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.

What’s a self-torturer to do?

A person has an electrical torturing device attached to his body, and gets paid $10,000 for every increase in intensity level. That’s the premise for a philosophy puzzle introduced by Warren Quinn in 1993. On Monday afternoon, professor Sergio Tenenbaum presented his take on the puzzle as part of the Centre for Ethics’ seminar series. The paper, called “Vagueness, Plans, and the Puzzle of the Self-torturer,” was co-authored by professor Diana Raffman.

Back to the self-torturer: according to the orthodox Rational Choice Theory, the self-torturer would prefer to stop at the higher of two consecutive settings. (Since the increments in current are tiny, he can’t distinguish between adjacent settings anyway.) The theory states that choices are rational if they come from a transitive preference over alternative choices.

But the self-torturer can distinguish between settings that are far apart, and he knows there is a setting at which he would experience unbearably excruciating pain. (He knows this because once a week he is allowed to explore the various settings. But afterwards, he has to return to the setting he was at before.)

The self-torturer understandably doesn’t want to live in overwhelming pain, even for a lot of money, so he would also prefer to stop at the lower of two consecutive settings lest he hit the level that would cause too much pain. That’s the crux of the puzzle, and the challenge to Rational Choice Theory.

One of the responses to RCT is that because the self-torturer’s preferences are intransitive, he is irrational and must revise his preferences. Professor Tenenbaum called this response the “hard-nosed solution.” He argued for an unorthodox solution, centred around “non-segmentation.” According to Tenenbaum, a solution satisfies non-segmentation if it permits or mandates that the self-torturer stops at a certain level when facing a series of choices, but always recommends moving to the next level when there’s only one choice.”

The talk, which contained jargon and very fine-grained philosophical arguments, was mostly attended by philosophy students and faculty. A few people without philosophy backgrounds showed up, too. Among them was Ori Barbut, a graduate student in engineering, who said that he appreciated the mental exercise. Barbut added that the event provided students with a great opportunity to learn about a field of study different from their own.

Professor Tenenbaum’s research interests are in ethics, practical reason, and Kant. He is the author of Appearances of the Good (Cambridge UP, 2007).

Silver Starling takes flight

Montreal will eat its young, but Montreal won’t let us down—at least not when it comes to music. The latest from Montreal is Silver Starling, an indie act whose lush, sweeping melodies sound like a “sailboat on a sunny day,” as the band itself put it. In anticipation of their debut Silver Starling and upcoming show at the Drake, we got ahold of lead singer Marcus Paquin before he went off to his “day job” of mastering the new Arcade Fire album.

The Varsity: Thanks for taking the time to talk to us! I’m sure you’re extremely busy, what with your first record about to come out.

Marcus Paquin: It’s a good kind of busy.

TV: So on September 22 your debut album officially drops, as they say. Are you excited for Silver Starling to fly from its nest?

MP: Haha, I like that. Definitely, we’re super excited for the record to come out.

TV: How’d you choose the name for the band and eponymous album?

MP: We started off with the name Mothers Fathers, but that was very similar to other bands out there. To avoid confusion, we decided to choose something else we all liked… The interesting thing about starlings, if you’ve ever seen them in flight, is that they fly in these huge formations—it’s beautiful. And they’re songbirds.

TV: Just like you guys!

MP: Haha, just like us.

TV: In what little has been written about your fledgling band thus far, much has been made of your connections with Arcade Fire. What’s it like working under such a long shadow?

MP: Shadow? I’d say it’s more like a ray of light. We’re happy to be friends with them. Obviously they’ve achieved a lot—I think I’ve read that once or twice. If we could achieve just a little of their success, we’ll be happy.

TV: In that vein, you helped master an Arcade Fire album, and you are currently working behind the scenes engineering the upcoming one. What made you want to take the leap to forming your own band?

MP: I’ve been playing in bands as long as I can remember. The recording stuff was to broaden the palette; I wanted to explore the many facets of making music. It’s like a painter who mixes his own colours—there’s so much depth you can achieve.

TV: What got you into music in the first place? What was your major influence?

MP: Bits and pieces of countless things, but it’s your earliest influences that tend to be the most iMPortant. I listened to the Beatles’ Abbey Road endlessly as a child and I still have the record my mother lent me. I’ve worn the grooves out on that one.

TV: You’ve played a few shows already. How did they go?

MP: Yeah, we’ve played Hillside, Osheaga, shows around Montreal…We’re finding our voice as a live band. We’re learning to project and make a show of it, to blend images and sound.

TV: Images and sound? Is your live act a multimedia experience?

MP: When you check out the record, there’s a lot of imagery associated with what we do. We’re trying to evoke in people the emotions we felt while recording it.

TV: I’ve heard the album’s sound and emotional resonance was largely informed by your close friend’s battle with cancer and untimely death.

MP: The songs are directly and indirectly informed by it. It gives you a different perspective when one of your best friends is sick—it gives you an appreciation of resilience and generosity; an appreciation of being alive…There is a certain beauty in sad things. Will it break you or will it make you stronger?

TV: Was the process of recording this album cathartic?

MP: I think it’s good to talk about your emotions. I did a lot of talking and a lot of song-writing.

TV: You’re playing the Drake soon for the album release party. What should we expect?

MP: People have been really enthusiastic so far. We’re pretty under the radar, but people have been singing along, buying T-shirts, asking for the album. It’s been great…New fans can expect a deep show. We’re excited to play music and hope to put on a beautiful show.

Silver Starling play at the Drake Hotel with Final Flash on September 25. Tickets are $12.50 at Rotate This and Soundscapes.

Student arrested in York sexual assault

A York University student has been charged with one count of sexual assault after an incident that occurred in the university’s Scott Library. Aaron Zukewich, 21, is currently awaiting a bail hearing.

On September 15, a 23-year-old female student reported to York security that she was followed by a man into a secluded section of the library and sexually assaulted. She was not injured.

In a similar incident on Sept. 18, an anonymous female caller reported that she had been sexually assaulted in the library. She left the library before police could interview her.

Security located a suspect and notified the police. Zukewich was linked with the first assault and charged.

Police are trying to determine if there were any other incidents. Anyone with information is asked to call the police at 416-808-3104. More information can be found at the York Security website: www.yorku.ca/security/CampusAlerts.

Source: Toronto Star

Still too hot for TV: Jerry Springer: The Opera

It’s been said that the real Jerry Springer once envisioned his show, with its outrageous characters and trashy scenarios, being made into a country-western musical one day. But British duo Stewart Lee and Richard Thomas took a less predictable route in re-envisioning the famed talk show as an operatic saga. Their work, Jerry Springer: The Opera, had its Canadian premiere last winter with an immensely popular run at Hart House Theatre.

To satisfy demand for more Springer, the theatre’s 2009-2010 season opens with a restaging of the hit play. Last year’s assistant director Mark Selby takes over the director’s chair from Richard Ouzounian, while Byron Rouse reprises his lead role as ex-mayor of Cincinnati and beloved talk-show legend Jerry Springer.

While some have been eager to write off the show based on its crass subject matter, Selby warns audience members not to be fooled by the silly premise. “People come in expecting two fun hours at the theatre, and are a little shocked by the intellectual angle that the show suddenly takes [in the second act].”

Although on the surface, it’s not meant to be taken seriously, there is an underlying sophistication buried beneath the bitch fights and four-letter words. Those who protest the show, Selby remarks, “are the ones that just hear that we have a gay Jesus, or a tap-dancing Ku Klux Klan member…but the fact is that this show actually makes a point.”

“It’s a satire,” Rouse explains. “I’ve said this before and I’ve gotten in trouble for it, but I’ll say it again: smart people understand satire.”

The cast’s attitude is anything but amateur, and both Selby and Rouse applaud the ensemble.

“They are all fantastic musicians and all terrific actors,” Selby gushes. “They all bring so much to the studio audience [played by] the cast of the show. I mean, everyone’s really stepping up and making it an incredible experience.”

Rouse has a similar admiration for his co-stars: “I’ve been in big shows before, but when they say that it’s ‘starring Byron Rouse’ I don’t necessarily believe it. Actually, it’s the ensemble that’s the star, because they do some really great work. They put a ton of work into this show.”

Most importantly, Selby and Rouse advise the audience to (in the words of the character Jerry Springer himself) “have yourselves a good time” and get tickets early. If last year’s production was any indication, this show is going to sell out pretty quickly.

Jerry Springer: The Opera runs at Hart House Theatre from September 24 to October 10. Tickets are $15 for students.

Hazing party won’t ground Carleton women’s soccer

The women’s soccer team at Carleton University will only suffer a two-game suspension for a party that resulted in one player being hospitalized for excessive alcohol consumption. The hazing party allegedly took place over a week ago, on Sept. 13. The team missed games against U of T and Ryerson last weekend.

“The university has concluded that the two-game suspension by the team was an appropriate penalty and the team will resume regular play this Wednesday against the University of Ottawa,” reads a press release from the Carleton administration.

Carleton suspended the whole team, rather than individuals, to send a stern warning that they will not tolerate hazing. Admin said that all other disciplinary measures would be handled internally.

Before the suspension, the women’s soccer team had a record of 2-2-1.

Source: The Ottawa Citizen