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Sunday, May 5, 2013

Will Downey suit up again after $175M 'IM3' haul?

LOS ANGELES (AP) ? Iron Man reigns as the standard-bearer of Hollywood superheroes with a $175.3 million domestic opening weekend for his latest sequel and an overseas haul of a half-billion dollars in less than two weeks.

According to studio estimates Sunday, "Iron Man 3" has raced to a worldwide total of $680.1 million. That includes $175.9 million in its second weekend overseas, where the film has rung up $504.8 million so far.

No other solo superhero ? not even Batman or Spider-Man ? has managed this kind of business.

Yet the future of Marvel Studios' flagship franchise is in the hands of a mortal man with no metal armor, gadgets or special powers, other than his ability to rebound from Hollywood pariah to hottest star on the planet.

"Iron Man 3" hints that Robert Downey Jr.'s Tony Stark might hang up his high-tech suits and live a normal life from now on. As the centerpiece behind not only the "Iron Man" flicks but also Marvel's superhero ensemble "The Avengers," Downey seems crucial to this comic-book world.

Could Disney's Marvel Studios conjure anywhere near the same magic if it relaunched "Iron Man" with another actor? Without Downey, would the upcoming "Avengers" sequel have quite the same appeal as last year's record-grossing first installment?

"Your guess is as good as mine," said Dave Hollis, head of distribution for Disney. "Marvel has found a way to tell interesting stories with a variety of characters over time, and it will continue to do so."

"Iron Man 3" had the second-biggest domestic debut ever, behind the $207.4 million start over the same weekend last year for "The Avengers," which teamed Downey's Stark with other Marvel Comics heroes. The new sequel surpassed the $169.2 million opening for 2011's "Harry Potter" finale, the previous second-place debut.

In just nine days, the film shot past the $312 million international total for "Iron Man 2" in its entire theatrical run.

Among the overseas totals so far: $63.5 million in China, $42.6 million in South Korea, $38.3 million in Great Britain and $35.8 million in Mexico.

Domestically, "Iron Man 3" far outpaced the franchise's first two movies. "Iron Man" launched the series with a $98.6 million domestic debut in 2008, while 2010's "Iron Man 2" opened with $128.1 million.

The film also opened higher than last year's Batman finale "The Dark Knight Rises" ($160.9 million) and the biggest of the Spider-Man movies ($151.1 million for "Spider-Man 3").

If Downey doesn't sign on for more, it would leave a gaping hole in the expanding superhero universe Marvel is taking to the big-screen.

"I honestly don't know how you can go on with that character without Downey," said Paul Dergarabedian, an analyst with box-office tracker Hollywood.com. "I think he's as important to this franchise and to Marvel as any actor is to any character."

Downey seems just as vital to "The Avengers." That ensemble probably could thrive without him, given how the first film and previous solo superhero adventures have established a team that includes Chris Hemsworth's Thor, Chris Evans' Captain America, Scarlett Johansson's Black Widow and Mark Ruffalo's Hulk.

But without Downey, Marvel might have to settle for something less than the colossal $1.5 billion worldwide results for "The Avengers."

"He's the spark that ignites all those characters, it seems," Dergarabedian said. "He's the lead guitarist, and they're just all kind of following him."

Before convincing reluctant Marvel executives that he was the man to put on the metal suit, Downey still was trying to live down drug addiction and jail time in his 20s and 30s that nearly ruined his career.

The success of "Iron Man" led to another blockbuster franchise in "Sherlock Holmes," and Downey's professional choices now look limitless.

In an interview before the release of "Iron Man 3," Downey said that "Avengers" director Joss Whedon had been editing a first cut of that film and told him the movie didn't really start until Stark and girlfriend Pepper Potts (Gwyneth Paltrow) appeared together on screen.

Downey said that was a testament to the groundwork laid years earlier in "Iron Man," which "when we were shooting it, this kind of became the heart of several franchises."

"So you know we're having a nice time," Downey said, sidestepping comment on whether he might return for more "Iron Man" and "Avengers" sequels.

"Iron Man 3" did four times the domestic business of every other movie out there; the combined total of all other releases was $43.7 million, according to Hollywood.com.

While it was a huge weekend for Marvel and Disney, the overall industry continued to slump, thanks to the record start for "The Avengers" over the same weekend a year ago. Domestic revenues this weekend totaled $219 million, down 15 percent from the $258.1 million during that "Avengers" weekend last year.

Hollywood's domestic revenue this year is at $3.14 billion, off 11 percent from 2012's pace, according to Hollywood.com.

Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Where available, latest international numbers are also included. Final domestic figures will be released Monday.

1. "Iron Man 3," $175.3 million ($175.9 million international).

2. "Pain & Gain," $7.6 million.

3. "42," $6.2 million.

4. "Oblivion," $5.8 million ($6.5 million international).

5. "The Croods," $4.2 million ($9 million international).

6. "The Big Wedding," $3.9 million.

7. "Mud," $2.2 million.

8. "Oz the Great and Powerful," $1.8 million.

9. "Scary Movie 5," $1.4 million.

10. "The Place Beyond the Pines," $1.3 million.

___

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___

Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.

Source: http://news.yahoo.com/downey-suit-again-175m-im3-haul-172452508.html

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Malaysia's long-ruling coalition hangs on to power

Malaysian Prime Minister Najib Razak, center, arrives at his ruling National Front coalition's headquarters in Kuala Lumpur, Malaysia, Sunday, May 5, 2013. Malaysia's ruling coalition took an early lead in results for national elections Sunday after a record number of voters cast ballots, with some choosing to extend the coalition's 56-year rule and others pressing for an unprecedented victory by an opposition that pledges cleaner government. (AP Photo/Lai Seng Sin)

Malaysia opposition leader Anwar Ibrahim, left, and his wife Wan Azizah speak during a press conference at a hotel in Kuala Lumpur , Monday, May 6, 2013. Malaysia's governing coalition fends off tough election challenge, extending its 56-year rule. (AP Photo/Vincent Thian)

Malaysian voters wait in a line to cast their ballots in the general elections at a polling station in Pekan, Pahang state, Malaysia, Sunday, May 5, 2013. Malaysians have begun voting in emotionally charged national elections that could see the long-ruling coalition ousted after nearly 56 years in power. (AP Photo/Lai Seng Sin)

A Malaysian voter shows her finger marked with indelible ink after casting her ballot in the general elections at a polling station in Pekan, Pahang state, Malaysia, Sunday, May 5, 2013. Malaysians have begun voting in emotionally charged national elections that could see the long-ruling coalition ousted after nearly 56 years in power. (AP Photo/Lai Seng Sin)

Malaysian opposition leader Anwar Ibrahim votes with his wife Wan Azizah at a polling station at Penanti in Penang state in northern Malaysia, Sunday, May 5, 2013. Malaysian's go to the polls Sundy in what could be the toughest test of the ruling coalition's 56-year grip on power in Southeast Asia's third-largest economy. (AP Photo/Mark Baker)

KUALA LUMPUR, Malaysia (AP) ? Malaysia's long-governing coalition won national elections Sunday to extend its 56 years of unbroken rule, fending off the strongest opposition it has ever faced but exposing vulnerabilities in the process.

The Election Commission reported that Prime Minister Najib Razak's National Front coalition captured 127 of Malaysia's 222 parliamentary seats to win a majority Sunday. Opposition leader Anwar Ibrahim's three-party alliance seized 77 seats, and other races were too close to call.

It was the National Front's 13th consecutive victory in general elections since independence from Britain in 1957. It faced its most unified challenge ever from an opposition that hoped to capitalize on allegations of arrogance, abuse of public funds and racial discrimination against the government.

Najib urged all Malaysians to accept his coalition's victory. "We have to show to the world that we are a mature democracy," he said.

"Despite the extent of the swing against us, (the National Front) did not fall," he said in a nationally televised news conference.

Anwar signaled the opposition might dispute the results, saying "irregularities" cost his alliance numerous seats with narrow margins. Within minutes of the National Front's declaration of victory, thousands of Malaysian opposition supporters replaced their Facebook profile photos with black boxes in a coordinated sign of dismay.

The Election Commission estimated more than 10 million voted for a record turnout of 80 percent of 13 million registered voters. They were also voting to fill vacancies in 12 of Malaysia's 13 state legislatures.

Though it retained power, the National Front is weaker than it was at its peak in 2004, when it won 90 percent of Parliament's seats, and about the same as it was a month before the vote, when it held 135 seats. Its hopes were dashed of regaining the two-thirds legislative majority that it held for years but lost in 2008.

Three well-known Cabinet ministers and at least one state chief minister were likely to lose their parliamentary seats. The Malaysian Chinese Association, the second-biggest party in the ruling coalition, saw many of its candidates defeated as Malaysia's ethnic Chinese minority community continued to abandon the National Front.

Among the major differences between the National Front and Anwar's alliance are coalition affirmative-action policies that benefit the majority but often poor Malay population. Malay leaders in the National Front say those policies are still needed to help poorer Malays, but opposition critics say they've been abused to benefit mainly well-connected Malays, and that all underprivileged Malaysians should get help regardless of race.

"I am really fed up," said Andrew Charles, a Malaysian businessman working in Australia who flew home to vote for the opposition in a suburb outside Kuala Lumpur. "There are more abuses in the system and there is no equality among the races. After 56 years, it is time to give others a chance to change this country."

Others saw the National Front as the path of stability.

"The government has made some mistakes but the prime minister has made changes and I believe they (the National Front) will do their best to take care of the people's welfare," said Mohamed Rafiq Idris, a car business owner who waited in a long line at a central Selangor state voting center with his wife and son.

Some voters lined up for more than an hour at schools and other polling places, showing off fingers marked with ink to prevent multiple voting after they had finished.

Najib said one of his priorities would be a "national reconciliation" plan to ease what he called a worrying trend of political polarization. He did not give details, but noted that ethnic Chinese, who comprise about a quarter of Malaysia's population, turned away from the National Front in what he called a "Chinese tsunami."

An opposition win would have represented a remarkable comeback for Anwar, a former deputy prime minister who was fired in 1998 and subsequently jailed on corruption and sodomy charges that he says were fabricated by his political enemies. He was released from jail in 2004.

Anwar and other opposition leaders voiced suspicions Sunday about electoral fraud. Claims of bogus ballots and an apparent ease in which some voters cleaned the ink stains off their fingers dominated social media.

Opposition leaders said the National Front used foreign migrants from Bangladesh, the Philippines and Indonesia to vote unlawfully. Government and electoral authorities denied the allegations, saying private donors had paid for legitimate voters to fly home.

The opposition stayed in control of northern Penang state, one of Malaysia's wealthiest territories, and remained strong in Kuala Lumpur, where middle-class voters have clamored for national change.

The National Front's held firm in many traditional rural strongholds, especially in Borneo, where Anwar's alliance had been hoping to make major inroads to bolster its chances of victory.

The National Front's aura of invincibility has been under threat since three of Malaysia's main opposition parties combined forces five years ago. In recent years the National Front has been increasingly accused of complacency and heavy-handed rule.

Najib, who took office in 2009, embarked on a major campaign to restore his coalition's luster. In recent months, authorities have provided cash handouts to low-income families and used government-linked newspapers and TV stations to criticize the opposition's ability to rule.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-05-05-Malaysia-Elections/id-872fb21fbf364011a430597b9d39ef87

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Fans flock to Scranton, Pa., for 'The Office' fete

The "Office" actors, Phyllis Smith and Ellie Kemper, sign autographs outside the Radisson Lackawanna Station Hotel, Friday, May 3, 2013 in Scranton, Pa. The cast and crew are in town for the Office Wrap Party, a day of events celebrating the show and its ties to Scranton as it comes to an end. (AP Photo/Scranton Times & Tribune, Jason Farmer) WILKES BARRE TIMES-LEADER OUT; MANDATORY CREDIT

SCRANTON, Pa. (AP) ? The actors who play Pam, Jim, Dwight and other beloved characters from the popular NBC show "The Office" are bidding farewell to the northeastern Pennsylvania city of Scranton that served as the TV setting for their fictional paper company for nine seasons.

The NBC mockumentary about cubicle-dwellers at the fictional Dunder Mifflin wraps up May 16. And thousands attended a "Wrap Party" in Scranton on Saturday.

Jenna Fischer, John Krasinski and Rainn Wilson rode in classic convertibles and posed for hundreds of photos as fans thronged around them. The stars later took the stage in front of the Lackawanna County courthouse and played a concert as "The Scrantones."

Cast member Paul Lieberstein, who plays Toby, thanked the crowd. "Who gets a parade," he said. "This doesn't happen in real life."

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/4e67281c3f754d0696fbfdee0f3f1469/Article_2013-05-04-TV-Office%20Wrap%20Party/id-dc329cb3a8e142da966828c1ff234fa3

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In Malaysia, online election battles take a nasty turn

By Jeremy Wagstaff

KUALA LUMPUR (Reuters) - Ahead of Malayasia's elections on Sunday, independent online media say they are being targeted in Internet attacks which filter content and throttle access to websites, threatening to deprive voters of their main source of independent reporting.

Independent online news sites have emerged in recent years to challenge the dominance of mostly government-linked traditional media. The government denies any attempts to hobble access to the Internet in the run-up to a close-fought election.

"During the 2008 election we were wiped off the Internet," said Premesh Chandran, CEO of independent online news provider Malaysiakini.

"Our concern is that we'll see a repeat of that on May 5. Can we really live without independent media on election night, given that both sides might not accept the result?"

Malaysiakini was set up in the late 1990s to test the government's push to lure technology companies to the country by promising not to censor the Internet. Other news websites have followed, including The Malaysian Insider, which set up shop down the street from Malaysiakini in 2008.

Such websites have emerged as an important source of news to counter the traditional media, most of which are owned by interests linked to the ruling Barisan Nasional or BN coalition.

The BN's dominance of media is one of its crucial advantages as it fends off an increasingly potent opposition that made impressive election gains in 2008. Sunday's election is expected to be the closest yet, though Malaysian Prime Minister Najib Razak is favored to win.

Leading opposition politicians who attract big campaign crowds in cities say they get a much cooler reception in rural areas, where access to the Internet is rarer.

Malaysia ranked 145th on a list of 179 countries in this year's World Press Freedom report released by Reporters Without Borders. It was Malaysia's lowest ever ranking.

A survey released on Friday by the University of Nottingham's Malaysia campus and Malaysia's Centre for Independent Journalism found that online media gave almost equal coverage to the opposition and government parties, while traditional media focused on the ruling BN coalition and its parties "by a significant margin".

POLICE RAIDS TO ONLINE ATTACKS

Malaysiakini, the most popular of such websites, has weathered several storms, including police raids, denied access to press conferences, accusations of being linked to foreign agents and requests to take down content, Chandran said.

But in recent years the tactics appear to have shifted towards knocking the site offline, primarily through distributed denial of service, or DDOS, attacks, where servers are deluged by thousands of requests at the same time.

Harlan Mandel, CEO of New York-based Media Development Investment Fund, which has worked with Malaysiakini for more than a decade and is a minority investor, said in an email interview that Malaysiakini had become a focus for attack after "establishing itself as the go-to site for reliable election reporting for millions of Malaysians" in 2008.

"Since then, it has come under repeated cyber attacks, generally coinciding with sensitive political events like local elections and political rallies, said Mandel.

Malaysiakini is not alone. Last month a DDOS attack brought down three related London-based radio web portals, according to Clare Rewcastle Brown, their Malaysian-born founder.

Jahabar Sadiq, CEO of Kuala Lumpur-based The Malaysian Insider, said his news service had come under heavy DDOS attack shortly after six of his staff were summoned to the regulator, the Malaysian Communications and Multimedia Commission or MCMC, a few weeks ago. They were asked, among other questions, for technical details about their service provider.

"It can't be a coincidence," he said in an interview. "They were asking questions about our architecture which weren't required."

BACKUP U.S. SERVERS

At least half a dozen news or political websites have now shifted their servers to U.S.-based CloudFlare, which offers protection against DDOS attacks for a fraction of the cost other companies charge. CloudFlare said that attacks on such sites had increased in the past week, mostly from Malaysia-based computers or IP addresses it had not previously seen involved in attacks.

Now, Malaysiakini's Chandran and others say, their attackers appear to have shifted gear again.

The Malaysian Insider's mail service, which allows users to email articles to others, was hacked two weeks ago, Sadiq said, triggering it to queue tens of thousands of emails to send to users within a couple of hours.

Malaysiakini's Chandran says the most recent wave of disruptions began late last month when users complained the site could only be accessed intermittently. One minute users could access the site, the next they couldn't.

They figured out that only those using Internet service providers who channel their traffic through state-controlled Telekom Malaysia Berhad were affected, while those accessing through smaller ISPs who use an international gateway were still able to access the site.

"It's a smarter way to do it," said Chandran. "It's a guerrilla style in that it creeps up on you and it's harder to detect."

Shortly after complaining informally to the MCMC, Chandran said, the attack stopped.

Since then, Malaysiakini discovered that some political sensitive videos it had posted on YouTube could not be viewed if accessed from some local ISPs and some Facebook pages featuring election-related content were also affected.

Such tactics appear to be using what is called deep packet inspection, where Internet traffic is monitored and filtered via specific keywords, links or digital signatures, which would require access to the ISP.

INVESTIGATION LAUNCHED

The MCMC said on Thursday that it was investigating such complaints but that "preliminary investigations indicate that there were no such restrictions by ISPs as alleged by certain quarters".

Telekom Malaysia said in a written response to questions from Reuters that it had set up a taskforce and network operating center to ensure that its network ran smoothly for its customers during the election period.

"Malaysia has a free, open and robust online media environment. The government does not censor the internet and welcomes constructive criticism as part of the democratic process," said a government spokesman told Reuters.

"We deny any involvement in cyber-attacks. The government does not condone attacks against the media in any form."

Indeed, Malaysiakini's Chandran and others are careful not to accuse the government or Telekom Malaysia directly.

"We are an Internet-based company, we don't want to pick a fight with a telco, we need them," Chandran said. "Besides we can't tell whether they're doing it on purpose."

It's almost impossible to figure out who is behind the attacks and not easy to distinguish between a deliberate assault and the technical issues of handling large and fluctuating waves of traffic. Independent security experts said the available evidence appeared to confirm Malaysiakini's conclusions.

Dhillon Andrew Kannabhiran, Malaysian founder and CEO of the Hack In The Box conferences, said that "stuff is being filtered or slowed down or otherwise being messed around with for sure" on Telekom Malaysia's network, but he said that it could have been done without the company's say-so or knowledge.

In the meantime, websites are preparing for the worst by mirroring content on other domain names and on Facebook. The Malaysian Insider has also set up a mirror outside the country at themalaysianoutsider.com.

Whatever the outcome of Sunday's election, Malaysia's increasingly sophisticated Internet battleground reflects the future of struggles to control and influence of information.

The election-related DDOS attacks in Malaysia "follows a trend we've seen elsewhere where DDOS is becoming a part of many elections", said Matthew Prince, co-founder CEO of CloudFlare.

Malaysia illustrated how political parties and the powers-that-be are starting to use the Internet, said Mikko Hipponen, chief research officer of Helsinki-based internet security company F-Secure which has large lab in Kuala Lumpur.

"They are taking a much more active role and, in some parts of the world, they are not afraid to use the more offensive technologies to get what they want," said Hipponen.

"I believe we'll be seeing much more of this."

(Reporting by Michael Perry)

Source: http://news.yahoo.com/malaysia-online-election-battles-nasty-turn-043117057.html

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Thursday, May 2, 2013

A Sleep Gene Has A Surprising Role In Migraines

Geneticist Emily Bates of Brigham Young University was on a team studying the link between sleep patterns and migraine.

Mark A. Philbrick/Courtesy of Brigham Young University

Geneticist Emily Bates of Brigham Young University was on a team studying the link between sleep patterns and migraine.

Mark A. Philbrick/Courtesy of Brigham Young University

Bates experienced migraines as a child. She made this painting to depict how they felt to her.

Courtesy of Emily Bates

Bates experienced migraines as a child. She made this painting to depict how they felt to her.

Courtesy of Emily Bates

Mutations on a single gene appear to increase the risk for both an unusual sleep disorder and migraines, a team reports in Science Translational Medicine.

The finding could help explain the links between sleep problems and migraines. It also should make it easier to find new drugs to treat migraines, researchers say.

And for one member of the research team, Emily Bates, the discovery represents a personal victory.

Bates remembers getting a lot of migraines in elementary school. They would start with nausea and changes in vision, she says. Then came the pain.

"Loud sounds and light kind of hurt my eyes and my ears and my head," she says. Moving or applying any sort of pressure to her skin also hurt.

The problem was embarrassing and caused her to miss a lot of school, Bates says. It also was frustrating, she says, because back then, in the 1990s, no one could tell her much about what was causing her migraines or how to stop them.

So Bates decided to become a scientist in order to understand "these bizarre, awful migraines." She earned a doctorate in genetics at Harvard in 2005. Then, a couple of years later, while working in a lab at the University of California, San Francisco, she got a remarkable opportunity.

Researchers in Los Angeles had been studying a family with a lot of migraines. The team discovered something really surprising about this family: They were early birds who were usually asleep by 8 p.m. and up by 5 a.m. The scientific name for the condition is "advanced sleep phase."

The researchers were able to trace the family's sleep disorder to a mutation on a gene that helps control circadian rhythms, says Andrew Charles, a neurologist at UCLA. "We then turned our attention to the question of how this gene mutation could be involved in migraine," he says.

The first step was to show that the gene really could cause both sleep problems and migraines. So the team found a second family being studied at UCSF that had a slightly different mutation on the same gene. Sure enough, many members of this family were also early birds who had migraines.

The next step was to study mice carrying the mutated gene. And that's where Emily Bates got a chance to help explain the disorder that had so disrupted her childhood.

Bates' boss at UCSF, Louis Ptacek, had asked her to study the behavior of mice carrying the mutated gene and to find out whether they were experiencing any symptoms of migraines.

There's no sure way to know if a mouse has a headache, Bates says. So she began looking for some of the other migraine symptoms she knew so well ? things like sensitivity to heat and touch ? and she found them.

"All of the things that we looked at basically said these mice are more susceptible to migraine than a normal mouse," she says. The mice also had brain changes similar to those seen in people experiencing a migraine.

The findings should help explain the elusive link between sleep patterns and migraine, Charles says. "Disruptions of sleep are very well known to be a migraine trigger," he says. "And many migraine patients will tell you that their migraine attack will only end if they're able to get to sleep."

The results also serve as a reminder that there is a lot more to a migraine than headache and pain, Charles says. He says the study represents "another step toward bringing migraine forward as a disorder of the brain and a disorder for which there's a genetic basis."

But the ultimate payoff of the new research should be new ways to treat or prevent migraines, says Bates, who is now on the faculty at Brigham Young University.

"I know so well how frustrating and really demoralizing it can be to get a migraine," she says. "But I think once we understand the mechanism we can design better drugs."

Source: http://www.npr.org/blogs/health/2013/05/01/180074502/a-sleep-gene-has-a-surprising-role-in-migraines?ft=1&f=1007

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Tuesday, April 16, 2013

Transcription factors regulating blood oxygen linked to melanoma metastases

Apr. 16, 2013 ? Researchers at the University of North Carolina have discovered that transcription factors regulating the levels of oxygen in the blood also play a role in the spread of the skin cancer melanoma.

In research published April 8 in the Journal of Clinical Investigation, a research team led by William Kim, MD, member of the UNC Lineberger Comprehensive Cancer Center, and graduate student and first author Sara Hanna, linked melanoma metastases to a pair of transcription factors known as HIF1 and HIF2.

Researchers found that HIF1 and HIF2 are overexpressed in melanoma tumors. In healthy cells, HIF1 and HIF2 assist in regulating hypoxia, the state caused by low levels of oxygen in the blood. Hypoxia has been linked to metastases in several sold tumors, and the UNC team has found that it promotes the spread of melanoma from the skin to other sites in the body through the lymphatic system.

Patients who are diagnosed with early stage melanomas have a high rate of survival, but the prognosis worsens significantly once the tumors spread to other sites throughout the body. Using in vitro systems and mouse models, researchers suppressed the expression of HIF1 and HIF2 in the melanoma tumors. While the inactivation of the transcription factors did not reduce the growth of the initial tumors, it did reduce the rate at which the melanoma spread to other sites in the body.

Both HIF1 and HIF2 independently activate the protein kinase SRC using different signaling pathways. The SRC protein has been linked to several different cancers, and the identification of its role in melanoma suggests that existing therapies targeting SRC may prove to be a viable target for therapies aimed at reducing the spread and ultimate lethality of the cancer.

"What we are trying to do now is inhibit these pathways with drugs in the mice to see if we see a decrease of metastasis," said Hanna.

UNC researchers who contributed to this article include Bhavani Krishnan, PhD; Sean Bailey; Stergios Moschos, MD; Pei-Fen Kuan, PhD; Marni Siegel and C. Ryan Miller, MD, PhD, of the Lineberger Cancer Center; and Lukas Osborne, E. Tim O'Brien III and Richard Superfine, PhD, of the UNC Department of Physics and Astronomy.

This research was supported by the National Institutes of Health (P30-DK-034987), the National Cancer Institute (3P30CA016086), the Department of Defense (W81XWH-09-2-0042) and the University Cancer Research Fund.

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The above story is reprinted from materials provided by University of North Carolina School of Medicine.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Sara C. Hanna, Bhavani Krishnan, Sean T. Bailey, Stergios J. Moschos, Pei-Fen Kuan, Takeshi Shimamura, Lukas D. Osborne, Marni B. Siegel, Lyn M. Duncan, E. Tim O?Brien, Richard Superfine, C. Ryan Miller, M. Celeste Simon, Kwok-Kin Wong, William Y. Kim. HIF1? and HIF2? independently activate SRC to promote melanoma metastases. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI66715

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/RqPeuRc4VtI/130416102125.htm

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