Sunday, June 23, 2013

Starbucks raising some U.S. cafe drink prices

NEW YORK (Reuters) - Starbucks Corp will increase the price of some of its beverages in U.S. company-operated cafes by as much as 10 cents, the first price change in up to two years, a spokeswoman said on Friday.

The price hike will be effective June 25, Starbucks spokeswoman Lisa Passe said.

"Less than a third of beverages will be affected by the price increases," Passe said. "In most stores, the price of a Grande or Venti brewed coffee, as well as Frappuccino and Refreshers, will remain the same."

Nationally, the average beverage purchase price increase will be about 1 percent, she said.

The most a tall brewed coffee will increase by is 10 cents, while some markets will not see any increase in brewed coffee, she said.

Green arabica coffee prices dropped to a four-year low on the ICE Futures U.S. market at $1.1710 per lb on Thursday.

Coffee commodity costs make up less than 10 percent of Starbucks' overall store operating and occupancy expenses, Passe said.

(Reporting by Marcy Nicholson; Editing by Gerald E. McCormick)

Source: http://news.yahoo.com/starbucks-raising-u-cafe-drink-prices-212307929.html

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Kerio Operator Box 1210


For many small businesses, getting set up with voice-over-IP telephony generally meant one of two things: consumer-focused platforms that were affordable but didn't really offer business-specific features, or complex enterprise-class PBX systems that were expensive and too difficult to deploy. Luckily for the SMB, Kerio Technologies offers the Kerio Operator Box 1210, a PBX chock-full of enterprise-class features that is fairly easy to deploy, straightforward to use, and at just the right price-point for small budgets.

Why would a small business want to shift to a VoIP?system instead of just sticking with the normal business phone service from the local phone carrier? For starters, it could help make the business look bigger, with auto-attendant recordings, specialized messages for after hours, and the ability to handle calls, such as providing hours of operation or product information via pre-recorded messages, even when the line is busy.

Kerio actually offers the SMB-class PBX in various forms. There is the Kerio Operator Box 1210 ($900 for a five-user license), a small appliance small enough to sit comfortably on a desk, and the Kerio Operator Box 3210 (starting at $1400 for a five-user license), a 1U server. Administrators can download the Kerio Operator software and install it onto their own hardware. Kerio also offers Operator as a VMware virtual appliance (vmx and ovf formats) for organizations who prefer virtual environments. The low cost of entry is a big plus for the small business.

For this review, I looked at the Kerio Operator Box 1210.

Looking at the Hardware
Measuring 10.7 by 7.7 by 1.7 inches?(HWD) and tipping the scale at just over 4.4 pounds, the desktop PBX is a distinctive orange and easy to see. The rear panel has four Ethernet ports, two of which are Gigabit, along with two USB ports, a power button, and the port for the power cord. The front panel has LEDs for power, status (usually means disk activity), and one for each network port. I had the desktop PBX running on my desk for several months, and the unit never got noisy or hot to touch.

The Operator Box 1210 has 2GB of memory and 8GB of industrial grade compact flash disk storage. Kerio Operator is based on Asterisk, the open-source SIP communication software, which is why it can work with a wide range of IP phones and softphones, including models from Cisco, Snom, Polycom, and Yealink/Well. Operator Box 1210 can support up to 50 concurrent calls and concurrently record up to 10 calls. The appliance comes with 4GB of on-board storage for voicemails. The 3210 supports a higher call volume.

At $900, the Kerio Operator Box 1210 comes with five users by default. Organizations can buy additional licenses per user for $30, in additional groups of five, to add more users to the system.

Getting Started
Setup is not that difficult, unlike many business-class PBX systems which generally require a technician or a reseller to come on site to help with the deployment. However, Kerio Operator Box 1210 has a lot of steps, and each one has to be done exactly as they are listed in the installation guide. The box ships by default with a static IP address already assigned. I connected the Kerio box with a testing machine so that I could open up the Web-based interface.

I created a password for the Administrator account and then stepped through the setup wizard to set the time zone and other basics. I changed the IP address assigned to the box to one that fit my network. While I had the option to use DHCP, network devices should have static IP addresses. After changing the IP address, I plugged the Kerio box directly into the switch so that it was on the network.

As mentioned earlier, it is extremely important to follow the installation instructions carefully. For example, when trying to get to the Web-based administrator interface for the first time, I was supposed to plug one end of the Ethernet cable into the Operator Box's port 1. And it has to be port 1. I wasted a lot of frustrating minutes trying to troubleshoot why I couldn't ping the box or open the Web interface before realizing that I'd plugged cable in to port 4. As soon as I switched ports, everything worked.

I decided to deploy the Kerio Operator behind a firewall. I specified on the interface, under System, that there was a firewall, and entered my public IP address. This meant I had to add port forwarding rules to handle incoming SIP?traffic (port 5060). I didn't need to open the other TCP ports specified in the manual since I didn't need features like being able to access the Web-interface directly from the Internet?Next: Kerio Operator Box Web Interface, PBX Features

Source: http://feedproxy.google.com/~r/ziffdavis/pcmag/~3/xVBU-z5i4yI/0,2817,2419785,00.asp

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Saturday, June 22, 2013

Lewis leads group atop NW Arkansas Championship

ROGERS, Ark. (AP) ? Stacy Lewis has made no secret about her desire to earn a championship in front of her adopted hometown fans.

The world's No. 2 golfer has also been open about how that internal pressure has caused her to struggle in recent years at the LPGA NW Arkansas Championship.

Lewis put all distractions aside on Saturday, shooting a 6-under 65 to join a group of four players atop the leaderboard at 10 under overall after the second round of the tournament at Pinnacle Country Club.

The round was a welcomed bit of excitement for a surging and vocal gallery that followed Lewis' every shot. It was especially gratifying for the former world No. 1, who played collegiately at nearby Arkansas ? and who has struggled to contend in recent years at the tournament.

Lewis earned an unofficial win at the rain-shortened event as an amateur in 2007. Since then, however, the former Rookie of the Year and last year's Player of the Year entered this week having finished in an average of 23rd place in front of her many fans ? including a 49th-place finish last year.

Back-to-back wins earlier this year briefly vaulted Lewis into the top spot in the world rankings, a position she said prepared her for the hectic schedule she faces this week.

"It's everything I deal with this year with the week that I became No. 1 in the world. It was just chaos," Lewis said. "Dealing with that pressure of being No. 1 in the world, I learned a lot from that.

"I honestly think that's why I've come here this week and it doesn't seem so busy anymore, doesn't seem too hard to play with all the fans."

Chie Arimura and Beatriz Recari both equaled Lewis' 65 on Saturday and are tied entering the final round with So Yeon Ryu.

I.K. Kim and defending champion Ai Miyazato tied for the lowest round of the day, each shooting a 7-under 64.

First-round leader Mika Miyazato shot a 70 and is three shots back, while top-ranked Inbee Park leads a group of three players two shots back at 8 under.

They will all be chasing Lewis on Sunday, at least in terms of the attention from the galleries to begin with. She will be paired with Recari in the final grouping of the day, and she is well aware of the excitement she will feel.

"I think the harder part is I'm going to want it so bad, and I know the fans are going to want me to get it really bad," Lewis said. "So, it's going to be hard. The hardest part is going to be staying patient and not trying to force putts and running them four feet by (the hole)."

Lewis was as low as 11 under after 17 holes on Saturday, thanks in large part to needing only 27 putts for her round ? a number that included several near misses and a three-putt on her final hole. The 28-year-old Lewis, who played during the morning, thrilled her pro-Arkansas gallery with four straight birdies on her first nine holes.

After starting on the back nine, she birdied holes 14-17 to reach 8 under before the par-5 18th took its toll. Lewis' approach on her third shot came up just short and rolled to the bottom of the hill in front of the green. Her following chip did the same.

Fortunately for Lewis, she managed to save bogey with an up-and-down ? thanks to her fifth straight one-putt. She then reached 11 under after four more birdies later in her round before bogeying her final hole of the day.

Lewis will have plenty of challengers Sunday on a leaderboard that features seven players within two shots of the lead, including Park ? with two major wins this year.

Arimura, the rookie from China, also needed only 27 putts on Saturday in shooting a bogey-free 65. She tied for the lead with birdies on her final two holes. Ryu birdied the par-5 7th hole ? her 16th hole of the round ? to reach 10 under in the final tournament before next week's U.S. Open.

Recari also posted a bogey-free round, birdieing four of her first seven holes before making the last of her six birdies on the par-5 14th. The Spanish golfer already has one win this year, the Kia Classic in March.

"I think overall I'm pretty happy and proud of how I handled myself the last two days," Recari said. "I have a very clear idea of what I have to do mentally, so I feel very confident and very good for my last round."

Kim, Pornanong Phatlum and Ji Young Oh are each at 8 under along with Park, while amateur Lydia Ko and Miyazato are at 7 under.

Juli Inkster followed an opening 71 with a 6-under 65 on Saturday.

Lewis, meanwhile, said she planned to play a round of golf with her nephew on Saturday afternoon before relaxing for the rest of the day in anticipation of what she hopes is a hometown celebration on Sunday.

"I'm definitely going to use the crowd some, but then I need to also just kind of scale it back and just stay in what I am doing right now because it's working," Lewis said.

Source: http://news.yahoo.com/lewis-leads-group-atop-nw-arkansas-championship-235555077.html

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Tokyo court says Samsung infringed Apple 'bounce-back' patent

By Nobuhiro Kubo

TOKYO (Reuters) - A Tokyo court ruled on Friday that Samsung Electronics Co Ltd had infringed rival Apple Inc's patent for a so-called bounce-back feature on earlier models of its popular smartphones.

Samsung and Apple, the world's top two smartphone makers, are fighting patent disputes across the globe as they compete to dominate the lucrative mobile market and win customers with their latest gadgets.

Apple claimed that Samsung had copied the feature, in which icons on its smartphones and tablets quiver back when users scroll to the end of an electronic document. Samsung has already changed its interface on recent models to show a blue line at the end of documents.

The Japanese court's decision comes after the U.S. Patent and Trademark office judged earlier this year that Apple's bounce-back patent was invalid, allowing older Samsung models that had a similar feature to remain on sale.

However, the U.S. agency subsequently decided that several aspects of the bounce-back feature were actually patentable, according to documents filed by Apple in U.S. court last week.

(Additional reporting by Dan Levine in San Francisco; Editing by Richard Chang)

Source: http://news.yahoo.com/tokyo-court-says-samsung-infringed-apple-bounce-back-050406105.html

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Israeli killed by guard at Jewish holy site in Jerusalem

JERUSALEM (Reuters) - A security guard shot and killed a Jewish Israeli man on Friday at one of Judaism's holiest sites in Jerusalem, the Western Wall, which was immediately shut to visitors, police said.

The guard opened fire after the man, in an adjacent restroom, was heard shouting "Allahu Akbar," Arabic for "God is greatest", police spokesman Micky Rosenfeld said.

Rosenfeld said the guard opened fire with his pistol because he suspected the man was a Palestinian militant. The victim turned out to be an Israeli Jew in his 40s.

"The fact he shouted Allahu Akbar, that seems to be why the security guard drew his weapon and fired a number of shots at him," he said.

"We are looking into what (the dead man's)... motives were," Rosenfeld added.

The incident occurred as hundreds gathered for prayer in one of Jerusalem's most sensitive areas. The Western Wall is one of Judaism's holiest sites, where thousands worship each week.

The plaza where the wall is located is next to the Temple Mount, revered by Jews as the place where two biblical temples stood, and the site of Islam's third holiest mosque, al-Aqsa.

(Writing by Allyn Fisher-Ilan; Editing by John Stonestreet)

Source: http://news.yahoo.com/israeli-killed-guard-jewish-holy-jerusalem-051830299.html

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one year ago / canon rebel & expired Kodak Gold ? Orange County ...


El Capitan Canyon | Santa Barbara, CA
June 2012

*

One year ago I made the decision to use film for my personal work and family photos. I picked up the only film camera I had on hand (a 90?s Canon Rebel) and in the same bag found ten rolls of Kodak Gold 400. So that?s what I used on my first foray back to the medium from whence I came. And this is the first time I used it. Getting these scans back was like getting an email from your best friend from sixth grade, the one you haven?t talked to in fifteen years, but who stills feels like the peanut butter to your jelly, the sun to your sky. Like, ?WHERE HAVE YOU BEEN ALL THESE YEARS?!? And, ?WHY DID WE EVER FALL OUT OF TOUCH?!?

I didn?t know this at the time, but with expired film you actually need to overexpose, and I didn?t. So a lot of these are underexposed and grainy, but I?m okay with that. Because that?s the deal with film, you get what you get. You get what you get.

*

I have an elderly Aunt and Uncle who are in the process of cleaning out their home and giving things away. Things they have had tucked away in their cupboards and garage for thirty or forty years. Last Thanksgiving, Uncle Leonard brought a Nikon One-Touch to my mom?s house, thinking ?one of us kids? might like it. It was perfectly timed, because after six months of use, my Canon Rebel had begun breaking down. I was having trouble locking focus and the battery door insisted on popping open, batteries falling out and camera rendered useless at the most inopportune moments, so I was ecstatic to have another option fall into my lap. One with sentiment attached, even better. It?s entirely possible that the camera had recorded me, as a child, and I like the notion of that.

So, for the first half of this year, I have used the Nikon One-Touch as my main form of documenting my children and my life. This point and shoot camera (like all point and shoot cameras) has given me freedom from technical thought, which is what the iPhone camera also brings to the table, and what I mean is ? I don?t have to think about exposure. I only have to look, see, and then push a button. In certain aspects of my personal and family work, I appreciate the speed and ease this camera offers me. The images themselves feel so cut directly from the moment, like there?s nothing in between you when you see them in front of you. It?s exactly what was in front of me, nothing more and nothing less. No shallow depth of field to manipulate the viewer?s eye into being drawn to a certain place, no fancy bells and whistles.

*

I recently picked up a Canon EOS 3, a film SLR. Which I wanted for the entirely opposite reason that I have come to appreciate in the Nikon One-Touch. I want to have some control. I want some depth of field. I want a little more quality and depth to the images. I haven?t run any film through it yet, but I?m getting ready to.

*

Here?s a link to the ?film? blog category I created to keep everything organized in one place.

*

Happy Friday.

Source: http://tarawhitney.com/justbeblogged/2013/06/one-year-ago-canon-rebel-expired-kodak-gold/

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Obama Is Getting Ready to Rein In Power Plant Pollution

By Alex Dobuzinskis and Antonio Denti LOS ANGELES/ROME (Reuters) - Doctors at a Rome hospital battled for 40 minutes to try to save the life of James Gandolfini, best known for his Emmy-winning role as a mob boss in the TV series "The Sopranos," before pronouncing him dead, the emergency room chief said on Thursday. Gandolfini, 51, whose performance as Tony Soprano made him a household name and help usher in a new era of American television drama, was vacationing in Rome and had been scheduled to attend the closing of the Taormina Film Festival in Sicily on Saturday. ...

Source: http://news.yahoo.com/obama-getting-ready-rein-power-plant-pollution-112349352.html

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Sunday, June 2, 2013

MGH-led studies shed new light on targeted lung cancer therapy

MGH-led studies shed new light on targeted lung cancer therapy [ Back to EurekAlert! ] Public release date: 1-Jun-2013
[ | E-mail | Share Share ]

Contact: Katie Marquedant
kmarquedant@partners.org
617-314-3986
Massachusetts General Hospital

2 studies confirm crizotinib's superiority to chemotherapy for ALK-positive lung cancer, report first crizotinib resistance in ROS1-positive lung tumor

Research teams led by Massachusetts General Hospital (MGH) Cancer Center investigators are publishing two important studies regarding use of the targeted cancer drug crizotinib for treatment of advanced lung cancer driven by specific genetic mutations. The first reports the final results of a global, phase 3 trial showing that crizotinib is superior to standard chemotherapy for treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). The second paper describes the first report of resistance to crizotinib treatment in a patient with ROS1-positive NSCLC and reveals the mechanism underlying that resistance. Both papers are being published online in the New England Journal of Medicine to coincide with the American Society of Clinical Oncology annual meeting.

One of a group of drugs that directly targets genetic mutations spurring the uncontrolled growth of cancer, crizotinib has regulatory approval for the treatment of advanced NSCLC driven by rearrangements of the ALK gene and is being investigated for treatment of tumors driven by the MET and ROS1 genes. While previous studies showed that crizotinib was effective in treating ALK-positive lung cancer, the activity of standard chemotherapy against that type of tumor -- which had only recently been described -- was not known.

"This is the first randomized study to compare crizotinib with standard chemotherapy in advanced ALK-positive lung cancer," says Alice Shaw, MD, PhD, of the MGH Cancer Center, the first author and lead investigator for the study. "This study supports the full FDA approval of crizotinib in the U.S. and has also led to approval of crizotinib in many countries around the world." Preliminary results from this trial were first reported at the European Society for Medical Oncology meeting in September 2012.

The trial enrolled 347 patients with advanced ALK-positive NSCLC that had progressed after first-line treatment. Participants were randomly assigned to receive either oral crizotinib twice a day or standard chemotherapy with the intravenous drugs pemetrexed or docetaxel, given once every three weeks. Patients in the chemotherapy group whose tumors progressed were allowed to cross over to receive crizotinib.

Compared to chemotherapy, crizotinib more than doubled the average progression-free survival, from 3 months with chemotherapy to 7.7 months. The response rate with crizotinib was 65 percent, more than triple that of chemotherapy. Crizotinib more powerfully suppressed and prevented the recurrence of symptoms and resulted in significantly greater quality-of-life improvements. While overall survival rates for both groups were quite similar, more than 60 percent of those in the chemotherapy group eventually began receiving crizotinib which, the authors note, probably confounded the survival analysis.

"This study shows that patients with advanced ALK-positive lung cancer respond better to crizotinib and for longer periods of time," Shaw says. "Equally important, patients treated with crizotinib report better symptom control and quality of life than those treated with chemotherapy." Another ongoing phase 3 trial is comparing crizotinib to chemotherapy as first-line treatment for newly diagnosed patients.

The second paper describes an NSCLC patient who was treated with chemotherapy after initial genetic studies found none of the tumor-associated mutations known at the time. When her cancer continued to progress, additional molecular testing identified a rearrangement in ROS1 that Shaw and her colleagues had only recently described and shown could be treated with crizotinib. At first, the patient's tumor responded quickly, with symptomatic improvement after less than a week of crizotinib therapy. But after three months symptoms returned and her tumor resumed growing, eventually leading to the patient's death.

While the development of resistance to targeted cancer therapies is common, this is the first report of crizotinib resistance in ROS1-positive NSCLC. Detailed molecular analysis revealed a secondary mutation in the initial ROS1 rearrangement. The researchers then determined exactly how crizotinib binds to the ROS1 protein and showed that the new mutation, which is similar to one that confers resistance in ALK-positive tumors, interferes with binding and prevents the drug from inhibiting ROS1-driven tumor growth. Postmortem samples found this resistance mutation in every site to which the tumor had spread.

"Finding that mutation at all sites of disease suggests that it was an early and critical event in the development of resistance," says Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, one of the senior authors of the study. "A similar and highly resistant mutation also occurs in ALK-positive tumors treated with crizotinib, so finding therapies that can overcome this particular type of mutation will be very important."

###

Dong-Wan Kim, MD, PhD, of Seoul National University Hospital is co-lead author of the crizotinib/chemotherapy study, and Pasi Jnne, MD, PhD, Dana-Farber Cancer Institute is co-senior author. Additional co-authors include Benjamin Solomon, MB, BS, PhD, Peter MacCallum Cancer Centre, Melbourne, Australia; Fiona Blackhall, Ph.D., Christie National Health Service Foundation Trust, Manchester, U.K.; Ross Camidge, MD, PhD, University of Colorado at Aurora; Tony Mok, MD, Chinese University of Hong Kong; Vera Hirsh, MD, McGill University Health Centre; Keith Wilner, PhD, Pfizer Oncology. Mark M. Awad, MD, PhD, of the MGH Department of Medicine is lead author of the ROS1 resistance mutation study. Additional co-authors include Ryohei Katayama, PhD, Luc Friboulet, PhD, Elizabeth Lockerman and Justin F. Gainor, MD, MGH Medicine; Subba Digumarthy, MD, MGH Radiology; and James Stone, MD, PhD, Mari Mino-Kenudson, MD, and John Iafrate, MD, PhD, MGH Pathology.

Both studies were supported by grants from Pfizer, which markets crizotinib under the brand name Xalkori, and the second was also supported by the National Cancer Institute and the V Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."


[ Back to EurekAlert! ] [ | E-mail | Share 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.


MGH-led studies shed new light on targeted lung cancer therapy [ Back to EurekAlert! ] Public release date: 1-Jun-2013
[ | E-mail | Share Share ]

Contact: Katie Marquedant
kmarquedant@partners.org
617-314-3986
Massachusetts General Hospital

2 studies confirm crizotinib's superiority to chemotherapy for ALK-positive lung cancer, report first crizotinib resistance in ROS1-positive lung tumor

Research teams led by Massachusetts General Hospital (MGH) Cancer Center investigators are publishing two important studies regarding use of the targeted cancer drug crizotinib for treatment of advanced lung cancer driven by specific genetic mutations. The first reports the final results of a global, phase 3 trial showing that crizotinib is superior to standard chemotherapy for treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). The second paper describes the first report of resistance to crizotinib treatment in a patient with ROS1-positive NSCLC and reveals the mechanism underlying that resistance. Both papers are being published online in the New England Journal of Medicine to coincide with the American Society of Clinical Oncology annual meeting.

One of a group of drugs that directly targets genetic mutations spurring the uncontrolled growth of cancer, crizotinib has regulatory approval for the treatment of advanced NSCLC driven by rearrangements of the ALK gene and is being investigated for treatment of tumors driven by the MET and ROS1 genes. While previous studies showed that crizotinib was effective in treating ALK-positive lung cancer, the activity of standard chemotherapy against that type of tumor -- which had only recently been described -- was not known.

"This is the first randomized study to compare crizotinib with standard chemotherapy in advanced ALK-positive lung cancer," says Alice Shaw, MD, PhD, of the MGH Cancer Center, the first author and lead investigator for the study. "This study supports the full FDA approval of crizotinib in the U.S. and has also led to approval of crizotinib in many countries around the world." Preliminary results from this trial were first reported at the European Society for Medical Oncology meeting in September 2012.

The trial enrolled 347 patients with advanced ALK-positive NSCLC that had progressed after first-line treatment. Participants were randomly assigned to receive either oral crizotinib twice a day or standard chemotherapy with the intravenous drugs pemetrexed or docetaxel, given once every three weeks. Patients in the chemotherapy group whose tumors progressed were allowed to cross over to receive crizotinib.

Compared to chemotherapy, crizotinib more than doubled the average progression-free survival, from 3 months with chemotherapy to 7.7 months. The response rate with crizotinib was 65 percent, more than triple that of chemotherapy. Crizotinib more powerfully suppressed and prevented the recurrence of symptoms and resulted in significantly greater quality-of-life improvements. While overall survival rates for both groups were quite similar, more than 60 percent of those in the chemotherapy group eventually began receiving crizotinib which, the authors note, probably confounded the survival analysis.

"This study shows that patients with advanced ALK-positive lung cancer respond better to crizotinib and for longer periods of time," Shaw says. "Equally important, patients treated with crizotinib report better symptom control and quality of life than those treated with chemotherapy." Another ongoing phase 3 trial is comparing crizotinib to chemotherapy as first-line treatment for newly diagnosed patients.

The second paper describes an NSCLC patient who was treated with chemotherapy after initial genetic studies found none of the tumor-associated mutations known at the time. When her cancer continued to progress, additional molecular testing identified a rearrangement in ROS1 that Shaw and her colleagues had only recently described and shown could be treated with crizotinib. At first, the patient's tumor responded quickly, with symptomatic improvement after less than a week of crizotinib therapy. But after three months symptoms returned and her tumor resumed growing, eventually leading to the patient's death.

While the development of resistance to targeted cancer therapies is common, this is the first report of crizotinib resistance in ROS1-positive NSCLC. Detailed molecular analysis revealed a secondary mutation in the initial ROS1 rearrangement. The researchers then determined exactly how crizotinib binds to the ROS1 protein and showed that the new mutation, which is similar to one that confers resistance in ALK-positive tumors, interferes with binding and prevents the drug from inhibiting ROS1-driven tumor growth. Postmortem samples found this resistance mutation in every site to which the tumor had spread.

"Finding that mutation at all sites of disease suggests that it was an early and critical event in the development of resistance," says Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, one of the senior authors of the study. "A similar and highly resistant mutation also occurs in ALK-positive tumors treated with crizotinib, so finding therapies that can overcome this particular type of mutation will be very important."

###

Dong-Wan Kim, MD, PhD, of Seoul National University Hospital is co-lead author of the crizotinib/chemotherapy study, and Pasi Jnne, MD, PhD, Dana-Farber Cancer Institute is co-senior author. Additional co-authors include Benjamin Solomon, MB, BS, PhD, Peter MacCallum Cancer Centre, Melbourne, Australia; Fiona Blackhall, Ph.D., Christie National Health Service Foundation Trust, Manchester, U.K.; Ross Camidge, MD, PhD, University of Colorado at Aurora; Tony Mok, MD, Chinese University of Hong Kong; Vera Hirsh, MD, McGill University Health Centre; Keith Wilner, PhD, Pfizer Oncology. Mark M. Awad, MD, PhD, of the MGH Department of Medicine is lead author of the ROS1 resistance mutation study. Additional co-authors include Ryohei Katayama, PhD, Luc Friboulet, PhD, Elizabeth Lockerman and Justin F. Gainor, MD, MGH Medicine; Subba Digumarthy, MD, MGH Radiology; and James Stone, MD, PhD, Mari Mino-Kenudson, MD, and John Iafrate, MD, PhD, MGH Pathology.

Both studies were supported by grants from Pfizer, which markets crizotinib under the brand name Xalkori, and the second was also supported by the National Cancer Institute and the V Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."


[ Back to EurekAlert! ] [ | E-mail | Share 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/2013-06/mgh-mss053013.php

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