrects the article DOI: 10.1371/journal.pone.

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides.

ELISPOT Refinement Using Spot Morphology for Assessing Host Responses to Tuberculosis.

Tuberculosis is a global health problem. The Mycobacterium bovis Bacille Calmette Guerin (BCG) vaccine has variable efficacy (0-80%) so there is a drive to develop novel vaccines. The cytokine, interferon gamma (IFNγ), is an essential component of the protective response to M.

A multiple-plane approach to measure the structural properties of functionally active regions in the human cortex.

Advanced magnetic resonance imaging (MRI) techniques provide the means of studying both the structural and the functional properties of various brain regions, allowing us to address the relationship between the structural changes in human brain regions and the activity of these regions. However, analytical approaches combining functional (fMRI) and structural (sMRI) information are still far from optimal. In order to improve the accuracy of measurement of structural properties in active regions, the current study tested a new analytical approach that repeated a surface-based analysis at multiple planes crossing different depths of cortex.

A comparison of reconstruction algorithms for C-arm mammography tomosynthesis.

Digital tomosynthesis is an imaging technique to produce a tomographic image from a series of angular digital images in a manner similar to conventional focal plane tomography. Unlike film focal plane tomography, the acquisition of the data in a C-arm geometry causes the image receptor to be positioned at various angles to the reconstruction tomogram. The digital nature of the data allows for input images to be combined into the desired plane with the flexibility of generating tomograms of many separate planes from a single set of input data.

Biodistribution and persistence of an MVA-vectored candidate HIV vaccine in SIV-infected rhesus macaques and SCID mice.

Recombinant modified vaccinia virus Ankara (MVA) is together with a few other attenuated viral vectors on the forefront of human immunodeficiency virus type 1 (HIV-1) vaccine development. As such, MVA-vectored vaccines are likely to be administered into immunocompromized individuals. Here, we demonstrated in a good laboratory practice study safety and biological clearance of candidate HIV-1 vaccine MVA.

Postoperative upper extremity radiographs using the image intensifier: a simple adjunct to the "inverted" C-arm technique.

When the C-arm is used as a table in upper extremity surgery, postoperative plain radiographs can be obtained by placing the x-ray cassette directly on the image intensifier. This has many advantages, including more rapid performance than conventional techniques, a high-quality image, and no need for a recovery room radiograph. Additionally, there is no overlying splint material to obscure image detail, and the extremity can be positioned as desired by the operating surgeon.

Bradykinin B1 receptor blocks PDGF-induced mitogenesis by prolonging ERK activation and increasing p27Kip1.

The mechanism by which the bradykinin B1 receptor (B1R) inhibits platelet-derived growth factor (PDGF)-stimulated proliferation was investigated in cultured rat mesenteric arterial smooth muscle cells. The B1R agonist des-Arg9-bradykinin (DABK) was found to inhibit PDGF-mediated activation of the cyclin E-cyclin-dependent kinase 2 (Cdk2) complex and to prevent hyperphosphorylation of retinoblastoma protein. DABK did not inhibit upregulation of cyclin E expression but increased expression of the Cdk2 inhibitor p27Kip1 and the association of p27Kip1 with the cyclin E-Cdk2 complex.