Rondo leads Celtics past Nets 93-76

NEW YORK (AP) — Rajon Rondo lost his cool, and any chance at history, in the second quarter when Boston last met Brooklyn.

This time, the second period featured some of the best basketball the Celtics have played this season.

Rondo scored 19 points in his first full game against the Nets this season, and the Celtics won 93-76 on Tuesday in another game with some heated moments between the division rivals.

Rondo, sidelined in the first meeting and thrown out of the second after shoving Nets forward Kris Humphries into the courtside seats, outplayed counterpart Deron Williams and helped the Celtics take control early.

"We moved the ball; we rebounded the ball," Rondo said. "They beat us pretty bad on the glass, so tonight we did an exceptional job on the glass, taking care of the defensive rebounds, and we got stops."

A month after the teams scuffled in Boston, there was another skirmish in the fourth quarter that resulted in four technical fouls. But that was the most fight the Nets put up in a disappointing performance on the national stage of the Christmas opener. They were never in the game after the first 20 minutes, and their fans headed to the exits with under 2 minutes left as a "Let's go Celtics!" chant broke out.

"It was a big game for us. It was a division rival. We were ready for a big game. It just didn't happen," Williams said.

Rookie Jared Sullinger tied a career high with 16 points and Jeff Green had 15 for the Celtics (14-13), who avoided falling under .500 with just their second victory in six games.

The Celtics took control with a 23-5 run in the second quarter of the opener of their four-game road trip. They had 11 assists on 13 baskets and outscored the Nets 34-18 in the period after dropping the previous two meetings.

"It was good to get off to this start. It was good to finally play from start to finish, especially with the way we've been playing against Brooklyn," said Paul Pierce, who had just eight points on 3-of-10 shooting. "So it was a well-balanced game, but I'm happy with the start of the trip."

Gerald Wallace and Brook Lopez each scored 15 for the Nets, who have lost four of five. Struggling to find anything that worked, they played Lopez and fellow center Andray Blatche together with three guards at one point, but Brooklyn shot just 41 percent and committed 20 turnovers that led to 25 points.

Williams had only 10 points on 3-of-7 shooting and Joe Johnson, his partner in a high-priced backcourt, shot 4 of 14 for his 12 points.

"This one hurts. We didn't play our game. They beat us from the opening tip," Wallace said. "We didn't make shots. We turned the ball over too easy. Our defense just wasn't there tonight. We were not ourselves tonight."

Boston's Kevin Garnett had eight points and 10 rebounds on the day he tied Charles Oakley for 15th place on the NBA's career list with his 1,282nd game. He was also front and center when things got testy.

Wallace was fouled with 9:31 remaining and appeared to hold onto Garnett's uniform to balance himself and not fall. Garnett was fine with that but then objected to how long Wallace hung on to his shorts, and they said something to each other as they tried to push themselves free. That led to technical fouls on the two, along with Blatche and Courtney Lee.

Garnett said he asked Wallace what he was doing but got no response.

"I don't know where in America you can (yank) somebody's pants off, or shorts off. I don't know what the hell was going on," Garnett said.

Sullinger delivered a flagrant foul on Wallace a few minutes later, but there was nothing further.

In the Nets' Nov. 28 victory in Boston, Rondo, Humphries and Wallace were ejected.

It was the second quarter of that game where things got away from the Celtics, and Rondo's frustrations soon followed when he shoved Humphries after the Nets forward fouled Garnett. That ruined the point guard's chance to extend what was then a 37-game streak with double-digit assists, tied for second-longest ever, by finishing with three. He had five assists and six rebounds Tuesday.

This time, the second period belonged to the guys in green.

With the Celtics down three, Green had six points in a 10-0 run that made it 36-29. After Johnson's basket, Boston answered with a 13-3 spurt. Jason Terry made a 3-pointer before Rondo converted a three-point play to push the Celtics' lead to 49-34 with 3:56 to go.

The Celtics opened a 21-point lead early in the third quarter and cruised from there. Terry finished with 11 points.

Notes: As with everyone playing on Christmas, players, coaches and referees wore green ribbons in tribute to the families of Sandy Hook Elementary School. ... Humphries was out with an abdominal strain and will be re-evaluated after the Nets return from Milwaukee. He had mostly been a starter but then didn't play at all Sunday against Philadelphia. ... Feeling Avery Bradley isn't ready yet, Celtics coach Doc Rivers decided not to bring the guard on the road trip so he can continue working his way back from shoulder surgery in Boston. Rivers said the shoulder is strong but that Bradley has had only 2½ practices.

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Square Feet: Moving Ahead to Update the Pier 17 Mall

Nearly two months after Hurricane Sandy devastated the South Street Seaport on the East River in Lower Manhattan, Dumpsters still line its cobblestone streets and nearly all of the stores west of the Franklin D. Roosevelt Drive remain closed.

But the storm surge largely spared Pier 17, the seaport’s long-maligned shopping mall to the east. The operators of the mall, the Howard Hughes Corporation of Dallas, say it escaped damage because it is three feet above the pier, which in turn sits well above the water. And so, the company, which holds the ground lease to the city-owned pier, is moving forward with its plans to transform its dated festival marketplace into an open and airy three-story retail and entertainment center.

The local community board voted last month to support the proposal, despite reservations about the signage and some other design features. Though the plan is still working its way through the city’s land use process, the developer’s agreement with the city Economic Development Corporation requires that construction begin on July 1. David R. Weinreb, the chief executive of Howard Hughes, said in a telephone interview that the company would meet that deadline.

After being blocked off by metal gates and closed until this month because of concerns about the stability of the pier, the mall is now open, though some stores are still closed. Inspectors from Halcrow, an international engineering company hired by Howard Hughes, recently determined that the structure was sound. The pier is south of the Brooklyn Bridge, just beyond Fulton Street.

“The pier got a solid rating,” Christopher J. Curry, a senior executive vice president at Howard Hughes, said in a recent interview at the company’s offices on Fulton Street. City officials confirmed that no problems were found at the pier.

In addition to Pier 17, the company controls 170,000 square feet of space further inland at the seaport, including stores like Brookstone, Ann Taylor and Coach, which suffered extensive storm damage.

“We’re working diligently to remediate the shops,” Mr. Weinreb said. Asked whether the closed stores would remain at the seaport, he said, “We’re in discussions with our tenants about what is in their best interests. Many of those tenants enjoy very good sales and fully expect and want to be back open.”

From the mid-1980s to the early ’90s, the seaport was a big draw, especially for young people, who crowded its bars and restaurants. But then it fell out of favor with New Yorkers, though it has remained a must-see for visitors taking in other downtown sites, retail specialists said.

The operators of the mall at Pier 17 have long wanted to give it more cachet with city residents. Shortly before the economic crisis, a previous owner, General Growth Properties, a mall developer, introduced a much more ambitious plan for the seaport, including a 42-story tower, which was unpopular with residents.

The Howard Hughes Corporation, which is primarily known for its vast master-planned communities like Summerlin, near Las Vegas, acquired the shopping center in 2010, when it was spun off from General Growth as the mall company was emerging from bankruptcy.

Completed in 1985, the Pier 17 shopping center was developed by the Rouse Company, the creator of marketplaces in Boston and Baltimore. (General Growth bought Rouse in 2004.)

But by the time the mall opened, the marketplace concept may already have been outmoded. The existing mall “has basically been a disappointment to everyone over its life,” Hardy Adasko, a senior vice president for planning at the city Economic Development Corporation, testified last week at a City Planning Commission hearing. His agency sees the redevelopment of the pier as a way of advancing its long-term investment in the waterfront, he said.

In contrast to the marketplace design, which was intended to shield visitors from the grittiness of the port, the new structure will capitalize on its waterfront location, offering abundant views of the bridge. Outdoor space on either side of the pier also will be enhanced.

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Sprint salesman refuses to sell iPhone to customer, says his ‘fingers are too fat’ to use it

We’ve known for a while now that some mobile carriers have been instructing their sales staff to start pushing their customers away from Apple’s (AAPL) iPhone and toward Android or Windows Phone devices. The reason is simple: carriers pay a lot more to subsidize Apple’s popular smartphone than they do with other devices and they’d prefer to have higher gross margins at the end of each quarter. But now a Tom’s Hardware reader reports that a Sprint (S) representative has taken pushing non-iPhone products to a whole new level and is actually insulting people who insist on buying the device.

[More from BGR: Online retailers caught using ‘discriminatory’ practices to target shopping discounts]

When the customer told the Sprint representative that he wanted to get an older iPhone 4 for free as part of his upgrade, the representative called the device “a piece of s—” that breaks too easily and is too small for many users.

[More from BGR: First photos of BlackBerry 10 ‘N-Series’ QWERTY smartphone leak]

Instead, the salesman recommended that the customer by a Samsung (005930) Galaxy S III. When the customer again refused, the salesman took things a step farther and told the man that his fingers were simply too fat to use the iPhone and that he’d need a larger screen to use a smartphone properly.

Needless to say, these up-sell-by-insult tactics weren’t exactly effective for the salesperson and the customer angrily stormed out of the store without buying a new phone.

This article was originally published by BGR

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Gaza Cease-Fire Expands Fishing Area, but Risks Remain

Relaxed Rules Restore Old Opportunities:
As a part of last month's cease-fire agreement between Hamas and Israel, Gazans can now fish 6 miles off the coast, doubling the previous limit.

GAZA CITY — Khader Bakr, a 19-year-old fisherman, was thrilled to hear that he could now fish up to six nautical miles from the coast, up from the three-mile limit Israel had had in place since 2009. The change was part of the cease-fire deal that halted last month’s fighting in Gaza between Israel and Hamas.

But testing the waters late last month, Mr. Bakr apparently sailed out too far. An Israeli gunboat patrolling against arms smuggling ordered him to stop and strip to his underwear. As the Israelis sank his boat, he jumped into the sea, and was hauled aboard the Israeli vessel for questioning.

“I spent four hours trembling,” he said, before the Israelis ordered another Palestinian fishing boat to ferry Mr. Bakr back to shore.

Run-ins with Israeli patrols are still the bane of Gaza fishermen. But in most respects, the new arrangement has been a boon.

The fishermen have raced to take advantage of broader fishing grounds, farther from the shore where sewage is pumped into the water untreated. Catches have improved in quantity, quality and freshness, and thus price. The fish are bigger and include desirable species like grouper, red mullet and Mediterranean sea bass that were no longer present closer to land.

But the fisherman risk rapidly overfishing. “In the first few days, I caught fish worth $1,580 to $1,850,” said Yasser Abu al-Sadeq. “Today, I made around $1,050.” But the situation is still better, he said. “Before the cease-fire, I would barely catch $790.”

“It’s like when you come to a house that’s been abandoned for years and start cleaning it,” he said. “When you start cleaning, you get out a lot of trash, but when you clean daily, you get out only a little.” He and his crew go out for 24 hours at a time, he said, cooking the small crabs and squid they catch in the nets. He described an early trip out past the six-mile limit, when an Israeli gunboat circled his boat, shaking it in the wake, and ordered him back toward shore.

He remembers a golden time before the second Palestinian intifada in 2000, when he could go out as far as 12 nautical miles, where he could find sardines and what he called guitarfish, a small ray. “There, it’s a reserve protected by God,” he said.

The fishermen say they estimate their distance, since most of them lack precise navigational systems, but there is usually one indicator. “When we were allowed within 3 miles, the gunboats would attack us at 2.5 miles,” said Monzer Abu Amira, as he repaired his green nylon nets. “Today, they hit us when we are at 5.5 miles.”

The Israelis generally use loudspeakers and water cannons, but sometimes they shoot live ammunition at fishing gear, the motor or the boat itself. Gazans in principle can apply for compensation if boats are damaged or destroyed, but in practice few do.

A senior Israeli official said that there had never been an official announcement that the fishing limit had been extended from three miles to six, but he confirmed that six was the new reality. Israel is continuing to negotiate indirectly with Hamas, the Islamist movement that rules Gaza, with Egypt as an intermediary, to turn the cease-fire agreement into something more permanent, the official said.

“We have an interest in prolonging the longevity of the quiet,” the official said. “We understand that relaxation of some of the restrictions is conducive to that goal. Quiet is in our interest. So we have an interest in showing flexibility where we can, and to show the Egyptians that we’re serious.”

There were problems in the period immediately after the cease-fire, the Israeli official said, because “some in Gaza were interested in testing the limits and pushing the envelope,” and because the expansion of the fishing zone meant deploying more Israeli resources to cover more sea.

“But if people don’t exceed the six-mile limit, it’s O.K.,” he said.

The Israelis are not interested in the smuggling of small-caliber weapons like “Kalashnikovs and bullets,” he added, but in preventing Iran from resupplying longer-range missiles and preventing Hamas from smuggling in foreign experts to aid them in missile development and technology.

“The important thing for us is to prevent Hamas from rearming,” he said.

Ed Ou contributed reporting.

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Measles: Measles Epidemic Is Spreading in Central Africa

Jehad Nga for The New York Times

An internally displaced persons camp in Goma, in the Democratic Republic of Congo. In addition to recent violence in the country, a spreading measles epidemic is further endangering the lives of thousands of children there.

A large measles epidemic is spreading in Central Africa, endangering the lives of thousands of children, the medical charity Doctors Without Borders warned last week.

Since October, the charity has vaccinated more than 226,000 children in the eastern part of the Democratic Republic of Congo. The organization has also treated nearly 13,000 Congolese for the effects of the disease.

Measles is very contagious. In places where many children are malnourished and vitamin-deficient, it kills 1 percent to15 percent of those who don’t receive medical care, Doctors Without Borders estimated. (Even in the United States in the 1990s, although cases were rare, the fatality rate was 0.3 percent, according to the Centers for Disease Control and Prevention. In AIDS patients, the rate is 30 percent.)

The eastern Congo basin has serious shortages of medical workers and of drugs. While there is no treatment for measles itself, antibiotics can save those who develop pneumonia, meningitis or other secondary infections. Measles can also cause blindness by scarring the eyeball.

The outbreak is taking place despite enormous success against the disease worldwide. According to a study released earlier this year, deaths from measles have dropped by almost 75 percent since 2000.

Most of the lives saved were in Africa and India. Measles shots are often cited as one of the chief reasons that deaths of children under age 5 around the world have fallen steadily.

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Sri Lanka arrests 100 Chinese for cyber fraud, police say

COLOMBO (Reuters) – Sri Lanka on Saturday arrested at least 100 Chinese nationals accused of an internet fraud scheme targeting people in their home country, a police spokesman said.

The accused, all in Sri Lanka on tourist visas, are suspected of hacking into computers in China and then demanding their owners transfer them money, police spokesman Prishantha Jayakodi told Reuters.

Chinese police requested help from Sri Lanka, he said.

Officials at the Chinese embassy in Colombo were not available for comment.

China has been the top lender to Sri Lanka since the end of a 25-year war in May 2009 and thousands of Chinese are working in the country on Chinese-funded infrastructure projects.

(Reporting by Shihar Aneez; editing by Jason Webb)

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Syrian Airstrikes Reportedly Kill Dozens at Bakery

BEIRUT, Lebanon — A Syrian warplane was reported to have conducted airstrikes that killed dozens of people lined up for bread at a bakery in the central town of Hilfaya, according to antigovernment activists in the area.

The attack, and its toll, could not immediately be confirmed. Samer, a local activist in the town, said he ran to the bakery soon after he heard a warplane, followed by bomb explosions and finally the sound of ambulances. “There were bodies everywhere,” he said, adding that he saw tens of bodies taken away in cars.

Photographs he said he took at the bakery showed bodies in a heap on a bloody sidewalk outside a low-slung building that was blackened with soot and stained with patches of blood, high on the walls. Amateur video showing what activists said was the aftermath of the attack showed roughly a dozen people lying on the ground, some wounded and several apparently dead.

In one of Samer’s photograph, a man stared in shock at the scene, with his hands resting on his head, while another carried body parts. Bystanders searched for survivors under rubble from the building. Another man picked up a piece of bread, lying next to someone’s slippers.

The reason for the attack was unclear, but activists said that rebel fighters occupied Hilfaya last week as part of a broader offensive to seize territory around the city of Hama, where the government has kept tight control after suppressing protests in the city last year.

Civilians have been caught between the two sides. On Friday, rebel fighters posted a video threatening to attack Christian villages with artillery while asserting that the residents were shielding government loyalists. In the last few days, Hilfaya has come under repeated shelling from loyalist positions in a neighboring village, activists said.

The bakery was one of three in the city. When word spread on Sunday that a flour shipment from Turkey had come in, people began lining up around noon, waiting for their turn at its windows for bread after a stretch of days when the bakeries had been idled. At least three bombs fell near the bakery, Samer and other activists said.

The attack came as the international envoy to Syria, Lakhdar Brahimi, arrived in the capital, Damascus, where he was expected to meet with President Bashar al-Assad. His visit had been rumored but not previously announced, signaling concerns about security as the fighting between opposition fighters and the government intensified in the capital.

Mr. Brahimi made no public comment on Sunday, and the Syrian information minister said during a news conference that he had no knowledge of the envoy’s visit. Mr. Brahimi traveled by land from Beirut because of fighting between the rebels and government forces near the Damascus airport, Lebanese airport officials told The Associated Press.

His visit was likely to add fuel to the speculation about a deal to remove Mr. Assad from power. Rebel forces have claimed gains near government strongholds, and international aid agencies are warning of a growing humanitarian crisis in the winter months.

Russia, one of Syria’s most reliable allies, has recently sent signals that it is distancing itself from the Syrian president. On Saturday, the Russian foreign minister, Sergey V. Lavrov, said several countries in the region had offered Mr. Assad asylum, while adding that Moscow was not willing to mediate on their behalf.

Ellen Barry contributed reporting from Moscow; Hala Droubi from Jidda, Saudi Arabia; and Hwaida Saad from Beirut.

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Bengals clinch playoff spot, edge Steelers 13-10

PITTSBURGH (AP) — Andy Dalton and A.J. Green have the Cincinnati Bengals back in the postseason.

Dalton hit Green for a 21-yard pass in the final moments, setting up Josh Brown's 43-yard field goal with 4 seconds remaining. That lifted the Bengals over the Pittsburgh Steelers 13-10 on Sunday, sending Cincinnati into the playoffs for a second straight season.

It's the first time since 1981-82 that Cincinnati made the playoffs in consecutive years — and the first time not involving a strike season.

Brown missed a 56-yarder earlier in the quarter. He earned a second chance when Reggie Nelson picked off Ben Roethlisberger and returned it to the Pittsburgh 46 with 14 seconds remaining. Andy Dalton found Green down the right sideline, setting up Brown's winner.

Dalton completed 24 of 41 for 278 yards and two interceptions for the Bengals (9-6), who snapped a five-game losing streak to Pittsburgh (7-8). Green caught 10 passes for 116 yards for Cincinnati.

Roethlisberger completed 14 of 28 passes for 220 yards with a touchdown and two interceptions, including his costly mistake in the final seconds that ended Pittsburgh's playoff hopes. It marked the second straight week a Roethlisberger pick cost the Steelers: He threw an interception on the second play of overtime in last week's loss at Dallas.

The Steelers needed to win out to play into January, but couldn't manage any momentum against a Cincinnati defense that gave Roethlisberger problems all afternoon. The Bengals sacked Roethlisberger four times and allowed Pittsburgh to complete just 2 of 14 third downs.

Cincinnati wasn't much better, managing all of 14 yards rushing against the NFL's top-ranked defense. But Dalton and Green worked just enough magic.

Pittsburgh did a decent job of keeping Dalton and Green in check, forcing a season-high three turnovers and making a season-high six sacks. But the offense couldn't take advantage.

Still, the Steelers had one last chance when they took over with 44 seconds left. Roethlisberger rolled right and tried to hit Mike Wallace down the sideline. The ball sailed over Wallace's head and into the arms of Nelson, who had dropped an earlier pick.

It was just enough time for Dalton and Green to get together one last time and help Cincinnati take one more step away from its mediocre past.

The Steelers, meanwhile, head into next week's season finale trying to avoid their first losing season under coach Mike Tomlin after falling for the fifth time in six games.

Both teams squandered opportunities earlier in the fourth quarter.

The Bengals drove into Pittsburgh territory before stalling at the Steelers 38. Cincinnati coach Marvin Lewis sent out Brown to attempt a 56-yard field goal into the tricky Heinz Field winds.

The kick was never close, giving the Steelers premium field position with 3:18 left.

Pittsburgh, however, had its own kicking issues. The Steelers moved to the Cincinnati 36, then brought out Shaun Suisham for a 53-yard attempt that was short all the way.

The Steelers spent the week insisting they play their best when backed into a corner, then spent most of the first half getting pushed around by the Bengals. Roethlisberger, who had been critical of offensive coordinator Todd Haley after the loss to Dallas, struggled getting into a rhythm.

The quarterback had voiced concern over the inability to get the ball to tight end Heath Miller against the Cowboys and tried to make up for it early. Cincinnati was waiting.

Leon Hall stepped in front of a crossing pass to Miller late in the first quarter and sprinted 17 yards for a touchdown to give the Bengals the lead. Pittsburgh, fueled by the return of running back Rashard Mendenhall following a one-game suspension for conduct detrimental to the team, drove deep into Cincinnati territory only to have Suisham shank a 24-yard field goal wide left following a botched snap.

The Bengals eventually went up 10-0 on a 41-yard field goal by Brown late in the second quarter before the Steelers finally found some life. Brown streaked down the sideline for a 60-yard touchdown catch to pull Pittsburgh within 10-7.

___

Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL

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Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct

C.J. Gunther for The New York Times

Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.

For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.

Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.

No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.

And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”

At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.

Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.

“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.

The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.

The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”

Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.

Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.

The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?

In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.

But Nutlins did not work as drugs because they were not absorbed into the body.

Roche, Merck and Sanofi persevered, testing thousands of molecules.

At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.

The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.

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Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct

C.J. Gunther for The New York Times

Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.

For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.

Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.

No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.

And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”

At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.

Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.

“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.

The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.

The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”

Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.

Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.

The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?

In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.

But Nutlins did not work as drugs because they were not absorbed into the body.

Roche, Merck and Sanofi persevered, testing thousands of molecules.

At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.

The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.

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