UTM breakthrough could reduce chemo side effects

Cancer is one of the leading causes of death in North America today. The Canadian Cancer Society estimates that in 2009 alone, 171,000 Canadians will be diagnosed. While there is no cure yet, a recent discovery at U of T Mississauga may give chemotherapy an added edge in the ongoing battle with this disease.

Patrick T. Gunning, professor in the Department of Chemical and Physical Sciences at UTM, is currently working with scientists at the University of Central Florida and Princess Margaret Hospital to improve the treatment of human cancers.

STAT3 (Signal Transducer and Activator of Transcription 3), a protein present in cancer cells, causes drug therapy resistance when it pairs up with another copy of itself. Gunning and his team have developed a way to break apart this cancer protein pair, to possibly increase the effectiveness of chemotherapy. His research team has successfully developed inhibitor molecules that work to stop STAT3 protein activity.

“We have managed to develop small molecules that target STAT3–STAT3 protein complexes” said Gunning. Targeting the protein-protein interactions of STAT3 disrupts the protein’s biological function.

Increased STAT3 activity is observed in multiple human cancers and plays a key role in cancer progression. In healthy individuals, STAT3 activity is transitory and highly regulated, lasting only a couple of minutes to a couple of hours. However, in cancer cells STAT3 is for some reason permanently activated, resulting in the expression of genes that promote cancer growth, survival, and differentiation.

Gunning’s research team is currently working to increase the stability and effectiveness of the STAT3 inhibitor molecules. “Our global objective is to develop novel molecular therapeutics to target human cancers. In particular, our research has focused on targeting protein-protein interactions—a particularly difficult medicinal challenge,” Gunning explained.

Traditional chemotherapy induces cell death in both healthy and cancerous cells, resulting in devastating side effects. Gunning’s preliminary STAT3 inhibitors display impressive selectivity for cancer cells over healthy cells, and hold promise for improving the effectiveness of chemotherapeutic techniques.

The team’s discovery highlights the importance and targetablity of protein-protein interactions. Gunning explained, “Despite the important role STAT3 plays in biological function, targeting protein–protein interactions is still regarded as high-risk. We want to illustrate through our molecular therapeutics that these important interactions are targetable and that a greater effort should be made on investigating them. STAT3 protein-protein interactions should be targeted because, if successful, the potential benefits are huge.”

Lead inhibitor compounds are now in pre-clinical trials. Gunning hopes that knocking out STAT3 will make cancer cells more susceptible to antineoplastics, thus reducing the dosage required and subsequently lowering the adverse side-effects associated with aggressive chemotherapy.

The results of this study can be found in the September issue of ChemBioChem: A European Journal of Chemical Biology.

Zero Heroes

As the afternoon closed on Varsity Stadium, Saturday had an unjustly indecisive air for both men’s and women’s Varsity Blues soccer as they came out of what was supposed to be a double-header against the Carleton Ravens.

“Unjust” because both teams are looking strong in the early season.

With the women’s team now 3-0-2 to Carleton’s 2-4-2, it would be reasonable to expect the Blues were anticipating their early-afternoon game until it was cancelled. As was later reported, Carleton suspended the women’s team the day before the game after the team broke the university athletics department’s code of conduct by holding a rookie initiation party where drinking was so excessive that one player was taken to hospital by ambulance. At game time, however, no explanation had been given to Varsity Athletics.

The men’s game, which did go ahead, was a more even match. It’s early going still, but the Blues are ranked second in the OUA East, and the Ravens, third. However, the reality on the field—that the Blues dominated for the majority of the play—didn’t translate to the board, with the game ending in a scoreless draw.

That it did end nil-all speaks to the strength of the Ravens defence, and especially goalie Samuel Hincks, who often had to step into the front-of-net maelstrom, smother the ball, and launch it midfield, only to have it returned to him shortly after. But Carleton showed trouble throughout the game with ball control. As one Blues fan and Ravens heckler noted, you’re supposed to keep the ball off the blue track that surrounds the field.

The Blues, by comparison, were all offense. Fourth-year striker Nordo Gooden’s fancy footwork set the game’s tone—and the fans’ hopes—early on as he showed the Ravens how it’s done, practically dancing the ball down the touchline. Gooden was a clear fan favourite of the game along with second-year midfielder Geoffrey Borgmann, who showed ease turning around an opposing play even while in a crowd.

The Ravens did bring their game back in the second half, though with the play waning on, it was clear the offense became increasingly frustrated. By the end of the second, Carleton had been issued three yellow cards to Toronto’s one, all of which were earned as players lost control in what were otherwise good aggressive maneuvers.

This isn’t to say that the Blues didn’t make their own mistakes. Their offensive strength didn’t count where it had to: on the scoreboard. Sloppiness at points showed a lack of focus and drive. Early in the second, Toronto narrowly avoided what could have become a heartbreaking own-goal as what appeared to be a daydreaming Scott Nesbitt passed to goaltender John Smits, who, caught unawares, was left scrambling to keep the ball on the right side of the goal line. The clearly shaken Smits didn’t appreciate the lack of communication from his teammate, as everyone in the stands heard.

The payback in sports usually comes only after a lot of legwork. On Saturday, the Blues did a lot of legwork, but once they got to the decisive moment, pulled back. With five minutes to go, the game could have been theirs after Gooden was scuffed by a Carleton defender in the penalty area, earning Toronto a penalty kick. But midfielder Vlejko Lukovic’s attempt soared so high over the cross bar, you had to wonder, did the Blues want it after all?

Blues lose, but remain optimistic

The Varsity Blues women’s rugby team hosted the McMaster Marauders at the University of Toronto’s Back Campus last Saturday. The Blues put up a strong defensive front, but were defeated 27-0. The Blues were able to demonstrate their skills in the second half, however, revealing that they boast many talented players on their roster.

The game got off to a decisive start when the Marauders scored their first try in the opening minutes. They quickly followed it up with four more tries and one conversion, bringing the score to 22-0 in only 40 minutes. The Marauders dominated the scrums thanks to strong forwards, and were quick to get the ball out to their wing line, who fed it down in a series of clean passes.

As the game progressed, U of T remained resilient. “We really gave it to them in the second half,” said Blues co-captain and hooker Sonya Kuwiz. The Blues tightened up their defence and began to react faster to the Marauders’ attempts to score. They caught onto Marauders’ eight-man Natasha Turner, and her repeated efforts to pick the ball from the scrum.

The Blues’ backs reorganized so that co-captain Hannah Ehrhardt remained at fly half, followed by centres Silvana Skoko and Charlotte Cooper, and Jana Davis moved to the wing. Gwen Kern continued to play strong as the Blues’ fullback. Although it was only a slight reconfiguration of the field, it proved incredibly advantageous. The backs worked well together to move the ball fluidly when they received it from scrum half Sarah Stainton, and were aggressive in their attempts to take advantage of the play.

The entire team was determined to stave off attempted tries by McMaster. The Marauders scored only one more try in the second half of the game—the result of an unexpected breakaway during the last five minutes of play.

Last season the Marauders played a close semi-final game against the 2008 OUA Champions Guelph Gryphons, losing by only 16 points. More recently, on Sept. 12, they blanked the York Lions 43-0. McMaster is recognized as a strong team and consequently the small margin of victory they had over the Blues is viewed with optimism. Head coach Shannon Smith was in positive spirits post-game and admitted that she was very proud.

The roster this season is composed primarily of new players—only 15 out of the 33 are returning from 2008. Although mostly rookies, the team demonstrates a lot of potential: they may just need a little bit more time to feel each other out. “[The women are working] to start playing as a team and get the cohesion up,” said co-captain Ehrhardt.

The season is short, but Ehrhardt has faith. One thing she hopes the team can accomplish this year is to make the playoffs.

The game against the Marauders proved that the Blues are more than capable of becoming a top-ranked team in the future. They displayed an abundance of talent from both the returning players and the newer members. Veteran Kern produced some near impossible catches as fullback, in addition to the fantastic tackles she made to stunt the Marauders mid-breakaway. Stainton, who was not on last year’s team, was aggressive and quick to react. She entered the game near the end of the first half, and within seconds had intercepted the ball, giving the Blues the advantage.

With the help of fan support, the team will be able to step it up a notch and reach their full potential.

Latin lives!

This September, an unusually high demand for third-year Latin led the department to raise the enrolment cap for the first time to accommodate extra students. In 2008, a fourth section in the first-year introductory Latin course was added. The Classical Association of Canada says more college and university students across the country are taking Latin, reported the Globe and Mail last week.

According to professor Alison Keith, chair of the U of T Classics department, most students are first-timers to the language, but some took it in high school and can skip to intermediate classes.

While the numbers are modest, they are steadily increasing. Keith attributes this increase to several factors.

Latin was traditionally taught as a language that builds critical reading, writing, and analytical skills, which can be applied to the study of literature, law, medicine, and other professional areas. Keith said she has taught students from various areas of study, from chemistry to political science to women’s studies.

She also noted Latin is relevant to the study of any romantic languages such as French, Spanish, and Italian, since these are all derived from vulgar Latin. (Vulgar Latin means “spoken Latin,” used by the masses, as opposed to “written Latin,” which is what is now studied. The difference had a profound effect on the evolution of the romance languages.)

Romance languages are not only based on the syntax of vulgar Latin, but also on the morphology, phonology, and lexicon. Latin gives birth to the sounds used to impart meaning in words, the words themselves, and how they are used in sentences to express ideas.

“I’d say the Romans have never gone out of fashion, but the convergence of all these media on ancient Rome is particularly terrific for generating student interest in Latin,” Keith said, citing pop culture as a potential influence. Media ranging from movies and novels to comic books and video games have established a greater awareness and interest in learning the language and culture surrounding ancient Rome.

As interest increases, Latin still faces difficulties in recognition.

“I wanted to enroll in introductory Latin, however, I thought Spanish would be more useful than Latin since more people speak it,” said Alan Wu, a Master’s engineering student who had considered taking Latin as an elective during the last two years of his undergraduate degree.

Echoing this sentiment, U of T’s Classics department has struggled to place Latin back on as a “teachable” at the Faculty of Education, which removed it several years ago. Aspiring education students must have two “teachables,” or subjects of expertise.

Starting next year, York University will be adding Latin as an accepted teachable for its own teacher’s college.

The stem cell hierarchy

Stem cells are a promising weapon for combating certain degenerative conditions, such as cancers and organ failure. Both of the two types of stem cells, embryonic and adult, are able to regenerate new cells and tissue, but embryonic stem cells (obtained from an early-stage embryo) can also differentiate into specialized cell types. The discovery of a unique property of mesenchymal stem cells (MSCs) at the University of Toronto may lead to an alternate way to grow specialized cell tissue while avoiding ethical controversy.

Professor J.E. Davies and Dr. William Stanford from the Institute of Biomaterials and Biomedical Engineering at U of T, Dr. Armand Keating, Director of the Cell Therapy program at Princess Margaret Hospital, and their students Rahul Sarugaser and Lorraine Hanoun recently found that MSCs are able to stimulate bone and cartilage growth, speed up wound repair, and increase autoimmune function.

In an interview with the Vancouver Sun, Keating said, “Scientists had seen potential in MSCs but had been largely unable to establish definitively that they had the properties of stem cells. Methods for isolating them were also inefficient, as they had to be extracted from the bone marrow of human donors or, more recently, from fat removed in liposuction.”

In their study published in Public Library of Science, Davies and his team discovered that MSCs are specific cells with the unique ability to differentiate into a variety of body cell types. “In particular, MSCs are known for differentiating into cells required in the support tissues of the body such as bone and collagen,” explains Davies. However, “In bone marrow, about one in every 100,000 nucleated cells is a mesenchymal stem cell. These kinds of numbers make it very difficult to experiment with.” Due to these low numbers, the scientific community has been slow to accept evidence for the existence of MSCs.

Since 2002, Davies’ group hypothesized that MSCs could be localized in connective tissue. “In fact, from our previous studies, we have found that the richest source of MSCs is the human umbilical cord, which is essentially all connective tissue. What is more surprising is that this rich source is discarded as medical waste in the millions by families every year,” explains Dr. Davies. With the help of this abundant MSC source, Davies and his team have finally provided concrete evidence for human MSCs at the single-cell level.

In addition to determining the existence of MSCs, they provided evidence of the two factors that characterize stem cells: self-renewal and differentiation. “As an MSC gives rise to a progenitor cell, it loses some ability to differentiate,” says Davies. Thus, there exists a hierarchy for MSCs, each having distinct differentiating capacities.

An MSC at the top of the hierarchy can give rise to any one of the five different lineages (bone, cartilage, fat, muscle, and fibroblasts). As you go down the hierarchy, a MSC loses the ability to differentiate into one of these cell types and ultimately becomes completely specialized. This finding enabled researchers to isolate MSCs at different stages and use them for drug screening and other clinical treatments.

Canada boasts an impressive list of accomplishments in the field of stem cell biology. Work done by pioneers James Till and Ernest McCulloch of the Ontario Cancer Institute in Toronto sparked the field of stem cell research in the 1960s, and Canada continues to be ranked in the top six countries internationally for its ongoing leadership in stem cell research.

Stem cell research has branched out into many discrete and exciting fields over the past 50 years. Davies’ fellow investigator Dr. Stanford and his team work on trying to model human diseases with genetically altered mice. “Now we can model human diseases with a rich human sample of MSCs that have been shown to exist and act in a similar manner to pluripotent stem cells [which have the potential to develop into a wide range of cell types],” explains Stanford.

Unlike other types of stem cells (i.e. embryonic), MSCs from either adult bone marrow or the umbilical cord are not under the same ethical scrutiny. Adult bone marrow is voluntarily provided and umbilical cords are essentially medical waste thrown out by many families. “MSCs are ready to be used for clinical applications right away and don’t require much more research before being implemented into clinical medicine,” says Stanford.

Currently there are close to 60 MSC trials in progress worldwide, showing great potential for the realistic applications of these stem cells. In addition to their regenerative role, MSCs possess a unique property which enables them to go undetected by the hosts’ immune system. This avoids the issue of matching the patient’s cells with MSCs and allows for a wider range of uses.

“This new research has immediate implications in the field of cell-based therapy and personalized medicine, which is one of the exciting [applications] of these mesenchymal stem cells,” explains Stanford.

Latin’s not the only rarely-spoken language on campus

OLD NORSE

“It’s natural for any English speaker to be interested in Old Norse,” said Ian McDougall, a professor of Old Norse at the Centre for Medieval Studies.

The language has contributed much to modern-day English, including an endless list of vocabulary—where would we be without “oaf,” “freckle,” or “keg”?). Many common phrasal verbs (verbs that have a particle, like “to take out”) also come from Old Norse.

“It also goes without saying that learning to read Old Norse provides one access to one of the great literatures of the Middle Ages, and one which, if you ask me, affords the most vivid picture available of everyday life in Northwestern Europe before the 14th century,” said McDougall, who is working on a dictionary of Old English.

Old Norse is also the ancestor of continental Scandinavian languages, and of modern Icelandic. It serves as a natural introduction to present-day Icelandic.

INUKTITUT

The claim that there are more Inuktitut students in France than Canada spurs on professor Alana Johns. There are 28 students in Paris learning Inuktitut, more than in Toronto, Montreal or Vancouver, according to Canadian Geographic. Take Bruno Perrone, who already speaks six languages fluently. “Some of my colleagues play golf. I study Inuktitut,” he said. Interest runs high: in summer 2004, Inuktitut students in Paris opened Espace Culturel Inuit to showcase art, books, films, and photographs portraying daily life in Canada’s North.

Johns is determined to change this state of affairs. She works with an international research group who collaborates with northern communities on the future of their languages.

ANCIENT EGYPTIAN

Ronald Leprohon, an Ancient Egyptian professor at the Department of Near and Middle Eastern Studies, says that there’s a really easy answer to the question.

“I love the pure magic that comes from the fact that someone is talking to me from across the ages.”

“These texts were written thousands of years ago and here I am, sitting here and now, reading them. Someone is actually talking to me from 4,000 years ago. What a trip!”

To study a culture in depth, it’s necessary to read the texts from the original language, said prof Katja Goebs. “One quickly becomes aware how little has changed between then and now in some ways, while other areas are extremely different. This helps us to situate ourselves in world history, with all the benefits that a greater awareness brings,” she added.

Goebs also said Ancient Egyptian is particularly fascinating because it is a “picture script” that places itself into a zone between art and text, which the ancient Egyptians played to with great effect. That, and “it is simply lovely to look at.”

ONEIDA

Oneida is an endangered Iroquoian language that has fewer than 250 fluent speakers. Teaching it is important so that the aboriginal culture and traditions can grow stronger, said Grafton Antone, a sessional instructor and an Elder at U of T’s First Nations House.

“What I like about the language is that it opens up a whole new way of speaking: it helps us to understand Mother Earth…it brings us into contact with all creations and the cosmos,” Antone said.

In the Introduction to an Iroquoian Language course (ABS220Y), students learn more than just the language. Through the Iroquois creation story, the class provides a cultural base to ceremonies, healing ways, and reciprocal connections with the earth. Students also learn the social songs that are sung with the water drum to help keep their focus and connection to the Creator.

“This course brings the past, the present, and future together in a way that will promote how the Peace Maker worked hard in the past to set up a peaceful way for people to work together,” said Antone.

The science behind slumber

It’s been a long day. You’re convinced this lecture was supposed to end hours ago. As your eyelids get heavier, your thoughts start losing focus. You’re drifting in and out of consciousness, and before long, you can’t help it anymore. You’ve fallen asleep.

Sleep is a natural part of human biological rhythms, so it’s quite accurate when people say they can’t live without it. But for many of us, sleep remains something of an enigma. What exactly is this thing that we spend one third of our lives doing?

In an attempt to answer this question, scientists use a number of instruments to measure activity in the brain and body while we sleep. The most important of these is the electroencephalograph (EEG), which measures electrical activity in the brain over time.

Based on these brainwave measurements, sleep is divided into five stages. Before the onset of sleep, a period of drowsiness serves as a prelude to the typical sequence of slumber. Electrical activity in the brain during this brief period is dominated by alpha waves, which are also characteristic of meditative states or what athletes experience when they’re “in the zone.”

Sleep begins at Stage One, which usually only lasts a few minutes, and is characterized by theta waves. Stage One is the transition period between sleep and wakefulness, and the experience is similar to that of relaxation. Stage Two lasts slightly longer, and contains a mix of EEG activity. Both Stages One and Two are ‘light sleep,’ so if someone was awoken during these stages they would probably not recall falling asleep at all. Stages Three and Four consist of slow-wave sleep, which is a period of deep sleep dominated by delta waves. These stages are very similar, and correspond with deep sleep.

The fifth stage of sleep is called the rapid eye movement (REM) stage, and that’s where things start getting interesting. REM sleep is the dream stage, where brain waves resemble the electrical activity of someone who is awake. However, the body is virtually paralyzed during the REM stage, which is why we don’t physically act out our dreams.

Research on sleep disorders investigates all the things that can go wrong in and around the sleep period. Insomnia is a chronic problem that involves difficulty getting to sleep, while narcolepsy is a condition marked by sudden and uncontrollable onsets of sleep during normal waking periods. Another unusual condition is somnambulism, or sleepwalking, in which sleepers are up and wandering around while remaining in slow-wave sleep.

All the research being devoted to sleep patterns, mechanisms, and disorders goes to show that sleep is serious business. U of T has its own Centre for Sleep Medicine and Circadian Biology, while a number of its affiliated hospitals and rehab facilities run sleep labs. When it comes to research, sleep really is a full-time job.

Toronto Star exposes unregulated security academies

The Canadian Security Academy has received a number of complaints from its graduates, prompting an investigation from the Ministry of Community Safety and Correctional Services. The academy, founded by Mark Morell, offers training for security guard jobs.

The Toronto Star’s Brett Popplewell went undercover and had to spend only $80 to become a security guard, and another $80 to receive his private investigator’s license. Defending his school to the Star as doing things “quite professionally,” Morell has apparently been guaranteeing job placement to students.

After another Star reporter posing as a student graduated in as little as 15 days without any clinical training, Ken Miller’s Ontario Academy of Science and Technology has been closed down for producing unqualified health care workers. As a young Filipino nanny who attended the college told the Star, “now I have no future. I have to start all over again.”

Source: Toronto Star