an-open-source-normothermic-perfusion-system-designed-for-research

An Open-Source Normothermic Perfusion System Designed for Research Scientists

The integration of ex vivo perfusion machines for human organs prior to transplantation has improved outcomes for recipients and increased organ ...

National Institutes of Health

A Randomized Study of Olaparib or Placebo in Patients with Surgically Removed Pancreatic Cancer who have a BRCA1, BRCA2 or PALB2 Mutation (The APOLLO Trial).

Stage IA gastric adenocarcinoma, characterized by foci of intramucosal signet ring cells (SRC), is found in nearly all asymptomatic patients with germline pathogenic CDH1 variants and hereditary diffuse gastric cancer syndrome (HDGC). The molecular steps involved in initiating malignant transformation and promoting SRC dormancy in HDGC are unknown. Here, whole-exome bulk RNA sequencing (RNA-seq) of SRCs and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from patients with HDGC (Clinicaltrials.gov ID: NCT03030404). In total, 20 patients (6 male, 14 female) with confirmed HDGC were identified. Analysis of differentially expressed genes (DEG) demonstrated upregulation of certain individual EMT and proliferation genes. However, no oncogenic pathways were found to be upregulated in SRCs. Rather, SRC regions had significant enrichment in pathways involved in T-cell signaling. CIBERSORTx predicted significant increases in the presence of regulatory T cells (Treg) specific to SRC regions. IHC confirmed an increase in FOXP3+ cells in SRC foci, as well as elevations in CD4+ T cells and HLA-DR staining. In summary, the tumor immune microenvironment is microscopically inseparable from stage IA gastric SRCs using a granular isolation technique. An elevation in CD4+ T cells within SRC regions correlates with clinically observed SRC dormancy, while Treg upregulation represents a potential immune escape mechanism.

Article	Year
A Randomized Study of Olaparib or Placebo in Patients with Surgically Removed Pancreatic Cancer who have a BRCA1, BRCA2 or PALB2 Mutation (The APOLLO Trial). Annals of surgical oncology\| PubMed ID: 35668307	2022
Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis. Molecular cancer research : MCR\| PubMed ID: 37707375	2023

Stephanie C. Lux

Biography

JoVE Journal Publications

Other Publications