Gene variations predict chemotherapy side effects

Apr. 9, 2013 ? Seemingly benign differences in genetic code from one person to the next could influence who develops side effects to chemotherapy, a Mayo Clinic study has found. The study identified gene variations that can predispose people to chemotherapy-induced peripheral neuropathy, a condition that is hard to predict and often debilitating enough to cause cancer patients to stop their treatment early.

Results of the research were presented today at the American Association for Cancer Research Annual Meeting 2013 in Washington, D.C.

The study, which implicates the genes EPHA5, ARHGEF10, and PRX, is the first to mine large swaths of the human genome for predictors of chemotherapy side effects. Further research into these genes and others may enable clinicians to use genomic information to more safely deliver these potentially toxic treatments.

"Our study creates a path for how to approach the whole genome in order to tailor cancer treatments," says Andreas Beutler, M.D., an oncologist at Mayo Clinic Cancer Center and senior author of the study. "That is important because we would not only like to cure people's cancer or help them live longer, but we also wish to provide them with the best quality of life."

Chemotherapy-induced peripheral neuropathy affects an estimated 20 to 30 percent of cancer patients treated with chemotherapy agents. The symptoms can be as mild as a light tingling or numbness, but can progress to a loss of feeling in the hands and feet, or to the point where patients can no longer walk normally and are left with a permanent feeling of numbness or pain. Currently, there is no way to predict which patients undergoing chemotherapy will develop this side effect or to what degree.

There are approximately 50 genes linked to a hereditary form of peripheral neuropathy. However, many of the people who have a mutation in one of these genes experience no symptoms until they are exposed to chemotherapy. Dr. Beutler decided to first consider those 50 genes as the most likely suspects, and then expand his search to the wider human genome for other predictors of chemotherapy-induced peripheral neuropathy.

Dr. Beutler's approach relied on exome sequencing, a type of DNA sequencing that focuses on the exonic regions of the genome that code for functional proteins. These protein-coding regions are believed to harbor about 85 percent of all disease-causing mutations.

Dr. Beutler and his colleagues performed exome sequencing on 20,794 genes from 119 cancer patients, over half of whom had developed chemotherapy-induced peripheral neuropathy during the course of a chemotherapy clinical trial.

First, they looked at the 50 hereditary neuropathy genes and found one -- EPHA5 -- that appeared to predispose the patients to chemotherapy-induced peripheral neuropathy. Next, researchers analyzed the remaining 20,000 genes and discovered two new genes -- ARHGEF10 and PRX -- that are also associated with chemotherapy-induced peripheral neuropathy. They validated those findings in another group of 75 cancer patients.

The results suggest that the two conditions, hereditary neuropathy and chemotherapy-induced peripheral neuropathy, may share genetic roots in some patients. They also point to ways that clinicians can improve cancer treatment. For instance, if clinicians know which patients are at risk for a particular chemotherapy side effect, they can use the information to individualize treatment.

Dr. Beutler and his team plan to expand their study to look at the entire genome, not just the protein-coding regions, in as many as 1,000 cancer patients. Dr. Beutler says any additional genes they find will add to the larger picture of symptom control in cancer treatment.

"What we are doing at Mayo is much larger than just uncovering a handful of genes," says Dr. Beutler. "We are using cutting-edge genomics research to enhance our strengths in clinical trials and develop new methods to individualize medicine."

Co-authors include, Amit Kulkarni, M.B.B.S.; Rahul Kanwar; Rui Qin, Ph.D.; Zhifu Sun, M.D.; Anh Le-Lindqwister, Terry Therneau, Ph.D.; and Charles Loprinzi, M.D., all of Mayo Clinic.

Funding for the study was provided by the American Cancer Society, the National Institutes of Health grants CA124477 and CA37404, the Mayo Clinic Center for Individualized Medicine and the Richard M. Schulze Family Foundation.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Mayo Clinic.

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

---

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/~3/2fR2tyYtLVU/130409110001.htm

weather channel Rivals Kaepernick Eddie Vanderdoes puppy bowl national pancake day bar refaeli

Ex-Tenn. judge sentenced in drugs, sex scheme

GREENEVILLE, Tenn. (AP) ? A former county judge in Tennessee has been sentenced to six months in federal prison for lying to cover up a scheme that provided him with painkillers and sex.

Richard Baumgartner expressed remorse at sentencing Wednesday in federal court, saying he was greatly shamed and regretted his actions. The 65-year-old former Knox County judge was convicted in November of five counts of misprision of a felony.

Authorities said he lied to cover up a conspiracy involving a defendant from his court, a woman about half his age who had supplied him with pills and sex.

An investigation also found he was using large amounts of painkillers while presiding over trials and had purchased drugs inside the county courthouse building starting around 2007 until he stepped down in 2011.

"I will forever be remorseful for any disgrace I have brought to that profession," the disgraced judge said, speaking at his sentencing hearing in Greeneville.

Baumgartner resigned from the bench and pleaded guilty in March 2011 to a state charge of official misconduct after a probe by the Tennessee Bureau of Investigation found he was addicted to painkillers and purchased pills from Deena Castleman, who had graduated from his drug court program. He did not receive jail time for that plea.

Federal prosecutors had requested Baumgartner serve two years in prison, saying his actions severely disrupted the Knox County courts and required retrials of half a dozen people. In particular, retrials were ordered for two defendants in highly publicized trials involving the 2007 torture slayings of a young Knoxville couple.

The prosecutors told U.S. District Judge J. Ronnie Greer in a memo that "Baumgartner engaged in despicable conduct that has shaken the public's confidence in the criminal justice system."

But Baumgartner's attorney, Donald Bosch, pleaded for probation. The defense attorney said Baumgartner had already been publicly humiliated, financially ruined, debarred and now is a convicted felon.

In sentencing Baumgartner to prison, Greer said the defendant should serve some prison time because judges should be held to a higher standard. Greer said Baumgartner also must undergo drug testing and drug and mental health treatment upon his release.

First appointed to the Knox County Criminal Court in 1992, Baumgartner once presided over many high-profile criminal cases in Knoxville. He also launched the county's drug court.

Source: http://news.yahoo.com/ex-tenn-judge-sentenced-drugs-sex-scheme-174702293.html

Lisa Robin Kelly Nexus 4 Girl Meets World Jason Babin Nolan Daniels angus t. jones monday night football

Jurassic Park's Dinosaur Sound Effects Were Actually Animal Sex Sounds

So, uh, this is an uncomfortable one. You know the dinosaur sounds from Jurassic Park that framed the way you imagined every dinosaur ever? They were actually recordings of animals boning, or just about to bone. More »

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/JBSniEA6QlM/jurassic-parks-dinosaur-sound-effects-were-actually-animal-sex-sounds

big ten tournament big east tournament 2012 solar storm solar flares spanx aurora borealis gcb

Otterbox Commuter case for the HTC One

Does one of the biggest names in smartphone protection turn a sexy piece of silver into a tank? Let's find out

Ever think about buying a Corvette and then wrapping it in the shell of an Abrams tank? That's often what you think about when you take the latest and greatest Android smartphone and put it inside an Otterbox case. But you're not buying an Otterbox for sex appeal alone, right? You're buying it because it protects your phone. Period.

So we've got the HTC One. And we've got the Otterbox Commuter case, with its rubber sleeve and hard, outer plastic shell. Beauty and the beast? We've got a quick look, after the break.

read more

Source: http://feedproxy.google.com/~r/androidcentral/~3/JSDTaQ6Le7w/story01.htm

undercover boss barbara walters tupelo honey limp bizkit stations of the cross nike foamposite galaxy bill maher

Tim Armstrong Defends Aol's Content Business, Announces New Ad ...

Aol CEO Tim Armstrong sang the praises of programmatic, automated advertising today during his keynote presentation at the Ad:Tech conference in San Francisco, and he announced a new Marketplace tool to help publishers manage their ads. So when Fortune?s Adam Lashinsky took the stage to interview him, he asked: Was it meaningful that Armstrong didn?t talk about Aol?s content and publishing business?

After all, Lashinsky pointed out that Aol has made some pretty big investments in content, especially with the acquisition of properties like the Huffington Post and, yes, TechCrunch. Armstrong answered that he still sees content as a big opportunity ? he was just tailoring his message to the audience.

Indeed, if you look at companies like Amazon, Netflix, Google and Microsoft, it seems like more tech companies are getting into the content business. Armstrong argued that Aol was one of the first online ad companies to ?try and jump in and do both sides.?

At the same time, Armstrong acknowledged that there does seem to be a shortage of big-name talent in web content and that he?s looking forward to seeing ?a lot of the brainpower? moving from offline to online. (I?m not sure what kind of talent he was referring to, so I?ll try not to take that personally.)

?If we were to take all the technology people in this room and switched them to content management systems, the opportunity is just as big,? Armstrong added.

Continuing on that theme, Lashinsky said that traffic to Aol properties doesn?t seem to be growing. Armstrong said it?s been ?a very, very challenging situation? because Aol is trying to ?switch the engines while the plane is flying? ? there are new properties that are growing, but the company is also saddled with others that are declining or that it has shut down. The good thing, Armstrong said, is that the mix of Aol?s traffic ?looks different than it did three years ago,? that ?Wall Street has gotten more excited,? and that ?we?ve been able to stuff the company with lots of talent.?

Lashinsky also asked Armstrong about his earlier statement that if he was making the decision for himself (rather than Aol), he?d be interested in buying Time Inc. Armstrong said that?s because he?s a big believer in the media brands that Time has built: ?People undercut how powerful brands are.?

My boss Alexia Tsotsis really hates that word, but to illustrate his point, Armstrong said that Fortune hosts a successful conference every year based on the magazine?s brand ? if Armstrong wanted to start ?Tim?s online finance site? and hold his own conference, he said, ?I would bet on Fortune more than Tim?s finance.? He also said that Aol is trying to acquire ?meaningful? online brands. That was the rationale behind the HuffPo and TechCrunch acquisitions, and he said they?ve led to traffic and revenue that has ?exploded.?

As for the new Marketplace product, it?s a supply-side platform that Aol is pitching as a competitor to Google and as something that completes the company?s ad-tech stack.

May 24, 1985

April 12, 2009, NYSE:AOL

AOL is a global advertising-supported Web company, with display advertising network in the U.S., a substantial worldwide audience, and a suite of popular Web brands and products. The company?s strategy focuses on increasing the scale and sophistication of its advertising platform and growing the size and engagement of its global online audience through leading products and programming. History of Aol: AOL was founded in the early 1980?s as Control Video Corp, with an online service, Gameline, for the Atari 2600 console. ...

? Learn more

Tim Armstrong was appointed CEO and Chairman of AOL in March 2009. Before becoming the CEO of AOL, Armstrong presided over Google?s North American and Latin American advertising sales and operations teams. His team provided customers with local partnerships as well as centralized sales and services. They worked with some of the world?s most widely recognized brands and advertising agencies in addition to some of the fastest growing medium-sized companies. Armstrong joined Google from Snowball.com, where he was vice president of...

? Learn more

Source: http://techcrunch.com/2013/04/09/tim-should-talk-about-techcrunch-more/

12 12 12 Anne Hathaway Wardrobe Malfunction man of steel man of steel Adrienne Maloof Telemundo real housewives of beverly hills

US says hacking undermines China's interests

BEIJING (AP) ? Hacking that originates inside China is undermining its relationship with the United States and harms Beijing's long-term interests, a top U.S. diplomat said Tuesday, in the latest high-level public expression of concern over a problem that has prompted threats of commercial retaliation from Washington.

The U.S. believes cyber intrusions originating from China that result in the theft of sensitive information have reached very high levels, adding to existing problems with the lack of protection for intellectual property rights, U.S. undersecretary of state for economic growth, Robert Hormats said.

He urged China to take firm action against hacking and said Chinese officials needed to question whether such activity "serves China's real interests" as it seeks to upgrade its economy, the world's second largest.

"The long term interest of the Chinese government is to investigate and halt these cyber intrusions wherever in this country they come from," Hormats said. "The U.S. government is taking an active role in addressing this issue and we continue to raise our concerns with senior Chinese officials."

Hormats' comments in an address to an Internet Industry conference in Beijing follow a forensically detailed report by Internet security company Mandiant that accused a Chinese military unit of carrying out a years-long hacking attack against U.S. companies.

China's government and military deny carrying out cyberattacks. A senior Chinese official attending the conference repeated Beijing's contention that Beijing was itself a victim of hacking.

"Our opposition to all forms of hacking is clear and consistent," said Qian Xiaoqian, a vice minister and deputy director of the State Internet Information Office.

"Lately people have been cooking up a theory of a Chinese Internet threat, which is just an extension of the old 'China threat' and just as groundless," Qian said.

Such statements seem to be doing little to allay concerns over a suspected official role in wholesale hacking linked to China. Foreign military and government organizations have been targeted by the attacks, as well as private companies, including those in sensitive industries such as energy and aerospace.

Craig Mundie, a senior adviser to the CEO of Microsoft, a sponsor of the conference, said that regardless of whether China-based hacking was the work of rogue actors, Beijing's efforts to stop it are clearly not effective.

"And given that China's policy position is that such activity is absolutely illegal, our two countries clearly need to work together to figure out how to enforce that policy more effectively, because right now the evidence suggests China's policy enforcement approaches are not working adequately," Mundie said.

Mandiant, a Virginia-based cybersecurity firm, released a torrent of details in February that tied a secret Chinese military unit in Shanghai to years of cyberattacks that compromised more than 140 companies. Mandiant linked the breaches to the People's Liberation Army's Unit 61398.

In response to the hacking reports, the Obama administration has been considering fines and other trade actions against China or any other country guilty of cyberespionage.

However, the administration is expected to proceed cautiously because of the issue's sensitivity, and Hormats and other conference attendees repeatedly called for communication and joint efforts against hacking rather than outright confrontation.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/495d344a0d10421e9baa8ee77029cfbd/Article_2013-04-09-China-US-Hacking/id-6a5df253f45443a9a6500098da9bd83d

philip humber red sox white sox chuck colson ufc 145 results orrin hatch marlon byrd

NKorea urges foreigners to vacate South Korea

A North Korean soldier stands beneath roadside propaganda which reads "Let's Uphold the Military First Revolutionary Leadership of the Great Comrade Kim Jong Un With Loyalty" in Pyongyang on Tuesday, April 9, 2013. (AP Photo/David Guttenfelder)

A North Korean soldier stands beneath roadside propaganda which reads "Let's Uphold the Military First Revolutionary Leadership of the Great Comrade Kim Jong Un With Loyalty" in Pyongyang on Tuesday, April 9, 2013. (AP Photo/David Guttenfelder)

A North Korean flag hangs on a light pole as a pedestrian passes by along a Pyongyang street on Tuesday, April 9, 2013. (AP Photo/David Guttenfelder)

U.S. Army soldiers drive armored vehicles during annual military drills in Yeoncheon, South Korea, near the border with North Korea, Tuesday, April 9, 2013. North Korea has unleashed a flurry of war threats and provocations over U.N. sanctions for its last nuclear test, and over the ongoing U.S.-South Korean military drills, which the allies say are routine but Pyongyang says is a preparation for a northward invasion. (AP Photo/Ahn Young-joon)

A U.S. Army soldier stands on an armored vehicle during annual military drills in Yeoncheon, South Korea, near the border with North Korea, Tuesday, April 9, 2013. North Korea has unleashed a flurry of war threats and provocations over U.N. sanctions for its last nuclear test, and over the ongoing U.S.-South Korean military drills, which the allies say are routine but Pyongyang says is a preparation for a northward invasion. (AP Photo/Ahn Young-joon)

U.S. Army soldiers prepare for an exercise during their annual military drills with South Korea in Yeoncheon, South Korea, near the border with North Korea, Tuesday, April 9, 2013. North Korea has unleashed a flurry of war threats and provocations over U.N. sanctions for its last nuclear test, and over the ongoing U.S.-South Korean military drills, which the allies say are routine but Pyongyang says is a preparation for a northward invasion. (AP Photo/Ahn Young-joon)

PYONGYANG, North Korea (AP) ? North Korea on Tuesday urged all foreign companies and tourists in South Korea to evacuate, saying the two countries are on the verge of a nuclear war. The new threat appeared to be an attempt to scare foreigners into pressing their governments to pressure Washington and Seoul to act to avert a conflict.

Analysts see a direct attack on Seoul as extremely unlikely, and there are no overt signs that North Korea's army is readying for war, let alone a nuclear one.

In Pyongyang, there were no signs of a military buildup. Scores of people were armed on a cold spring day with shovels, not guns, and were busy planting trees as part of a forestation campaign. The national flag fluttered across the city as North Korea marked the 20th anniversary of late leader Kim Jong Il's appointment as chairman of the National Defense Commission, and workers began preparing the city for the April 15 birthday of late President Kim Il Sung.

South Korea's military has reported missile movements on North Korea's east coast, but nothing pointed toward South Korea.

"The situation on the Korean Peninsula is inching close to a thermonuclear war due to the evermore undisguised hostile actions of the United States and the South Korean puppet warmongers and their moves for a war against" the North, said a statement by the North Korean Asia-Pacific Peace Committee, an organization that deals with regional matters.

The statement is similar to past threats that analysts call an attempt to raise anxiety in foreign capitals.

Analysts see the threats of war as a bid to win Pyongyang-friendly policy changes in Seoul and Washington. Last week, North Korea told foreign diplomats in Pyongyang that it will not be able to guarantee their safety starting Wednesday. It is not clear what significance that date holds.

Observers also say the torrent of North Korean prophecies of doom and efforts to raise war hysteria are partly to boost the image and military credentials of young leader Kim Jong Un.

Air Koryo's daily flight from Beijing was only half full on Tuesday. Flight attendants in red suits and blue scarves artfully kept in place by sparkling brooches betrayed no sense of fear or concern.

Among the tourists who arrived Tuesday was Mark Fahey, a biomedical engineer from Sydney, Australia, who said he thought a war was "pretty unlikely."

Fahey, a second-time visitor to North Korea, said he booked his trip to Pyongyang six months ago, eager to see how North Korea might have changed under Kim Jong Un. He said he chose to stick with his plans, suspecting that most of the threats were rhetoric.

"I knew that when I arrived here it would probably be very different to the way it was being reported in the media," he told The Associated Press at Pyongyang airport. He said his family trusts him to make the right judgment, but "my colleagues at work think I am crazy."

He said he took no special precautions. "I haven't brought anything at all - just a camera," he said with a laugh. But he noted that several other tourists who had been slated to travel with his group had canceled their journeys.

Chu Kang Jin, a Pyongyang resident, said everything is calm in the city.

"Everyone, including me, is determined to turn out as one to fight for national reunification ... if the enemies spark a war," he said, using nationalist rhetoric employed by many North Koreans when speaking to the media.

South Korean President Park Geun-hye, who has sought to re-engage North Korea with dialogue and aid since taking office in February, expressed exasperation Tuesday with what she called the "endless vicious cycle" of Seoul answering Pyongyang's hostile behavior with compromise, only to get more hostility.

U.S. and South Korean defense officials have said they've seen nothing to indicate that Pyongyang is preparing for a major military action, and there was no sign of an exodus of foreign companies or tourists from South Korea.

Still, the United States and South Korea have raised their defense postures, as has Japan, which deployed PAC-3 missile interceptors in key locations around Tokyo on Tuesday as a precaution against possible North Korean ballistic missile tests.

In Rome, U.N. Secretary-General Ban Ki-moon described the tensions on the Korean Peninsula as "very dangerous" and said that "any small incident caused by miscalculation or misjudgment" may "create an uncontrollable situation."

Also Tuesday, North Korea pulled out more than 50,000 workers from the Kaesong industrial park, which combines South Korean technology and know-how with cheap North Korean labor. It was the first time that production has been shut down at the complex, the only remaining product of economic cooperation between the two countries that began about a decade ago when relations were much warmer.

Other projects from previous eras of cooperation such as reunions of families separated by war and tours to a scenic North Korean mountain stopped in recent years.

___

Associated Press writers Hyung-jin Kim in Seoul, South Korea, and Nicole Winfield in Rome contributed to this report.

___

Follow AP's Korea bureau chief on Twitter at twitter.com/newsjean.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-04-09-Koreas-Tension/id-dad3e0b271d949c0b3a49d3e86def3ae

judi dench bobby brown leaves funeral donnie mcclurkin whitney houston funeral live stream kevin costner whitney houston whitney houston funeral live pat buchanan