Publications

Publications

Mentors and the butterfly effect: triggers for discovering signalling by proteinases via proteinase-activated receptors (PARs) and more.

By:
Contributors: Morley Hollenberg Research Group
Clin Invest Med. 2012 Feb 1;35(6):E378-91.

Abstract

The essential role of proteinases as regulatory digestive enzymes, recognized since the late 1800s, has been underscored by the discovery that more than 2% of the genome codes for proteinases and their inhibitors. Further, by the early 1970s it was appreciated that in addition to their digestive actions, proteinases can affect cell function: (1) by the generation or degradation of peptide hormones and (2) by the direct regulation of signalling by receptors like the one for insulin. It was the discovery in the 1990s of the novel G-protein-coupled ‘proteinase-activated receptor’ (PAR) family that has caused a paradigm shift in the understanding of the way that proteinases can regulate cell signalling. This overview provides a perspective for the discovery of the PARs and my laboratory’s role in (1) understanding the molecular pharmacology of these fascinating receptors and (2) identifying the potential pathophysiological roles that the PAR family can play in inflammatory disease. In this context, the overview also portrays the essential impact that seemingly minor comments/insights provided by my lifelong mentors have had on kindling my intense interest in proteinase-mediated signalling. The ‘butterfly effect‘ of those comments has led to an unexpectedly large impact on my own research directions. Hopefully my own ‘butterfly comments’ will also be heard by my trainees and other colleagues with whom I am currently working and will promote future discoveries that will be directly relevant to the treatment of inflammatory disease.

 

PubMed

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The Calgary Prostate Cancer Centre has the highest accrual for a novel ultrasound study in prostate cancer

“We have enrolled over 400 patients at our site, reaching our enrollment goal much faster than all other sites across North America. We are now planning on adding in 250 more patients to this trial because of the encouraging results found with the first arm of the trial. Our site tied with the highest accrual goal and surpassed all other sites to meet our enrollment goal.”

The study is a “Multi-Center trial of high-resolution transrectal ultrasound versus standard low-resolution transrectal ultrasound for the identification of clinically significant prostate cancer”

The only definitive method for diagnosing prostate cancer is through a prostate biopsy. This procedure includes the use of an ultrasound machine to guide both freezing needles and biopsy needles into the prostate. The ultrasound machine that is currently in use is a low-resolution ultrasound machine which means that although it is good at seeing the entire prostate gland to guide the needles, it is often unable to visualize the prostate in enough detail to be able to see different lesions and areas of concern within it. Thus, many biopsy samples are taken systematically with two samples from each section of the prostate. Recently a new ultrasound machine has been created that gives images of the prostate with much higher resolution, allowing the radiologist performing the biopsy to see details within the prostate that were previously inaccessible. A study using this new high-resolution ultrasound machine is being completed at the Prostate Cancer Centre to compare the adequacy of this new machine to detect prostate cancer over the standard low-resolution machine. Over 650 patients will be enrolled in this study!

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- Eric Hyndman