Novel combination therapy shuts down escape route, killing glioblastoma tumor cells

Feb. 26, 2013 ? Glioblastoma, the most common and lethal form of brain tumor in adults, is challenging to treat because the tumors rapidly become resistant to therapy. As cancer researchers are learning more about the causes of tumor cell growth and drug resistance, they are discovering molecular pathways that might lead to new targeted therapies to potentially treat this deadly cancer.

Scientists at the Ludwig Institute for Cancer Research in San Diego worked collaboratively across the laboratories of Drs. Paul Mischel, Web Cavenee and Frank Furnari to investigate one such molecular pathway called the mammalian target of rapamycin or mTOR. This signaling pathway is hyperactivated in close to 90 percent of glioblastomas and plays a critical role in regulating tumor growth and survival. Therapies that inhibit mTOR signaling are under investigation as drug development targets, but results to date have been disappointing: mTOR inhibitors halt the growth, but fail to kill the tumor cells.

A study published this week in the Proceedings of the National Academy of Sciences uncovers an unexpected, but important molecular mechanism of mTOR inhibitor resistance and identifies a novel drug combination that reverses this resistance.

The story begins with a closer look at a gene-encoded protein called promyleocytic leukemia gene or PML. The study investigators explored the role of PML in causing resistance to mTOR inhibitor treatment. They found that when glioblastoma patients are treated with drugs that target the mTOR pathway, the levels of PML rise dramatically. Further, they showed that PML upregulation made the tumor cells resistant to mTOR inhibitors, and that if they suppressed the ability of the tumor cells to upregulate the PML protein, the tumor cells died in response to the mTOR inhibitor therapy.

"When we looked at cells in in vivo models and patients treated in the clinic, it became clear that the glioblastoma cells massively regulated PML enabling them to escape the effects of mTOR inhibitor therapy," reported senior author Paul Mischel, MD, Ludwig Institute member based at the University of California at San Diego.

"Our team hypothesized that if we could use a pharmacological approach to get rid of PML and combine it with an mTOR inhibitor, it could change the response from halting growth to cell death. The question was how?" added Mischel.

Previous research had shown that the use of low-dose arsenic could cause degradation of the PML protein in patients with leukemia. The team hypothesized that if arsenic could degrade PML, it may reverse resistance to mTOR inhibitors. The combination of mTOR and low-dose arsenic in mice indeed showed a synergistic effect, with massive tumor cell death along with very significant shrinkage of the tumor in mice with no ill side effects.

"Current therapy upregulates PML, turning off the mTOR signaling pathway. The tumor cells hide, waiting for the target signal to return," said Mischel. "When low-dose arsenic is added, not only does it stop the cell from returning, it shuts down the escape route killing the tumor cell."

These results present the first clinical evidence that mTOR inhibition promotes PML upregulation in mice and patients, and that it mediates drug resistance. The clinical relevance was confirmed when researchers looked at before- and after-treatment tissue samples from patients treated with mTOR inhibitors, confirming that PML goes up significantly in post treatment of mTOR inhibitors.

"These data suggest a new approach for potential treatment of glioblastoma," said Mischel. "We are moving forward to test that possibility in people."

Post-doctoral students Akio Iwanami and Beatrice Gini from the Mischel lab, as well as Ciro Zanca from the Furnari/Cavenee lab also contributed significantly to this paper.

This work was supported by the Japan Society for the Promotion of Science, the Uehara Memorial Foundation, three NIH grants: NS73831, CA 119347 and P01-CA95616, the Ziering Family Foundation in Memory of Sigi Ziering and the Ben and Catherine Ivy Foundation.

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Story Source:

The above story is reprinted from materials provided by Ludwig Institute for Cancer Research.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. A. Iwanami, B. Gini, C. Zanca, T. Matsutani, A. Assuncao, A. Nael, J. Dang, H. Yang, S. Zhu, J. Kohyama, I. Kitabayashi, W. K. Cavenee, T. F. Cloughesy, F. B. Furnari, M. Nakamura, Y. Toyama, H. Okano, P. S. Mischel. PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1217602110

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/BY1dFrC_5v8/130226135525.htm

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British cardinal will skip upcoming papal conclave

VATICAN CITY (AP) ? In a season of startling change for the Catholic Church, the latest break with tradition was as unexpected as it was a wakeup call to the 115 men who will elect the next pope.

Britain's highest-ranking Catholic leader resigned and removed himself Monday from the upcoming conclave, saying he did not want allegations that he engaged in improper conduct with priests to be a distraction during the solemn process of choosing the next leader of the church's 1.2 billion-member flock.

It was the first time a cardinal has recused himself from a conclave because of personal scandal, according to Vatican historians.

The Vatican insisted that Pope Benedict XVI accepted Cardinal Keith O'Brien's resignation purely because O'Brien was nearing the retirement age of 75 ? not because of the accusations.

But O'Brien himself issued a statement Monday saying he would skip the conclave because he wanted to avoid becoming the focus of media attention at such a delicate time.

"I do not wish media attention in Rome to be focused on me ? but rather on Pope Benedict XVI and on his successor," said O'Brien, who had been archbishop of St. Andrews and Edinburgh. "However, I will pray with them and for them that, enlightened by the Holy Spirit, they will make the correct choice for the future good of the church."

Through his spokesman, O'Brien has contested allegations made Sunday in a British newspaper that three priests and a former priest had filed complaints to the Vatican alleging that the cardinal acted inappropriately with them.

There were no details about the behavior, and the Observer newspaper did not name the priests. It said the allegations date back to the 1980s.

The cardinal's action comes in the wake of a grassroots campaign to shame another cardinal, retired Los Angeles Cardinal Roger Mahony, into refraining from participating because of his role protecting sexually abusive priests.

Mahony, however, has defiantly said he would participate in the voting for the new pope.

The difference boils down to the fact that O'Brien himself was accused of improper behavior, whereas Mahony was shown to have covered up for other priests who raped and molested children. That distinction has long shielded bishops from Vatican sanction.

Several other cardinals who will elect the next pope have been accused ? and some have admitted ? to failing to protect children from abusive priests. If all of them were to recuse themselves for negligence, the College of Cardinals would shrink by quite a few members.

Terrence McKiernan of BishopAccountability.org, an online database of records on clergy abuse cases, urged other whistleblowers to come forward if they have information about other compromised cardinal electors.

"It is a public demonstration of the role that clerics with inside information can have in bringing accountability to a church where secrecy has led to a crisis of sexual misconduct," he said. "Cardinals who are tainted by the crisis cannot choose the person who will solve it."

With O'Brien's recusal and the decision of a frail Indonesian cardinal to stay home, there are expected to be 115 cardinals under age 80 who are eligible to vote in the conclave.

Separately Monday, Benedict changed the rules of the conclave, allowing cardinals to move up the start date if all of them arrive in Rome before the usual 15-day waiting period between the end of one pontificate and the start of the conclave. It was one of his last acts as pope before stepping down Thursday.

The date of the conclave's start is important because Holy Week begins March 24, and Easter Sunday is March 31. In order to have a new pope in place for the church's most solemn liturgical period, he would need to be installed by Sunday, March 17, a tight timeframe if a conclave were to start on March 15, as previous rules would have required.

Also Monday, Benedict decided that the contents of a secret investigation into the 2012 leaks of Vatican documents won't be shared with the cardinals ahead of the conclave. Benedict met Monday with the three elderly cardinals who conducted the probe and decided that "the acts of the investigation, known only to himself, remain solely at the disposition of the new pope," a Vatican statement said.

Speculation has been rife in the Italian media that the three cardinals ? Julian Herranz, Jozef Tomko and Salvatore De Giorgi ? would be authorized to share the information with fellow cardinals before the conclave. That assumed the cardinal electors would want to know details about the state of dysfunction in the Vatican bureaucracy and on any potentially compromised colleagues before possibly voting one into office.

Benedict appointed the three men last year to investigate the origins of leaks, which revealed petty wrangling, corruption, cronyism and even allegations that senior Vatican officials conspired to out a prominent Catholic newspaper editor as gay.

The pope's butler was convicted of aggravated theft in October for having stolen the papers and given them to a journalist who then published them in a blockbuster book.

The three cardinals cannot share the full contents of their investigation, but it's unclear if they could give subtle hints about potential papal candidates to the electors. The Vatican's assertion that only the pope knew the contents of the dossier was a clear message to readers of Italian newspapers, which have run several articles purporting to know the contents of the report.

O'Brien's decision to remain home rather than participate in the conclave made his the first head to roll in the remarkable two weeks since Benedict, 85, stunned the world and announced he was becoming the first pope in 600 years to resign.

Monday's announcement marked a dramatic end to a career that got off to a rocky start when in 2003, as a condition of being made a cardinal, O'Brien was forced to issue a public pledge to defend church teaching on homosexuality, celibacy and contraception. He was pressured to make the pledge after he had called for a "full and open discussion" on such matters.

At the time, O'Brien said he had been misunderstood and wanted to clarify his position. But it's clear now he never really changed his mind. On Friday, three days before his resignation was made public, O'Brien told the BBC that celibacy should be reconsidered since it's not based on doctrine but rather church tradition and "is not of divine origin."

It appeared to be something of a parting shot, reasserting beliefs that he had kept quiet for a decade.

At home, at O'Brien's St. Mary's Roman Catholic Cathedral in Edinburgh, his decision was met with shock and disbelief.

"There are a lot of unanswered questions here, and I am unhappy about that. People can make such serious charges while remaining anonymous," said David Murphy, an administrator from Edinburgh. "It's like he's been hounded out of office without a proper chance to defend himself."

But Peter Mitchell, a churchgoer from Fife, conceded that the church may have to brace itself for scandal. "These don't appear to be random allegations. We are talking about three serving priests who are being very specific, and I don't think they would lie in this way."

O'Brien said in a statement that he was in "indifferent health" and had offered his resignation last November ? a statement confirmed by the Vatican spokesman, the Rev. Federico Lombardi.

Lombardi said the pope had merely acted on the resignation now as he clears up final tasks before stepping down. Usually the pope waits until after a cardinal's 75th birthday to accept a resignation. In this case, Benedict acted a few weeks early.

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Katz reported from London

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Associated Press Writer Ben McConville in Edinburgh also contributed to this report.

Source: http://news.yahoo.com/british-cardinal-skip-upcoming-papal-conclave-210958525.html

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Powers to offer Iran sanctions relief at nuclear talks

ALMATY (Reuters) - Major powers will offer Iran some sanctions relief during talks in Almaty, Kazakhstan, this week if Tehran agrees to curb its nuclear program, a U.S. official said on Monday.

But the Islamic Republic could face more economic pain if it fails to address international concerns about its atomic activities, the official said ahead of the February 26-27 meeting in the central Asian state, speaking on condition of anonymity.

"There will be continued sanctions enforcement ... there are other areas where pressure can be put," the official said, on the eve of the first round of negotiations between Iran and six world powers in eight months.

A spokesman for European Union foreign policy chief Catherine Ashton, who leads the talks with Iran on behalf of the powers, said Tehran should understand that there was an "urgent need to make concrete and tangible progress" in Kazakhstan.

Both Russia and the United States stressed there was not an unlimited amount of time to resolve a dispute that has raised fears of a new war in the Middle East.

"The window for a diplomatic solution simply cannot by definition remain open forever. But it is open today. It is open now," U.S. Secretary of State John Kerry said in London.

"There is still time but there is only time if Iran makes the decision to come to the table and negotiate in good faith," he added in a news conference in London. "We are prepared to negotiate in good faith, in mutual respect, in an effort to avoid whatever terrible consequences could follow failure."

It was not clear what he meant by "terrible consequences." Top U.S. officials have repeatedly said the United States will not take any options off the table, code for the possibility of a military strike. They also fear Iran's getting a nuclear weapon could set off an arms race across the Middle East.

Russian Deputy Foreign Minister Sergei Ryabkov said there was "no more time to waste", Interfax news agency quoted him as saying in Almaty.

The immediate priority for the powers - the United States, Russia, China, Germany, Britain and France - is to convince Iran to halt its higher-grade enrichment, which is a relatively short technical step away from potential atom bomb material.

Iran, which has taken steps over the last year to expand its uranium enrichment activities in defiance of international demands to scale it back, wants a relaxation of increasingly harsh sanctions hurting its lifeline oil exports.

Western officials say the Almaty meeting is unlikely to produce any major breakthrough, in part because Iran's presidential election in June may make it difficult for it to make significant concessions before then for domestic reasons.

But they say they hope that Iran will take their proposals seriously and engage in negotiations to try to find a diplomatic settlement.

"No one is expecting to walk out of here with a deal but ... confidence building measures are important," one senior Western official said.

The stakes are high: Israel, assumed to be the Middle East's only nuclear-armed arsenal, has strongly hinted at possible military action to prevent its old foe from obtaining such arms. Iran has threatened to retaliate if attacked.

GOLD SANCTIONS RELIEF?

The U.S. official said the powers' updated offer to Iran - a modified version of one rejected by Iran in the unsuccessful talks last year - would take into account its recent nuclear advances, but also take "some steps in the sanctions arena".

This would be aimed at addressing some of Iran's concerns, the official said, while making clear it would not meet Tehran's demand of an easing of all punitive steps against it.

"We think ... there will be some additional sanctions relief" in the powers' revised proposal," the official said, without giving details.

Western diplomats have told Reuters the six countries will offer to ease sanctions on trade in gold and precious metals if Iran closes its Fordow underground uranium enrichment plant.

Iran has indicated, however, that this will not be enough.

Tehran denies Western allegations it is seeking to develop the capability to make nuclear bombs, saying its program is entirely peaceful. It wants the powers to recognize what it sees as its right to refine uranium for peaceful purposes.

The U.S. official said the powers hoped that the Almaty meeting would lead to follow-up talks soon.

"We are ready to step up the pace of our meetings and our discussions," the official said, adding the United States would also be prepared to hold bilateral talks with Tehran if it was serious about it.

Ashton's spokesman, Michael Mann, said the updated offer to Iran was "balanced and a fair basis" for constructive talks.

(Additional reporting by Yeganeh Torbati and Dimitry Solovyov and by Arshad Mohammed and Mohammed Abbas in London; Editing by Jon Hemming)

Source: http://news.yahoo.com/major-powers-offer-iran-sanctions-relief-nuclear-talks-125535303.html

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One corner of Manhattan still a ghost town months after Sandy

NEW YORK (AP) -- The historic cobblestone streets and 19th-century mercantile buildings near the water's edge in lower Manhattan are eerily deserted, a neighborhood silenced by Superstorm Sandy.

Just blocks from the tall-masted ships that rise above South Street Seaport, the windows of narrow brick apartment buildings are still crisscrossed with masking tape left by their owners before the storm. Store interiors are stripped down to plywood and wiring. Restaurants are chained shut, frozen in time, saddled with electrical systems that were ruined by several feet of salt water that raced up from the East River and through their front doors.

"People have no clue that this corner of Manhattan has been hit so badly," said Adam Weprin, manager of the Bridge Cafe, one of the city's oldest bars that sits on a quiet street near the seaport. "Right now, it's a ghost town and a construction site."

Nearly four months after the storm, roughly 85 percent of small businesses near the South Street Seaport are still boarded up. It could be months before some reopen, while others may never return. On Fulton Street, the wide tourist-friendly pedestrian walkway that comprises the seaport's main shopping district, not a single one of the major chain stores ? which include Coach, Ann Taylor and Brookstone ? has reopened.

Among local business owners, there is a pervasive sense that their plight has been ignored by the rest of the city. A state senator who represents the area estimates at least 1,000 jobs were lost in lower Manhattan ? 450 of them in the seaport neighborhood alone.

From its red wood-frame building in the shadow of the Brooklyn Bridge, the Bridge Cafe has dealt with its share of changes over the last two centuries, including stints as a Civil War-era brothel and a bootlegging speakeasy during Prohibition. It has endured economic slumps, nor'easters and the Sept. 11 terrorist attacks. But after the basement was flooded to the rafters and water destroyed the building's wood foundation, Weprin faced the prospect of shutting its doors for good.

"The neighborhood's been beaten," Weprin said. "You walk around here and it's like Chernobyl. At night, it's vacated."

The small businesses of the seaport were far less resilient than the neighboring skyscrapers that house many of lower Manhattan's large financial companies.

Some corporations were displaced for weeks after the storm, forced to relocate to temporary office space farther uptown while flood-damaged skyscrapers fixed their infrastructure and moved electrical systems to higher floors. Con Edison said 10 major buildings remained without power as of Feb. 13, most operating on emergency generators.

At 110 Wall St., a 27-story office tower that occupies a full block near the New York Stock Exchange, all leases were terminated because the building was so badly damaged by flooding. It remains empty while its management company comes up with a long-term plan for weathering future storms.

"How do we protect the lobby?" said William Rudin, the company's CEO. "How do we protect the retail spaces?"

Spotty phone and Internet service also hampered business activity after underground copper cables operated by Verizon, the area's largest network provider, were wrecked by flooding. By mid-February, Verizon said 10 percent of its customers still had little or no service.

It's unclear how many residents of lower Manhattan fled the neighborhood after Sandy. But 2 Gold St., a flood-damaged luxury residential skyscraper with nearly 1,000 residents, did not allow tenants to start moving back in until last week.

"These offices, these high-rise apartments, they need to be reoccupied," said Lee Holin, who owns Meade's Restaurant, which sits on the edge of the seaport a few blocks from Sandy-damaged skyscrapers on Water Street. "All of our customers who live there have not been here in a long time."

Meade's was only able to reopen thanks to a $25,000 grant that Holin received from the Downtown Alliance, a neighborhood association that has doled out 100 grants to small businesses totaling about $1.5 million.

The grant program was so popular that it was suspended two weeks after its debut in mid-November.

"We don't have a lot of traffic," said Nicole Osborne, who was tending the bar at Meade's on a weekday afternoon. "It's like we've been forgotten."

In the darkened window of Stella Manhattan Bistro, an Italian restaurant on Front Street, hung an American flag reminiscent of those displayed all over the city after Sept. 11. Alongside it, someone had posted a sign that said: "Thank you for all your support. Stay strong."

Most of the Front Street buildings had a geothermal heating and cooling system that was destroyed in the flood, said Jordan Barowitz, a spokesman for the developer, The Durst Organization, Inc. The repairs, which include moving the mechanical systems to the roof, are expected to drag on for months.

"We hope that they will come back," Barowitz said of the shuttered businesses. "It's very challenging."

The future of the South Street Seaport is equally uncertain. Howard Hughes Corp, which controls the former 19th-century counting houses that are home to the retail chains, said it does not yet know which ? if any ? of the major retailers will come back. The hope is to have Fulton Street in working order again before Memorial Day, when the summer season kicks off and the seaport will desperately need an influx of visitors.

But in a case of unfortunate timing, Pier 17, the shopping mall housed inside a rustic wooden building on the pier, is slated to close for a long-planned renovation in June that will transform it into a modern glass-walled structure with a rooftop plaza. The impending renovation has only added to the misery of shop owners who lost so much revenue since the storm and haven't recouped their losses.

Milad Doos, an immigrant from Egypt, is planning to close his jewelry and collectibles store for good.

"Like you see, there's nobody," said Doos, who earned just $5 on a recent afternoon. "After the storm, this whole place has become dead place."

At the Bridge Cafe, most of the wood foundation will be gutted, sparing only two pillars and a wall behind the bar that are part of the original building. Repairs will cost around $400,000.

Weprin, who has no flood insurance, launched a fundraising page online to appeal for financial help from the restaurant's many loyal patrons. To his astonishment, many of them didn't even realize the place was closed.

That's because nobody has frequented the neighborhood for weeks.

"During the day, you have tourists who are coming to look at the carnage," Weprin said. "That's about it. Before Sandy, it was a neighborhood."

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Associated Press Writer Tom Hays contributed to this report.

Source: http://news.yahoo.com/nyc-seaport-ghost-town-months-074608566.html

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Raul Castro announces retirement in 2018

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Enrique De La Osa / REUTERS

Cuba's President Raul Castro (R) gestures while talking to the media at the Soviet Soldier monument in Havana February 22, 2013.

By Marc Frank, Reuters

HAVANA - Cuban leader Raul Castro announced on Sunday he would step down from power after his second term as president ends in 2018, and the new parliament named a 52-year-old rising star to become his first vice president and most visible successor.

Castro, 81, made the announcement in a nationally broadcast speech shortly after the Cuban National Assembly elected him to a second five-year term in the opening session of the new parliament.

"This will be my last term," Castro said.

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In a surprise move, the new parliament named as his first vice president Miguel Diaz-Canel, a member of the political bureau who rose through the party ranks in the provinces to become the most visible possible successor to Castro. Diaz-Canel would succeed Castro if he cannot serve his full term.

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The new government will almost certainly be the last headed up by the Castro brothers and their followers who have ruled Cuba since they swept down from the mountains in the 1959 revolution.

Raul Castro starts his second term immediately, leaving him free to retire in 2018, aged 86.

Former president Fidel Castro joined the meeting, in a rare public appearance. Since falling ill in 2006 and ceding the presidency to his brother, the elder Castro, 86, has given up official positions except as a deputy in the National Assembly.

Governments, Cuba watchers and Cubans were keenly observing to see if any new, and younger, faces might appear among the Council of State members, in particular its first vice president and five vice presidents.

Their hopes were partially fulfilled with Diaz-Canel's ascension. He replaces former first vice president, Jose Machado Ventura, 82, who will continue on as one of five vice presidents. Commander of the Revolution Ramiro Valdes, 80, and Gladys Bejerano, 66, the comptroller general were also re-elected as vice presidents.

Two other newcomers, Mercedes L?pez Acea, 48, first secretary of the Havana communist party, and Salvador Valdes Mesa, 64, head of the official labor federation, also earned vice presidential slots.

Former vice president Esteban Lazo, member of the political bureau of the Communist Party, 68, left his post upon being named parliament president on Sunday, replacing Ricardo Alarcon, who served for 20 years.

Six of the Council's top seven members sit on the party's political bureau which is also lead by Castro.

The National Assembly meets for just a few weeks each year and delegates its legislative powers between sessions to the 31-member Council of State, which also functions as the nation's executive through the Council of Ministers it appoints.

Eighty percent of the 612 deputies, who were elected in an uncontested vote February 3 and with an average age under 50, were born after the Revolution.

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Source: http://worldnews.nbcnews.com/_news/2013/02/24/17077928-raul-castro-announces-retirement-in-2018?lite

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Celebrity Baby Alert: Who is (NOT) Expecting?

Source: http://www.thehollywoodgossip.com/2013/02/celebrity-baby-alert-who-is-not-expecting/

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Happy Everything Collection & Three Attachments ($197 value)

February 24, 2013 by Aimee ?

I love adding simple touches to my home that get my family excited about upcoming small and big events, the Happy Everything Collection is the perfect addition to my home!? This collection can be found at Coton Colors ? a store with unique, personalized, handcrafted pottery, Christmas ornaments, and creative giftware for everyone and I am so excited to host a giveaway from them for you.

Here?s how the Happy Everything Collection works?start off by choosing a neutral or colorful base platter, soap dispenser, frame, cookie jar?etc, which has unbelievably strong velcro?ready for the addition of super cute attachments to represent whatever it is you are celebrating throughout the year?there are over 80 additional attachment options, everyday fun, sports-oriented designs, an a great variety of holiday!? I have the Happy Everything Collection and it goes great with my neutral home decor?there?s the right size, shape, and color of base products for every home.? Coton Colors has a very cute blog?that you will want to check out too, it is adorable and filled with lots of inspiration.

Win a neutral Happy Everything Platter with stand and a frosty, menu, and party hat attachment!? Easy Rafflecopter entry, but first, head on over to Coton Colors and check out their website, then leave a comment below in the comment section with what you LOVE.

a Rafflecopter giveaway

Disclaimer: I was provided with items to review from Coton Colors, but the opinions are my own. These are beautiful products and I think you would love them!

It's Overflowing is a lifestyle blog, founded by Aimee Lane, sharing simply inspired diy & decor projects, useful crafts, organization tips, and photography tutorials. Subscribe, learn more, or connect with Aimee on Twitter, Facebook, Instagram, or Pinterest. Subscribe to Barns & Noodles for Aimee's favorite recipes.

It's Overflowing is an amazon affiliate.

Disclosure of Material Connection: I received one or more of the products or services mentioned in some of my posts in the hope that I would give it a good review on my blog. Regardless, I only recommend products or services I use personally and believe my readers will enjoy. I am disclosing this in accordance with the Federal Trade Commission?s 16 CFR, Part 255: ?Guides Concerning the Use of Endorsements and Testimonials in Advertising.?

Source: http://www.itsoverflowing.com/2013/02/happy-everything-collection/

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