Lakers snap Christmas Day streak with win over Knicks

Lakers 100, Knicks 94 (final)

The Lakers closed out the New York Knicks on Christmas Day to win their fifth in a row, avenging a Dec. 13 loss in New York, the low point of the season during a four-game losing streak. 

The Lakers haven't dropped a game since.

With the Lakers up by three points, Pau Gasol found a lane to the basket from the high post and flushed down a dunk to seal the victory with 11.6 seconds left.  Steve Nash, in his second game back from a leg injury, scored 16 points and dished 11 assists.

The Lakers shot 48.1% from the field but it was their defense that was instrumental in the victory, holding New York to only 16 points in the fourth quarter.

The Knicks shot 42.7% from the field despite 34 from Carmelo Anthony (13-23 shooting), who exploded in the third quarter to give the Knicks a nine-point lead.  The Lakers never led by more than five points.

Kobe Bryant also scored 34 points on 14-for-24 shooting.  Metta World Peace fouled out after scoring 20.  For the second consecutive game, Pau Gasol had six assists.

Knicks center Tyson Chandler also fouled out, finishing with six points and nine rebounds.  J.R. Smith helped carry the offensive load for New York with 25 points.

The Lakers will play on Wednesday night against the Nuggets in Denver.

Knicks 78, Lakers 77 (end of third quarter)

The Lakers survived a 17-point quarter from Carmelo Anthony to close to within one point after three quarters.

Falling behind by as many as nine points after halftime, the Lakers had a chance to go up by a point but Kobe Bryant missed a pair of free throws with 2.6 seconds left in the quarter.

Anthony climbed to 27 points for the game on 11-for-20 shooting while his Knicks shot 43.8% through three.  J.R. Smith contributed 20 points off the bench.

The Lakers were led by Bryant's 26 points on 11-for-18 shooting, while getting 18 points from Metta World Peace and 14 from Steve Nash.

Some of New York's lead was earned from behind the three-point line with eight makes in 22 tries.  The Lakers shot 48.3% from the field but only five of 18 (27.8%) from three-point range.

World Peace started the second half in place of Darius Morris but Anthony had the hot hand.

Lakers 51, Knicks 49 (halftime)

For the second consecutive quarter, the Lakers closed well against the Knicks. After New York's reserves had helped push the Knicks to a six-point advantage, the Lakers rallied to take a two-point lead at halftime.

Carmelo Anthony and Metta World Peace battled through a very physical period, challenging each other in the post. Anthony finished the half with 10 points while World Peace had a game-high 16 points after coming off the Lakers' bench.

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Jessica Simpson’s Christmas gift: She’s pregnant

NEW YORK (AP) — Jessica Simpson‘s daughter has the news all spelled out: “Big Sis.”

Simpson on Tuesday tweeted a photo of her baby daughter Maxwell playing in the sand, the words “Big Sis” spelled out.

The 32-year-old old singer and personality has been rumored to be expecting again. The tweet appears to confirm the rumors.

“Merry Christmas from my family to yours” is the picture’s caption. Simpson used a tweet on Halloween in 2011 to announce she was pregnant with Maxwell. She is engaged to Eric Johnson and gave birth to Maxwell in May.

One possible complication regarding her pregnancy: She is a spokeswoman for Weight Watchers.

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Dueling Santa trackers are off and running

A screen grab from Google's Santa Tracker. (Google / December 24, 2012)

By Deborah Netburn

December 24, 2012, 1:11 p.m.

All year long Santa keeps an eye on you. Now it's time to turn the tables.

One day a year, you are invited to keep an eye on Santa as he whips around the world in his sleigh, delivering a dizzying number of presents to children all over the world.

If you'd like to see where Santa is at the moment, you've got choices. Google and NORAD, which used to team up for your Santa tracking pleasure, have gone their separate ways this year and created two distinct tracking options.

Google's Santa Tracker is the slicker of the two. It takes you to Santa's Dashboard, where you can see Santa's current location, his next location, the number of miles traveled, and the number of presents delivered. Santa is also adding Twitter like status updates. The most recent one as of this writing: "Rudolph's nose just turned red." 

PHOTOS: Google Doodles of 2012

You can also click on the map and see where Santa has been, as noted by little present icons on the map. Click on the icon and you'll see how many presents Santa has delivered in each city. When Santa is on the move, you'll see him flying on the map in a sleigh. When he's stopped to deliver presents, you'll see him shoving presents down a chimney.

Over at the official NORAD Tracks Santa website you'll also find a running tally of how many presents Santa has delivered as well as what city he just left and what city he's currently headed toward. NORAD also offers Santa Cams that show animations of Santa flying around the world. 

Both Santa tracking services offer loads of extras. If you visit Santa's Village on Google's tracker you can send a message from  Santa to a friend or family member. And NORAD has more than 1,200 volunteers staffing a Santa hotline to answer all your Santa questions.  (877-HI-NORAD).

In the spirit of the season you might try them both out, but hurry up. The trackers shut down a few hours before Christmas morning. 

Happy tracking!

ALSO:

Rumored iPad 5 to be thinner -- and land in March

Battle of the Santa trackers: Google takes on NORAD

deborah.netburn@latimes.com

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Find room for God in fast-paced world, pope says on Christmas eve

VATICAN CITY (Reuters) – Pope Benedict, leading the world’s Roman Catholics into Christmas, on Monday urged people to find room for God in their fast-paced lives filled with the latest technological gadgets.

The 85-year-old pope, marking the eighth Christmas season of his pontificate, celebrated a solemn Christmas Eve mass in St Peter’s Basilica, during which he appealed for a solution to the Arab-Israeli conflict and an end to the civil war in Syria.

At the mass for some 10,000 people in the basilica and broadcast to millions of others on television, the pope wove his homily around the theme of God’s place in today’s modern world.

“Do we have time and space for him? Do we not actually turn away God himself? We begin to do so when we have no time for him,” said the pope, wearing gold and white vestments.

“The faster we can move, the more efficient our time-saving appliances become, the less time we have. And God? The question of God never seems urgent. Our time is already completely full,” he said.

The leader of the world’s some 1.2 billion Roman Catholics said societies had reached the point where many people’s thinking processes did not leave any room even for the existence of God.

“Even if he seems to knock at the door of our thinking, he has to be explained away. If thinking is to be taken seriously, it must be structured in such a way that the ‘God hypothesis’ becomes superfluous,” he said.

“There is no room for him. Not even in our feelings and desires is there any room for him. We want ourselves. We want what we can seize hold of, we want happiness that is within our reach, we want our plans and purposes to succeed. We are so ‘full’ of ourselves that there is no room left for God.”

PEACE CANDLE

Bells inside and outside the basilica chimed when the pope said “Glory to God in the Highest,” the words the gospels say the angels sang at the moment of Jesus’ birth.

Earlier on Monday the pope appeared at the window of his apartments in the apostolic palace and lit a peace candle, as a larger-than-life nativity scene was unveiled in St Peter’s Square below.

Reflecting on the gospel account of Jesus born in a stable because there was no room for Mary and Joseph in the inn, he said when people find no room for God in their lives, they will soon find no room for others.

“Let us ask the Lord that we may become vigilant for his presence, that we may hear how softly yet insistently he knocks at the door of our being and willing.

“Let us ask that we may make room for him within ourselves, that we may recognise him also in those through whom he speaks to us: children, the suffering, the abandoned, those who are excluded and the poor of this world,” he said.

He asked for prayers for the people who “live and suffer” in the Holy Land today.

The pope called for peace among Israelis and Palestinians and for the people of Syria, Lebanon and Iraq and prayed that “Christians in those lands where our faith was born may be able to continue living there, that Christians and Muslims may build up their countries side-by-side in God’s peace.”

The Vatican is concerned about the exodus from the Middle East of Christians, many of whom leave because they fear for their safety. Christians now comprise five percent of the population of the region, down from 20 percent a century ago.

According to some estimates, the current population of 12 million Christians in the Middle East could halve by 2020 if security and birth rates continue to decline.

At noon (1100 GMT/6 AM ET) the pope will deliver his twice-yearly “Urbi et Orbi” (to the city and the world) blessing and message from the central balcony of St Peter’s Basilica.

(Reporting By Philip Pullella; Editing by Myra MacDonald)

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‘Not Fade Away’: An Age Gap Defined by the Rolling Stones

LOS ANGELES (TheWrap.com) – For David Chase, the counterculture revolution that consumed the 1960s was a generational conflict that played out against a soundtrack of killer rock songs.

“The Sopranos” creator is poised to make his film directing debut this week with the release of “Not Fade Away” at the age of 67, but for his first foray into big screen entertainment he is fixated on a younger generation, albeit one from a very different era. The movie centers on a rock band coming of age in New Jersey, and never quite making it to the big time.

It stars John Magaro (a dead-ringer for Bob Dylan), Bella Heathcote (“Dark Shadows”) and “The Sopranos” veteran James Gandolfini, here standing in for exasperated parenthood.

For Magaro, the film is really a distillation of the conflict between art and war – with the younger generation siding more with music, while the older one opted for arms.

“It’s about the threat of nuclear war in the ’60s countered by the life and hope that rock ‘n’ roll gave to a generation,” he said. “It’s the ultimate choice, really.”

That kind of generational clash was never wider than during that tumultuous decade, argues music supervisor and executive producer Steven Van Zandt, who is, after all, something of an authority on the situation thanks to his work with Bruce Springsteen’s E Street Band.

“It’s a little hard to explain to people now, but I don’t think it’s happened before the ’60s, and it hasn’t happened since,” Van Zandt said at a press conference for the film last weekend. “So maybe it was a very unique period of time, but there’s an expression called the generation gap, and it really did exist. It was the only time in history I think where the parents and their own children were completely at odds with each other. They did not relate to each other at all.”

“Not Fade Away” is not a musical, but it is a movie in which music is paramount to the story — indeed, some sections play out almost as music videos for anthems like the Rolling Stones‘ “Lady Jane” or Joey Dee and the Starliters’ “The Peppermint Twist.”

In fact, music is more totemic for the band of aspiring rockers than major historical events like the Vietnam War and the Martin Luther King Jr. assassination that unfold around them and define the decade. Van Zandt claims that kind of tunnel vision reflects his own experience during the period.

“I was there and, you know, it was, like, yeah, civil rights going on, the cities are burning down and assassinations and Vietnam, but let’s get the chords to the new Yardbirds song,” he said.

For the characters, the defining moment instead is not news reports of riots in Watts or shots of bodybags being loaded onto Chinook helicopters. Rather it is the first U.S. national television appearance by the Rolling Stones on “The Hollywood Palace” in 1964 that makes the biggest impression.

During the program, an eye-rolling Dean Martin makes it clear that the Stones’ brand of sensual blues is at odds with his Vegas style crooning.

“I saw that when it happened,” Gandolfini recalled during the press conference. “And I saw my past and future in front of me. Dean Martin making fun of the Rolling Stones. And it was the most important moment of – well, first or second most important moment of my life because the Beatles happened four months earlier, which was the first most important moment of my life.”

To help the twenty-somethings tapped to portray the film’s youthful protagonists understand the impact this music had on Gandolfini’s generation, Paramount, the studio behind the film, sent them dozens of records from the likes of the Stones and the Paul Butterfield Blues band. Though Chase joked that many actors auditioning for the roles mispronounced Mick Jagger as Mick Yagar, he found that his troop of actors quickly embraced the music that forms the spine of his movie.

“It’s so much better than what has mass appeal today,” Heathcote told TheWrap. “There’s something about it, particularly with the Stones, they don’t give a s—, they just carried that air, and Mick Jagger and Keith Richards were sexy guys. There was something about them that was original and so timeless.”

It also called for Van Zandt to run a musical boot camp for Magaro and the other actors who make up the band, none of whom played the instruments they were expected to use on screen. After three months of drilling, Magaro said he got the hang of the drums.

“I wouldn’t say I’m the next Ginger Baker, but I was able to play the songs,” he said. “I was lucky, because early rock ‘n’ roll like Chuck Berry and the Kinks used really simple beats.”

It all builds up to a final evocative image of a young girl, the sister of Magaro’s character and the film’s narrator, dancing in the middle of a deserted Sunset Boulevard. As she sways, she talks about the choice between Armageddon and rock. It’s clear, where Chase sides.

“What she says is a thought that I had one time at a Stones concert and it was my way of saying how powerful and how beautiful that music really is,” Chase said.

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Gifts That Keep Giving (if Not Exploding)

Gregory Tobias/Chemical Heritage Foundation Collections

A Chemcraft set from the mid-1950s. More Photos »

Ask scientists of a certain age about their childhood memories, and odds are they’ll start yarning about the stink bombs and gunpowder they concocted with their chemistry sets. Dangerous? Yes, but fun.

“Admittedly, I have blown some things up in my time,” said William L. Whittaker, 64, a robotics professor at Carnegie Mellon University who unearthed his first chemistry set, an A. C. Gilbert, in a junkyard around age 8. By 16, he was dabbling in advanced explosives. “There’s no question that I burned some skin off my face,” he recalled.

Under today’s Christmas tree, girls and boys will unwrap science toys of a very different ilk: slime-making kits and perfume labs, vials of a fluff-making polymer called Insta-Snow, “no-chem” chemistry sets (chemical free!), plus a dazzling array of modern telescopes, microscopes and D.I.Y. volcanoes. Nothing in these gifts will set the curtains on fire.

“Basically, you have to be able to eat everything in the science kit,” said Jim Becker, president of SmartLab Toys, who recalled learning the names of chemicals from his childhood chemistry set, which contained substances that have long since been banned from toys.

Some scientists lament the passing of the trial-and-error days that inspired so many careers. “Science kits are a lot less open-ended these days,” said Kimberly Gerson, a science blogger who lives outside Toronto. “Everything is packaged. It’s either ‘yes’ or ‘no.’ If you don’t get the right result, you’ve done it wrong and you’re out of chemicals.”

Others, though, say the new crop of science toys — even with their cartoonish packaging and heavy emphasis on neon goo — actually represent progress. More entertaining, educational and accessible than earlier products, which relied heavily on a child’s inner motivation, these toys may actually help democratize the learning of science and introduce children to scientific methods and concepts at an earlier age.

“I grew up in the 1960s, and a lot of the chemistry sets were kind of boring,” said William Gurstelle, a science and technology writer. “You’d go through the book, and at the end of the experiment you’d get some light precipitate at the bottom of the beaker. Maybe at most it changes color or something.”

Mr. Gurstelle’s books, which include “Whoosh Boom Splat” and “Backyard Ballistics,” teach people how to make dangerous projectiles, like a potato cannon that uses hair spray as launching fluid. But he had high praise for commercial science kits, which show children (among other things) how to make slime.

Jeff Swensen for The New York Times

William L. Whittaker at the Planetary Robotics Lab at Carnegie Mellon University surrounded by the robots he has created.

“Well, that’s a pretty cool thing to have when you’re done,” Mr. Gurstelle said. “You’re not going to really learn to be a chemist from a chemistry set when you’re in seventh grade; you’re just going to be inspired. The point is that new chemistry sets and new toys are just better, because the manufacturers have figured out how to make them more fun.”

Some toy makers, like SmartLab, Mr. Becker’s company, have used this philosophy to give classic toys a makeover. One of SmartLab’s takes on a chemistry set, for instance, is the Extreme Secret Formula Lab, which comes with “squishy-lidded bubble test tubes” and “an abundance of glow-in-the-dark powder.” The game of Mousetrap has been re-envisioned as the Weird and Wacky Contraption Lab, meant to bring out children’s Rube Goldberg talents. And the slot car tracks that Mr. Becker recalls snapping together in his youth have been translated into a robot called ReCon 6.0, which children can program to roam around.

Mike Kane for The New York Times

Jim Becker of SmartLab Toys.

“What we do is give kids the opportunity to learn through problem solving,” Mr. Becker said.

Of course, technology has also remade the experience of learning science. Children may be more likely to click on a science app than to go play outside.

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Raging fire guts Kabul market

KABUL, Afghanistan -- Firefighters battled through the night to contain a raging fire that swept through a market in the Afghan capital.

No injuries were reported, but the blaze destroyed hundreds of stores and millions of dollars worth of merchandise, Afghan police and firefighters said at the scene. 

Dealers at the neighboring currency exchange, the city’s largest, said they evacuated cash, computer equipment and records from their shops as the flames approached during the night. But in the morning, the market was jammed with people haggling over thick stacks of notes as smoke billowed overhead.

Col. Mohammed Qasem, general director of the Kabul fire department, said he suspected an electrical short was to blame for the fire. 

Gas canisters used to heat the stores propelled the flames, along with the cloth and clothing sold by many of the vendors, Qasem said. “It made it very big in a short time.”

Firefighters from the Afghan defense department and NATO forces were sent to assist. But the city’s notorious traffic and the market’s narrow lanes made it difficult for responders to maneuver their vehicles, Qasem said.

Abdulrahman, who like many Afghans has only one name, squatted near a fire truck with his head in his hands  as responders aimed a hose at the blackened ruins of a building still smoldering at noon Sunday, more than 12 hours after the fire broke out.

He said the building had contained three shops that he owned and a warehouse full of glassware, crockery and kitchen utensils. 

“I lost everything,” he said.

Shirali Khan complained that police hadn't allowed him to remove the goods from his four clothing stores.

“They thought we were all robbers,” he said.  “There’s only ashes left.”

ALSO:

Pope pardons former butler convicted of theft

Bombing kills local official, 7 other people in Pakistan

Tensions high as vote on proposed Egyptian constitution continues

Special correspondent Hashmat Baktash contributed to this report.

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‘Hobbit’ extends No. 1 journey with $36.7 million

LOS ANGELES (AP) — Tiny hobbit Bilbo Baggins is running circles around some of the biggest names in Hollywood.

Peter Jackson’s “The Hobbit: An Unexpected Journey” took in $ 36.7 million to remain No. 1 at the box office for the second-straight weekend, easily beating a rush of top-name holiday newcomers.

Part one of Jackson’s prelude to his “The Lord of the Rings” trilogy, the Warner Bros. release raised its domestic total to $ 149.9 million after 10 days. The film added $ 91 million overseas to bring its international total to $ 284 million and its worldwide haul to $ 434 million.

“The Hobbit” took a steep 57 percent drop from its domestic $ 84.6 million opening weekend, but business was soft in general as many people skipped movies in favor of last-minute Christmas preparations.

“The real winner this weekend might be holiday shopping,” said Paul Dergarabedian, an analyst for box-office tracker Hollywood.com.

Tom Cruise‘s action thriller “Jack Reacher” debuted in second-place with a modest $ 15.6 million debut, according to studio estimates Sunday. Based on the Lee Child best-seller “One Shot,” the Paramount Pictures release stars Cruise as a lone-wolf ex-military investigator tracking a sniper conspiracy.

Opening at No. 3 with $ 12 million was Judd Apatow’s marital comedy “This Is 40,” a Universal Pictures film featuring Paul Rudd and Leslie Mann reprising their roles from the director’s 2007 hit “Knocked Up.”

Paramount’s road-trip romp “The Guilt Trip,” featuring “Knocked Up” star Seth Rogen and Barbra Streisand, debuted weakly at No. 6 with $ 5.4 million over the weekend and $ 7.4 million since it opened Wednesday. Playing in narrower release, Paramount’s acrobatic fantasy “Cirque du Soleil: Worlds Away” debuted at No. 11 with $ 2.1 million.

A 3-D version of Disney’s 2001 animated blockbuster “Monsters, Inc.” also had a modest start at No. 7 with $ 5 million over the weekend and $ 6.5 million since opening Wednesday.

Domestic business was off for the first time in nearly two months. Overall revenues totaled $ 112 million, down 12.6 percent from the same weekend last year, when Cruise’s “Mission: Impossible — Ghost Protocol” debuted with $ 29.6 million, according to Hollywood.com.

Cruise’s “Jack Reacher” opened at barely half the level as “Ghost Protocol,” but with a $ 60 million budget, the new flick cost about $ 100 million less to make.

Starting on Christmas, Hollywood expects a big week of movie-going with schools out through New Year’s Day and many adults taking time off. So Paramount and other studios are counting on strong business for films that started slowly this weekend.

“‘Jack Reacher’ will end up in a very good place. The movie will be profitable for Paramount,” said Don Harris, the studio’s head of distribution. “The first time I saw the movie I saw dollar signs. It certainly wasn’t intended to be compared to a ‘Mission: Impossible,’ though.”

Likewise, Warner Bros. is looking for steady crowds for “The Hobbit” over the next week, despite the debut of two huge newcomers — the musical “Les Miserables” and the action movie “Django Unchained” — on Christmas Day.

“We haven’t reached the key holiday play time yet,” said Dan Fellman, head of distribution for Warner. “It explodes on Tuesday and goes right through the end of the year.”

In limited release, Kathryn Bigelow’s Osama bin Laden manhunt saga “Zero Dark Thirty” played to packed houses with $ 410,000 in just five theaters, averaging a huge $ 82,000 a cinema.

That compares to a $ 4,654 average in 3,352 theaters for “Jack Reacher” and a $ 4,130 average in 2,913 cinemas for “This Is 40.” ”The Guilt Trip” averaged $ 2,217 in 2,431 locations, and “Monsters, Inc.” averaged $ 1,925 in 2,618 cinemas. Playing just one matinee and one evening show a day at 840 theaters, “Cirque du Soleil” averaged $ 2,542.

Since opening Wednesday, “Zero Dark Thirty” has taken in $ 639,000. Distributor Sony plans to expand the acclaimed film to nationwide release Jan. 11, amid film honors and nominations leading up to the Feb. 24 Academy Awards.

Opening in 15 theaters from Lionsgate banner Summit Entertainment, Naomi Watts and Ewan McGregor’s tsunami-survival drama “The Impossible” took in $ 138,750 for an average of $ 9,250.

A fourth new release from Paramount, “The Sopranos” creator David Chase’s 1960s rock ‘n’ roll tale “Not Fade Away,” debuted with $ 19,000 in three theaters, averaging $ 6,333.

Universal’s “Les Miserables” got a head-start on its domestic release with a $ 4.2 million debut in Japan.

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

1. “The Hobbit: An Unexpected Journey,” $ 36.7 million ($ 91 million international).

2. “Jack Reacher,” $ 15.6 million ($ 2.5 million international).

3. “This Is 40,” $ 12 million.

4. “Rise of the Guardians,” $ 5.9 million ($ 13.7 million international).

5. “Lincoln,” $ 5.6 million.

6. “The Guilt Trip,” $ 5.4 million.

7. “Monsters, Inc.” in 3-D, $ 5 million.

8. “Skyfall,” $ 4.7 million ($ 9 million international),

9. “Life of Pi,” $ 3.8 million ($ 23.2 million international).

10. “The Twilight Saga: Breaking Dawn — Part 2,” $ 2.6 million ($ 6.6 million international).

___

Estimated weekend ticket sales at international theaters (excluding the U.S. and Canada) for films distributed overseas by Hollywood studios, according to Rentrak:

1. “The Hobbit: An Unexpected Journey,” $ 91 million.

2. “Life of Pi,” $ 23.2 million.

3. “Rise of the Guardians,” $ 13.7 million.

4. “Skyfall,” $ 9 million.

5. “Wreck-It Ralph,” $ 7.3 million.

6. “The Twilight Saga: Breaking Dawn — Part 2,” $ 6.6 million.

7. “Pitch Perfect,” $ 6 million.

8. “Les Miserables,” $ 4.2 million.

9. “Love 911,” $ 3.2 million.

10. “De L’autre Cote du Periph,” $ 3.1 million.

___

Online:

http://www.hollywood.com

http://www.rentrak.com

___

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

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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.

Read More..

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.

Read More..