Possible new acute leukemia marker, treatment target identified

May 13, 2013 ? A study has identified microRNA-155 as a new independent prognostic marker and treatment target in patients with acute myeloid leukemia that has normal-looking chromosomes under the microscope (that is, cytogenetically normal acute myeloid leukemia, or CN-AML).

The study was led by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James). The researchers found that when microRNA-155 (miR-155) is present at abnormally high levels in CN-AML cells, patients are less likely to have a complete remission, and they experience a shorter disease-free period and shorter overall survival. The effect is independent of other known prognostic gene mutations present in the cells.

Published in the Journal of Clinical Oncology with an accompanying editorial and an "Understanding the Pathway" article, the findings suggest that miR-155 plays a pivotal role in CN-AML development, and that it could be a valuable target for the emerging class of drugs designed to inhibit microRNAs, says first author Dr. Guido Marcucci, professor of hematology, a leukemia specialist and associate director for Translational Research at the OSUCCC -- James.

"MiR-155 would be relatively easy to measure at the time of diagnosis," Marcucci says. "We believe it will prove to be a good marker for stratifying patients according to recurrence risk and a good target for emerging compounds designed to inhibit microRNAs."

Principal investigator Dr. Clara D. Bloomfield, Distinguished University Professor and Ohio State University Cancer Scholar and Senior Advisor and William Greenville Pace III Endowed Chair in Cancer Research notes that, "Overall, our findings indicate that miR-155 expression is a strong and independent prognostic marker in CN-AML, and they provide clinical validation of data from preclinical models that support a crucial role of miR-155 in leukemia."

The researchers also note that because a molecule called NF-kB is believed to regulate miR-155, treatments that inhibit that molecule might also help patients with high miR-155 levels.

Cells use microRNA molecules to help regulate the kinds and amount of proteins they make. Abnormal levels of certain microRNAs are likely to play a key role in cancer development. Abnormally high expression of miR-155 is associated with lymphoma, aggressive chronic leukemias and certain solid tumors, and microRNA levels have been associated with patient survival.

For this study, Marcucci, Bloomfield and their colleagues analyzed bone-marrow or blood specimens from 363 CN-AML patients, 153 of whom were under age 60 and 210 were age 60 and over. All were treated on Cancer and Leukemia Group B (CALGB) clinical trials.

The researchers evaluated the association of abnormal miR-155 expression levels with clinical and molecular characteristics and with disease-free survival and overall survival.

The study's key technical findings include:

• Overall, patients with high miR-155 expression were about 50 percent less likely to achieve complete remission, and to have a 60 percent increase in the risk of death compared to patients with low miR-155 expression.
• High miR-155 expression was associated with pro-survival, proliferation and inflammatory gene activity, suggesting a pivotal role in leukemia development.
• In patients under age 60, higher miR-155 expression was associated with a lower complete response rate, and shorter disease-free survival and overall survival; in older patients, higher miR-155 expression was associated only with a lower complete response rate and shorter overall survival.
• The difference between older and younger patients may be related to differences in the intensity of consolidation therapy administered to younger versus older patients, as well as to biological differences.

Funding from the NIH/National Cancer Institute (grants CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657 and CA140158), The Coleman Leukemia Research Foundation, the Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation, the Pelotonia Fellowship Program and the Conquer Cancer Foundation supported this research.

Other researchers involved in this study were Klaus H. Metzeler, Stefano Volinia, Yue-Zhong Wu, Krzysztof Mr?zek, Susan P. Whitman, Jason H. Mendler, Sebastian Schwind, Heiko Becker, Ann-Kathrin Eisfeld, Ramiro Garzon and Michael A. Caligiuri of The Ohio State University; Kati Maharry, Deedra Nicolet and Jessica Kohlschimdt of Ohio State and of the Alliance for Clinical Trials in Oncology Statistics and Data Center; Andrew J. Carroll of University of Alabama at Birmingham; Bayard L. Powell of Wake Forest University; Jonathan E. Kolitz of Monter Cancer Center; and Richard M. Stone of Dana Farber Cancer Institute.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/lnHaUgfJ0lY/130513131509.htm

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Deadly bomb strikes civilian area in east Libya

TRIPOLI, Libya (AP) ? A deadly car bomb exploded Monday near a hospital in a busy area packed with civilians in the eastern Libyan city of Benghazi, destroying part of the facility, officials said.

Officials gave conflicting casualty figures, with death tolls ranging from three to 10 in the chaotic aftermath of the attack.

Benghazi, which was the birthplace of the revolution that led to the ouster of dictator Moammar Gadhafi, has suffered a series of assassinations and other attacks, including the Sept. 11 assaults on the U.S. diplomatic mission that killed Ambassador Chris Stevens and three other Americans.

The oil-rich North African nation is still largely dominated by militias, many including fighters who battled Gadhafi's forces during the 2011 civil war, and many attacks are blamed on them as infighting is rampant in the battle for control.

But witnesses and analysts said Monday's explosion stood out because it struck during the day in a crowded area, putting civilians at risk.

"The bombing is significant in that it is the first that targets civilians," Frederic Wehrey of the Carnegie Endowment for International Peace said in an email.

"The bombing is going to put renewed pressure on an already embattled Ministry of Interior to reign in the revolutionary brigades," he added, referring to militias.

The blast took place on Beirut Street, a residential and shopping area in Libya's second-largest city and quickly drew protesters to the streets to call for stronger security measures. Other vehicles on the street were destroyed, and the windows of nearby buildings were shattered.

Jalaa hospital, just a few hundred meters (yards) away from the explosion, had been protected for months by Ansar al-Shariah, an extremist group that disbanded its work as a militia following protests by Benghazi residents after the attack on Stevens. The hospital is now secured by a mix of militias and special army forces.

Libyan Prime Minister Ali Zidan acknowledged the government was in part to blame for the instability and lawlessness that continue to plague the North African nation 19 months after Gadhafi was captured and killed.

"Authorities did not take adequate precautions," he said in remarks carried live on Libya's al-Ahrar TV channel.

Zidan, who did not take questions from reporters, said that Libya is still trying to create a security force capable of tackling such attacks.

It was not immediately clear who was behind the attack. Zidan suggested it could be Gadhafi supporters or "other factions" ? leaving the door open for a range of groups.

In New York, the U.N. Security Council " condemned in the strongest terms the deadly attack" and "underlined the need to bring the perpetrators of this act to justice." It urged all countries to cooperate with Libyan authorities to pursue the case.

Fathi al-Ubaidi, a top commander of Libya Shield, an umbrella group of militias aligned with the military, said one man was arrested but refused to give further details.

Small protests erupted in Benghazi and Tripoli after the attack, with people chanting: "Where is the army" and "Oh Zidan, oh Zidan, the Libyan people's blood is everywhere."

Witnesses and other residents said the daytime explosion was unusual since past attacks have occurred at night and have targeted police stations or foreign missions.

"The mood is bad because the explosion took everybody by surprise," said International Crisis Group consultant Claudia Gazzini, who was in Benghazi. "People in Benghazi see this as a turning point because it is the first time to see an indiscriminate attack with civilian casualties."

Dr. Habib Mohammed el-Obeidy said three bodies had been brought to Benghazi's main Jalaa Hospital after the explosion that struck just outside its doors. He blamed the confusion over the number of dead on the fact that body parts were brought in in several bags, making a final casualty figure difficult to assess.

He also said there was no security on the street.

"When we see police stations hit we understand because a large portion of security worked closely with Gadhafi, but this is hitting a civilian area with no security in sight. It is as if someone is shuffling cards around," he said.

Over the weekend explosions went off outside three Benghazi police stations. No one claimed responsibility for those attacks.

Senior security official Abdel-Salam al-Barghathi said 10 people had been killed in the bombing when attackers used a remote control to detonate the explosives-laden car, which was parked outside a bakery near the hospital. Weapons including Kalashnikov rifles were found inside the car, he said.

"This is meant to kill civilians and to destabilize the security of the city of Benghazi," he said.

The Tripoli-based Interior Minister Ashour Shwayel said earlier in an interview with al-Ahrar TV that two or three people were killed. Meanwhile, Benghazi police chief Tarek al-Kharaz said at least 13 people were killed and 41 wounded.

Nozha al-Mansouri, a 38 year-old resident of Bengazhi, said the attack was likely meant to embarrass the central government.

"Today's incident definitely draws attention to the government's shortcomings," she said.

Militias have grown bold in the past two years, taking on greater roles post-Gadhafi by providing border protection and security of airports to fill the vacuum as the central government has been unable to exert control.

But Libyans had hoped a return to normalcy after militias ended their nearly two week siege of two government ministries in the capital over the weekend, demanding that the prime minister and other Cabinet officials resign.

___

Batrawy contributed to this report from Cairo.

Source: http://news.yahoo.com/deadly-bomb-strikes-civilian-area-east-libya-202707379.html

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Worst Performance Ever By a White House Press Secretary (Powerlineblog)

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Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/305081016?client_source=feed&format=rss

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Senator blasts IRS over 'Tea Party' apology as hearings loom

By Patrick Temple-West and Kim Dixon

WASHINGTON (Reuters) - A senior Republican senator condemned the Internal Revenue Service on Saturday for singling out conservative political groups for extra scrutiny, while the IRS described the incident as isolated and not politically motivated.

"When we start letting the IRS impose its will on people and doing it in a partisan, biased way, then we're exposing our country to some real problems," Senator Orrin Hatch told Reuters.

The Utah lawmaker spoke a day after an IRS official apologized for the practice, which has embarrassed the tax-collecting agency and could haunt the Obama administration.

"I suspect there are some whistleblowers ready to come out and expose this and that's why (the IRS) came out and apologized ... . Whoever did this ought to be exposed," Hatch said.

An investigative report on the issue is expected within days from the Treasury Department's inspector general for tax administration.

Representative Darrell Issa, a California Republican, requested the report last year after accusing the IRS of targeting conservative groups.

He has vowed to investigate, and the House committee he chairs has the power to issue subpoenas.

At least one other congressional panel intends to hold hearings, giving Republicans multiple opportunities to hammer the agency and the White House over the affair that had been brewing for months.

BEYOND CINCINNATI?

In an interview with Reuters before speaking at a legal conference, Hatch said the IRS should "come forth and quit acting like this was just some obscure number of employees in Cincinnati," an IRS paperwork processing center.

"I doubt seriously if it was just in Cincinnati," he said on the sidelines of the American Bar Association conference in Washington.

On Friday at the same conference, Lois Lerner, director of the IRS tax-exempt office, publicly apologized for subjecting conservative political groups to "inappropriate" scrutiny.

In a practice that drew complaints during the 2012 general election campaign, groups with the words "Tea Party" or "patriot" in their names were flagged for closer IRS review when they applied to the agency for tax-exempt status.

"We would like to apologize for that," said Lerner. She said the practice "was absolutely incorrect and it was inappropriate."

She also said the scrutiny was "absolutely not" influenced by the Obama administration.

White House spokesman Jay Carney said after Lerner spoke that the IRS action as they were reported were "inappropriate."

"And we would fully expect the investigation to be thorough and for corrections to be made in a case like this," he said.

Lerner said revenue agents in Cincinnati targeted the conservative groups "without talking to managers" and that politics had played no role in the screening.

The Cincinnati staffers were trying to deal with a crush of applications for tax-exempt status by using key words to get through the paperwork faster, she said.

About 300 applications were initially flagged for closer scrutiny. Of those, 75 were chosen for that treatment based on the presence of the key words in their names. Lerner said none of the applicants was denied tax-exempt status.

Each year the IRS reviews as many as 60,000 tax-exempt applications from groups ranging from charities to labor unions. Some are classified as 501(c)(4) groups after the section of the tax code that makes them tax-exempt. Such organizations can collect money from anonymous donors and spend it on advertising.

PRESERVING TAX-EXEMPT STATUS

To get and keep their tax-exempt status, 501(c)(4) groups cannot endorse a political candidate or a political party.

The number of groups seeking 501(c)(4) status more than doubled from 2010 to 2012, coinciding in part with the surge of Tea Party enthusiasm. In 2010 the U.S. Supreme Court issued its "Citizens United" decision lifting government limits on corporate spending in federal elections.

Consumer groups have been pushing the IRS to clarify the standards for "social welfare organizations," as they are known in Section 501(c)(4) of the tax code, to ensure that they are not abusing their tax-exempt status.

Last year then-IRS Commissioner Doug Shulman said there was no targeting of conservatives by the IRS.

Shulman stepped down at the end of the year when his term ended, and Steven Miller was named acting head of the agency that each year collects federal tax revenue and enforces the tax laws.

(Editing by Kevin Drawbaugh and Xavier Briand)

Source: http://news.yahoo.com/senator-blasts-irs-over-tea-party-apology-hearings-053716772.html

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A Comic Told In Mime - Pietrolino - Bleeding Cool Comic Book ...

Cameron Hatheway writes;

To quote Prince John in Robin Hood: Men in Tights, ?A mime is a terrible thing to waste.? That?s why I store mine in the freezer, and take it out when I?m tired of the same old meals. Does it taste kind of funny? Of course, but it beats Top Ramen.

The graphic novel Pietrolino stars a down on his luck mime with magical hands and powerful stage presence during the aftermath of World War II. Set in France, we?re first introduced to Pietrolino and his small band of traveling circus performers as they move throughout Nazi-occupied France seeking to perform in restaurants and cafes to make a little money. After one show is interrupted by a small group of Nazi soldiers who aren?t fond of his act, Pietrolino?s hands are broken, as is his spirit to perform and continue bringing joy to the masses.

?? After slaving away with broken hands in a prison camp, the war has ended and he and his best friend Simio must find a way to entertain people again with whatever skills they still possess. Hiding Pietrolino?s useless hands underneath a pair of boxing gloves, their act changes for the best and pretty soon Pietrolino is well-known throughout France as the famous boxing clown. From then on out we follow Pietrolino as he dabbles in love, rises through the entertainment ranks, and seeks his revenge on the one who helped break his hands in the first place.

Written by Alexandro Jodorowsky (The Incal) and illustrated by O.G. Boiscommun (The Book of Jack), Pietrolino is a touching tale of a mime who never gave up, no matter how badly his situation looked. He performs for the audience, his friends, and the girl he eventually falls in love with just to bring joy to the world, broken hands be damned. It?s rather quite inspiring to see his transformation throughout the book, for with an injury so grave, most would have simply retired. Jodorowsky originally wrote it as a stage play for the famous French mime Marcel Marceau, but with Boiscommun?s illustrations I?m glad they decided to go the graphic novel route instead.

Boiscommun?s style and feel is definitely European, reminding me slightly of Guarnido?s Blacksad at certain points. The painterly colors helped make the characters leap-off the pages, for the amount of detail put into every panel was simply astounding. His backgrounds are just as dazzling as the characters that are front and center, and the facial expressions were extremely well done throughout.

While I haven?t read the comic in the original language it was translated from, I thought Humanoids did a superb job adapting it for Western audiences. When I finally got to the last page, I found myself chanting for an encore. While I?ve said before how the market consisting of World War II comics is terribly dull, it?s comics like Pietrolino that still find a way into my heart, reminding me of the power of this wonderful medium.

Pietrolino (Humanoids)
Written by Alexandro Jodorowsky
Illustrated by O.G. Boiscommun
96 Pages, FC
$29.95

?

Cameron Hatheway is the host of Cammy?s Comic Corner and Arts & Entertainment Editor of the Sonoma State STAR. You can watch him try and escape from a glass box on Twitter @CamComicCorner.

Source: http://www.bleedingcool.com/2013/05/11/a-comic-told-in-mime-pietrolino/

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Website Marketing Tips That Anyone Can Follow. - Maynas Eric

Many business have found that they prefer Internet marketing over any other type of marketing available. From running up websites, to sending emails, to setting up social media accounts, today there are a huge number of ways to market your business online. Look at this article to find out how you can use Online marketing to your advantage.

When marketing your product, it is important that you have a FAQ. For all questions or issues on the site, you should have a good response that helps to alleviate any concerns the customer may have. You can word your questions so that your replies promote your products as solutions.

You can trick your readers into clicking on the ads you have by creating an image that is discreet and that will link your readers to a product page. It is possible to utilize text that is similar to that used in your articles and insert the image toward the end of your articles. You should create something that won?t look like an advertisement.

TIP! Keep an eye on competitors and their tactics, and react accordingly. Could you see yourself being tempted by their products, even though you of course should be supporting your own? Then they?re doing something right, and you should be learning from their strategies.

To convince people to purchase the products you are selling, consider sending them a content page filled with product information and maybe even a video. Customers like to feel that they are making an informed decision before purchasing your product. This demonstrates that you aren?t just after a sale, but that you want to make sure they are well informed about a particular product before deciding whether or not they want to purchase it.

Earn more subscribers to make bigger profits. Try split testing to see what sort of web design works the best. Offer one version of your webpage to one group and another version to another group. You?ll discover which methods are working best when you look at the subscription numbers for each site version.

Always be prepared to cover any questions that your guests may have. People visit your site looking for information, and if you do not give them the answer to their question, they will move on. Providing them with detailed information satisfies them and will make it so they may buy from you.

TIP! A FAQ (frequently asked questions) section on your website is a convenience that your customers will appreciate. This will enable your customers to get answers quickly and will make your site more user friendly, in general.

Try to minimize the use of AJAX and Flash so customers are not overwhelmed or bombarded with them on your site. Though you may like the visual and interactive appeal, they do nothing for your search engine rankings. Flash is unnecessary for SEO purposes, and a successful Internet site can engage customers without it.

Offer special sales on your site?s check-out page. For example, you can offer products at half-price if the customer orders a certain amount. Most customers enjoy getting a bonus and this tactic also helps you get rid of slow selling items.

Do everything you can to stay abreast of the latest trends on the Internet and the social media outlets. Keep pace with all the rapid changes and improvements on the Internet so you can always be ready to get your services placed in front of as many eyes as possible.

TIP! When designing a website, focus on creating comprehensive and high-quality content. Your website needs to inform readers about your products or services in the quickest, most engaging way possible, so they will be less likely to surf away.

You may be able to enhance your website?s appeal by doing some research on psychology studies that analyze how the design of a web page and the use of Internet promotion elements influence a person?s opinion of the site. Some of the psychological factors that effect how you perceive things can impact what you read online and what you click on. If you understand the negative and positive ways these factors can affect a person?s judgment, you can use the information to maximize your website?s appeal, thereby increasing your potential for profit.

Your website should be coded in a way that links are easily visible. The last thing you want on your website are hard to find links and lack of usability for your audience.

Don?t spend too much for advertising. You don?t want to spend any money on advertising that won?t help out your business. Banner advertising is a form of advertisement that might be more likely to pay back your investment, so you reap benefits from those hard-earned dollars.

TIP! If you give your customers the chance to subscribe to your company?s Ezine, you?ll be able to use it as an effective element of your marketing mix. Your goal will be to develop an Ezine that your customers will see as the voice of your company so you can build a long-term relationship with them.

Internet promotion is not as hard to understand as you think. Try the tips here if you want to make your online presence known by marketing to a particular customer base. Most consumers like getting information through the Internet these days, which is why Internet promotion is ideal for expanding your business.

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Source: http://www.maynaseric.com/website-marketing-tips-that-anyone-can-follow

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Prince Harry Meets Michelle Obama, Surprises Military Moms

Military moms and their kids got a royal sized surprise when Prince Harry joined their tea party yesterday at the White House!

The Prince is currently on a U.S. tour, where he'll visit areas hit by Hurricane Sandy and participate in a polo match, but his appearance at the tea party was impromptu.

"Well...surprise!" the First Lady told families as Harry entered the room to applause. "He's only got a limited amount of time with us but when he heard about the tea party and all of you, he wanted to be a part of it to personally thank you for your service."

Harry has extensive experience in the military himself, having served in Afghanistan. Michelle explained to the group that he "spends much of his time supporting our wounded, warriors and families of our fallen."

Well done, Harry!

By Cristina Gibson

You may also be interested in: michelle obama, prince harry

Source: http://www.cambio.com/2013/05/10/prince-harry-meets-michelle-obama-surprises-military-moms/

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