A recent study published in Nature Genetics sought to determine the effects of hypoxia — low levels of molecular oxygen — on the development of cancer, including how it may speed up cancer growth. Lead author Vinayak Bhandari, a PhD candidate in U of T’s Faculty of Medicine and the Ontario Institute for Cancer Research, examined hypoxia in over 8,000 tumors across 19 tumour types.

Hypoxia can have detrimental health effects, one of which is that it can cause cancer cells to proliferate. 

According to Bhandari, normally, blood vessels in our bodies are well-organized and able to transport nutrients, including oxygen, to all cells. This changes in tumours.

“In tumours, the blood vessels are often very disorganized and have sluggish blood flow,” wrote Bhandari in an email to The Varsity. This leads to low-oxygen tumours. “Around half of all solid tumours end up with low levels of oxygen.”

Hypoxic conditions can accelerate the spread of aggressive cancer cells. In tumours, cancer cells exist with different sets of mutations. Some cancer cells will be susceptible to hypoxic environments due to their specific mutation, and these cells often do not survive. 

“But other cells that have a specific mutation may not be affected by low oxygen,” wrote Bhandari. “So you end up enriching the tumour for cells with that aggressive mutation that can survive an extreme environment and you get a more aggressive cancer.”

Despite the threat that hypoxia poses, it has previously been a challenge to study its effects due to the invasive and difficult process of measuring oxygen levels in tumours. 

To remedy this, Bhandari and his team created an innovative method for examining tumour hypoxia in more detail. 

“We used several mRNA signatures to computationally quantify tumour oxygen levels with existing patient data. We then used this hypoxia information and looked broadly at lots of different genomic features of tumours and found some really interesting links in several cancers,” wrote Bhandari. “We then dug deeper into prostate cancer where we have really good long term data for how patients respond to treatments and we looked further into interactions between hypoxia, changes in the DNA and also how tumours change over time.”

Dr. Paul Boutros — former Associate Professor at U of T’s Department of Medical Biophysics, now at the University of California, Los Angeles, and the supervisor for this study — added that hypoxia and its relevance to cancer growth is still not well understood, but that this research is a significant step. 

“I think other researchers are going to be able to take advantage of these data to explore a lot of new angles,” wrote Boutros. 

Boutros believes that other researchers will begin to look at genomics associated with hypoxic cancer cells, and begin to look more into genomic data in a new light. Boutros also adds that this research highlights how hypoxic environments arise due to different factors aside from genetic mutations, including cell morphology and evolutionary properties. 

Bhandari emphasized the multidisciplinary nature of the team involved in the research, and how it was an asset. 

“We were only able to do this because we had biologists, chemists, data scientists, statisticians, engineers, pathologists and radiation oncologists come together to work on this problem in asymmetric fashion. Everyone contributed in important ways over many years and I think this is the best way forward for answering difficult questions.”

Governing Council’s Planning and Budget Committee (PBC) has unanimously voted to recommend the transformation of the FitzGerald Building from hosting research labs to space for administrative office spaces. Following the PBC’s recommendation on January 10, the Report of the Project Planning Committee for FitzGerald Building Revitalization must still go through the Academic Board, Business Board, and Executive Committee for discussion, prior to receiving final approval from Governing Council on February 28.

The FitzGerald Building, located on 150 College Street, was vacated by the Faculty of Dentistry and the Faculty of Medicine in July. Both have since moved to new or renovated spaces on campus.

According to the report, the Faculty of Medicine had conducted studies that demonstrated “significant challenges and costs” to continued use of the building. Further, the report states that “there have not been any significant upgrades to the building infrastructure in many years, and the wet research space in particular has deteriorated.”

Constructed in 1927, the FitzGerald Building has heritage status, meaning that it cannot be demolished. According to Vice-President University Operations Scott Mabury, the refurbished building will only provide half the occupancy space that is available at the administration’s current 215 Huron Street location, “but it’s going to be a much better space to work in.”

Administrative offices, including Financial Services and Human Resources & Equity, operate at 215 Huron Street, which Mabury said the university hopes to replace with a “data sciences kind of building… that will house a number of researchers across the campus.”

If the report is approved by Governing Council, construction on the building will commence in May, with full operational occupancy expected by October 2020.

This was the second committee meeting this academic year. The initial second meeting, scheduled on October 31, had been cancelled. PBC Secretary Joan Griffin told The Varsity in mid-October that there was “no business to transact by the Committee during [that] cycle.”

Need a vaccination for an upcoming trip? Is a refill on your prescription required soon? While these might seem like easy problems to fix, getting that vaccine or refill could be harder than you think.

Though Health Canada created a Multi-Stakeholder Steering Committee on Drug Shortages in 2012 to tackle the drug shortage issue and also implemented mandatory reporting of anticipated and actual drug shortages by drug manufacturers in 2017, the problem continues to persist.

Dr. Jacalyn Duffin, Professor Emerita at Queen’s University and graduate of U of T’s Faculty of Medicine, has been a staunch communicator on the issue.

Duffin founded canadadrugshortage.com, a platform that tracks drug shortage issues in Canada. According to Duffin, individuals who rely on generic products are most likely to be affected by drug shortages.

She also pointed out that “people can be affected by it without knowing,” expressing her concern that media attention on the shortages of bupropion and EpiPens takes away from the fact that “there are literally [hundreds] of other drugs in short supply at any given time.”

Since 2010, physicians and pharmacists in Canada have been struggling to get vaccinations and prescription medications to their patients due to a drug shortage problem. As a result, those who require these medications end up relying on alternatives that could be less safe and less effective.

One of the drugs undergoing a national shortage is the antidepressant bupropion. This shortage is especially problematic since there are no available alternatives to the medication.

Also of concern is the shortage of EpiPens, which are manufactured by only one supplier in Canada. This shortage is so extensive that Health Canada has gone so far as to recommend patients keep and use expired EpiPens in cases of an allergic reaction. Considering that about four per cent of Canadians have food allergies, it’s not farfetched to assume that many U of T students would be affected by this shortage.

It might be confusing that drug companies, whose priorities are to research, develop, and supply drugs to people in need, are failing at one of these vital tasks. However, getting a pill or vaccine to the public is a process that involves much more work than one might think.

A single drug must go through review, authorization, manufacturing, procurement, and distribution before it can be delivered to patients by their primary health care providers. A holdup during any one of these processes can cause a drug shortage.

Among the most prevalent of these setbacks are a lack of raw materials, difficulties in manufacturing, regulatory disturbances, business decisions, and unexpected surges in public demand.

Many of these issues are difficult for both pharmaceutical companies and the Canadian government to combat as they arise. For example, raw materials required for certain drugs often need to be imported from other countries. Issues like contaminated supply from one of these imports can cause an immediate holdup in the drug manufacturing pipeline.

The expiration of medications and vaccines is another way in which the science of drugs and vaccines can also play into shortages. Vaccines especially should not be administered after their expiration date, as they lose their potency and efficacy over time. Companies seek to clear their shelves before vaccines expire, as it can be an expensive ordeal to make them just to throw them away, but this makes maintaining a backup supply difficult if a surge in public demand occurs.

“We can’t talk about solutions [until] we understand the causes,” wrote Duffin.

She also added that we can’t understand these causes until shortages are measured and an essential medicines list is made to better monitor drug supplies and sources.

Such a list would include 200–500 medicines that the government would commit to keeping in stock at all times. In a 2016 report, Duffin laid out the costs and benefits of such a commitment and provided examples of where such a list has improved the quality of care in at least seven other countries.

With shortages averaging 1,000 per year in Canada between 2014–2017 and affecting more than 1,200 products, the drug shortage problem is only on the rise. In a more recent report on the current situation, Duffin and her colleagues urged Health Canada to provide an annual report on the drug shortage problem to “define it, explain it and, above all, solve it.”

Until then, U of T students and other residents of Canada will have to hope that a drug shortage won’t affect them next.

Akin to a black box in an aircraft, a black box in the operating room (OR) can provide valuable insights.

The OR black box records information during a surgery that is then analyzed to determine how interactions between the surgical team, the environment, and human components factor into patient outcomes.

Dr. Teodor Grantcharov, staff surgeon at St. Michael’s Hospital and professor in the Faculty of Medicine, developed the OR black box in 2017. One of the driving reasons for creating it is that the operating room can be secretive.

“The reason why we developed it is because we felt that we lack transparency, we lack data about our performance as surgeons, as teams, as organizations. We lack data from the operating room,” said Grantcharov.

“Nobody knows what happens there,” said Grantcharov. “Whatever happens there stays there, and we make mistakes, we have successes and failures, but we have very little opportunity to understand them, to study them, and to improve in the future.”

According to Grantcharov, the black box could change this and allow health care providers to recognize and learn from their mistakes, and improve medical outcomes for patients.

“Without data, we can’t improve, and we felt that the OR black box could provide some more insight and some more data that we could use to critically reflect and see opportunities to get better,” said Grantcharov.

The black boxes document everything that occurs in an operating room, and not just the surgical procedure.

It collects video recordings, audio, environmental factors like fluctuations in noise levels and temperature, and minute details like the opening and closing of doors. Furthermore, it collects information on the performance of the surgical team, patient physiology, and the instruments used.

Grantcharov added that the black box analyzes correlations “between performance and outcomes, between stress and performance, between fatigue and performance, and between communication and performance, in any particular outcome.”

Improvements in health care can be made from analyzing such data.

For example, data from the black box indicated that the more people were in the room, the higher the risk of an error.

“We looked at the policy of our hospital which was ‘keep room traffic to a minimum,’” explained Grantcharov.

“So now, we can say for this type of procedure, there shouldn’t be more than 10 people or eight people, and if there are more they [have to] come another day,” continued Grantcharov. “[We] can create the system where we reduce, we restrict access, we can create a system where we eliminate the external communication, especially in most critical steps of the procedure.”

Currently, OR black boxes are used at St. Michael’s Hospital, Humber River Hospital, and North York General Hospital.

To evaluate the effectiveness of the OR black box, Grantcharov and his team need sufficient data to observe trends and draw conclusions.

In fact, associate professor at the Dalla Lana School of Public Health Patricia Trbovich and her research team are using grants from the Natural Sciences and Engineering Research Council and the Ontario Centres of Excellence to examine the data black boxes collect and their overall effectiveness.

The instrument also allows medical staff from around the world to learn from one another.

“We can see, if we do something here and a team of surgeons does the same thing in Amsterdam… what are the things that we do better than them so that they can learn from us,” said Grantcharov. “And we want to see what are the things they do better than us so we can learn from them. There is always something to learn from others.”

The OR black box has been used for minimally invasive procedures like laparoscopic surgeries, in which operations happen through small incisions with the aid of a camera. But Grantcharov added that the black box can capture data from any procedure, even ones outside of the OR.

For Grantcharov, the optimal achievement of the OR black box lies in culture change.

“[It can] allow us to make surgery more open, more transparent, and less mystical for patients. [It makes] the operating room more collaborative,” said Grantcharov.