Gastro-Oesophageal Cancer

Associate Professor Reginald V. N. Lord is the head of the Gastro-oesophageal Cancer Program, in addition to being a consultant surgeon at St Vincent's Hospital, St Vincent's Private Hospital, and St Vincent's Clinic, and conjoint Associate Professor at the University of New South Wales. He trained at St Vincent's Hospital and at the University of Southern California, Los Angeles. His program is the first surgical research group to be housed at AMR.

The Gastro-oesophageal Cancer Program

The Gastro-oesophageal Program continues to grow at a steady pace since our formation in 2007 at the Centre for Immunology. Our program works collaboratively with Australia-wide partners such as the Queensland Institute of Medical Research and the Flinders University in South Australia.

The key subjects investigated by the research laboratory are:

  • gene expression and DNA methylation in Barrett's oesophagus and oesophageal adenocarcinoma,
  • immune regulation and stem cells in this disease,
  • pharmacogenetics of response to chemotherapy for oesophageal adenocarcinoma,
  • genetic profile of the neosquamous oesophagus after Barrett's radiofrequency ablation,
  • Mechanisms of metabolic benefits incurred with surgical weight loss,
  • aetiology of achalasia.

The gene expression and DNA methylation tissue studies have resulted in validation of more than 20 genes that are likely to be important in this disease. This study validates our methods and previous findings including our microarray results. We have identified novel pathways to oesophageal adenocarcinoma including the netrin/netrin receptor pathway and tetraspanin family of genes. We completed a study on HSV-tk/GCV suicide gene therapy with the Grp-78 stress-inducible promoter. This reported the most successful gene therapy strategy, with complete abolition of tumours in vivo in nude mice.

The studies on immune activation and inflammation in this disease resulted in the first identification of the presence, and possible importance aetiologically, of dendritic cells. We identified a putative stem cell for Barrett's oesophagus with dysplasia and oesophageal adenocarcinoma (Musashi-1 positive cells).

We introduced radiofrequency ablation of Barrett's oesophagus technology to Australia. A 40 gene mRNA expression study of selected progression-related genes in 20 patients who underwent this new therapy showed that the neosquamous mucosa which replaces the Barrett's premalignant mucosa is similar to normal oesophageal mucosa and dissimilar to Barrett's oesophagus. An NHMRC funded project grant with Flinders University and University of Melbourne is underway to further investigate the effectiveness of competing therapies for Barrett's oesophagus.

Studies on surgical weight loss and its effect on obesity co-morbid conditions are in progress in collaboration with A/Prof K. Samaras and the Garvan Institute Diabetes and Obesity Research Group. These studies have demonstrated the importance of visceral fat expression of multiple genes in diabetes improvement and the rapid attenuation of arterial stiffness.

Achalasia is the commonest named motility disorder of the oesophagus but its aetiology is entirely unknown. It is characterised by absence of peristalsis in the oesophageal body and a hypertensive, poorly relaxing, lower oesophageal sphincter. We have demonstrated that interstitial cells of Cajal, the "pacemaker cells" of the gut, are present in normal numbers in this disease. We are investigating the function of these cells in achalasia and normal oesophagus in an effort to discover the cause of this mysterious disease.