Biological markers increase clinical trial success rate of new breast cancer drugs

Public release date: 1-Oct-2012
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Contact: Nicolle Wahl
nicolle.wahl@utoronto.ca
905-569-4656
University of Toronto

Using biological markers--genetic characteristics that are associated with some patients with breast cancer--can increase the success rate of clinical trials for breast cancer drugs by almost 50 per cent, says new research from the University of Toronto Mississauga.

"It's been increasingly difficult for pharmaceutical companies to bring new drugs to market," says Jayson Parker, a faculty member in the Department of Biology and medical biotechnology analyst at the University of Toronto. "On average, about 80 per cent of drugs fail at some point in the clinical trial process."

There are currently no clear estimates of success rates in clinical trials for breast cancer drugs and the factors that can impact success. The research team examined clinical trial drug development programs from 1998 to 2012 to determine how often breast cancer drugs were brought to market. The study examined advanced and metastatic breast cancer as well as patients that have been exposed to the chemotherapy drugs taxane and anthracycline.

"We found that only 14 per cent of drugs that undergo human testing for advanced and metastatic breast cancer are eventually approved," says Parker. "This is worse than the average for the industry as a whole."

According to Parker, some researchers have hypothesized that in the era of personalized medicine, biological markers, or biomarkers, could be used to improve clinical trial success rates and help bring more drugs to market faster. To test this hypothesis, Parker and his team examined the clinical trial success rates for drugs tested on breast cancer patients who have a particular biomarker (HER2). Biomarkers form part of the pathway involved in cancer cell development and can influence how a patient responds to therapy.

When the team compared clinical trials that targeted patients with the HER2 biomarker to those that did not, they found the success rate of drug development increased from 15 per cent to 23 per cent.

Improving the success rate of clinical trials also has an economic impact. Parker's team found that using the HER2 biomarker in the design of clinical trials resulted in a cost savings of 27 per cent. "This can means millions of dollars in cost reduction for a clinical trial," says Parker.

Although this finding may be limited to the HER2 biomarker in breast cancer, Parker says the results are encouraging. "This is the first study that has made a systematic comparison between patients with and without a biomarker," he says. "It provides us with concrete initial evidence that the use of a biomarker can help improve clinical trial success rates in breast cancer. We are now exploring whether this finding holds true for other biomarkers in other cancers."

###

Parker conducted the study with graduate students in the UTM Master of Biotechnology program (MBiotech), Nadia Lushina and Prabjot Bal, along with an oncologist at Johns Hopkins Medical School, Dr. Gilberto Lopes and oncologists at Sunnybrook Health Sciences Centre, Dr. Rebecca Dent and Dr. Teresa Petrella. The paper was published in the journal of Breast Cancer Research and Treatment.

MEDIA CONTACTS

Jayson Parker
Department of Biology
University of Toronto at Mississauga
jayson.parker@utoronto.ca

Nicolle Wahl
U of T Mississauga Communications
905-569-4656
nicolle.wahl@utoronto.ca

---

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 1-Oct-2012
[ | E-mail | Share ]

Contact: Nicolle Wahl
nicolle.wahl@utoronto.ca
905-569-4656
University of Toronto

Using biological markers--genetic characteristics that are associated with some patients with breast cancer--can increase the success rate of clinical trials for breast cancer drugs by almost 50 per cent, says new research from the University of Toronto Mississauga.

"It's been increasingly difficult for pharmaceutical companies to bring new drugs to market," says Jayson Parker, a faculty member in the Department of Biology and medical biotechnology analyst at the University of Toronto. "On average, about 80 per cent of drugs fail at some point in the clinical trial process."

There are currently no clear estimates of success rates in clinical trials for breast cancer drugs and the factors that can impact success. The research team examined clinical trial drug development programs from 1998 to 2012 to determine how often breast cancer drugs were brought to market. The study examined advanced and metastatic breast cancer as well as patients that have been exposed to the chemotherapy drugs taxane and anthracycline.

"We found that only 14 per cent of drugs that undergo human testing for advanced and metastatic breast cancer are eventually approved," says Parker. "This is worse than the average for the industry as a whole."

According to Parker, some researchers have hypothesized that in the era of personalized medicine, biological markers, or biomarkers, could be used to improve clinical trial success rates and help bring more drugs to market faster. To test this hypothesis, Parker and his team examined the clinical trial success rates for drugs tested on breast cancer patients who have a particular biomarker (HER2). Biomarkers form part of the pathway involved in cancer cell development and can influence how a patient responds to therapy.

When the team compared clinical trials that targeted patients with the HER2 biomarker to those that did not, they found the success rate of drug development increased from 15 per cent to 23 per cent.

Improving the success rate of clinical trials also has an economic impact. Parker's team found that using the HER2 biomarker in the design of clinical trials resulted in a cost savings of 27 per cent. "This can means millions of dollars in cost reduction for a clinical trial," says Parker.

Although this finding may be limited to the HER2 biomarker in breast cancer, Parker says the results are encouraging. "This is the first study that has made a systematic comparison between patients with and without a biomarker," he says. "It provides us with concrete initial evidence that the use of a biomarker can help improve clinical trial success rates in breast cancer. We are now exploring whether this finding holds true for other biomarkers in other cancers."

###

Parker conducted the study with graduate students in the UTM Master of Biotechnology program (MBiotech), Nadia Lushina and Prabjot Bal, along with an oncologist at Johns Hopkins Medical School, Dr. Gilberto Lopes and oncologists at Sunnybrook Health Sciences Centre, Dr. Rebecca Dent and Dr. Teresa Petrella. The paper was published in the journal of Breast Cancer Research and Treatment.

MEDIA CONTACTS

Jayson Parker
Department of Biology
University of Toronto at Mississauga
jayson.parker@utoronto.ca

Nicolle Wahl
U of T Mississauga Communications
905-569-4656
nicolle.wahl@utoronto.ca

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2012-10/uot-bmi100112.php

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Why your money may be at risk after bank cyberattacks

7 hrs.

Paul Wagenseil , SecurityNewsDaily

For the past two weeks, an unknown attacker or group of attackers has disrupted access to the websites of five major American banks: Bank of America, JPMorgan Chase, Wells Fargo, U.S. Bank and PNC Bank.

Many customers have?had trouble reaching the sites?to check their account balances or move money around, thanks to what appears to be a series of coordinated attacks.

It's not clear exactly who's behind the disruptions, despite the claims of a previously unknown Islamist group, or even what sort of methods they're using, but here's what we do know.

What's really happening?
Someone's flooding the Web servers of the banks' websites with tons of useless requests for information that can't be fulfilled, overwhelming the servers. Experts call this a?distributed denial-of-service (DDoS) attack.

As a tactic, it's crude but temporarily effective; it doesn't crash the servers, get into databases or cause lasting damage, but it does make the sites hard to reach by clogging the pipes.

Graham Cluley, senior technology consultant at the British anti-virus company Sophos, once likened a DDoS attack to "15 fat men trying to get through a revolving door at the same time."

Hacktivist groups such as Anonymous often use?DDoS as a form of protest, effectively blockading the sites of organizations without damaging them. Yet well-defended sites, such as the banks presumably have, would normally be able to blunt a DDoS attack.

[Hey Stupid: Why Internet Hacking Is Your Fault]

Are there any risks to customer accounts or personal information?
There shouldn't be any, if these are indeed just DDoS attacks.

"There's absolutely no risk to?customer information," said Dmitri Alperovitch, chief technology officer of the security firm CrowdStrike. "They're just not able to get to the site for a few hours."

Cluley agreed.

"I think the only impact of the DDoS attacks on customers is that they may not be able to access their bank's website," Cluley said. "It shouldn't pose any risk to their accounts other than problems accessing them online."

Steve Santorelli, a researcher at Lake Mary, Fla.-based nonprofit security firm Team Cymru, isn't so sanguine about the bank attacks.

"There are three concepts to security: availability, confidentiality and integrity," Santorelli said. "Any event that compromises even just one of them can have complex repercussions and also, of course, takes monitoring and response resources away from any synchronized unauthorized logins to accounts."

Sure it's not just a series of server failures?
One bank's site going down?could be just a technical issue, but five major banks having similar problems is beyond coincidence.

Futhermore, online postings by the group claiming responsibility have told the world ahead of time which bank's going to be hit on which day, and they've mostly been accurate.

CrowdStrike's Alperovitch said there's no question that these are deliberate assaults.

"We're tracking this one," he said. "It's definitely a denial-of-service attack."

Could cybercriminals out for financial gain be behind the attacks?
It might just be possible that the service disruptions are a smokescreen to cover for raids on customer accounts, though experts disagree on how likely that is.

In the same way that the bank robbers in the 1969 crime caper "The Italian Job" created a traffic jam (by hacking into a computer that controlled traffic lights) to paralyze the police response, the DDoS attacks could be meant to divert digital-security personnel's attention away from protecting information.

The FBI released an advisory in November 2011?warning of such scenarios, and even cited a form of banking Trojan that was designed for such attacks.

"Nowadays it's commonplace to have criminals combine banking Trojan attacks with DDoS attacks," said Mikko Hypponen, chief security officer of Helsinki, Finland anti-virus firm F-Secure. "When they score a big transfer from a company's or an individual's accounts, they launch a DDoS against the online bank.

"This accomplishes two things: 1) the victim can't log in to the bank and see that he's been robbed 2) the bank staff is busy fighting the DDoS and might miss the illegal transfers (although in most cases it would be different people in the bank's organization in charge of those things)."

Robert Graham, chief executive officer of Errata Security in Atlanta, admitted that was a possibility, "but then pretty much any speculation is possible."

"There is a question of the sort of DDoS attacks [taking place]," Graham said. "Are they simply website requests, taking down the websites? Or are they specific queries, trying to flood backend transaction servers in an attempt to hide some other activity? We need more information to figure that out."

Chet Wisniewski of Sophos' Vancouver, B.C., office, had doubts that regular cybercriminals were involved, doubts that Alperovitch echoed.

"Honestly, I am not sure it would make sense for this sort of crime," Wisniewski said. "If you were to use a DDoS as a diversion, it would be used for you to get a foothold for a targeted attack, not traditional banking fraud/Trojans."

"Banking Trojans?work so well that they don't need a cover," Alperovitch said.

Why aren't the banks saying more?
Despite all of the publicity, none of the banks have said much beyond apologize for the inconvenience to customers.

"What's the advantage of admitting you were hit by a DDoS attack?" Graham said. "Banks are shy of litigation ? they don't admit anything."

"There is still a stigma, a perception, that customers do not like their accounts being handled by a bank that is not 'safe,'" Santorelli said. "Banks, like every other industry that has embraced the internet, do not like bad publicity. ... It's not a?data breach, so it is not covered by the 'new data breach notification' legislation in the U.S."

Wisniewski pointed out that the banks might be legally barred from releasing details.

"There is likely an ongoing investigation by the FBI prohibiting them from discussing any details publicly," Wisniewski said. "I don't think there is any shame in [admitting being under attack], but who knows ? maybe they have something to hide."

Who's behind this?
Even with criminals ruled out, it's still tough at this stage to know who's really behind the disruptions.

A previously unknown Islamist group calling itself the "Qassam Cyberbrigades" or "Cyber Fighters of Izz al-din al-Qassam" has?posted messages in English and Arabic?on online forums claiming responsibility for the attacks, and accurately predicted which banks were going to be hit.?

The "Cyberbrigades," whose name refers to the military wing of the Palestinian Islamist party Hamas, claim the attacks are retaliation for the offensive YouTube clip "Innocence of Muslims." They vow to continue the attacks until the video is entirely removed from YouTube.

But anonymous national-security experts told NBC News last week that it's unlikely that amateur hackers could have mounted such massive DDoS attacks against well-protected websites of American banks. Instead, they said, there's a more likely culprit: the government of Iran.

Sen. Joe Lieberman, I-Conn., repeated that theory last week, telling a C-SPAN interviewer that Iran was probably behind the attacks.

Alperovitch said either theory was possible, though he doubted it was a response to "Innocence of Muslims."

"We believe it's either a hacktivist group, or what Senator Lieberman has declared," he said. "It would take months of planning to organize this."

Cluley, on the other hand, thought it best to gather evidence first.

"Any joker can post messages on the Internet claiming to be responsible ? but that's very different from finding a smoking gun," Cluley said. "We should all be careful about jumping to conclusions or pointing fingers in particular directions until convincing evidence is presented."

Wisniewski didn't think the scale of attacks necessarily pointed at a nation-state.

"I have not seen nor heard of any serious evidence that Iran is behind these attacks," he said. "Any criminal with a wish to cause mischief certainly could. DDoS may not trivial at this scale, but it is relatively cheap to rent?very large numbers of bots."

The Jester, a well-known "patriotic hacker," put up a blog posting earlier this week?detailing an Internet Relay Chat conversation?he had with a botnet renter. The Jester pretended to be an Islamist friend of the Qassam Cyberbrigades, and was given a price of $200 for a 1,000-hour DDoS attack.?

Independent security expert Dancho Danchev does think the attack may have come from Iran ? but not from the Iranian government.

On his blog Friday, Danchev?showed what he said was evidence?that a young Iranian woman began a grassroots hacktivist campaign by posting a link from her Facebook page to a download. The download links have since spread to websites and forums frequented by Islamists.

The download contains a simple "htm" file, which displays page housed on the user's own computer in a Web browser. The page contains a message in Arabic and English, a list of targets and a simple button. Pushing the button launches an attack from the user's computer against the bank websites.

How are they doing it?
Danchev said the tool being used was a version of a free server-load-testing application called the?Low Orbit Ion Cannon, which the hacktivist group Anonymous has used in the past.

But knocking a major bank's website offline would take many times the firepower that any hacktivist group would normally possess.

"The level of sophistication is moderate to low," Alperovitch said. "What's interesting is the volume."

Threatpost, the consumer-oriented blog of Russian security firm Kaspersky Lab, said some of the traffic hitting the banks' servers?reached 100 gigabits per second, as opposed to the regular DDoS attack volume of 5 to 10 gigabits per second. It did not cite its source.

"Someone clearly had motivation to put this together," Alperovitch told SecurityNewsDaily. "It's unlikely that a kid would make that much effort. The only thing we know at this point is that it's organized and whoever's behind it has spent a lot of effort."

Graham wasn't so certain.

"Any joker even without the right tools can disrupt a heavily protected site," he said.

How can you protect yourself?
Again, if this is really just a DDoS attack, the banks' customers are not in much danger of losing money or personal information.

But there are still basic precautions that any online banking user should take, regardless of the present danger.

"Use, and regularly change,?strong passwords?for your accounts," Santorelli said. "Keep your machine patched and theanti-virus?and firewall automatically updated.

"If you don't need?Java?and Adobe software, uninstall it, although many banks require Java," he added. "Of course, use an up-to-date browser."

All those tips will protect your personal information and screen out malware, but there's still the chance a smart banking Trojan could get in.

"If you are really worried," Santorelli said, "use a?dedicated clean machine?to access your accounts and never use it for anything else. ... if customers prevent anyone stealing their banking credentials in the first place, they have little to fear other than the inconvenience of not being able to get to their online accounts."

Copyright 2012?SecurityNewsDaily, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Source: http://www.nbcnews.com/technology/technolog/why-your-money-may-be-risk-after-bank-cyberattacks-6200003

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More than 1K students hit coffee fields | News is my Business

An unidentified student (left) picks ripe coffee beans alongside Agriculture Secretary Neftal? Soto.

More than 1,000 students hit Puerto Rico?s coffee fields over the weekend to pick the ripe beans alongside a crew of government officials, the Agriculture Department confirmed.

Led by Secretary of State Kenneth McClintock and Agriculture Secretary Neftal? Soto, students enrolled in public and private schools, as well as belonging to Boys Scouts troops, picked coffee at 14 farms along Puerto Rico?s coffee belt: Lares, Las Mar?as, Maricao, San Sebasti?n, Utuado and Adjuntas.

This initiative aims to move youth from the city to the country, while helping farmers who are hard-pressed to find willing coffee pickers to harvest this year?s crops.

?If we want to develop future farmers, we need to encourage the commitment and interest of young people in agriculture at an early age,? Soto said. ?So it?s important that these young people get real work experience in agricultural projects.?

The initiative is one of several the agency is conducting to recruit full time coffee pickers during this year?s harvest, mostly government assistance programs beneficiaries, who will not be penalized for working in the fields.

Source: http://newsismybusiness.com/more-than-1k-students-hit-coffee-fields/

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Living Life In Costa Rica blog: TATTOO CONVENTION Costa Rica

The tattoo convention is back at Club Moon Saturday with live music, tattoo tents and presentations from famous artists. Courtesy of Paradise International Tattoo Convention

Sorry for the delay in posting this but I JUST saw it and I'm posting it in case someone interested in Tattoo's in Costa Rica seeks some leads on it.
WHEN:? Saturday and Sunday - September 29 and 30, 2012

WHERE:? CLUB MOON Nightlife and Business - Frente a las Bodegas de Florida Ice a
I'm sharing this info AFTER the fact in case anyone is seeking info on Tattoos in Costa Rica - or for next years Tattoo Convention.

ESPANOL:
Fue en el a?o 2010 que se inici? este proyecto como ?Expo Tattoo Costa Rica? con la empresa Freak Productions y su organizador Andy Morales, para unificar el arte corporal entre artistas nacionales.

Poco a poco fue creciendo y madurando la idea y ahora en el 2012 se presenta la tercera fecha del mismo evento como ?PARADISE? Tattoo Convention Costa Rica 2012, junto a Nueva Calavera JLO S.A. y Johnn L?pez, con un esquema e ideas diferentes para seguir mejorando la industria y unir a m?s artistas de gran trayectoria, adem?s de dar oportunidades para profesionales donde reciban seminarios educativos, informaci?n de proveedores y al p?blico en general un excelente entretenimiento e informaci?n sobre esta tendencia cultural.

Para este a?o 2012 contaremos con la participaci?n del gran artista y modificador corporal Lukas Zpira desde Francia.

?PARADISE? Tattoo Convention Costa Rica2012 se realizar? los d?as viernes 28 de septiembre con un seminario impartido por dicho invitado especial con un cupo limitado, en donde se impartir?n temas importantes sobre body piercing y modificaciones corporales.

El gran show para artistas en general y p?blico presente se llevar?n a cabo los d?as 29 y 30 de septiembre en donde abr?n shows continuos de m?sica en vivo, pasarela de marcas nacionales e internacionales, freak show, demostraci?n de skate, premiaci?n a mejor tatuaje de la convenci?n, miss pin up "CHICA PARADISE" 2012, body paint y mucho mas.

El lugar de la convenci?n ser? en el Club Moon Nightlife & Business Frente a las Bodegas de Florida Ice & Farm San Joaqu?n de Heredia el 29 y 30 de septiembre

Las entradas estar?n a la venta en los estudios participantes y lugares patrocinadores y tendr?n un precio de 5mil colones por d?a o una promoci?n de 16mil por 4 entradas.

Por ustedes y por la industria es que trabajamos fuerte en este proyecto, sigamos manteniendo nuestro apoyo que ya lo ha sido por tres fechas consecutivas y seamos de esto una sola unidad

EL SEMINARIO EDUCATIVO SERA IMPARTIDO POR EL GRAN MODIFICADOR LUKAS ZPIRA DESDE FRANCIA SOBRE MODIFICACIONES CORPORALES EL DIA VIERNES 28 DE SEPTIEMBRE A LAS 10AM EN LAS INSTALACIONES DE NEW SKULL EN SAN PEDRO E INCLUYE:
* CERTIFICADO DE PARTICIPACIO* GAFETES
* PROCEDIMIENTOS EN VIVO CON EL ARTISTA PARA ALGUNOS DE LOS PARTICIPANTES
* TRADUCTOR
* MATERIAL
* REFRIGERIO

ENTRE OTROS METODOS Y CONSULTAS A TRATAR

COSTO POR PERSONA: $150 CUPO LIMITADO DE 30 Y EXCLUSIVO PARA ARTISTAS DE ESTUDIOS

INFORMACION DE STANDS
* 3X3
* MESA
* ELECTRICIDAD
* 4 PARES DE GUANTES
* 2 CAMPOS ESTERILES
* AGUA
* 2 SILLAS
* BOLSA DE DESECHO
* BOTE DE DESECHO BIOPELIGROSO
* GAFETES

Para m?s informaci?n de stands y del evento en general pueden contactar a:

ENGLISH
It was in 2010 that started this project as "Costa Rica Tattoo Expo" with the company Freak Productions and organizer Andy Morales, to unify body art among artists.Little by little the idea grow and mature in 2012 and now presents the third round of the same event as "PARADISE" Costa Rica Tattoo Convention 2012, alongside New Skull JLO SA Johnn and Lopez, with a scheme and different ideas to further improve the industry and unite more artists of great experience, in addition to providing opportunities for professionals where they receive educational seminars, information providers and the general public an excellent entertainment and information on this cultural trend.For this year 2012 will have the participation of the great artist and body modifier Lukas Zpira from France."PARADISE" Costa Rica2012 Tattoo Convention will be held on Friday, September 28 with a seminar given by the special guest with limited space where important topics are taught about body piercing and body modification.The great show for artists and general audience will be held on 29 and 30 September where Abram shows continuous live music, gateway national and international brands, freak show, skate demo, awards for the best tattoo convention, miss pin up "girl PARADISE" 2012, body paint and much more.The venue of the convention will be at Club Moon Nightlife & Business Facing Bodegas Florida Ice & Farm San Joaquin de Heredia on 29 and 30 SeptemberTickets will be on sale in studies sponsors and participants and places will cost colones per day 5mil or 16mil promotion for 4 tickets.For you and for the industry is that we work hard on this project, we maintain our support and has been for three consecutive dates and let this one unit
EDUCATIONAL SEMINAR will be taught by LUKAS MODIFIER GREAT FROM FRANCE ON Zpira body modifications on Friday, September 28 at 10am at SKULL NEW FACILITY IN SAN PEDRO AND INCLUDES:* CERTIFICATE Participaci? * BADGES* PROCEDURES LIVE WITH ARTIST FOR SOME OF THE PARTICIPANTS* TRANSLATOR* MATERIAL* SNACKOther methods and consultations TREATCOST PER PERSON: $ 150 SPACE IS LIMITED TO 30 EXCLUSIVE FOR ARTISTS AND STUDYINFORMATION STANDS* 3X3* TABLE* ELECTRICITY* 4 pairs of gloves* 2 sterile fields* WATER* 2 CHAIRS* Waste bag* JAR biohazardous waste* BADGESFor more information booth and the event in general can contact:
Oficinas: (506) 2-524-2973? ?? ParadiseTattooConvention@hotmail.com

Johann L?pez:? (506) 8-834-8255? ?? johannlop@hotmail.com
Andy Morales:? (506) 8-655-8963? ?? andriska25@hotmail.com

Dale Like a nuestro facebook y participa en entradas y promociones el d?a del evento

facebook.com/pages/Paradise-Tattoo-Convention/442597739108322
facebook.com/pages/Johann-Lopez-Official/212975718735432

.

Source: http://livinglifeincostarica.blogspot.com/2012/10/tattoo-convention-costa-rica.html

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New Selena Gomez Tattoo Honors Family Member

Source: http://www.thehollywoodgossip.com/2012/10/new-selena-gomez-new-tattoo-honors-family-member/

Eagles' gamble pays off vs. Giants

Timeout gives Tynes 2nd chance at game-winning FG, but his miss gives Philly 19-17 win

By ROB MAADI

updated 11:39 p.m. ET Sept. 30, 2012

PHILADELPHIA - Eli Manning had the New York Giants in position to pull off another comeback win until Lawrence Tynes missed his second-chance kick.

Tynes was short on a 54-yard field goal attempt with 15 seconds left and the Philadelphia Eagles held on for a 19-17 victory over the Giants on Sunday night.

Tynes' first try was wide left, but the Eagles called timeout.

"I tried to make it straighter. And I did that. But it wasn't far enough, and it just fell short," Tynes said. "It was a tough kick, yes, but it was one that I can make, and I have made it before. I feel bad, in that spot, that I didn't come through for my team."

With LeSean McCoy leading the way on the ground, Michael Vick guided Philadelphia (3-1) to its third comeback win.

The Eagles became the first team in NFL history to have each of their first three wins by two points or less according to information provided to the Eagles by the Elias Sports Bureau.

Alex Henery kicked a 26-yard field goal with 1:49 left and the Eagles overcame two pass interference penalties on New York's final drive.

The defending Super Bowl champion Giants (2-2) have struggled against Philadelphia, losing eight of the last nine meetings.

Manning, who led the Giants to a late win over Tampa Bay two weeks ago, nearly did it again. But New York fell to 0-2 in the division.

"We feel good in those situations, and we feel we can put ourselves in a position to win," Manning said. "We got down there, but we didn't finish the job. There's always something that can go wrong in the NFL, and that's one of the things about always being in those positions, you just never know if you're going to get a bad bounce. That happened for us tonight, and we didn't get a chance to fix it."

McCoy had 121 of his 123 yards rushing in the second half. The All-Pro had six carries for 2 yards at halftime.

"It's just the Giants and Eagles, this is what it comes down to," McCoy said. "Eventually our running game would crack it and that's what we did."

Vick threw TD passes in the final two minutes in consecutive 1-point wins over Cleveland and Baltimore the first two weeks before a 26-7 loss at Arizona.

After Manning tossed a go-ahead 6-yard TD pass Bear Pascoe, Vick drove the Eagles to the Giants 2 before Osi Umenyiora sacked him for a 6-yard loss on third down. Henery then hit his fourth field goal to put Philadelphia ahead to stay.

Henery also connected from 48, 35 and 20 yards.

A pass interference penalty on Dominique Rodgers-Cromartie kept the Giants' last drive alive and put the ball at the Eagles 35 after Manning threw an incomplete pass on fourth-and-1. Another pass interference call on Nnamdi Asomugha on third-and-10 moved it to the Eagles 27.

Then Ramses Barden got called for offensive pass interference to move it back to the 36.

"I thought it was on him," Barden said of Asomugha. "But I know he's a competitor, and he came to play tonight. We were both fighting for position and it's just one of those things."

Giants coach Tom Coughlin wasn't sure of the call.

"The only thing I can say is the pass interference is the worst thing that could have happened," he said. "If it's incomplete, we're still OK because of where the ball was."

After an incomplete pass, the Giants sent out Tynes to try for the winning kick on third-and-18 because they didn't have any timeouts remaining.

"I don't believe in icing the kicker," Vick said. "You let him kick it and if it's in, it's in. You can't play games. I don't know where that started. We got to end that tradition."

Vick was 19 of 30 for 241 yards and the turnover-prone Eagles protected the ball. The Eagles led the NFL with 12 turnovers through three games, but didn't commit any.

Manning completed 24 of 42 passes for 309 yards, two TDs and one crucial interception.

He threw a pick in the end zone after a 30-yard pass to Victor Cruz on fourth-and-1 got the Giants to Philadelphia's 10 on the final play of the third quarter.

Rodgers-Cromartie intercepted Manning's underthrown pass into triple-coverage and returned it 14 yards to the Eagles 9. The Eagles slowly moved the ball on the ground to set up Henery's 35-yarder that made it 16-10.

Manning redeemed himself on New York's next possession. He completed passes of 31 yards to Barden and 41 yards to Domenik Hixon. He then found Pascoe wide open over the middle for a 17-16 lead with 6:45 left.

McCoy finally broke loose by running for 56 yards on consecutive carries in the third. He was stopped at the 1 on a 22-yard gain, and then couldn't get in on three straight carries. The Eagles settled for a 20-yard field goal by Henery that made it 10-3.

"The O-line found themselves as the game wore on," Reid said. "They were able to block well enough to where McCoy had big yards."

The Giants answered after David Wilson ran the kickoff back 45 yards to the 43.

Mixing run and pass effectively, the Giants moved to the 14. On third-and-3, Manning threw a TD pass to Cruz, who celebrated with his trademark salsa dance in the stadium where it all started. Cruz burst on the scene with a breakout performance in a 29-16 win at Philadelphia last September.

Vick threw a 27-yard pass to Brent Celek and then scrambled 18 yards to set up Henery's 48-yard field goal late in the third that made it 13-10.

? 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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Rethink NFC East expectations?

PFT: Eli Manning's mistakes sink the Giants (2-2), while LeSean McCoy's brilliance continues to boost Philadelphia (3-1). If the Eagles really kick this thing into gear, they could be the one ruling the NFC East.

Eagles' gamble pays off vs. Giants ? |? ??Highlights

Given a second chance, Lawrence Tynes couldn't make the Philadelphia Eagles pay for a tactical gamble that nearly backfired. Tynes missed two field-goal tries from 54 yards with 15 seconds left and Philadelphia held on for a 19-17 victory over the New York Giants on Sunday night.

Source: http://nbcsports.msnbc.com/id/49235315/ns/sports-nfl/