RESEARCH PROJECTS
Defining the Role of
Post-surgical Infectious Complications on
Cancer Recurrence
Through both clinical and bench research we have explored the basic hypothesis that post-surgical complications increase cancer metastasis. This hypothesis was generated from a recurring anecdotal clinical observation of very early cancer recurrence in some patients on whom we had operated on for esophageal cancer suffering an anastomotic leak.
Our group has published several retrospective clinical studies, both at the single institution and population-based levels, revealing a clear association of post-operative infection and early cancer specific death after surgery for esophagus (Ferri et al, Annals of Surgical Oncology 2006) and lung cancer (Andalib et al, Journal of Thoracic Oncology 2013)
This clinical observation prompted fundamental research into bacterial antigen receptors and cancer progression, resulting in several manuscripts implicating Toll like receptors in cancer metastasis (Hsu et al, Cancer Research 2011, Rousseau et al, Surgery 2013, Chow et al, International Journal of Cancer 2014 ). This research program exploring pathogen antigen receptors continues to be very active in the laboratory.
Identifying
Neutrophils as
Mediators of Metastasis
Neutrophils represent the first and most abundant leukocyte recruited to a site of infection. Given our clinical finding of an association between infection and cancer progression, the lab sought out to explore the influence of neutrophils on cancer metastasis.
Indeed, our laboratory was one of the first laboratories in North America to pursue this line of investigation and we have shown through several manuscripts the close interactions of these polymorphonuclear granulocytes and cancer cells.
This research topic is currently very active in the laboratory and is funded by a 5 year CIHR grant ending in 2019.
These series of publications have demonstrated:
A Cancer cells and neutrophils frequently co-localize in the liver of inflamed animals at the early adhesive steps of metastasis
B Neutrophils and cancer cells bind through Mac-1 mediated adhesion, and elimination of neutrophils in states of acute inflammation greatly diminish cancer metastasis
C Neutrophil extracellular traps (NETs), a newly described aspect of neutrophil biology, not only captures cancer cells during models of post-op infection, but they also potentiate hepatic metastasis.
Investigating the Genetic Determinants and Molecular Mechanisms of Peritoneal Metastasis from Gastro-Esophageal Cancer
Peritoneal metastasis is the leading cause of death from gastric cancer, yet it is the least understood and hardest form of cancer progression to treat.
Our lab has initiated a new translational and bench research program exploring both the genetic determinants as well as the molecular mechanisms of this complex disease process.
I am exploring gene expression signatures (RNA seq) in human tissue predictive of developing peritoneal metastasis as well as driver mutations for this form of metastasis in matched triplets (whole exome sequencing) of patient tissue.
Furthermore, we have developed novel functional assays of peritoneal metastasis (in vitro and ex vivo) to explore and validate putative gene targets identified from the above next generation sequencing methods.
Want to join the Thoracic Surgery & Upper GI Cancer Lab?
Contact Ms. Betty Giannias
Email
514-934-1934 ext. 76102