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WASHINGTON ? The top GOP aide to a House committee investigating Solyndra Inc. once worked for a lobbying firm that helped the now-bankrupt solar company apply for a half-billion-dollar federal loan.
Gary Andres, staff director of the House Energy and Commerce Committee, was a vice chairman at Dutko Worldwide until last December, when he was appointed to his current post by Rep. Fred Upton, R-Mich., chairman of the energy panel. The committee is investigating Solyndra, which received a $528 million Energy Department loan in 2009. The company later went bankrupt and laid off its 1,100 workers.
The Kalamazoo Gazette reported Monday that Solyndra paid Dutko $30,000 in 2008 to handle its application for the federal loan.
Alexa Marrero, a spokeswoman for the committee, said Andres never worked on behalf of Solyndra and was not aware until recently that Dutko had represented Solyndra in 2008.
Marrero said the revelation that Solyndra hired Dutko, now known as Dutko Grayling, does not change the facts of the case.
"Despite serious warning signs from within the (Obama) administration that a federal loan to Solyndra would be a losing proposition, the Department of Energy gave a green light to a half-billion dollar loan to this company, followed by a restructuring that put taxpayers at the back of the line," she said. "Now the committee is asking what went wrong, and what can be done to ensure taxpayers aren't left on the losing end of this kind of bad bet ever again."
John Waltz, a Democrat running for Upton's seat in 2012, said Monday that Upton should have disclosed Dutko's involvement with Solyndra once he became aware of it. Andres should recuse himself from the Solyndra investigation, Waltz said.
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ADDS NAME OF CANDIDATE ON POSTER - An Egyptian woman rests in front of campaign posters for Waleed Abou Heissa from the Egyptian Citizen Party outside a polling station on the first day of parliamentary elections in Alexandria, Egypt, Monday, Nov. 28, 2011. Shaking off years of political apathy, Egyptians on Monday began voting in their nation's first parliamentary elections since Hosni Mubarak's ouster, a giant step toward what many in the country hope will be a democratic Egypt after decades of dictatorship.(AP Photo/Tarek Fawzy)
ADDS NAME OF CANDIDATE ON POSTER - An Egyptian woman rests in front of campaign posters for Waleed Abou Heissa from the Egyptian Citizen Party outside a polling station on the first day of parliamentary elections in Alexandria, Egypt, Monday, Nov. 28, 2011. Shaking off years of political apathy, Egyptians on Monday began voting in their nation's first parliamentary elections since Hosni Mubarak's ouster, a giant step toward what many in the country hope will be a democratic Egypt after decades of dictatorship.(AP Photo/Tarek Fawzy)
Egyptian women wait at a polling station to vote in the country's parliamentary election in the Zamalek neighbourhood of Cairo, Egypt, Monday, Nov. 28, 2011. Shaking off years of political apathy, Egyptians on Monday began voting in their nation's first parliamentary elections since Hosni Mubarak's ouster, a giant step toward what many in the country hope will be a democratic Egypt after decades of dictatorship.(AP Photo/Maya Alleruzzo)
An Egyptian army soldier stands guard next to posters of parliamentary candidates on a wall outside a polling center in Assuit, Egypt, Monday, Nov. 28, 2011. Voting began on Monday in Egypt's first parliamentary elections since longtime authoritarian leader Hosni Mubarak was ousted in a popular uprising nine months ago. The vote is a milestone many Egyptians hope will usher in a democratic age after decades of dictatorship. (AP Photo/Khalil Hamra)
Egyptian voters line up outside a polling center in Assuit, Egypt, Monday, Nov. 28, 2011. Voting began on Monday in Egypt's first parliamentary elections since longtime authoritarian leader Hosni Mubarak was ousted in a popular uprising nine months ago. The vote is a milestone many Egyptians hope will usher in a democratic age after decades of dictatorship. (AP Photo/Khalil Hamra)
An Egyptian Army soldier stands guard as voters wait outside a polling center in Assuit, 320 kilometers (200 miles) south of Cairo, Egypt, Monday, Nov. 28, 2011. Voting began on Monday in Egypt's first parliamentary elections since longtime authoritarian leader Hosni Mubarak was ousted in a popular uprising nine months ago. The vote is a milestone many Egyptians hope will usher in a democratic age after decades of dictatorship. (AP Photo/Khalil Hamra)
CAIRO (AP) ? Shaking off years of political apathy, Egyptians turned out in long lines at voting stations Monday in the first parliamentary elections since Hosni Mubarak's ouster, a giant step toward what they hope will be a democracy after decades of dictatorship.
Some voters brought their children along, saying they wanted them to learn how to exercise their rights in a democracy as they cast ballots in what promises to be the fairest and cleanest election in Egypt in living memory. With fears of violence largely unrealized, the biggest complaint was the hours of standing in long, slow-moving lines.
"If you have waited for 30 years, can't you wait now for another hour?" an army officer yelled at hundreds of restless women at one polling center in Cairo.
After the dramatic, 18-day uprising that ended Mubarak's three decades of authoritarian rule, many had looked forward to this day in expectation of a celebration of freedom. But Mubarak's fall on Feb. 11 was followed by nearly 10 months of military rule, divisions and violence and when election day finally arrived, the mood was markedly different. People were eager to at last cast a free vote, but daunted by all the uncertainty over what happens next.
"I never voted because I was never sure it was for real," said Shahira Ahmed, 45, waiting with her husband and daughter with around 500 other people at a Cairo polling station. "This time, I hope it is, but I am not positive."
Even as they vote, Egyptians are sharply polarized and confused over the nation's direction.
On one level, the election will be a strong indicator of whether Egypt is heading toward Islamism or secularism. The Muslim Brotherhood, Egypt's largest and best organized group, along with other Islamists are expected to dominate in the vote. Many liberals, leftists, Christians and pious Muslims who oppose mixing religion and politics went expressly to the polls to try to stop them or at least reduce their victory.
The U.S. and its close ally Israel, which has a long-standing peace treaty with Egypt, worry that stronger Brotherhood influence could end Egypt's role as a major moderating influence in Middle East politics.
Also weighing heavily on voters' mind was whether this election can really set Egypt on a path of democracy while it is still under military rule. Only 10 days before the elections, major protests erupted around the country demanding the ruling generals accused of bungling the transition step aside and hand power immediately to a civilian authority.
Another concern is that the parliament that emerges may have little relevance because the military is sharply limiting its powers, and it may only serve for several months.
The Egyptian election is the fruit of the Arab Spring revolts that have swept the region over the past year, toppling several authoritarian regimes. In Tunisia and Morocco, Islamic parties have come out winners in elections the past month, but if the much larger Egypt does the same, it could have an even greater impact.
Even before voting began at 8 a.m., people stood in lines stretching several hundred yards outside many polling stations in Cairo, suggesting a respectable turnout. Under heavy security from police and soldiers, segregated lines of men and women grew, snaking around blocks and prompting authorities to extend voting by two hours.
Many said they were voting for the first time. For decades, few Egyptians bothered to cast ballots because nearly every election was rigged, whether by bribery, ballot box stuffing or intimidation by police at the polls. Turnout was often in the single digits.
"I am voting for freedom. We lived in slavery. Now we want justice in freedom," said 50-year-old Iris Nawar at a polling station in Maadi, a Cairo suburb.
"We are afraid of the Muslim Brotherhood. But we lived for 30 years under Mubarak, we will live with them, too," said Nawar, a first-time voter.
Waiting for hours, people joked, squabbled, and bought sandwiches from delivery men taking advantage of an eager, captive market.
Under a heavy rain in the Mediterranean coastal city of Alexandria, a women's line displayed Egypt's religious spectrum ? Christians and Muslims with their hair loose, others in conservative headscarves, still others blanketed in the most radical garb, the black robes that cover a woman's entire body, leaving only the eyes exposed. At a nearby station, one soldier shouted through a megaphone, "Choose freely, choose whomever you want to vote for."
The Brotherhood entered the campaign armed with a powerful network of activists around the country and years of experience in political activity. Even though it was banned under Mubarak's regime, its politicians sat in parliament as independents. Also running is the even more conservative Salafi movement, which advocates a hard-line Saudi Arabian-style interpretation of Islam. While the Brotherhood shows at times a willingness to play politics and compromise in its ideology, many Salafis make no bones about saying democracy must take a back seat to Islamic law.
In contrast, the secular and liberal youth groups that ousted Mubarak failed to capitalize on their astonishing triumph to effectively contest the election. They largely had to create all-new parties from scratch, most of which are not widely known among the public and were plagued by divisions through the past months.
"The Muslim Brotherhood are the people who have stood by us when times were difficult," said Ragya el-Said, a 47-year-old lawyer in Alexandria, a stronghold for the Brotherhood. "We have a lot of confidence in them."
But the Brotherhood faces still opposition. Even some who favor more religion in public life are suspicious of their motives, and the large Christian minority ? about 10 percent of the population of around 85 million ? deeply fear rising Islamism.
"I'm a Muslim but won't vote for any Islamist party because their views are too narrow," said Eman el-Khoury, 53, as she looked disapprovingly at Brotherhood activists handing out campaign leaflets near an Alexandria polling station, a violation of election rules. "How can we change this country when at an opportunity for change, we make the same dirty mistakes."
For many of those who did not want to vote for the Brotherhood or other Islamists, the alternative was not clear.
"I don't know any of the parties or who I'm voting for," Teresa Sobhi, a Christian voter in the southern city of Assiut, said. "I'll vote for the first names I see I guess."
The election is a long and unwieldy process. It will be held in stages divided up by provinces. Voting for 498-seat People's Assembly, parliament's lower chamber, will last until January, then elections for the 390-member upper house will drag on until March.
Each round lasts two days. Some voters said they feared vote rigging or ballot stuffing because the ballot boxes would be left at polling stations overnight.
Monday and Tuesday's vote will take place in nine provinces whose residents account for 24 million of Egypt's estimated 85 million people.
The ballots are a confusing mix of party lists that will gain seats according to proportions of votes and individual candidates ? who will have to enter run-off votes after each round if no one gets 50 percent of the first-round vote. Mixed in are candidates labeled as "farmer" or "worker" who must gain a certain number of seats, a holdover for socialist days that Mubarak's regime manipulated to get in cronies.
Moreover, there are significant questions over how relevant the new parliament will even be. The ruling military council of generals, led by Field Marshal Hussein Tantawi, insists it will maintain considerable powers after the election. It will put together the government and is trying to keep extensive control over the creation of an assembly to write a new constitution, a task that originally was seen as mainly in the parliament's hands.
The protesters who took to Cairo's Tahrir Square and other cities since Nov. 19 in rallies recalling the uprising that ousted Mubarak on Feb. 11 demand the generals surrender power immediately to a civilian government.
Some hoped their vote would help eventually push the generals out.
"We are fed up with the military," said Salah Radwan, waiting outside a polling center in Cairo's middle-class Abdeen neighborhood. "They should go to protect our borders and leave us to rule ourselves. Even if we don't get it right this time, we will get it right next time."
On Monday morning in Tahrir, a relatively small crowd of a few thousand kept the round-the-clock protests going. Clashes during the protests left more than 40 dead and had heightened fears of violence at polling stations.
Turnout among the estimated 50 million voters will play a key role. A higher turnout could water down the showing of the Brotherhood, because its core of supporters are the most likely to vote.
If there are heavy numbers of voters, that could also give legitimacy to a vote that the military insisted go ahead despite the recent turmoil.
A referendum on constitutional amendments in March had a turnout of 40 percent ? anything lower than that could be a sign that skepticism over the process is high.
The Brotherhood, which used to run its candidates as independents because of the official ban on the group, made its strongest showing in elections in 2005, when it won 20 percent of parliament's seats. Its leaders have predicted that in this vote it could win up to 40 or 50 percent.
___
AP correspondents Maggie Michael in Cairo, Hadeel al-Shalchi in Alexandria, Egypt, and Aya Batrawy in Assiut, Egypt contributed to this report.
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NEW YORK (Reuters) ? Vampires feasted at the Thanksgiving weekend box office, bringing the newest "Twilight" movie its second win in a row, over a strong comeback for "The Muppets" and other family fare that filled theaters.
"The Twilight Saga: Breaking Dawn: Part 1" delivered an estimated $113.5 million around the globe from Friday through Sunday. The film ranked No. 1 for the second straight week at U.S. and Canadian theaters, where ticket sales hit $42 million for three days and $62.3 million over the five-day Thanksgiving holiday weekend.
The film's total box-office take since its release reached $489.3 million globally.
"Breaking Dawn: Part 1" is the fourth movie in the "Twilight" series, one of Hollywood's most lucrative franchises. The movies are based on best-selling novels by Stephenie Meyer about a human-vampire-werewolf love triangle, a story that has generated legions of die-hard female fans.
For the latest movie, "word of mouth is good. (Fans) are supporting the film," said Richie Fay, president of domestic distribution for independent studio Summit Entertainment, which backed the film.
In second place, audiences welcomed the Muppets back to theaters for the first time in 12 years.
New Disney movie "The Muppets," starring Jason Segel and Amy Adams alongside Kermit, Miss Piggy and their puppet friends, took in a strong $29.5 million at North American (U.S. and Canadian) theaters in three days. The five-day holiday weekend haul reached $42 million domestically. Two international markets added $1.6 million.
Disney bought the rights to the Muppets in 2004, and the media, entertainment and consumer-products giant is eager to interest a new generation in the characters.
"It's hard to have anyone argue we didn't bring them back," said Dave Hollis, Disney's executive vice president for motion picture sales and distribution. The movie's performance "exceeded expectations," he said.
The Muppets starred on a weekly television show in the 1970s and early 1980s plus a series of films, the last being 1999's "Muppets from Space."
Critics loved the new Muppets movie, with 98 percent giving it a favorable review, according to aggregation website Rotten Tomatoes. Audiences awarded an A rating on average, according to exit-polling firm CinemaScore. The movie cost about $45 million to produce.
FAMILY FILMS COMPETE
In third place for the weekend, dancing penguin sequel "Happy Feet Two" earned $13.4 million over three days domestically during its second weekend in theaters and $18.4 million through five days.
Rounding out the top five were two other new family movies that critics adored.
Animated 3D movie "Arthur Christmas," which cost about $98 million to produce, pulled in $12.7 million at domestic theaters over three days and $17 million in five days to finish in fourth place. The movie explains how Santa delivers presents around the world in one night and has earned $22.3 million overseas since opening two weeks ago.
Rory Bruer, president of worldwide distribution for Sony Pictures, said the film "opened about where we hoped it would," adding that he expected the Christmas theme would appeal throughout the holiday season.
"Hugo," a 3D family movie, ended the weekend in fifth place with $11.4 million over three days and $15.4 million over five days. The movie centers on an orphan living in a Paris train station in the 1930s.
The film exceeded studio forecasts for its release in about 1,300 locations, far fewer than the 3,000-plus for the other widely released films, said Don Harris, president of domestic distribution for Paramount.
In a small number of theaters, "My Week with Marilyn," starring Michelle Williams as Marilyn Monroe, opened with $1.8 million from 244 screens from Friday through Sunday. Critics have praised Williams' performance in the Weinstein Co. film and mentioned her as an Academy Award contender for the role.
Walt Disney Co released "The Muppets." Privately held Summit Entertainment released "Breaking Dawn: Part 1." "Arthur Christmas" was distributed by Sony, and "Hugo" was released by Paramount, a unit of Viacom Inc. Time Warner unit Warner Bros. distributed "Happy Feet Two."
(Reporting by Lisa Richwine; Editing by Bill Trott)
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Please post all "Players Wanted" threads in the Roleplayers Wanted forum!
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Will you reserve Lydia for me please?
Nova, someone might be reserving the spot, so I'll let you know rather you can have it or not depending on what they say ^^
Edit:
Just thought of a question Lovely Spade do you want, anime or real life or don't give a flip.
Anime pics would be great ^^
EDIT: Done!
Okie Dokie she's done Lovely Spade.
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ATLANTA ? More parents are opting out of school shots for their kids. In eight states now, more than 1 in 20 public school kindergartners aren't getting all the vaccines required for attendance, an Associated Press analysis found.
That growing trend among parents seeking vaccine exemptions has health officials worried about outbreaks of diseases that once were all but stamped out.
The AP analysis found more than half of states have seen at least a slight rise in the rate of exemptions over the past five years. States with the highest exemption rates are in the West and Upper Midwest.
It's "really gotten much worse," said Mary Selecky, secretary of health for Washington state, where 6 percent of public school parents have opted out.
Rules for exemptions vary by state and can include medical, religious or ? in some states ? philosophical reasons.
Reasons for skipping some school shots vary. Some parents are skeptical that vaccines are essential. Others fear vaccines carry their own risks. Some find it easier to check a box opting out than the effort to get the shots and required paperwork schools demand. Still others are ambivalent, believing in older vaccines but questioning newer shots against, say, chickenpox.
The number of shots is also giving some parents pause. By the time most children are 6, they will have been stuck with a needle about two dozen times ? with many of those shots given in infancy. The cumulative effect of all those shots has not been studied enough, some parents say.
"Many of the vaccines are unnecessary and public health officials don't honestly know what the effect of giving so many vaccines to such small children really are," said Jennifer Margulis, a mother of four and parenting book author in Ashland, Ore.
But few serious problems have turned up over years of vaccinations and several studies have shown no link with autism, a theory from the 1990s that has been widely discredited.
To be sure, childhood vaccination rates remain high overall, at 90 percent or better for several vaccines, including those for polio, measles, hepatitis B and even chickenpox. In many states, exemptions are filed for fewer than 1 percent of children entering school for the first time.
Health officials have not identified an exemption threshold that would likely lead to outbreaks. But as they push for 100 percent immunization, they worry when some states have exemption rates climbing over 5 percent. The average state exemption rate has been estimated at less than half that.
Even more troubling are pockets in some states where exemption rates much higher. In some rural counties in northeast Washington, for example, rates in recent years have been above 20 percent and even as high as 50 percent.
"Vaccine refusers tend to cluster," said Saad Omer, an Emory University epidemiologist who has done extensive research on the issue.
While parents may think it does no harm to others if their kids skip some vaccines, they are in fact putting others at risk, health officials say. No vaccine is completely effective. If an outbreak begins in an unvaccinated group of children, a vaccinated child may still be at some risk of getting sick.
Studies have found communities with higher exemption rates sometimes are places where measles have suddenly re-emerged in outbreaks. Vaccinated kids are sometimes among the cases, or children too young to be vaccinated. Last year, California had more than 2,100 whooping cough cases, and 10 infants died. Only one had received a first dose of vaccine.
"Your child's risk of getting disease depends on what your neighbors do," said Omer.
And while it seems unlikely that diseases like polio and diphtheria could ever make a comeback to the U.S., immunization expert Dr. Lance Rodewald with the federal Centers for Disease Control and Prevention says it could happen.
"Polio can come back. China was polio free for two decades, and just this year, they were infected from Pakistan, and there is a big outbreak of polio China now. The same could happen here," Rodewald said in an email.
He cited outbreaks of Hib, a disease that can lead to meningitis, among the Amish who don't consistently vaccinate their children. Russia had a huge diphtheria outbreak in the early to mid-1990s, he said, because vaccine coverage declined. "Measles is just visible, but it isn't the only concern," Rodewald said.
For its review, the AP asked state health departments for kindergarten exemption rates for 2006-07 and 2010-11. The AP also looked at data states had previously reported to the federal government. (Most states don't have data for the current 2011-12 school year.)
Alaska had the highest exemption rate in 2010-11, at nearly 9 percent. Colorado's rate was 7 percent, Minnesota 6.5 percent, Vermont and Washington 6 percent, and Oregon, Michigan and Illinois were close behind.
Mississippi was lowest, at essentially 0 percent.
The AP found that vaccine exemptions rose in more than half of states, and 10 had increases over the five years of about 1.5 percentage points or more, a range health officials say is troubling.
Those states, too, were in the West and Midwest ? Alaska, Kansas, Hawaii, Illinois, Michigan, Montana, Oregon, Vermont, Washington and Wisconsin. Arizona saw an increase that put that state in the same ballpark.
Exemption seekers are often middle-class, college-educated white people, but there are often a mix of views and philosophies. Exemption hot spots like Sedona, Ariz., and rural northeast Washington have concentrations of both alternative medicine-preferring as well as government-fearing libertarians.
Opposition to vaccines "is putting people together that normally would not be together," observed Elizabeth Jacobs, a University of Arizona epidemiologist looking at that state's rising exemption rates.
What many of exemption-seeking parents share, however, is a mental calculation that the dangers to their children of vaccine-preventable diseases are less important than the possible harms from vaccine. Or they just don't believe health officials, putting more stock in alternative sources ? often discovered through Internet searches.
"We are being told this by every government official, teacher, doctor that we need vaccines to keep us safe from these diseases. I simply don't believe that to be true. I believe all the diseases in question were up to 90 percent in decline before mass vaccines ever were given. I don't think vaccines are what saved the world from disease. I think effective sewer systems, nutrition, and handwashing (are the reasons)," said Sabrina Paulick, of Ashland, Ore. She's part-time as a caregiver for elderly people in their homes and a mother of a 4-year-old daughter.
Parents say they'd like to reserve the right to decide what vaccinations their children should get, and when. Health officials reply that vaccinations are recommended at an early age to protect children before they encounter a dangerous infection. "If you delay, you're putting a child at risk," said Gerri Yett, a nurse who manages Alaska's immunization program.
Analyzing vaccination exemptions is difficult. States collect data differently; some base their exemption rates on just a small sample of schools ? Alaska, for example ? while others rely on more comprehensive numbers. So the AP worked with researchers at CDC, which statistically adjusted some states' 2010-11 data for a better comparison.
It's also not clear when an exemption was invoked against all vaccines and when it was used to excuse just one or two shots. CDC officials think the second scenario is more common.
Also, states differ on some of the vaccines required and what's needed to get an exemption: Sometimes only a box on a form needs to be checked, while some states want letters or even signed statements from doctors.
Meanwhile, some parent groups and others have pushed legislators to make exemptions easier or do away with vaccination requirements altogether. The number of states allowing philosophical exemptions grew from 15 to 20 in the last decade.
Some in public health are exasperated by the trend.
"Every time we give them evidence (that vaccines are safe), they come back with a new hypothesis" for why vaccines could be dangerous, said Kacey Ernst, another University of Arizona researcher.
The exemption increases have come during a time when the government has been raising its estimates of how many children have autism and related disorders. Some experts suggest that parents have listened intently to that message, with some believing the growing roster of recommended shots must somehow be related.
"I don't understand how other people don't see that these two things are related," said Stacy Allan, a Summit, N.J., mother who filed religious exemptions and stopped vaccinating her three children.
Several parents said that while they believe many health officials mean well, their distrust of the vaccine-making pharmaceutical industry only continues to grow.
"I wouldn't be one to say I am absolutely certain these things are hurting our children," said Michele Pereira, an Ashland mother of two young girls. She is a registered nurse and married to an anesthesiologist. While her daughters have had some vaccinations, they have not had the full recommended schedule.
"I feel like there are enough questions out there that I don't want to take the chance," she said.
___
Associated Press writer Jeff Barnard in Grants Pass, Ore., contributed to this report.
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Public release date: 28-Nov-2011
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NYU Langone Medical Center / New York University School of Medicine
Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have discovered a new potential therapeutic target for Diffuse Large B-Cell Lymphoma (DLBCL), the most aggressive and common type of lymphoma in adults. The new study, published in the November 23 issue of Nature, reveals the underlying molecular mechanism contributing to the development of lymphomagenesis.
"We have discovered that the protein FBXO11 is a novel tumor suppressor in B-cells," said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. "Our new research findings show deletion or mutation of the FBXO11 gene in B-cells may lead to the formation of Diffuse Large B-Cell Lymphoma."
Lymphoma is a blood cancer that affects the lymphatic system, the body's infection and disease-fighting network. DLBCL is the most common type of adult lymphoma. This type of non-Hodgkin lymphoma develops within B-cells, a type of lymphocytes or white blood cells in the lymphatic tissue of the body. Mutations of certain genes in the B-cells located in the lymph nodes and other organs of the immune system contribute to the proliferation of DLBCL throughout the body.
The majority of patients with DLBCL overexpress the protein B-Cell Lymphoma 6 (BCL6). By binding to specific DNA sequences, BCL6 regulates the transcription of genes that are crucial to B-cell development and function. Deregulation of BCL6 leads to the pathogenesis of B-cell lymphomas as proven in experiments in mice expressing BCL6 in B-cells and developing DLBCL similar to human disease. In certain DLBCL patients, BCL6 overexpression is achieved through gene translocation or mutation of its promoter. However, many other patients with DLBCLs overexpress BCL6 through a mechanism that has been unknown until now.
In the study, NYU Langone researchers show FBXO11 as a novel tumor suppressor. FBXO11, part of a SKP1/CUL1/F-box protein (SCF) ubiquitin ligase protein complex, controls BCL6 degradation. FBXO11 functions to keep the levels of BCL6 in B-cells low. The new study shows that BCL6 protein is targeted for degradation by the B-cell's ubiquitin system, the cell-recycling system that helps limit unnecessary cell growth and prevent malignant cell transformation. FBXO11-mediated elimination of BCL6 prevents the development of DLBCL. Additionally, researchers discovered FBXO11 is deleted or mutated in many DLBCL cell lines and DLBCL patients. Experimentally, inactivation, mutation or deletion of FBXO11 in B-cells induces overexpression of BCL6. Moreover, reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells, by promoting BCL6 degradation, inhibits proliferation and induces the death of tumor cells.
"These findings reveal the molecular mechanism behind the overexpression of BCL6 in B-cell lymphomas," said Dr. Pagano. "Mutations and deletions of FBXO11 in B-cells contribute to lymphomagenesis. As lymphoma cells are addicted to BCL6 expression, FBXO11-mediated regulation of BCL6 is a new potential therapeutic strategy for the future treatment of lymphoma."
###
This study was a collaboration between NYU Cancer Institute, NYU School of Medicine, Howard Hughes Medical Institute, University of Torino, San Giovanni Battista Hospital, Dana-Farber Cancer Institute. The study was supported by funding from the National Institutes of Health, Howard Hughes Medical Institute, Susan G. Komen Foundation and Lymphoma Research Foundation.
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to http://www.NYULMC.org.
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Public release date: 28-Nov-2011 Share ] Contact: Lauren Woods
lauren.woods@nyumc.org
212-404-3555
NYU Langone Medical Center / New York University School of Medicine
Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have discovered a new potential therapeutic target for Diffuse Large B-Cell Lymphoma (DLBCL), the most aggressive and common type of lymphoma in adults. The new study, published in the November 23 issue of Nature, reveals the underlying molecular mechanism contributing to the development of lymphomagenesis.
"We have discovered that the protein FBXO11 is a novel tumor suppressor in B-cells," said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. "Our new research findings show deletion or mutation of the FBXO11 gene in B-cells may lead to the formation of Diffuse Large B-Cell Lymphoma."
Lymphoma is a blood cancer that affects the lymphatic system, the body's infection and disease-fighting network. DLBCL is the most common type of adult lymphoma. This type of non-Hodgkin lymphoma develops within B-cells, a type of lymphocytes or white blood cells in the lymphatic tissue of the body. Mutations of certain genes in the B-cells located in the lymph nodes and other organs of the immune system contribute to the proliferation of DLBCL throughout the body.
The majority of patients with DLBCL overexpress the protein B-Cell Lymphoma 6 (BCL6). By binding to specific DNA sequences, BCL6 regulates the transcription of genes that are crucial to B-cell development and function. Deregulation of BCL6 leads to the pathogenesis of B-cell lymphomas as proven in experiments in mice expressing BCL6 in B-cells and developing DLBCL similar to human disease. In certain DLBCL patients, BCL6 overexpression is achieved through gene translocation or mutation of its promoter. However, many other patients with DLBCLs overexpress BCL6 through a mechanism that has been unknown until now.
In the study, NYU Langone researchers show FBXO11 as a novel tumor suppressor. FBXO11, part of a SKP1/CUL1/F-box protein (SCF) ubiquitin ligase protein complex, controls BCL6 degradation. FBXO11 functions to keep the levels of BCL6 in B-cells low. The new study shows that BCL6 protein is targeted for degradation by the B-cell's ubiquitin system, the cell-recycling system that helps limit unnecessary cell growth and prevent malignant cell transformation. FBXO11-mediated elimination of BCL6 prevents the development of DLBCL. Additionally, researchers discovered FBXO11 is deleted or mutated in many DLBCL cell lines and DLBCL patients. Experimentally, inactivation, mutation or deletion of FBXO11 in B-cells induces overexpression of BCL6. Moreover, reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells, by promoting BCL6 degradation, inhibits proliferation and induces the death of tumor cells.
"These findings reveal the molecular mechanism behind the overexpression of BCL6 in B-cell lymphomas," said Dr. Pagano. "Mutations and deletions of FBXO11 in B-cells contribute to lymphomagenesis. As lymphoma cells are addicted to BCL6 expression, FBXO11-mediated regulation of BCL6 is a new potential therapeutic strategy for the future treatment of lymphoma."
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This study was a collaboration between NYU Cancer Institute, NYU School of Medicine, Howard Hughes Medical Institute, University of Torino, San Giovanni Battista Hospital, Dana-Farber Cancer Institute. The study was supported by funding from the National Institutes of Health, Howard Hughes Medical Institute, Susan G. Komen Foundation and Lymphoma Research Foundation.
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to http://www.NYULMC.org.
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2011-11/nlmc-npt112811.php
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