Novel therapeutic targets identified for small cell lung cancer

Public release date: 6-Sep-2012
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Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research

PHILADELPHIA Newly discovered molecular differences between small cell lung cancer and nonsmall cell lung cancer have revealed PARP1 and EZH2 as potential therapeutic targets for patients with small cell lung cancer, according to the results of a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

Currently, small cell lung cancer accounts for about 15 percent of lung cancer diagnoses in the United States. Patients with the disease will initially respond to chemotherapy, but almost all will have disease recurrence within a couple of months, according to Lauren A. Byers, M.D., assistant professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

"Unlike nonsmall cell lung cancer [NSCLC], where there have been new targeted drugs developed in the last ten years, the only currently approved treatments for small cell lung cancer are cytotoxic chemotherapies," Byers said. "Because most targeted therapies directly act on proteins, identifying if certain proteins are overexpressed in small cell lung cancer could have therapeutic applications."

In order to identify molecular differences between NSCLC and the more aggressive small cell lung cancer, Byers and colleagues used tools called reverse phase protein arrays. These allow the examination of the expression of about 200 proteins that are in key signaling pathways known to be involved in driving cancer growth.

"We discovered that small cell lung cancer and NSCLC have dramatically different protein profiles in terms of which proteins are 'turned on' and are driving the behavior of these cancers," Byers said. "In small cell lung cancer, proteins that were present at higher levels included several DNA repair proteins such as PARP1 and a protein involved in cancer stem cell renewal, EZH2."

PARP1 was further evaluated as a target for treatment of small cell lung cancer because there are several PARP inhibitors in advanced-stage clinical trials for other tumor types such as breast and ovarian cancers. Moreover, small cell lung cancer is sensitive to platinum-based chemotherapy, and PARP inhibitors have shown increased activity when used on other platinum-sensitive tumors.

Two PARP inhibitors were tested on small cell lung cancer cell lines alone and in combination with standard frontline chemotherapeutics, cisplatin and etoposide, or another commonly used chemotherapeutic, irinotecan. The inhibitors slowed the growth of small cell lung cancer cells, but not non-neuroendocrine NSCLC cells, according to the study. In addition, levels of PARP1 expression directly correlated with PARP inhibitor sensitivity.

As with many targeted drugs, it is possible that combining PARP inhibitors with other targeted drugs may significantly improve efficacy, according to Byers.

"Our next step is to begin to examine the use of PARP inhibitors in combination with other drugs in preclinical and clinical investigations of small cell lung cancer," she said.

###

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

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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: 6-Sep-2012
[ | E-mail | Share ]

Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research

PHILADELPHIA Newly discovered molecular differences between small cell lung cancer and nonsmall cell lung cancer have revealed PARP1 and EZH2 as potential therapeutic targets for patients with small cell lung cancer, according to the results of a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

Currently, small cell lung cancer accounts for about 15 percent of lung cancer diagnoses in the United States. Patients with the disease will initially respond to chemotherapy, but almost all will have disease recurrence within a couple of months, according to Lauren A. Byers, M.D., assistant professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

"Unlike nonsmall cell lung cancer [NSCLC], where there have been new targeted drugs developed in the last ten years, the only currently approved treatments for small cell lung cancer are cytotoxic chemotherapies," Byers said. "Because most targeted therapies directly act on proteins, identifying if certain proteins are overexpressed in small cell lung cancer could have therapeutic applications."

In order to identify molecular differences between NSCLC and the more aggressive small cell lung cancer, Byers and colleagues used tools called reverse phase protein arrays. These allow the examination of the expression of about 200 proteins that are in key signaling pathways known to be involved in driving cancer growth.

"We discovered that small cell lung cancer and NSCLC have dramatically different protein profiles in terms of which proteins are 'turned on' and are driving the behavior of these cancers," Byers said. "In small cell lung cancer, proteins that were present at higher levels included several DNA repair proteins such as PARP1 and a protein involved in cancer stem cell renewal, EZH2."

PARP1 was further evaluated as a target for treatment of small cell lung cancer because there are several PARP inhibitors in advanced-stage clinical trials for other tumor types such as breast and ovarian cancers. Moreover, small cell lung cancer is sensitive to platinum-based chemotherapy, and PARP inhibitors have shown increased activity when used on other platinum-sensitive tumors.

Two PARP inhibitors were tested on small cell lung cancer cell lines alone and in combination with standard frontline chemotherapeutics, cisplatin and etoposide, or another commonly used chemotherapeutic, irinotecan. The inhibitors slowed the growth of small cell lung cancer cells, but not non-neuroendocrine NSCLC cells, according to the study. In addition, levels of PARP1 expression directly correlated with PARP inhibitor sensitivity.

As with many targeted drugs, it is possible that combining PARP inhibitors with other targeted drugs may significantly improve efficacy, according to Byers.

"Our next step is to begin to examine the use of PARP inhibitors in combination with other drugs in preclinical and clinical investigations of small cell lung cancer," she said.

###

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

---

[ | 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/2012-09/aafc-ntt090412.php

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The Most Important Information Missing From Yelp

Tourists ride bicycles past the Golden Gate Bridge on May 24, 2012 in San Francisco, California.

Photograph by Justin Sullivan/Getty Images.

This article arises from Future Tense, a partnership of Slate, the New America Foundation, and Arizona State University. On Sept. 6, Future Tense will join Aventura Capital Partners in Mexico City to host a conference on the ?mobile city,? exploring how to make government information freely available to the public.

Having recently moved to a new city, I turn to Yelp whenever I am in need of a new restaurant, store, or even a refrigerator repairman. But as I learned the hard way, while Yelp can help me find the best calamari, it won?t tell me whether the restaurant has been spanked by the local health department.

Meanwhile, Yelp is filled with reviews that detail horrifying sanitation conditions at restaurants and bed-bug infestations at hotels. And yet these businesses? doors remain open because the local health department isn?t using the more than 30 million user reviews on Yelp to target their inspections. A small sampling:

?Bed Bugs (+not doing anything about it). STAY AWAY? ?Yelp San Francisco

?2 people in my party had to go to the hospital because they got bit by bed bugs! ?.. If you care about your health at all DO NOT STAY HERE! ??Yelp New York City

?Roach was crawling on the table right when they served the food. I jumped up and said, ?ROACH? and bunch of servers were trying to grab it. Needless to say, I was disgusted. They offer me free dinner and dessert for me and my friend but I never returned to that location.??Yelp Los Angeles

Around the world, Yelp and local governments collect complementary data, intended to help would-be customers make decisions about where to spend their money and what to put in their stomachs. Yet that information isn?t available in a central location, and that is creating a knowledge gap for consumers. And customers aren?t the only ones who can benefit from better crunching of ratings and reviews information. Building partnerships with companies that generate user content is an easy way for our cities to get free feedback on their services. What if government took a user-centered design approach to service delivery? They could use feedback provided on thousands of sites to identify what citizens want from their cities?and where to begin fixing things.

Cities are beginning to embrace the idea of opening data to the public. Last month, four major cities?San Francisco, New York City, Chicago, and Seattle?put statistics on things like crime reports, restaurant ratings, bed bug complaints, and public restroom locations online at cities.data.gov. Yelp and Google still can?t use the data easily, but the move signals that the cities are interested in putting their information in the hands of those who can mold it.

The phrase ?local government data? may make your eyes glaze, but those databases cover every municipal service we use daily. For example, a major frustration in urban centers is the amount of time spent trying to find a parking spot. To address this problem and improve air quality, San Francisco launched SFPark, a project that put sensors into 7,000 metered spaces and 12,250 in city garages. When one car leaves, the sensors communicate wirelessly with computers that in turn make the information available, in close to real-time. Now, imagine if Google or your car GPS used that data to show you where to find empty parking spots near an address you searched.

Or consider the Bike Accident Tracker, a tool created by the Bay Citizen that mapped all reported bicycling accidents in San Francisco over a five-year period. On the map, the intersection of Market and Castro was identified as a hot spot because it had five or more reported accidents. For cyclists, having access to this data is critical when planning routes to work or just getting from A to B in the city. Just this past April a cyclist hit and killed a pedestrian at that same intersection, according the San Francisco Chronicle. If accident data were integrated with a site like Google Maps, making the critical information more easily available, is it possible that the deadly accident at Market and Castro could have been avoided? I'm not sure, but it's worth looking into.

Source: http://feeds.slate.com/click.phdo?i=6a38e9f3cbe14b9552e023a126610038

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CSN: 'I want a championship. That's it,' Vick says

September 5, 2012, 9:00 am

He reached the playoffs the first time in 2002 as a 22-year-old scrambling phenom and took the upstart Falcons into hallowed Lambeau Field, where no opposing quarterback had ever won a playoff game. And he sprinted back to Atlanta with a stunning 27-7 win, the youngest quarterback in NFL history to win a playoff game.
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Two years later, he set an NFL quarterback playoff rushing record with 119 yards, completed 75 percent of his passes with touchdown passes to Alge Crumpler and Peerless Price, and the Falcons scored a franchise playoff-record 47 points in a 30-point rout of the Rams in the Georgia Dome on the way to the NFC Championship Game at the Linc.
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Michael Vick had already been to the playoffs twice, won a couple postseason games in record-setting fashion, joined Dan Marino and Bernie Kosar as the third quarterback to win playoff games in multiple seasons before his 25th birthday and reached an NFC Championship Game.

?It seemed so easy,? Vick marveled at his locker the other day. ?We went to the playoffs, we won playoff games, we came here to Philly and were within one game of the Super Bowl. I was young, and it just seemed so easy, and you start to think that it?s going to be like that every year, that you?re always going to go to the playoffs. But obviously it hasn?t happened like that.?
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Vick, who will make his sixth career opening-day start on Sunday, has started just one playoff game since that day in 2004 when the Eagles beat the Falcons 27-10 in the NFC title game and reached their only Super Bowl in the last 30 years, and he hasn?t won a postseason game in eight years.
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The Falcons didn?t reach the playoffs his last two years in Atlanta. Then came two years in prison, one year backing up Donovan McNabb and Kevin Kolb in Philly, a playoff loss to the Packers at the Linc in 2010 and a miserable 8-8 season last year.
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Vick isn?t a kid anymore. He?s 32 years old, the oldest player on the youngest Eagles team in 26 years and suddenly the sixth-oldest starting quarterback in the NFL, behind Peyton Manning, Tom Brady, Carson Palmer, Drew Brees and just a couple months younger than Tony Romo.
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Asked what would make 2012 a successful season, Vick ponders the question for a good 10 seconds, staring out into space as he stands at his locker.
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When he answers, he speaks in almost a whisper.
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?Man,? he says. ?I ain?t got no ring on my finger. I ain?t got one. That?s it. I don?t know what else.
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?I?ve been there. Playoffs is playoffs, you know? But that?s the road you?ve got to take to where you want to go. Like every quarterback, I want a championship. That?s it.?
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Two years ago, after his remarkable start following Kolb?s opening-day injury, Vick was the hottest player in the NFL. As of mid-December, the Eagles were 10-4 and on track for a first-round bye, and Vick was making a case for MVP honors.
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Then came that unfathomable, blizzard-delayed Tuesday loss to Joe Webb and the Vikings, a first-round playoff exit to the Packers and then last year.

Vick was 8-2 in his first 10 starts as an Eagle with 19 touchdowns and five interceptions but 7-8 with 20 touchdowns and 16 interceptions in 15 starts since.
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In his only playoff game since the NFC Championship Game in 2004, Vick was 20 for 36 for 292 yards with a touchdown and an interception on a potential game-winning pass on the final play of the game. The Packers won 21-16 on their way to the Super Bowl championship.
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?That playoff game in 2010, we wanted to win, and it was just like it suddenly happened and we were in the playoffs,? Vick says now. ?We just didn?t seize the moment. Now, it?s all about seizing the moment ? getting an opportunity and taking full advantage of it.
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?As a team, we just want to put ourselves in a position to compete. I think that?s where it all starts. Our short-term goals are to be the best that we can be, week in and week out, and that?s how we?ll advance to the postseason.?
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But coming off an utterly unremarkable preseason in which he didn?t complete a pass longer than five yards, Vick goes into the 2012 season with little of the cachet he?s had the last couple years.

He?s nobody?s MVP candidate anymore, nobody?s hotshot.
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?Eats me up,? he said. ?But it drives me. It motivates me, how quickly you can suddenly be overlooked.

?It?s always about your last game. I?ve always said you?re only as good as your last game, and not making the playoffs, you know, it does leave a bitter taste in your mouth because that?s what you?ve worked so hard for and the entire off-season is predicated on getting to the postseason and then when you don?t make it, it feels like it?s all for nothing. You did all that work, all for nothing. You let another opportunity pass you by.?
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The sub-context for this entire season will be owner Jeff Lurie?s dramatic disclosure last week that head coach Andy Reid will not return for a 15th season if the Eagles don?t improve dramatically over last year?s 8-8 disaster.
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?When I heard it, I didn?t need to hear that because I know exactly what we?re facing, what we want to accomplish this season, and if that?s not the goal, then what is it?? Vick said.
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?Our owner, he wants success for this football team, and he put the pieces in place for us and it?s up to us to go out and deliver. We just got to do it.?
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Lurie?s remarks don?t leave a lot of wiggle room for Vick. Vick understands that if Reid isn?t here, there?s a good chance he won?t be here, either.
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So another disappointing season means he could be a 33-year-old without a playoff win in nine years searching for a job, preparing to learn another new system, separated from his comfort zone of Reid and Marty Mornhinweg for the first time since he revived his career.
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?We feel like there is a need to win, and win quickly,? Vick said. ?Coach Reid talked to us [Monday] about staying the course, maintaining our focus, going in there week in and week out and controlling what we can control.
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?We can sit and talk all day until our faces turn blue, but ? we still have to make it happen. We have a lot of things to fight for, every individual in this locker room.?

E-mail Reuben Frank at rfrank@comcastsportsnet.com

Tags: michael vick, philadelphia eagles

Source: http://www.csnphilly.com/football-philadelphia-eagles/eagles-talk/For-older-and-wiser-Vick-its-Super-Bowl-?blockID=768073&feedID=704

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Obama gives himeself an 'incomplete' on economy

With 63 days to go to the election, President Obama says he still deserves an "incomplete" - rather than a letter grade - when asked to rate his performance on fixing the economy.

"You know, I would say incomplete," Obama said in an interview with Boulder, Colo., TV station KKTV.

"But what I would say is the steps that we have taken in saving the auto industry, in making sure that college is more affordable and investing in clean energy and science and technology and research, those are all the things that we are going to need to grow over the long term," he said. "One big piece of business that we still have to do is make sure our debts and deficits are brought under control, and I've put forward a balanced plan that would reduce our deficits by $4 trillion."

It's not the first time Obama has rated himself "incomplete" when asked about his first-term economic performance. But the latest assessment provides fresh fodder for Republican attacks at the start of the Democratic National Convention.

The interview excerpt has already been circulated by the RNC and Romney campaign as what they see as an acknowledgment of Obama's ineffectiveness.

In May, Obama told the ladies of ABC's "The View" that his record on the economy is still in progress. "It's still incomplete," he said. "We've still got work to do."

The president also told ABC's Jake Tapper the same thing during an October 2011 interview:

"Well, you know I'm not going to give myself a grade other than "incomplete" because the work that we started is not yet done," Obama told Tapper.

"But the fact is that the American people are rightly frustrated over what they see as a system in which responsibility is not always rewarded, where people who have done the right thing all their lives still seem to be struggling, that sense that the American dream is slipping away. I think that is something that helped get me elected but it hasn't been entirely solved yet, and in some ways it's gotten tougher for folks because of the financial crisis."

Also Read

Source: http://news.yahoo.com/obama-again-rates-himself-incomplete-economy-124305314--abc-news-politics.html

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Park City's beleaguered real estate market showing signs of life ...

(Kim Raff | The Salt Lake Tribune) People look out on the balcony of the 4,500-square-foot home on Dakota Trail in the Promontory in Park City Utah during the Park City Showcase of Homes on September 2, 2012.

Real estate ? Annual showcase highlights turnaround in market.

Over the past five years, Park City?s real estate market has suffered as sales of high-end real estate has plummeted. That?s why this year?s Park City Area Showcase of Homes has a distinctly upbeat vibe.

Luxury home sales nationwide are recovering, and Utah?s resort destination town is no exception. Home sales in the Park City area are at their highest level since the end of 2007, according to data from the Park City Board of Realtors. And home prices appear to have stopped falling, with the median selling price of $427,450 in the second quarter up from $412,500 at the same period last year.

?

If you go?

What ? Park City Area Showcase of Homes

When ? Through Monday, you can tour 11 high-end homes ranging in price from $600,000 to about $3.5 million.

Cost ? Tickets are $15 each and can be purchased at the first home in the showcase.

Info ? For more information, go to pcshowcaseofhomes.com

Another positive sign: The inventory of active listings in the Park City area is at the lowest level since 2007.

"It?s been a tough couple of years, but things are looking up," said Geri Strand, executive officer of the Park City Area Home Builders Association.

As is the case along the Wasatch Front, home-buying activity is increasing and in some cases, sellers are getting multiple offers ? a phenomenon not seen in nearly five years. While multiple offers are most common in the lowest price ranges, it starting to happen more in all price ranges as well. One of the homes in the Park City showcase, for example, has two buyers who bid up the asking price to $2.4 million from $2.2 million, Strand said.

This year?s showcase includes 11 homes priced at $600,000 to about $3.5 million. The number of featured homes is down from 20 in the boom years. But two years ago there were only nine homes.

While other parades of homes nationwide have moved toward more affordable luxury during the downturn, Park City?s showcase has kept its focus on luxury. Its lineup of homes this year, which range in size from about 3,000 to more than 7,000 square feet, have multi-car garages, gourmet kitchens, all the bells and whistles and "green" features as well as a plethora of bathrooms ? one home, for example, has seven bathrooms to go with five bedrooms.

As is the case in other areas of Utah as well as the rest of the country, home sales and prices have risen in part due to increased activity by bargain-hunters and investors ? not to mention super-low mortgage rates. Those who don?t need financing are buying homes, too.

"We?ve seen a lot of cash transactions," said Jeff Spencer, president-elect of the Park City Board of Realtors.

Some with cash are buying rentals; others are purchasing vacation homes.

story continues below

"Park City is a second, third, fourth home market," said Strand of the Park City Area Home Builders Association.

The Park City-area real estate market is a diverse one: Within the Park City limits, the median sales price is $1.1 million. The median sales price in the nearby Heber Valley, by comparison, though, is only $245,000 ? higher than Salt Lake County?s median but much more affordable than Park City.

Summit County real estate agents say they have noticed fewer deeply-discounted foreclosures hitting the market.

"The really incredible buys ? those have already been snatched up," Spencer said.

As just about everywhere else, the lowest-priced condos and homes ?in Park City that means anything under $400,000 or so ? don?t last long on the market. Sometimes they are snatched in hours.

The same dynamic of increased home sales and prices and lower inventory levels can be seen in Salt Lake County. A new report by the Salt Lake Board of Realtors shows that July marked the fourth consecutive month of rising home prices on a year-over-year basis.

The last time that home prices have risen for four consecutive months in the Salt Lake area was at the height of the market in 2007. The median price of all homes and condominiums sold in Salt Lake County in July was $192,000, up 1 percent compared to last year at the same time.

Next Page >

Copyright 2012 The Salt Lake Tribune. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Source: http://www.sltrib.com/sltrib/money/54814518-79/park-homes-lake-price.html.csp

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President Obama on Clint Eastwood: Big Fan!

President Barack Obama says he doesn't take the unexpected ribbing Clint Eastwood gave him at the RNC personally. In fact, he remains a big fan of the actor.

“I am a huge Clint Eastwood fan,” the president told USA Today.

“He is a great actor, and an even better director,” the Commander-in-Chief continued. “I think the last few movies that he’s made have been terrific.”

At the Republican National Convention, Eastwood roused the crowd with a 12-minute oratory that included a satirical interview with an invisible Obama.

The 82-year-old berated the President in the form of an empty chair. "Eastwooding" gave way to countless parodies and earned a place in the pop culture lexicon.

Coverage of Eastwood's speech in recent days eclipsed that of even Republican presidential candidate Mitt Romney, who took the stage shortly thereafter.

Most observers considered the routine bizarre (for better or worse), with some critics calling it borderline vulgar. Obama, however, was not offended by it.

“One thing about being president or running for president - if you’re easily offended, you should probably choose another profession,” the president said.

Obama, who did Tweet a response to the RNC speech, said not to expect any similar acts at this week's Democratic National Convention in Charlotte, N.C.

“I think we’ll be playing this pretty straight,” he said.

Who won the debate Thursday night?

Source: http://www.thehollywoodgossip.com/2012/09/president-obama-on-clint-eastwood-big-fan/

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Writing Your Way to the Past: 2012 Root Cellar Family History ...

Submissions are due October 1, 2012 for the Root Cellar Family History Writing Contest sponsored by the Sacramento Genealogical Society (SGS).? You do not need to be a member of the society and entries do not have to related to Sacramento or California.? According to the rules:

?The subject matter of the entries is to be family history or local-history stories, memoirs, or character sketches. Entries should be between 500 and 2,000 words in length. How-to articles or articles about the research process would not be acceptable for this contest.?

Winners will receive an assortment of prizes.? First place prizes include a six-month Ancestry.com membership, a copy of Family Tree Maker 2012, and a SGS membership.? Visit their website for complete rules and submission guidelines.

Need some convincing to write about your genealogy research?? See my post 4 Reasons to Convert Your Genealogy Research Into Writing.

Source: http://julietarr.blogspot.com/2012/09/2012-root-cellar-family-history-writing.html

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