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Breakthrough in the understanding of how pancreatic cancer cells ingest nutrients points to new drug target

May 13, 2013 ? In a landmark cancer study published online in Nature, researchers at NYU School of Medicine have unraveled a longstanding mystery about how pancreatic tumor cells feed themselves, opening up new therapeutic possibilities for a notoriously lethal disease with few treatment options. Pancreatic cancer kills nearly 38,000 Americans annually, making it a leading cause of cancer death. The life expectancy for most people diagnosed with it is less than a year.

Now new research reveals a possible chink in the armor of this recalcitrant disease. Many cancers, including pancreatic, lung, and colon cancer, feature a mutated protein known as Ras that plays a central role in a complex molecular chain of events that drives cancer cell growth and proliferation. It is well known that Ras cancer cells have special nutrient requirements to grow and survive. But how Ras cells cope to actually meet their extraordinary nutrient requirements has been poorly understood -- until now. In the study, led by Cosimo Commisso, a postdoctoral fellow in the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine, show for the first time how Ras cancer cells exploit a process called macropinocytosis to swallow up the protein albumin, which cells then harvest for amino acids essential for growth.

"A big mystery is how certain tumors meet their excessive nutrient demands ," says Dr. Commisso, whose work is funded in part by the Pancreatic Cancer Action Network. "We believe they accomplish this by macropinocytosis."

The findings suggest that Ras cancer cells are particularly dependent on macropinocytosis for growth and survival. When the researchers used a chemical to block the uptake of albumin via macropinocytosis in mice with pancreatic tumors, the tumors stopped growing and in some cases even shrank. Moreover, pancreatic cancer cells in mice featured more macropinosomes -- the vesicles that transport nutrients deep into a cell -- than normal mouse cells.

The discovery of a "protein eating" mechanism unique to some cancer cells sets the stage for drugs that could block the engulfing process without causing collateral damage to healthy cells and suggests new ways to ferry chemotherapeutic cargo into the heart of cancer cells.

"This work offers up a completely different way to target cancer metabolism," says lead principal investigator of the study Dafna Bar-Sagi, PhD, senior vice president and vice dean for Science, chief scientific officer and professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, who first identified macropinocytosis in Ras-transformed cancer cells. "It's exciting to think that we can cause the demise of some cancer cells simply by blocking this nutrient delivery process."

Crucial to the team's findings is the work of Matthew G. Vander Heiden, assistant professor of biology at the David H. Koch Institute for Integrative Cancer Research at MIT and Christian Metallo, assistant professor of bioengineering at the University of California at San Diego, who characterized how Ras cells derive energy from the constituent amino acids released after protein engulfment.

Other key contributors include Craig B. Thompson, president and CEO of the Sloan-Kettering Cancer Center and Joshua D. Rabinowitz, professor of chemistry at the Lewis Sigler Institute for Integrative Genomics at Princeton University.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/NCzfeSHn-QI/130513095020.htm

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DNA test shows Ohio kidnap suspect fathered girl

CLEVELAND (AP) ? As relatives of the Cleveland kidnapping and rape suspect recounted claims of his unnerving paranoia and violent outbursts, DNA testing confirmed the man who allegedly held three women captive for nearly a decade is the father of a 6-year-old girl who escaped from the house along with the women.

Ariel Castro, charged with rape and kidnapping, remained jailed Friday under a suicide watch on $8 million bond while prosecutors weighed more charges, including some that might carry the death penalty. Public defender Kathleen Demetz, who said she is acting as Castro's adviser while he awaits a full-time attorney, said Friday she can't speak to his guilt or innocence and said only that she advised him not to talk to reporters.

But those who know the 52-year-old Castro are speaking up, saying he was often angry, paranoid and prone to violent outbursts against the mother of his children. He frequently beat her, played bizarre psychological games and locked her indoors, they said.

The stories, repeated in separate interviews with The Associated Press by members of Castro's extended family, have surprised people who knew him as a musician who played bass in several bands around Cleveland the last two decades.

Miguel Quinones, manager of a group Castro played with twice as a backup bass player about five years ago, said he had nothing bad to say about Castro based on his own experiences.

But in the interviews, some of Castro's ex-relatives said he frequently flashed his compulsions for secrecy and terrifying rage that often led him to beat his common-law wife, Grimilda Figueroa.

Figueroa left Castro years ago and died in 2012 after a long illness. Their early years together were happy, but something inside Castro snapped after the birth of their first child, they said.

Castro pushed her down the stairs, fractured her ribs, broke her nose several times, cracked a tooth and dislocated both shoulders, they said. In one incident, he shoved Figueroa into a cardboard box and closed the flaps over her head, they said. He kept her and children imprisoned, cut off from friends and family, and Figueroa couldn't even unlock her own front door, they said.

Figueroa filed domestic-violence complaints, accusing Castro of threatening many times to kill her and her daughters. She charged that he frequently abducted the children and kept them from her, even though she had full custody, with no visitation rights for Castro.

"When I go over there to visit her, and I ask her, 'Nilda, I'm here, open the door,' she's like, 'I can't. Ariel has the key,'" Figueroa's sister, Elida Caraballo, recalled.

Two of the women freed from Castro's home, including the one who gave birth to the girl, returned to relatives' houses earlier this week. The third woman, Michelle Knight, was released from a hospital Friday with a request that her privacy be respected.

"Michelle Knight is in good spirits and would like the community to know that she is extremely grateful for the outpouring of flowers and gifts," the statement said.

On Friday, Knight's grandmother, Deborah King, visited the home of one of the captives, Gina DeJesus, to meet the DeJesus family.

She said she loved and missed Knight, "And if I get to, she's going to get the biggest hug and kiss from me that she ever did have."

A police report alleged that Castro impregnated one of his captives at least five times and made her miscarry by starving her and punching her in the stomach. The report also said another one of the women, Amanda Berry, was forced to give birth in a plastic kiddie pool.

Tests by the state attorney general's office on a sample of Castro's DNA confirmed he fathered Berry's 6-year-old daughter, who was rescued from his house, the office said Friday. After her release, the girl returned home with the 27-year-old Berry. Officials also were entering the DNA profile into a national database to see if it links him to other crimes.

The three women said Castro chained them up in the basement but eventually let them live on the home's second floor. Each woman told a similar story about being abducted after accepting a ride from him.

The FBI has not recovered human remains in its search of the house, spokeswoman Vicki Anderson said Friday. Agents removed more than 200 pieces of evidence, she added, declining to say what was found.

Berry and former captive Gina DeJesus, 22, went home with relatives Wednesday.

The AP does not usually name people alleging sexual assault without their consent, but the names of the three women were widely circulated by their families, the media and law enforcement for years.

___

Associated Press writers Meghan Barr, Mike Householder, Thomas J. Sheeran and Andrew Welsh-Huggins and AP freelance writer John Coyne in Cleveland; Brendan Farrington in Florida; and Dan Sewell in Cincinnati contributed to this report along with news researcher Rhonda Shafner in New York.

Source: http://news.yahoo.com/dna-test-shows-ohio-kidnap-suspect-fathered-girl-062758995.html

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Quantum Computer Kicks PC Ass in First Ever Head-to-Head Test

Scientists often claim that quantum computers will blow the competition away in the coming years?and now the world's first head-to-head test has shown they leave regular PCs reeling in their wake.

Quantum computer use the idea of quantum bits, called qubits, that can theoretically take the value of 0 and 1 at the same time?unlike normal digital computers that can only take one state. It's that blurring of 0s and 1s that gives rise to the claims of speed. But while quantum computers sound futuristic, there are already a handful of systems in existence. It's not yet clear that these devices are genuine quantum computers?it's actually impossible to tell whether they genuinely make use of the physics of quantum entanglement when they're running?but they're certainly based on the appropriate theory.

Now, D-Wave, which makes one of these quantum computers, has let Catherine McGeoch of Amherst College, Massachusetts, test it against a "high-end desktop computer". The D-Wave hardware is designed to solve a special kind of optimization problem, by minimizing the solution of a complicated equation?an incredibly common computer science puzzle. New Scientist describes how the competition went:

McGeoch gave each system roughly half a second to find the best solution to a version of the optimisation problem, and repeated the trial with 100 different versions. She then did the experiment for problems involving even more variables and a more complicated equation.

The D-Wave computer found the best solution every time within half a second. The three regular algorithms struggled to keep up for problems with more than 100 or so variables. The best of the three, CPLEX, had to run for half an hour to match D-Wave's performance on the largest problems.

That's 3,600 times longer?quite some difference. Of course, it's debatable as to whether it's a fair test: the quantum computer specializes in solving the problem, whereas the PCs are true all-rounders. But when thrown other kinds of problems, the quantum computer did match or outperform the other computers, too. Evidence, then, that quantum computers really do kick ass?it just might still be a few years before you lay your hands on one. [New Scientist]

Image by D-Wave

Source: http://gizmodo.com/quantum-computer-kicks-pc-ass-in-first-ever-head-to-hea-499681531

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House passes tactical Republican debt bill

By Rachelle Younglai

WASHINGTON (Reuters) - Republicans in the House of Representatives passed a bill on Thursday that would require the Obama administration to prioritize government debt payments and retirement benefits if Congress fails to reach a deal to raise the U.S. debt ceiling.

The legislation is not expected to go anywhere in the Democratic-controlled Senate and the White House has said it will veto the bill, but what is essentially a tactical maneuver will allow the Republicans, who control the House, to argue they have done their best to avoid a potential U.S. credit default.

By the end of next week, the Obama administration will no longer be able to borrow money to fund government operations because Congress has only agreed to extend the government's borrowing authority until May 19.

This will force the U.S. Treasury to start using its limited accounting maneuvers to extend the debt limit but such measures are not permanent and analysts say they could be exhausted by October.

The Republican bill, which passed 221-207 with a few Republicans dissenting and no Democratic support, would allow the U.S. Treasury to borrow more funds to pay the interest and principal on government bonds as well as retirement benefits.

Democrats called it the "pay China first" legislation as the Asian country holds more than $1.2 trillion in U.S. government bonds and is America's largest foreign creditor.

The bill "says we should pay the government of China before we pay our troops, before we pay our veterans, before we pay other bills here in the United States," said Chris Van Hollen, the top Democrat on the House Budget Committee.

But Republicans argued that it would take the threat of default off the table.

"Financial markets ought to be confident that their Treasury bonds are safe, regardless of what political storms are raging in Washington," said Republican Representative Tom McClintock of California, who crafted the original version of the bill.

REPUBLICAN STRATEGY

House Republicans are looking for ways to deal with the debt limit while staying true to House Speaker John Boehner's rule that any debt-cap increase be matched by budget cuts and reforms.

The Republicans have been trying to force the administration to slash government spending and reform Medicare and Social Security benefits in return for an increase in the debt ceiling.

However, with no deal along those lines in sight, some allies of chief Republican tax writer Dave Camp, a representative from Michigan, have floated the idea of linking a debt-limit increase to a revamp of the tax code and lower tax rates.

This would allow lawmakers to skirt the politically painful decisions to cut Medicare and Social Security.

However, it is unclear if mainstream party supporters, much less the conservative faction of the Republican Party, will go along with this.

"It wouldn't be enough," said Kevin Brady, a senior Republican from Texas who is on Camp's tax-writing committee.

He said reform of the Social Security and Medicare benefits programs still would be required.

Camp has been working for more than a year to draft an overhaul of the entire tax code and has vowed repeatedly to move legislation out of his Ways and Means Committee this year.

House Republican are due to hold a meeting next Wednesday to discuss the various options.

(Additional reporting by Kim Dixon; Editing by David Brunnstrom and Bill Trott)

Source: http://news.yahoo.com/house-set-pass-tactical-republican-debt-bill-050736930.html

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Today in History

Today is Friday, May 10, the 130th day of 2013. There are 235 days left in the year.

Today's Highlight in History:

On May 10, 1863, during the Civil War, Confederate Lt. Gen. Thomas "Stonewall" Jackson died of pneumonia, a complication resulting from being hit by friendly fire eight days earlier during the Battle of Chancellorsville in Virginia.

On this date:

In 1774, Louis XVI acceded to the throne of France.

In 1775, Ethan Allen and his Green Mountain Boys, along with Col. Benedict Arnold, captured the British-held fortress at Ticonderoga, N.Y.

In 1865, Union forces captured Confederate President Jefferson Davis in Irwinville, Ga.

In 1869, a golden spike was driven in Promontory, Utah, marking the completion of the first transcontinental railroad in the United States.

In 1913, the U.S. House of Representatives passed a resolution calling upon all federal officials, from the president on down, to wear a white carnation the following day in observance of Mother's Day.

In 1924, J. Edgar Hoover was given the job of FBI director.

In 1933, the Nazis staged massive public book burnings in Germany.

In 1941, Adolf Hitler's deputy, Rudolf Hess, parachuted into Scotland on what he claimed was a peace mission. (Hess ended up serving a life sentence at Spandau prison until 1987, when he apparently committed suicide.)

In 1963, the Rolling Stones recorded their first single for Decca Records in London, covering Chuck Berry's "Come On" (which ended up being redone) and "I Want to Be Loved" by Willie Dixon.

In 1973, the New York Knicks won the NBA Finals, defeating the Los Angeles Lakers in Game 5, 102-93.

In 1984, the International Court of Justice said the United States should halt any actions to blockade Nicaragua's ports (the U.S. had already said it would not recognize World Court jurisdiction on this issue).

In 1993, members of the Senate Armed Services Committee visited the Norfolk Naval Base in Virginia for a hearing on the issue of homosexuals in the military; most of the sailors who spoke said they favored keeping the ban on gays. At least 188 workers were killed in a doll factory fire in Bangkok, Thailand.

Ten years ago: The leader of Iraq's largest Shiite (SHEE'-eyet) Muslim group, Ayatollah Mohammad Baqir al-Hakim (BAH'-keer ahl hah-KEEM'), returned triumphantly to his U.S.-occupied homeland after two decades in Iranian exile. The New York Times announced on its website that one of its reporters, Jayson Blair, had "committed frequent acts of journalistic fraud."

Five years ago: Barack Obama erased Hillary Rodham Clinton's once-imposing lead among Democratic superdelegates as he added endorsements from Utah, Ohio and the Virgin Islands. A tornado in Picher, Okla., killed at least seven people. Jenna Bush married Henry Hager, the son of a Virginia Republican party official, at the Bush family ranch in Crawford, Texas.

One year ago: Republican presidential candidate Mitt Romney apologized for "stupid" high school pranks that might have gone too far and moved quickly to stamp out any notion that he'd bullied schoolmates because they were gay. JPMorgan Chase said it had lost $2 billion in six weeks in a trading portfolio designed to hedge against risks the company took with its own money. In Syria, twin suicide car bombs exploded outside a military intelligence building, killing 55 people. Carroll Shelby, 89, the legendary car designer, died in Dallas.

Today's Birthdays: Author Bel Kaufman ("Up the Down Staircase") is 102. Author Barbara Taylor Bradford is 80. Rhythm-and-blues singer Henry Fambrough (The Spinners) is 75. TV-radio personality Gary Owens is 74. Actor David Clennon is 70. Writer-producer-director Jim Abrahams is 69. Singer Donovan is 67. Singer Dave Mason is 67. Actor Bruce Penhall is 56. Former Sen. Rick Santorum, R-Pa., is 55. Actress Victoria Rowell is 54. Rock singer Bono (BAH'-noh) (U2) is 53. Rock musician Danny Carey (Tool) is 52. Actor Darryl M. Bell is 50. Playwright Suzan-Lori Parks is 50. Model Linda Evangelista is 48. Rapper Young MC is 46. Actor Erik Palladino is 45. Rock singer Richard Patrick (Filter) is 45. Actor Lenny Venito is 44. Actor-singer Todd Lowe is 41. Country musician David Wallace (Cole Deggs and the Lonesome) is 41. Actress Andrea Anders is 38. Race car driver Helio Castroneves is 38. Rock musician Jesse Vest is 36. Actor Kenan Thompson is 35. Rhythm-and-blues singer Jason Dalyrimple (Soul For Real) is 33. Rock musician Joey Zehr (The Click Five) is 30. Singer Ashley Poole (Dream) is 28. Actress Odette Annable is 28. Actress Lauren Potter is 23. Olympic gold medal swimmer Missy Franklin is 18.

Thought for Today: "The art of being wise is the art of knowing what to overlook." ? William James, American psychologist and philosopher (1842-1910).

(Above Advance for Use Friday, May 10)

Source: http://news.yahoo.com/today-history-050206767.html

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