Integrating endobronchial ultrasound bronchoscopy with molecular testing of immunotherapy biomarkers in non-small cell lung cancer.

Immunotherapy has transformed treatment of advanced non-small-cell lung cancer (NSCLC) patients leading to remarkable long-term survival benefit. However, only about 20% of advanced NSCLC patients typically respond to immune checkpoint inhibitors (ICIs) that target the PD-1/PD-L1 pathway. The only validated biomarker for ICI therapy is the PD-L1 immunohistochemistry (IHC) test, which is considered an imperfect assay due to several variables including availability and integrity of tumour tissue, variability in staining/scoring techniques and heterogeneity in PD-L1 protein expression within and across tumour biopsies.

Aspirin-Triggered Resolvin D1 Reduces Proliferation and the Neutrophil to Lymphocyte Ratio in a Mutant KRAS-Driven Lung Adenocarcinoma Model.

Tumour-associated neutrophils (TANs) can support tumour growth by suppressing cytotoxic lymphocytes. AT-RvD1 is an eicosanoid that can antagonise neutrophil trafficking instigated by ALX/FPR2 ligands such as serum amyloid A (SAA). We aimed to establish whether SAA and ALOX5 expression associates with TANs and investigate the immunomodulatory actions of AT-RvD1 in vivo.

Novel multiplex droplet digital PCR assay for scoring PD-L1 in non-small cell lung cancer biopsy specimens.

Objectives: Immune checkpoint inhibitors have become integrated into the clinical management of non-small cell lung cancer (NSCLC). Using RTqPCR, we have previously identified a gene expression panel that detected presence of malignant cells (MMP9:TIMP3 ratio) and quantified PD-L1 transcript levels in small biopsy specimens. However, RTqPCR has diagnostic limitations as it does not generate absolute copy number and is not readily multiplexed.

A Novel Approach to Detect Programed Death Ligand 1 (PD-L1) Status and Multiple Tumor Mutations Using a Single Non-Small-Cell Lung Cancer (NSCLC) Bronchoscopy Specimen.

Multiple biomarkers are under evaluation to guide the use of immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC), including programed death ligand 1 (PD-L1) tumor cell staining. We have developed a new approach that accurately quantifies PD-L1 status and identifies multiple mutations by using a single bronchoscopy specimen. A novel molecular marker was identified to detect the presence of malignant cells in radial endobronchial ultrasound bronchial brushings from NSCLC (n = 15) and benign (n = 13) nodules by quantitative real-time RT-PCR (RT-qPCR).

An immunohistochemical analysis of the effects of androgen receptor knock out on gubernacular differentiation in the mouse.

Aim: Cryptorchidism affects 2%-4% of newborn boys and causes infertility and cancer. While normal androgen function is required for successful inguinoscrotal descent, its exact role on gubernacular morphology remains unidentified. We aimed to decipher the effect of androgen blockade on the gubernaculum and surrounding structures.

Mouse minipuberty coincides with gonocyte transformation into spermatogonial stem cells: a model for human minipuberty.

As the transient postnatal hormone surge in humans, known as 'minipuberty', occurs simultaneously with key steps in germ-cell development, we investigated whether similar changes occur in the hypothalamic-pituitary-testicular axis of neonatal mice at a time that would coincide with gonocyte transformation into spermatogonial stem cells (SSC). Serum and testes were collected from C57Bl/6 mice at embryonic Day 17 (E17), birth (postnatal Day 0; P0) and daily until P10. Serum FSH and testosterone levels in both serum and testes were analysed and gene expression of FSH receptor (Fshr), luteinising hormone receptor (Lhr), anti-Müllerian hormone (Amh), octamer-binding transcription factor 4 (Oct-4), membrane type 1 metalloprotease (Mt1-mmp), proto-oncogene C-kit and promyelocytic leukaemia zinc finger (Plzf ) was quantified by real-time polymerase chain reaction.

Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment.

Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue.

Neurotrophin signaling in a genitofemoral nerve target organ during testicular descent in mice.

Background/aim: It has been proposed that androgens control inguinoscrotal testicular descent via release of calcitonin gene-related peptide (CGRP) from a masculinised genitofemoral nerve (GFN). As there are androgen receptors in the inguinoscrotal fat pad (IFP) during the window of androgen sensitivity (E14-17 in mouse embryos), we tested the hypothesis that neurotrophins in the IFP may masculinise the sensory fibers of the GFN supplying the gubernaculum and IFP prior to gubernacular migration.

Methods: Androgen-receptor knockout (ARKO) and wild-type (WT) mouse embryos were collected at E17, with ethical approval (AEC 734).

Oct4-GFP expression during transformation of gonocytes into spermatogonial stem cells in the perinatal mouse testis.

Background/aim: In cryptorchidism perinatal failure to switch off Oct4, a germ cell (GC) marker, may lead to carcinoma in situ. We aimed to analyze Oct4 expression during mouse gonocyte transformation into spermatogonial stem cells (SSC).

Materials And Methods: Testes from OG2 (Oct4-promoter driven eGFP) mice at embryonic day (E) 17 and postnatal day P0-10 underwent immunohistochemistry and immunoblotting.

Postnatal germ cell development during mini-puberty in the mouse does not require androgen receptor: implications for managing cryptorchidism.

Purpose: Undescended testis leads to infertility and malignancy resulting from aberrant germ cell development. Androgens are proposed to control early germ cell development during the transient postnatal surge of gonadotropins and androgen, known as mini-puberty. We assessed the effect of androgen receptor on perinatal germ cell development in mice.