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October 1, 2010
Retired NFL great George Martin, who walked from New York to San Diego in 2007-08 to help thousands of 9/11 rescue and recovery workers with serious medical conditions, is hitting the road once again. On Sunday, October 17, 2010, Martin will lead an assembly of former New York Giants and other NFL alumni, 9/11 first responders and others in the 2nd Annual "Giant Steps for 9/11″ Walk and Family Fun Day to raise funds for thousands of Ground Zero first responders.
"The care of our 9/11 first responders is a national problem and an American responsibility," said Martin, co-captain of the Super Bowl XXI Champion New York Giants (1986), who formed a Journey for 9/11 Foundation at the completion of his cross-country trek. "Government funding and insurance policies do not adequately cover the substantial cost of the care these people desperately need. As Americans, we must do more. We cannot turn our backs on those who answered the call and now suffer with serious medical conditions."
Beginning at 9 a.m., the 2nd Annual Giant Steps for 9/11 Walk is a family friendly, 10-mile walk from the George Washington Bridge to Fairleigh Dickinson University's ("FDU") Hackensack's campus. For less adventurous walkers, a shorter four-mile walk will start at approximately 10:45 a.m. at Hackensack University Medical Center and end at FDU. Following the walk event, a Family Fun Day for all registrants will commence on the FDU campus.
Registration for the walk event is $35 per person.… Continue reading
by Scott Ford
September 30, 2010
The following names are the people in Congress that voted AGAINST helping the 9/11 1st Responders with health care. There are about 900 dead responders since the attacks 9 years ago, and tens of thousands more sick and dying. When everybody was running away from Ground Zero, these people were running in to save as many people as they can. The people on this list feel that we should not help them. Please adjust your voter ballots accordingly in November.
No Votes (160)
Member, Party, District
Robert B. Aderholt, R, AL-4
Todd Akin, R, MO-2
Rodney Alexander, R, LA-5
Steve Austria, R, OH-7
Michele Bachmann, R, MN-6
Spencer Bachus, R, AL-6
J. Gresham Barrett, R, SC-3
Roscoe G. Bartlett, R, MD-6
Joe L. Barton, R, TX-6
Marion Berry, D, AR-1
Judy Biggert, R, IL-13
Brian P. Bilbray, R, CA-50
Gus Bilirakis, R, FL-9
Rob Bishop, R, UT-1
Marsha Blackburn, R, TN-7
John A. Boehner, R, OH-8
Jo Bonner, R, AL-1
Mary Bono Mack, R, CA-45
John Boozman, R, AR-3
Charles Boustany Jr., R, LA-7
Kevin Brady, R, TX-8
Bobby Bright, D, AL-2
Paul Broun, R, GA-10
Henry E. Brown Jr., R, SC-1
Ginny Brown-Waite, R, FL-5
Vern Buchanan, R, FL-13
Michael C. Burgess, R, TX-26
Dan Burton, R,… Continue reading
9/11 Health and Compensation Bill Passes House
Association of Fire Fighters
September 29, 2010 — Legislation to establish health treatment and monitoring
programs for World Trade Center responders was overwhelmingly approved by a
bipartisan majority of the U.S. House of Representatives.
H.R. 847, the James Zadroga 9/11 Health and Compensation Act, was approved
by a vote of 268-160. The vote to pass the bill followed an attempt by Representative
Christopher Lee (R-NY) and House Republican Leadership to amend H.R. 847 by
adding unrelated legislation to repeal a portion of the health care reform law
and reform the medical malpractice system. The motion failed by a vote of 185-244.
Had the motion succeeded, it would have effectively killed the bill.
"I am pleased that the 9/11 Act passed the House by an overwhelming and bipartisan
majority," says IAFF General President Harold Schaitberger. "World Trade Center
responders know they are finally one step closer to receiving the care and benefits
they need and deserve."
The September 29 vote follows a previous attempt to pass H.R. 847 in the House
earlier this year under rules requiring a two-thirds majority for passage. That
attempt fell 21 votes short of a two-thirds majority.
Following that setback, the IAFF lobbied extensively to bring the bill back
up under regular order, supplementing the efforts of New York Local 94 and Local
"Our two New York City affiliates, their leadership and their members lobbied
tirelessly to move the 9/11 Act forward," says Schaitberger. "Today's vote is… Continue reading
August 17, 2010
Donna Marsh O'Connor
September 11th Families for Peaceful Tomorrows
In February of 2002 a group of family members of 9/11 victims formed September 11th Families for Peaceful Tomorrows in order to challenge the ever inflating sentiment and hysteria that led our nation into (eventually) two wars; that led to the death of thousands of U.S. servicemen and women, countless civilian casualties, and an era of perpetual fear-mongering perpetrated by politicians that today places us squarely in the viral debate over a place of worship near Ground Zero.
Despite the fact that PT (as we often like to call ourselves) has been around from almost the beginning, it is this acrimonious debate, fueled by the mainstream media's voracious appetite for angry controversy that our voices are sought after.
When we asked for an end to the sentiments of retribution and hostility. Did anyone hear?
We asked for an end to war. More wars followed.
We try to hold Barack Obama true to his promise to close Guantánamo Bay, to follow the rule of law and the American Constitution. This is still a work in progress.
Each and every day, in one way or on one issue or another, we fight to have our voices count in the seemingly monolithic deployment of "9/11 families believe, think, say…", but we rarely hear our words echo above a whisper.
But now as our nation is engaged in the primal battle over what constitutes racism, religious freedom, and religious persecution, we are… Continue reading
BY Michael Mcauliff
July 28, 2010
WASHINGTON – The House votes Wednesday or Thursday for the first time ever on a bill to care for the heroes and victims of Sept. 11, 2001 – and it's likely to fail.
That's because Democratic House leaders decided Tuesday to push ahead with the Zadroga 9/11 Health and Compensation Act under a rule that requires two-thirds approval to pass.
Many Republicans are concerned about the $10.5 billion price tag, and many don't like the way it's paid for.
News of the scheme immediately alarmed 9/11 responders.
"Whoever votes 'No' tomorrow should go to jail for manslaughter," said John Feal, who lost half his foot at Ground Zero in the cleanup.
Feal thinks House leaders should have found a way to move the bill in the regular way, needing just a simple majority.
"They'll all go home and lick their wounds after the vote, but 9/11 responders are the ones who are going to suffer without health care after nine years," Feal said.
Sources told the Daily News that Democrats feared Republicans would attach toxic changes in a simple majority vote. No such tinkering is allowed under the two-thirds rule.
New York's legislators were still holding out hope they would prevail.
"Every time we had a vote on this, we did much better than people thought," said Rep. Anthony Weiner (D-Brooklyn/Queens).
And Republicans who oppose the bill can be cast in a politically poisonous light, Democrats said, noting the… Continue reading
New York City officials say a renewed search this year of debris in and around the World Trade Center site has recovered 72 human remains.
The sifting of more than 800 cubic yards (612 cubic meters) of debris recovered from ground zero and underneath roads around the lower Manhattan site began in April and ended Friday.
The greatest number of remains — 37 — were found from material underneath West Street, a highway on the west side of ground zero. The new debris was uncovered as construction work made new parts of the site accessible.
The city began a renewed search for human remains in 2006. More than 1,800 remains have been found.
Some have been matched to previously unidentified 9/11 victims.
June 9, 2010 Update
from Cindy Sheehan
On the 7th anniversary of the illegal and immoral invasion of Iraq, eight people were arrested in front of the White House protesting the continuing crimes-you know that place! It's a big White House-as a matter of fact it's a HUGE White House in the middle of a park-like estate where heavily armed thugs protecting war criminals roam. It's okay to stop and gawk and take pictures if you are decked out in Hawaiian shirts or sundresses, but exercising fundamental rights to free speech or to peaceable assemble is not.
On March 20th, about 8000 people attended a permitted and almost lethargically tame protest in Lafayette Park, which is next to the HUGE White House. Then there was a march around in circles that landed the protest right back in front of the White House. Four people decided to lie down on the sidewalk in protest (four out of 8000), and four of us decided to cross the police line (a metal barrier on the sidewalk between the street and the high iron-barred, sniper guarded fence that surrounds the HUGE White House), to try and join the measly four that were lying there begging people to join them.
I was one of the ones arrested for crossing the police line. I did not push the barrier down, but when it fell, I crossed-I was immediately body slammed and arrested. That was at approximately 2:44pm. An amended police report misleadingly lied and said that I was given three warnings to leave-I was not and subsequent evidence shows that the warnings to disperse over the bullhorn didn't even begin until after I had been arrested.…Continue reading
By Meghan Neal
Downtown Express – Volume 23, Number 3 | The Newspaper of Lower Manhattan | May 28 – June 3, 2010
U.S. Representatives Carolyn B. Maloney and Jerry Nadler paid a visit to ground zero on Sunday to highlight a 9/11 health care bill that has been dragging through Congress for nearly nine years. The bill cleared a huge hurdle on Tuesday when it passed its final committee vote, sending it to the house floor.
"It's a difficult bill, a complicated bill, a costly bill," said Maloney. The legislation would provide $11 billion in federal funds toward health care and compensation for first responders and survivors who are sick as a result of toxins left in the air after the 9/11 attacks.
Maloney and Nadler were joined by a group of the bill's supporters: police, firefighters, 9/11 first responders currently suffering from health problems, members of the New York delegation and Lower Manhattan residents.
"Every day another floor, another piece of steel goes into reconstructing ground zero, and yet we still haven't found a way to provide health care," Rep. Anthony Weiner said at the event. "We've waited far, far too long."
Now the bill is one step closer to becoming law. Having passed the House Energy and Commerce Committee Tuesday, it will be sent to the floor of congress for a vote,… Continue reading
David Ray Griffin
At 5:21 PM on 9/11, Building 7 of the World Trade Center collapsed, even though it had not been hit by a plane — a fact that is important because of the widespread acceptance of the idea, in spite of its scientific absurdity, that the Twin Towers collapsed because of the combined effect of the impact of the airliners plus the ensuing jet-fuel-fed fires. The collapse of World Trade Center 7 (WTC 7) thereby challenges the official account of the destruction of the World Trade Center, according to which it was accomplished by al-Qaeda hijackers, even if one accepts the government's scientifically impossible account of the Twin Towers. This fact was recently emphasized in the title of a review article based on my 2009 book, The Mysterious Collapse of World Trade Center 7, 1 by National Medal of Science-winner Lynn Margulis: "Two Hit, Three Down — The Biggest Lie." 2
The collapse of WTC 7 created an extraordinary problem for the official account of 9/11 for several reasons.
One reason is that, because of the collapse of WTC 7, the official account of 9/11 includes the dubious claim that, for the first time in the known universe, a steel-frame high-rise building was brought down by fire, and science looks askance at claims of unprecedented occurrences regarding physical phenomena. New York Times writer James Glanz, who himself has a Ph.D. in physics, wrote: "[E]xperts… Continue reading
Submitted by John Bursill
Story by Naomi Breeze
Below is a moving and powerful story by one of the hardest working and most determined 9/11 Truth Advocates I know, Naomi Breeze. She has guts and determination in spades and will not be stopped in her quest to get justice for the victims of the 9/11 attacks that include ten Australians!
Solo Truth Action in Newcastle, Australia on the 14 of May 2010
Story by Naomi Breeze
After stumbling across 9/11 Truth on the internet about three years ago I contacted John Bursill of 9/11 Truth Australia and have been a passionate 9/11 Truther ever since. I feel privileged to have been involved with two successful conferences in Sydney, Australia and am honoured to have met some of my 9/11 Truth heroes.
I attended a talk in my hometown of Newcastle on 14 May 2010 by ex-Fire Fighter, ex-Chief Dan Daly, about 9/11 and how it changed his life. The talk was organised by a Catholic Church Chaplain through his Passionist Family Group and cost $5.00. The Chaplain is a personal friend of Dan and was in New York on September 11, 2001.
Some background on Dan: http://www.chiefdaly.com/
Dan Daly was promoted to Fire Captain with Engine 52 in 2001. The service was to take place on September 12, 2001. On September 11, 2001 his rig was one of the last to arrive at the Twin Towers. He and his crew arrived from the Bronx just as WTC 7 collapsed. He… Continue reading
Following are three interviews provided by Jon Gold, long-time truth activist in Pennsylvania.
Jon Gold Interviews Cosmos, Founder of truthaction.org , at Ground Zero – 5/1/2010
"… Until there is justice for this mass murder, this gigantic mass murder, then it's going to be a part of my life and I'm going to be dedicated to doing what I can to get justice. All I'm interested in 9/11 is a legitimate, independent, criminal investigation of the crime, leading up to prosecution of those responsible for this crime. "
"One of the saving graces of being in this world is knowing that there are a few committed, caring people who are willing to do something despite the seemingly insurmountable odds, despite the fact that it seems like no one gives a shit – who, because they care, because they know it actually is important, they're willing to do something. To those people, I say thank you."
"… I've been involved actively in this cause since early 2002 so that's a little more than eight years now. Over the last two or three years I really reached a point where it's burnout, it's too much, it's too much trauma all the time. When you're really working against … seemingly insurmountable odds. At the same time you're being attacked by people who are supposedly 'on your side', on the same team. All the crap that goes with this, it's a burnout. So I was smart enough to just really try to take… Continue reading
April 8, 2010
by Julie Hollar
FAIR Blog
As yet another study is released documenting the damaging health effects of breathing in toxic Ground Zero dust, it's good to see corporate media outlets taking it seriously. (Most media outlets, anyway–the New York Post continues to give a platform to deniers.)
It's worth remembering, though–since they won't remind you–that for many months after 9/11, some outlets–the New York Times in particular–downplayed the fallout and mustered shockingly little journalistic skepticism of government reassurances about safety.
The attitude of Andrew Revkin, the Times' environmental reporter at the time, says it all. As I wrote in 2006:
The Times' Revkin told American Journalism Review (1–2/03), "We were, I think, bending over backwards to be sure we were reporting a risk only if we knew it, whereas others, I feel rather strongly, were flipping it the other way." Revkin cited the Daily News as an example. When asked how he thought the 9/11 health story would end, Revkin told AJR, "I think it s going to fade away."
Instead of acting as the watchdog it s supposed to be, the New York Times reinforced misleading government claims that directly impacted the lives and health of thousands of New Yorkers. It s an important history that you won t hear about from the Times, which has never acknowledged or apologized for its reporting.
You can read that history in my article, "Gullibility Begins at Home: NYT Accepted… Continue reading
March 12, 2010
New York City officials have agreed to pay up to 657.5m US dollars
(437m sterling) to thousands of rescue and clean-up workers after 9/11.
The settlement would compensate more than 10,000 plaintiffs who say they were
made sick by dust at the Ground Zero site of the attacks.
At least 95% of the plaintiffs must approve the deal for it to take effect.
The money would come from a federally financed insurance fund of almost $1bn
that the city controls.
The toxic cloud from the collapsed World Trade Center towers contained particles
of asbestos, lead, glass and cement.
A claims adjudicator, chosen by the lawyers involved in the case, would decide
on the validity of each plaintiff's claim and how much compensation they were
entitled to.
Respiratory illnesses
The agreement follows a long battle in the courts, but must still be approved
by a judge and agreed to by the claimants.
The announcement was made on Thursday evening by the World Trade Center Captive
Insurance Company, which was set up to handle the claims of those injured in
the rescue effort.
In a statement, New York Mayor Michael Bloomberg called the settlement "a
fair and reasonable resolution to a complex set of circumstances".
Some workers are expected to receive payments of only a few thousand dollars,
while others could be in line to get more than $1m, depending on their injuries.
'Fund depleted'
The BBC's Adam Brookes, in Washington, says the agreement means that the long-running… Continue reading
February 28, 2010
by Alison Gendar
New York Daily News
A lawyer in two Ground Zero sickness cases green-lighted for trial says he has a smoking gun: buried city documents that prove firefighters should have gotten respirators.
The papers emerged in a veritable mountain of files the city turned over to workers who believe they were sickened by toxins after the 9/11 terrorist attacks.
Lawyer Andrew Carboy, whose firm represents more than 600 firefighters, said the FDNY had rules on the book requiring Bravest be equipped with respirators before Sept. 11.
But memos showing that weren't handed over until this summer – in a data dump of 3 million documents – five years after the legal battle began. "They provide everyone with helmets, with bunker gear, with [air] packs. They could have done the same with respirators, and they withheld the documents saying they had a program to do it," Carboy said.
Carboy's firm represents Firefighters Frank Malone and the late Raymond Hauber, whose cases are among a dozen picked to go to trial, starting in May.
Four were chosen from more than 9,000 by a federal judge, four by the city, and four by plaintiffs' lawyers. More than $1 billion in damages hinge on the outcome.
To show the city is liable, Carboy plans to wield memos about the FDNY's "respiratory protection program," which was supposed to provide respirators for "reasonably foreseeable emergency situations" like building collapses.
The FDNY didn't follow its own guidelines and had only 600 respirators… Continue reading
By Michael Mcauliff
January 28, 2010
WASHINGTON – The White House revealed Thursday night it boosted funding for ailing 9/11 responders – pumping more money into the treatment program than ever before.
Team Obama disclosed the cash only after outraging New York lawmakers with the news that the administration won't back a permanent plan to help the dying Ground Zero responders.
The White House confirmed it will more than double the budget for treating ill responders to $150 million in 2011.
The abrupt revelation came after the Daily News reported New York lawmakers were shocked Wednesday when Health and Human Services Secretary Kathleen Sebelius said the administration does not support mandatory funding for the $11 billion permanent treatment plan.
"I was stunned – and very disappointed," said Sen. Kirsten Gillibrand.
"To say the least, I was flabbergasted," said Staten Island Rep. Mike McMahon.
Family members also were infuriated by the lack of permanent support. "I thought that these people would be taken care of. I would have expected better from this administration," said Lorie Van Auken.
The delegation hopes President Obama will reconsider and put victims of the terror strike on a footing close to wounded soldiers, perhaps even funding the 9/11 health bill with the military.
"We are focused on strengthening the World Trade Center health program and providing needed resources through the budget," White House spokeswoman Moira Mack said.
New York legislators were thrilled to learn of the one-year funding boost.
"I am… Continue reading
By Michael McAuliff
January 28, 2010
The Obama administration stunned New York's delegation yesterday, dropping
the bombshell news that it does not support funding the 9/11 health bill.
The state's two senators and 14 House members met with Health and Human
Services Secretary Kathleen Sebelius just hours before President Obama implored
in his speech to the nation for Congress to come together and deliver a government
that delivers on its promises to the American people.
So the legislators were floored to learn the Democratic administration does
not want to deliver for the tens of thousands of people who sacrificed after
9/11, and the untold numbers now getting sick.
"I was stunned — and very disappointed," said Sen. Kirsten
Gillibrand, who like most of the other legislators had expected more of a discussion
on how to more forward.
"To say the least, I was flabbergasted," said Staten Island Rep.
Mike McMahon.
The 9/11 bill would spend about $11 billion over 30 years to care for the growing
numbers of people getting sick from their service at Ground Zero, and to compensate
families for their losses.
The legislators were shocked the idea was falling lower on the administration
priority list than other parts of the war on terror and financial bailouts.
"She made it clear that the administration does not support any kind
of funding mechanism that goes into the bill," said Bronx Rep. Eliot Engel.
"I think it's fiscal restraint… but you know what? They find
money for everything else,… Continue reading
By Michael McAuliff
New York Daily News blog
Firefighter Brian McCauley died yesterday of cancer at the age of 42.
Today, his friends brought their grief and anger to the Long Branch, N.J., office of one of the congressmen who has failed to move legislation that would permanently help other people who sacrificed at Ground Zero.
"They're turning their backs on guys like Brian," said Larry Feilich, an FDNY dispatcher from the Bronx, who last saw McCauley about a month ago.
"I'm on my second set of widows," said the Rev. Bill Minson, who offered counseling after the attacks of Sept. 11, 2001, and finds himself doing it again and again.
Minson and Feilich were among dozens of protesters who targeted Rep. Frank Pallone for not moving a major part of the $11 billion legislation that would reopen the Sept. 11 victims' fund and guarantee health care for responders who don't have it.
Pallone heads the Energy and Commerce Committee's subcommittee on health, which has jurisdiction over about $3 billion of the bill, which would cover 30 years.
Pallone had promised to bring that legislation up for action back in September, but he has not.
His office responded that it hasn't moved because Pallone doesn't think the measure will pass.
"The congressman is a strong supporter of the bill and is working to get enough support to vote it out of committee," said spokesman Richard McGrath. "Right now there isn't enough support and if we bring it up for a… Continue reading
December 26, 2009
Daily News
A Sept. 11 hero died of cancer on Christmas Day. Jim Ryan was on the front lines during 9/11, a firefighter who spent many weeks rummaging through the destruction that encompassed Ground Zero, only to succumb to pancreatic cancer, according to a report.
The fire department confirms that his sickness was 9/11-related. And now his family — his three children, wife and all the people who loved him — mourn the death of a hero.
"He was just really really great," his grieving wife, Magda, told the Daily News.
Ryan, 48, was first diagnosed with cancer three years ago. He relapsed last year, reports the News.
A brave fighter until the end, Ryan desperately wanted to travel with his colleagues to Washington in November to campaign for the passage of legislation that would give $11 billion for those who contracted diseases on Sept. 11. That bill hasn't yet passed.
"It's about all the guys who are going to come after me," Ryan, who wasn't well enough to make the trip, told the News at the time. "And there's going to be plenty of them."
Ryan's family spent a quiet Christmas Eve at home, and just before 2 a.m. on Christmas Day, the Long Island father's teenage son realized he wasn't breathing, reports the News.
…Continue reading


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Venice comes to you with a dynamic, authentic, and passionate voice of truth that motivates, inspires, and challenges you and those seated next to you to not be afraid to reach your full potential.
Venice Garner Venice is a Bronx, NY native. She is a graduate from the High School for Health Professions & Human Services. She holds two bachelor degrees from Lincoln University, PA in Journalism and Human Services. While on Lincoln University's campus, Venice was an active Dean's List student. She was the Managing Editor of the Lincolnian, the President and Vice President of the junior and senior class, a Resident Advisor, and a former ...
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Laymon Hicks
A Youth Leadership Strategist Encouraging Youth to Get Up, Get Out, & Go Get It!
Laymon Hicks All teens are troubled. It goes with the territory. A part of the "passage." There is the typical "torment" of wanting to belong, to be the same, to be liked and accepted. Is my nose too big? My height too short? My hair too long? But not everyone belonged to the Brady Brunch. Drugs. Alcohol. Violence. Stress. Depression. Add the words bullying, peer pressure and self-doubt and you've entered the real world drama of too man...
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Bertrand Gervais
I teach students and young adults to build relationships that build dreams.
Bertrand Gervais Best Selling Author, Speaker, CEO of Success Mentor Education Entrepreneur.com calls him a "Power Mentor" and USA Today says he is one of the top young leaders in the country.He has collaborated with the hit ABC TV show Shark Tank, the White House, and is a guest columnist for Forbes, all before the age of 30. Bert Gervais, a.ka. The Mentor Guy, is America's number one speaker on mentorship and student achievemen...
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Karmetria Dunham Burton
Karmetria is best recognized personally for living her mantra: be Inspired. be Motivated. be Informed. 'Go over it, go around it, go under it, but NEVER give up. You have to SHOW UP, everyday!'
Karmetria Dunham Burton Touted as one of the Top 25 Women Impacting Diversity by DiversityPlus Magazine over the past two years, and recently named 2013 Woman of Excellence by the Atlanta Daily World, Karmetria Burton is igniting an inspirational fire among women AND men in the corporate world. The Houston, Texas native currently serves as General Manager - Strategic Programs with Delta Air Lines.In her challenging professional role, Karm...
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Derek Anderson, Sr.
I Refuse to Allow Someone's Negative Opinion of me to become My Reality
Derek L. Anderson, Sr. Derek is a screen writer, producer, inventor, entrepreneur and philanthropist who continues to expand his brand with various projects in the works such as an autobiography, Life Changing speaking engagements, and numerous film ventures.Derek is a man of integrity and character who lives his life with Love and LOYALTY. Career:Kentucky High School Basketball All-Star• 1996 - Won National Championship with The Univers...
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Cassandra Owens
Dynamic speaker who inspires her audiences with humor, hard facts, while tackling issues that most people find controversial.
Cassandra Y. Owens Cassandra is a one of a kind, dynamic, speaker. She inspires her audiences with humor, hard facts, while tackling issues that most people find controversial. Cassandra demonstrates sound moral concepts, while teaching proper ethics and providing road maps for moral edification, which provides encouragement and motivation for her listeners. Cassandra's views and acumen are secured in experience ranging fr...
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Charlie Hardy
The educator who was an eye witness to one of the most defining moments in the quest for equality.
Charlie E. Hardy, President & CEO Centre For Excellence, LLC Education July 2005, Master of Arts Degree, Organizational Management, University of Phoenix 1996 Life Underwriters Training Council Fellow, Washington, DC 1972 Registered Representative National Association of Securities Dealers May 1962, Bachelor of Science, Secondary Education, Alabama State University May 1958, High School Diploma, Booker T. Wash...
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Christopher Chestnut
National Emerging Leader
Christopher Chestnut "Pursuing Justice...Because You Deserve It" Acknowledged by President Barack Obama as a National Emerging Leader, Christopher M. Chestnut, Esq. is America's next great voice for legal justice. Chestnut, a Florida native and graduate of Florida State and University of Florida's Levine School of Law, served on the Florida finance team for then presidential candidate Obama, which helped lead to a convincing vi...
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Kionne McGhee
Florida State Representative, Attorney, Author, College Professor, and Motivational Speaker
Kionne L. McGhee Before Kionne —the State Representative, author, college professor, husband, and father—could realize his dreams, he had to fend off his nightmarish reality. A reality that consisted of a young, streetwise kid trying to survive living in one of South Miami's toughest communities—the Naranja Housing Projects—and whose existence centered on balancing the role of man of the house and fulfilling the statistical requirements o...
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Wendi Turner
"Meets You Where You Are." Author, Educator, Empowerment Speaker, and social change agent. Wendi's life mission is to empower the human condition-one life at a time.
Wendi J. Turner Wendi specializes in helping people unlock the power within. She does this by impacting at-risk youth and adults by means of "relationship empowerment." Realizing the need to extend her services for those who have no voice, she dedicated her efforts to bring liberation and relevancy to those in the Houston and surrounding areas. She has been invited as a featured keynote speaker on radio, television interviews and as a sem...
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Dr. Amy Freeman
Professor, Author, and Advocate for Women in STEM: Science • Technology • Engineering • Math
Dr. Amy L. Freeman Amy holds a Master of Science degree in Engineering and a Ph.D. in Workforce Education. This unusual combination has provided her with a professional skill set that includes both the technical and social sciences. Dr. Freeman has spoken in numerous business and professional venues as well as schools, churches and government institutions. Topics include lowering the stress level of working professionals, work-life balanc...
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subset: commoncrawl


text:
Keep up to date with the latest events from The Royal Collection
In the commemorative year marking the 200th anniversary of the Battle of Waterloo, discover the characters and stories behind this significant event in history in our new creative writing workshop, led by a published author. ... Read more about Waterloo: Winning words
Meet Private Fererick Pudge of the First regiment of Foot Guards, on 18 June 1815 at the end of the Battle of Waterloo, who is in his barrack room cleaning his kit after many hours of fighting. ... Read more about Wellington, Boots and All
Why were many castles built during the medieval period, what were they used for and who lived in them? Focusing on the story of this famous castle at Windsor from the Norman Conquest to the Barons' siege in 1216, a year after King John signed the ... Read more about What were Castles for?
What are The Queen's favourite hobbies and how would it feel to wear her Coronation robe and crown? What does The Queen do in the splendid rooms we see at the Castle today and how can we tell if she is there? What does she do to make someone a knight ... Read more about Who is The Queen?
Giovanni Benedetto Castiglione has been described as both a lost genius and a lawless rogue. His best-known works are large vibrant drawings in oil on paper but he was also one of Italy's most significant printmakers of the 1600's. However, he lived a turbulent life and often had to move between cities to escape the trouble he left behind. ... Read more about Who was Castiglione the Lost Genius?
Let the children's imagination run wild as we explore Windsor Castle as a favourite home and working palace of our Queen. Children discover the differences and similarities between The Queen's home and their own and how the Castle functioned as a ... Read more about Whose royal home is this?
... Read more about Windsor Castle: History around us
From the time of Queen Victoria to the current reign of Her Majesty The Queen, many important state occassions have taken place at Buckingham Palace. But what goes on behind the scenes to create the magic and magnificence of an official visit to the ... Read more about A Royal Welcome: Past and present at Buckingham Palace
This guided tour led by Chapel Stewards focuses on all the evidence to be found in St George's Chapel of its long association with Queen Victoria, her direct predecessors and her family. ... Read more about St George's Chapel and Queen Victoria
Completed during the reign of Henry VIII, who is one of ten kings buried here, St George's Chapel has a wealth of educational interest for primary school children. ... Read more about St George's Chapel and the Knights of the Garter
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he key is to have your food be simple, healthy, and tasty. You are not on a cooking show and nothing needs to be perfect or time consuming. Try some of these ideas.
Read Whole Story
If you are getting stuck in the "Chicken Patty rut," then perhaps you will find my list helpful. Please comment with other dishes your kiddos enjoy! I try to keep dishes simple and leftover friendly, so my feelings are not hurt when she turns her head to them.
When we come AT our children with rules and regulations, they instinctively resist. But when we enlist them in collectively addressing a problem by contributing possible solutions, they will also be more likely to adhere to agreements they took part in creating.
Each one of these recipes is basically one-and-done.
By Lynn Andriani
@media only screen and (min-width : 500px) {.ethanmobile { display: ...
Here's how one woman with three kids, a husband and a start-up helps get dinner on the table.
By Lynn Andriani
@media only screen and (min...
In a world of Seamless and sad desk lunches, traditional sit-down family dinners can sometimes seem at odds with contemporary life.
We often eat o...
Food is nourishment.
Food is medicine.
Food is pleasure.
Drop the dogma around food. Paleo, vegan, low-carb, high-protein, gluten-free, vegetarian...
While scrolling through my timeline on Facebook last week, I came across a post about a child who had been put on a "cleanse" to lose weight. I cannot tell you how that made my blood boil!!
There is a geographical midpoint between living to eat, and eating to live. It's where health comes from the pursuit of pleasure, and pleasure comes from the pursuit of health.
Sometimes, feeding my kids reminds me of that old saying, "you can lead a horse to water, but you can't make them eat anything other than dinosaur-shaped chicken nuggets."
There are three things I'll fall on my sword for in this life: faith, family and food. And they're all sort of wrapped up together.
It can take Jack an hour to eat a meal, during which I can feel the tug of unanswered emails, a deadline, and the unswept floor each minute. But, as I'm fond of asking Jack when he's driving his Matchbox cars rather than picking up his Lego before bedtime, what is your job right now?
Chuck E. Cheese elicits a flood of memories. Thing is, I wasn't remembering my own childhood; I was remembering my trip at the end of December 2013.
We're here to change your perception of meatloaf.
24. I am thankful my kids haven't realized that I have no clue what I'm doing.
Family gatherings over the holidays usually involve heightened emotions of all kinds. Such events might begin with an atmosphere of joy, connection, love and caring but they don't always end on the same note.
Bugs may be the protein of the future, so you might as well learn to love 'em.
There's one surefire way to lift your family's spirits when one or more of you happen to be having a bad day: announce that it's pizza night.
My favorite weeknight vegetarian dinners that take little more to make than a stock pot and a ladle.
Clients tell me they offer a variety of foods "all the time" and are frustrated by constant rejections. Many parents don't understand and are grateful to learn what a better "offer" looks like.
My suggestion is to be that unique parent that talks to your children about dangers and works with your child from a young age to build their trust. That way, when they receive a communication that makes them feel uncomfortable , they will talk to you, their parent, about it.
I really thought there was a Clean Plate Club.
Back when I was a kid, the country where kids-who-weren't-me were starving was Biafra, and my par...
Coming together around a table is an important part of my life. I'm a part of the Global Mom Relay today, so other families around the world have the chance to share good food and conversation together.
There are many lessons to be learned in moments from our pasts. Teach your children well and remember that food can be your tool.
Amanda Haas believes families benefit from eating healthy, homemade meals together -- so she's made it her life's work to help them do just that.
Get top stories and blog posts emailed to me each day..


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Label: Freelife Media Group
Manager: SirRah Pro Management
Bio: Producer, songwriter and musician Eddy J. Free's music has been heard on television shows nationwide including MTV's "The Real World." His sixth album "I Am the MaD hAtTeR" was released December 2011 and was nominated for BlogTalkRadio's Muse Cafe's 'Album of the Year' and also named one of the ...See Full Bio
: RT @SavvyBabii: Redefining Mental Illness http://t.co/vJjgEVvicM http://t.co/u3rhntgML7 RT @The_News_DIVA
"Just in love with yr stuff, man - melodic and club and artful. Ridiculous amounts of talent."


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OsoOvah Model
LifeFormsPhotographer Male FURLONG, Pennsylvania, US
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Geraldine 'Gerry' Metcalfe, 88
MEREDITH — Geraldine "Gerry" Marie Metcalfe, 88, of 153 Parade Road and formerly of Gilford and West Alton, died at Forestview Manor, Meredith on Friday, June 13, 2014. She was the widow of Francis "Frank" Metcalfe who died March 4, 2009.
Mrs. Metcalfe was born April 26, 1926, in Cambridge, Mass., the daughter of the late Richard and Theresa (Campbell) McCormick. She resided in Watertown, Mass., for many years before moving to Alton where she lived for 30 years. She was a secretary at Buckley & Scott for 25 years before retiring in 1983.
Survivors include two sons and daughters-in-law, Frank and Linda Metcalfe of Billerica, Mass., and Gilford, and Bruce and Patricia Metcalfe of Medway, Mass., and West Alton; six grandchildren, Jason Smith, Brian Smith, Francis Metcalfe, Jill Metcalfe, Michael Metcalfe and Matthew Metcalfe; four great-grandsons; a sister Paula MacAuley of Florida; many nieces and nephews.
In addition to her parents and her husband, Mrs. Metcalfe was predeceased by a daughter, Denise M. Smith, in 1996.
Calling Hours will be held on Tuesday, June 17, 2014, from 4-7 p.m. in the Carriage House of the Wilkinson-Beane-Simoneau-Paquette Funeral Home, 164 Pleasant St., Laconia. A Mass of Christian Burial will be celebrated on Wednesday, June 18, 2014, at 10 a.m. at St. Andre Bessette Parish at St. Joseph Church, 30 Church St., Laconia. Burial will follow the Mass at noon at the New Hampshire State Veterans Cemetery, 110 Daniel Webster Highway, Boscawen.
In lieu of flowers memorial donations be made to the Alzheimer's Association, N.H. Office, 5 Bedford Farms Drive, Suite 201, Bedford, NH
Wilkinson-Beane-Simoneau-Paquette Funeral Home & Cremation Services, 164 Pleasant St., Laconia, is assisting the family with the arrangements. For more information and to view an on line memorial go to www.wilkinsonbeane.com.
Last Updated on Monday, 16 June 2014 06:43
Hits: 349
Albert Laflam, 85
WASHINGTON, D.C. — Albert Laflam, formerly of Belmont, N.H., passed away on the 29th of May, 2014 at George Washington University Hospital in Washington, D.C., where he resided for many years. He was 85 years old. Albert died after a lengthy struggle with Lewy Body Dementia and was comforted in his last days by his loving wife Joan (Bissonette) Laflam. He is also survived by his sister-in-law Florence Laflam, his cousins Colonel Robert Laflam, Paul Laflam, Donald Laflam and Samuel Corriveau; his nephews Lawrence Laflam and Daniel Laflam and niece Christine Clark. He is the last surviving child of Albert Laflam, Sr. and Vilida (Cote) Laflam late of Belmont, New Hampshire. He was pre-deceased by his brother Armand and Armand's first wife Elizabeth and their child Jacqueline.
Albert graduated from Saint Michael's College in 1951 and returned to his home state of New Hampshire. He spent the next ten years working in the transportation industry, before moving to Washington, D.C. for a life in public service. Prior to leaving New Hampshire, Al met the young woman he would take as his bride nine years later. Al and Joan were married forty-five years, enjoying the social, cultural and political life of Washington, D.C.
Al's career was in the field of information technology. Computer utilization was in its infancy and Al was on the ground floor. Soon after arriving in Washington, D.C., he was assigned by the General Services Administration to one of the first task forces to develop an internal program to track inventory within the largest US government agency. That was the start of a career in project management that would span over thirty-five years, until the early stages of his disease made it difficult for him to function effectively.
Al loved his work and he especially loved to help young people navigate the emerging information technology. He also loved music and the performing arts. Al and Joan were long-standing patrons of the Kennedy Center for the Performing Arts in Washington, D.C., attending many performances until Al's illness made it difficult to manage.
Joan would like to thank the staff and nurses at the Sunrise Senior Living Center for their wonderful care.
There will be no calling hours.
There will be a Memorial Mass of Christian Burial at St. Joseph Parish in Belmont, N.H. on Saturday, June 21, 2014 at 10 a.m. followed by a reception in the parish hall. Interment at Sacred Heart Cemetery in Laconia, N.H. will follow the reception.
Contributions in Albert's memory may be made to Lewy Body Dementia Association, 912 Killian Hill Road, S. W. Lilburn, GA 30047.
Arrangements are entrusted to the care of Wilkinson- Beane-Simoneau-Paquette Funeral Home & Cremation Services, 164 Pleasant Street, Laconia, N.H. For more information and to view an online memorial go to www.wilkinsonbeane.com.
Last Updated on Monday, 16 June 2014 06:41
Hits: 376
Peter G. Burleigh, 73
ALTON — Peter Gregg Burleigh, loving father, educator, and adventurer, died unexpectedly of a heart attack on October 30th, 2013 at the age of 73. He was the third son of the late Joseph and Alice (Taggart) Burleigh. He was preceded in death by his brother, Joseph Harry and is survived by his son, Evan Burleigh of Braintree, Mass. and his brother, Hugh Burleigh of Tulsa, Okla. Peter was born on March 19, 1940 and grew up in Franklin, N.H. going to Franklin High School and graduated from UNH in 1962. He went on to continue his education in 1990 at Columbia University where he received a Masters in Educational Administration. He became an educator right after graduating from UNH and worked at numerous schools until he ended up teaching at Thayer Academy in Braintree, Mass. for 21 years and then spent the next 12 teaching at Catholic Memorial High School in West Roxbury. He retired in 2006 to his home in Alton, N.H. on Lake Winnipesaukee where he lived happily three seasons of the year while spending summers at his campsite in Connecticut. In the last year he learned to ski again on a new hip, upgraded his campsite, and improved his home in Alton. Peter had many passions, including sailing, skiing, photography, and especially learning and teaching. He touched many lives, and will be sorely missed, but forever remembered. Burial Service Friday, June 20, 2014 at 2 p.m. in Webster Place Cemetery in Franklin, N.H. In case of rain, Service will be held at H.L Young & Company Memorial Home, 175 South Main St., Franklin, N.H. instead. For detailed information visit www.burleigh.info
Last Updated on Friday, 13 June 2014 06:27
Hits: 441
Aaliyah A. Wilson
FRANKLIN — Aaliyah Ann Wilson was born on March 27, 2014 to parents David and Christine (Araujo) Wilson of Franklin, N.H. and passed away peacefully on June 9, 2014 with her parents by her side. Aaliyah was greeted at Heaven's gates by her grandmother Susan J. Alves. In her 10 weeks of life Aaliyah touched so many hearts and will be missed by so many. Besides her parents Aaliyah leaves behind her brother and sister David and Sophia Wilson who absolutely adored her. She also leaves her grandparents, Lauri Cannon of Venice, Fla. and Miguel Araujo of Cranston R.I., her uncle Mike Araujo of New Bedford Mass., her great-grandparents Elaine Wilson of Cranston R.I., Marion Cannon of Massachusetts and Miguel and Bertha Araujo of Rhode Island. Aaliyah leaves behind many other extended family members and her "Hannaford family".
Assisting with arrangements is the William F. Smart Sr. Memorial Home, of Tilton, N.H. No services are planned and a private burial will be held at a later date.
For more information go to www.smartfuneralhome.com
Last Updated on Monday, 16 June 2014 06:38
Hits: 484


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You can now invite anyone to meet at your favorite Starbucks.
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31 year old woman | Phoenix, AZ, USA | Seeking women 21-40 within 50 miles
Looking for my partner, lover and best friend.
I am looking for someone who will be my best friend and lover. I am interested in finding someone to spend time with who has goals and interests that are similar to mine. I love to live a very healthy and fit lifestyle and I'm looking for someone who enjoys the same. I am working on my bachelor's in psychology, and I work nights so my schedule can be a bit hectic at times. However, I am definitely willing to make time for that special someone. I love to laugh, smile, and just have a good time. I am pretty laid back and I love trying new exciting things. But, don't ask me to go bungee jumping or skydiving, I have to draw the line somewhere, haha! I am also looking for friends, so even if you're not romantically interested in me maybe we could still platonically hang out and have a good time. I'm looking forward to hearing from you :)
Camping , Coffee and conversation , Cooking , Dining out , Movies/Videos , Music and concerts , Exploring new areas , Nightclubs/Dancing , Performing arts , Playing sports , Shopping/Antiques , Travel/Sightseeing , Volunteering , Wine tasting
Aerobics, Cycling, Dancing, Inline skating, Other types of exercise, Running, Swimming, Walking / Hiking, Weights / Machines
I exercise 5 or more times per week.
I have Dogs
I like Birds, Cats, Exotic Pets, Fish, Horses
I have a funny, and hyper pomeranian.
Middle of the Road
Sedona, Vegas, LA, Santa Monica, Cleveland, Nassau. Miami, San Diego, Kona etc.
Lamson College, Tempe, AZ
I love Sushi, Chelsea Lately, Starbucks, Working Out, amd Wine.
I love working out, hiking, bicycling, rollerblading, reading, coffee, sushi, wine etc.
Are You There Vodka, It's Me Chelsea?
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'7" (170cms)
|5'0" (152cms) to 6'11" (210cms)
|Body type:
|Athletic and toned
|Slender, Curvy, Athletic and toned
|No preference
|No preference
|I'll tell you later
|No preference
|Social Drinker, Regularly, Moderately
|Self-Employed / Entrepreneur
|No preference
|I'll tell you later
|No preference
|Never Married
|No preference
|Have kids:
|No preference
|Wants kids:
|Not sure
|Not sure
|Black / African descent
|Asian, East Indian, Latino / Hispanic, Middle Eastern, Native American, Pacific Islander, White / Caucasian, Other
I am an African American woman who has an interest in women of different ethnicities.
|I'll tell you later
|No preference
|Associates degree
|No preference
I graduated with an associates degree and I am currently working on my bachelors degree in psychology. After I finish my bachelors next year I will be working on my masters degree. I love learning and working towards goals!


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A novel ribozyme, capable of selectively cleaving the bcr-abl mRNA of a cell containing the Philadelphia Chromosome, thereby blocking synthesis of BCR-ABL protein is provided. Methods for using the ribozyme for treating leukemia patients and methods of producing the ribozymes are also provided.
1. A synthetic RNA molecule useful for the treatment of a leukemia caused by the presence of a hybrid oncogene resulting from a chromosomal translocation, said RNA molecule comprising a single strand of ribonucleic acids comprising a sequence complementary to a sequence of the hybrid gene transcript 5' to the breakpoint of the translocation and capable of hybridizing thereto, a second sequence complementary to a sequence of the hybrid gene transcript 3' to the breakpoint of the translocation and capable of hybridizing thereto, and a sequence therebetween encoding a ribozyme capable of cleaving the hybrid gene transcript at or near the breakpoint, thereby blocking synthesis of the tumorigenic protein, said ribozyme comprising the nucleotide sequence: 3' A-A-G-C-A-G-G-A-G-U-G-C-C-U-G-A-G-U-A-G-U-C-5', wherein U is Uridine, C is Cytosine, G is Guanidine, and A is Adenine.
2. The RNA molecule according to claim 1 comprising the nucleotide sequence: 3' U-C-G-U-C-U-C-A-A-A-G-C-A-G-G-A-G-U-G-C-C-U-G-A-G-U-A-G-U-C-G-U-U-U-U-C-G-G-G-A-5', wherein U is Uridine, C is Cytosine, G is Guanidine, and A is Adenine.
3. The RNA molecule according to claim 1 wherein the oncogene is bcr-abl, and the protein is BCR-ABL.
4. A method for treating a patient having a leukemia characterized by the presence of a hybrid oncogene resulting from a chromosomal translocation comprising contacting cells of a patient suffering from leukemia with an amount of the RNA molecule of claim 1 sufficient for this RNA molecule to cleave the oncogene RNA transcript present in the cells, effectively blocking synthesis of a tumorigenic protein.
5. The method according to claim 4 wherein the cells are contacted with said molecule in vitro.
6. The method according to claim 4 wherein the cells are contacted with said molecule in vitro and subsequently re-introduced into the patient.
7. The method according to claim 4 wherein the cells are contacted with said molecule in vitro.
8. The method according to claim 4 wherein the leukemia is CML, ALL or contains an oncogenic gene product which is generated by the fusion of at least two genes.
9. The method according to claim 4 wherein the cells of the patient are contacted with said RNA molecule which is present in a recombinant vector.
10. A method for the treatment of disease associated with the expression of the Philadelphia Chromosome, comprising administration of the RNA molecule of claim 1.
11. The method according to claim 4 wherein the cells of the patient are contacted with said RNA molecule which is present in a lipid composition.
12. A recombinant vector comprising DNA which when expressed will yield the RNA molecule of claim 1.
13. The vector according to claim 12 capable of expressing the RNA molecule continually inside the cell.
14. The vector of claim 12 selected from the group consisting of a retroviral vector, an adenoviral vector, and a vaccinia vector.
15. A recombinant vector carrying the RNA molecule of claim 1 and capable of expressing the molecule in vitro.
16. The vector according to claim 15 comprising a vector selected from the group consisting of a mammalian vector, a bacterial vector, a yeast vector, a fungal vector, and an insect vector.
This application is a continuation of U.S. patent application Ser. No. 07/544,199, filed Jun. 26, 1990, now abandoned.
This invention refers generally to the treatment of cancers, and more specifically to methods for treating leukemias characterized by the presence of a chimeric protein such as those produced by a genetic translocation.
Philadelphia chromosome is a hybrid chromosome resulting from a chromosomal translocation in which a small portion of the long arm of chromosome 9 is transferred to the long arm of chromosome 22. This chromosomal abnormality consistently associates with human chronic myelogenous leukemia (CML). CML is a disorder of hematopoietic cells which results in marked proliferation of granulocytic cells and often megakaryocytes.
Recent studies indicate that more than 95% of CML patients as well as 15-25% of ALL (Acute Lymphocytic Leukemia) patients harbor Philadelphia Chromosome which is designated as Ph+. Molecular studies by several groups demonstrate that during the formation of Philadelphia Chromosome, a portion of the c-abl gene is translocated from chromosome 9q34 to chromosome 22q11. Significantly, this translocation disrupts two genes, c-abl of chromosome 9 and the bcr gene of chromosome 22, resulting in the generation of a new, fused gene comprising portions of bcr and c-abl.
This chimeric gene, termed bcr-abl, produces a new protein, BCR-ABL which has several unique properties and appears to be the causative agent of the cancers with which it is associated (See FIGS. 1A through 1E). BCR-ABL protein is present only in tumor cells and its synthesis in these tumor cells is believed to be related to tumorigenicity.
Presently CML and ALL patients are treated chemotherapeutically with conventional therapeutics and radiation. Such treatment is plagued by well-known side-effects and is often of limited effect. No effective treatment for these leukemias is known. Thus, other compositions and methods for treating such cancers are being sought.
Certain naturally occurring RNA molecules, called ribozymes, possess the property of self-catalyzed cleavage. This reaction is shared by a number of small circular molecules which replicate in plants, either viroid RNAs, such as the avocado sunblotch viroid (ASBV) or satellite RNAs which are dependent on helper viruses, such as the satellite RNAs of tobacco ringpost virus and lucerne transient streak virus [Haseloff et al, Nature, 334:585-591 (1988)].
Comparison of several self-cleaving RNA sequences has led to the identification of a consensus secondary structure, termed "hammerhead", containing 11-13 conserved nucleotides at the junction of three helices that are precisely positioned with respect to the cleavage site. A hammerhead of less than 60 contiguous nucleotides was found to be sufficient for rapid cleavage in the absence of any protein [D. E. Ruffner et al, Gene, 82:31-41 (1989)]. Natural catalytic centers may be formed by contiguous regions in the RNA [P. Keese et al, in Viroids and Viroid-Like Pathogens, J. S. Semancik, ed. (CRC Press, Boca Raton, Fla., 1987), pp. 1-47; A. C. Forster et al, Cell. 49:211 (1987)] or by regions separated by a large number of nucleotides [C. J. Hutchines et al, Nucleic Acids Res., 14: 3627 (1986); L. Epstein et al, Cell, 48: 535 (1987)]. Cleavage occurs 3' to the GUX triplet where X can be C, U, or A [O. C. Uhlenbeck, Nature, 328: 596 (1987); C. C. Sheldon et al, Nucleic Acids Res., 17:5679 (1989)]. The essential constituents for the hammerhead can be on separate molecules, with one strand serving as a catalyst and the other as a substrate. Furthermore, RNA catalytic sequences require the conserved cleavage domain (GUX) to serve as the compatible substrates [Haseloff et al, supra].
One such hammerhead ribozyme, consisting of three stems or helices and a catalytic center containing 11-13 conserved nucleotides (5'-GAAAC(N)n GUN(N)n CUGA(N)GA-3'), has been employed to cleave HIV I gag transcripts [N. Sarver et al, Science, 247:1222-1225 (1990)].
There remains a need in the art for effective therapeutic compositions and methods to treat leukemia or ameliorate its effect on a human patient.
The present invention provides therapeutic compositions and methods for the treatment of leukemias, which are characterized by the presence of a chimeric protein which results from a chromosomal translocation.
In one aspect, the invention provides a composition comprising a synthetic RNA molecule, useful for the treatment of a leukemia characterized by the presence of a hybrid gene resulting from a chromosomal translocation coding for a protein which confers tumorigenicity to a human cell. The synthetic molecule comprises a single strand of ribonucleic acids comprising a sequence complementary to a sequence of the coding strand of the hybrid gene 5' to the breakpoint of the translocation and capable of hybridizing thereto, a second sequence complementary to a sequence of the coding strand of the hybrid gene 3' to the breakpoint of the translocation and capable of hybridizing thereto, and a sequence therebetween encoding a ribozyme capable of cleaving the hybrid gene at or near the breakpoint. The ribozyme sequence is preferably a hammerhead motif.
In another aspect the invention provides a composition comprising a synthetic RNA molecule, useful for the treatment of CML characterized by the presence of the hybrid gene bcr-abl coding for the BCR-ABL protein which confers tumorigenicity to a human cell. The synthetic RNA molecule comprises a single strand of ribonucleic acids comprising a sequence complementary to a sequence of the coding strand of the bcr-abl gene 5' to the breakpoint of the translocation and capable of hybridizing thereto, a second sequence complementary to a sequence of the coding strand of the hybrid gene 3' to the breakpoint of the translocation and capable of hybridizing thereto, and a sequence therebetween encoding a ribozyme capable of cleaving the hybrid chromosome at or near the breakpoint. These molecules may be synthesized by conventional means, or expressed from a recombinant expression vector.
A further aspect of the present invention provides recombinant vectors carrying the synthetic RNA molecules described above. Vectors of this invention are capable of expressing the RNA molecule and delivering the RNA molecule into a cell of a leukemic patient. These vectors are preferably recombinant retroviral vectors which have been altered to eliminate their pathogenicity. Other mammalian vectors may also be employed for this purpose which are capable of delivering the RNA molecule to the cell without otherwise damaging the cells.
Still another aspect of the present invention provides a method of treating leukemia with the above-described molecules and recombinant vectors. This method entails contacting cells of a patient suffering from leukemia with an effective amount of the synthetic RNA molecule. Once in the cell, the synthetic RNA molecule binds repeatedly to copies of the hybrid gene and the ribozyme cleaves the gene in a catalytic manner, rendering it incapable of coding for the chimeric protein.
Other aspects and advantages of the present invention are disclosed in the following detailed description.
FIG. 1A illustrates chromosomes 9 and 22. FIG. 1B pictorially illustrates the formation of the Philadelphia chromosome from a translocation event between chromosomes 9 and 22. FIG. 1C schematically illustrates the c-abl gene on chromosome and the bcr gene of chromosome 22, and the location of the translocation. FIG. 1D schematically illustrates the chimeric chromosome where 3' bcr sequences have been replaced by c-abl sequences. FIG. 1E pictorially illustrates the Philadelphia chromosome, consisting of an approximately 8 Kb bcr-abl fused mRNA, which results in the expression of an approximately 210 Kd hybrid bcr-abl protein.
FIG. 2 illustrates the structure and sequence of one such synthetic ribozyme RNA molecule of this invention and the bcr-abl RNA substrate or "hammerhead" molecule. As is shown in FIG. 2, this RNA molecule is capable of forming duplexes with bcr-abl RNA.
FIG. 3 illustrates an autoradiogram demonstrating the effects of the RNA molecule on the bcr-abl gene transcript. Lane 2 contains the 32 P labelled bcr-abl RNA transcript and MgCl2 as a control; Lane 3 contains MgCl2 and the unlabelled ribozyme as a control; Lane 4 contains EDTA and the labelled bcr-abl transcript as a control; Lanes 5 and 6 each contain MgCl2, the ribozyme molecule and the labeled bcr-abl transcript; Lane 7 contains EDTA, the ribozyme molecule and the labeled bcr-abl transcript as a control. As seen in Lanes 5 and 6, when the bcr-abl RNA is exposed to the ribozyme molecule of this invention, the RNA is broken into two fragments of lower molecular weights, thereby rendering it inactive.
The compositions and methods of the present invention are designed for the treatment of any leukemia or other cancer which is characterized by the presence of a tumorigenic chimeric protein such as that resulting from a chromosomal translocation, the gene encoding the protein having a ribozyme cleavage site at or near the chromosomal breakpoint. Exemplary disorders characterized by such a protein include chronic myelogenous leukemia, acute lymphocytic leukemia, as well as other leukemias, such as those involving c-myc 8q24 and bcl-1 and bcl-2.
The invention provides a synthetic RNA molecule or ribozyme. For purposes of simplicity, the following description relates to a novel RNA molecule of this invention designed for the cleavage of the bcr-abl mRNA produced by the Philadelphia chromosome. However, as noted above, the present invention is not limited to this molecule, but encompasses other molecules designed according to this invention for cleavage of similar genes in other cancers. The novel ribozyme has been designed to cleave the selected target chimeric gene after the ribonucleic acid sequence G-U-X, wherein X is the ribonucleotides A, U or C.
To use ribozyme-based reactions as a potential therapy for human leukemias, a hammerhead ribozyme motif that can cleave specifically the bcr-abl RNA thereby blocking the synthesis of BCR-ABL protein, the primary cause of these leukemias, is provided by this invention. The design of the hammerhead is such that it can only affect the oncogenic bcr-abl gene product without having any effect on normal bcr and c-abl gene transcripts. By cleaving the bcr-abl gene transcript, this ribozyme can prohibit synthesis of the BCR-ABL protein associated with tumor cells and, return the cells to normalcy.
The hammerhead ribozyme, which is preferred in this invention, comprises separate sequences: a catalytic sequence and a substrate binding sequence in two parts (the bcr-abl mRNA is the substrate). The ribozyme is a synthetic, catalytic RNA of between 35-45 nucleotides in length. A presently preferred ribozyme is about 40 nucleotides in length. The designed ribozyme may vary in structure so long as it contains the catalytic sequence. However, the cleavage rates of the ribozyme will vary depending upon the secondary (and possibly tertiary) structures of the hammerhead.
The hammerhead ribozyme of this invention comprises a single strand of ribonucleic acids comprising:
(1) a sequence complementary to a sequence of the coding strand of the hybrid gene 5' to the breakpoint of the translocation and capable of hybridizing to that part of the gene (a first substrate binding sequence);
(2) a second sequence complementary to a sequence of the coding strand of the hybrid gene 3' to the breakpoint of the translocation and capable of hybridizing thereto (a second substrate binding sequence), and
(3) a sequence therebetween encoding a catalytic ribozyme domain capable of cleaving the hybrid chromosome at or near the breakpoint (the catalytic or ribozyme sequence).
Substrate binding sequences (1) and (2) above depend for their structure on the sequence of the hybrid gene which is targeted for destruction by the invention. These sequences are complementary to appropriate parts of the hybrid gene which flank the translocation breakpoint, e.g., the portion of the gene at which the two chromosomes are fused. The function of these sequences of the RNA molecule of this invention is to specifically isolate the hybrid gene RNA and position the ribozyme (3) for cleavage of the gene.
These sequences (1) and (2) are desirably between 5 to 11 nucleotides in length. More preferably, these flanking sequences are between 6 and 10 nucleotides in length. The length of these sequences provides a hybridization event with the target gene sufficient to permit cleavage of the gene at or near the breakpoint, thereby disabling the production of the hybrid tumorigenic protein. After the gene is cleaved, the RNA molecule is designed to dissociate from the pieces. The ability to release the fragments of the cleaved gene relates also to the length of the flanking sequences of the RNA molecule. The same RNA molecule may then encounter another gene and perform the same cleavage function repeatedly until the molecule is eventually degraded by the cell.
In a specific embodiment, a ribozyme molecule of this invention has a 40 nucleotide base sequence comprising ##STR1## wherein U is Uridine, C is Cytosine, G is Guanidine, and A is Adenine. Optionally, the ribozyme may be provided with a cap structure, e.g. a 5'GpppG, which acts as a stabilizer in an intracellular environment.
The sequence of the RNA oncogene bcr-abl, i.e., the site on the bcr-abl gene transcript where the RNA molecule of this invention will bind is: 5' A-G-C-A-G-A-G-U-U (cleavage site)-C-A-A-A-A-G-C-C-C-U 3'. The ribozyme is designed so that cleavage occurs after the 5' GUU 3' sequence of the bcr-abl mRNA. FIG. 2 illustrates the binding of the ribozyme to the substrate (the bcr-abl gene transcript).
The ribozyme of this invention can be prepared by chemical synthesis or produced in recombinant vectors by conventional means [see, T. Maniatis et al, Molecular Cloning (A Laboratory Manual), Cold Spring Harbor Laboratory (1982)].
As is described in exemplary form below, ribozyme RNA sequences may be synthesized conventionally by means of, for example, the RNA polymerase system such as T7 or SP6. bcr-abl mRNA substrates may be cloned from, for example, K562 cell line (available from the American Type Culture Collection, Rockville, Md., U.S.A., Accession Number ATCC# CCL 243) or BV173, EM2, Nalm-1, EM3, and any CML cell lines. The sequence of the bcr-abl gene is published in E. Shtivelman et al, Nature, 315:550-553 (1985). The RNAs are separated by electrophoresis and purified in acrylamide-urea gels.
The mechanism by which the ribozyme works is as follows: the substrate strand is designed in such a way that one half of it hybridizes to the bcr sequence of the hybrid gene and the other half of the substrate RNA binds to the abl sequence of the hybrid gene. The catalytic sequence is thereby placed in proximity to the 5'GUU3'sequence of the site of the targeted hybrid gene. Upon cleavage the bcr-abl gene transcript is destroyed, and the ability of the gene to direct the synthesis of BCR-ABL protein is interrupted. In the absence of the oncogenic protein, the cell returns essentially to normal.
Because the ribozyme effects only site-specific cleavage, normal cellular bcr and abl gene transcript sites therefore remain unaffected by the action of the ribozyme. Thus, only cells containing the translocation resulting in the Philadelphia Chromosome are altered by this ribozyme.
Desirably for both production of the ribozyme of this invention and to provide delivery systems for exposing bone marrow cells to the ribozyme, recombinant vectors are employed. The ribozyme construct may be placed in a viral vector, of which many are known to the art. Viral vectors are preferred because they have the capacity to infect the cell where the ribozyme must be located to function appropriately. Presently preferred vectors are retroviral vectors, adenoviral vectors, vaccinia vectors, and others, such as described by E. Gilboa, Adv. Exp. Med. Biol., 241:29 (1988) and P. H. Pouwels et al, "Vectors for Animal Cells", in Cloning Vectors: A Laboratory Manual, ch.7 (Elsevier, Amsterdam: 1985). Other conventionally employed vectors designed for use in mammalian, bacterial, yeast, fungal or insect systems may be employed to recombinantly express the ribozyme of this invention, but are not preferred for delivery purposes into the cells.
The resulting viral vector is then exposed to the cells wherein the cells become infected, the ribozyme is replicated and functions as described above.
Alternative delivery systems for the ribozyme may employ other known components, such as a lipid delivery system, first described in P. L. Felgner et al, Proc. Natl. Acad. Sci. U.S.A., 84:7413-7417 (1987). The lipid functions to fuse with the cells allowing the ribozyme to enter the cells. Transferrinfection of K562 cells, recently shown to be an effective alternative to retroviral infection, may be successfully employed as a delivery system [Cotten et al, PNAS, 87:4033 (1990)]. Other delivery systems may include direct addition of the ribozyme to cells, which has been shown to be successful with antisense DNA oligomers [S. L. Luke et al, PNAS, 86:3474-3478 (1989)].
The ribozyme of the present invention may thus be employed as a therapeutic agent in the treatment of leukemias and other cancers such as those characterized by the presence of the Philadelphia Chromosome. The method according to this invention may also be used in the treatment of other diseases, such as any leukemia or solid tumor which results from and contains the fusion of at least two normal genes, resulting in the generation of an abnormal chimeric gene product, or otherwise characterized by the presence of other chimeric gene products resulting from chromosomal translocations or other fusion mechanisms, wherein the resulting gene has a 5'GUX3' sequence close to the breakpoint. Other ribozymes may be designed according to this method for use in analogous treatments for these other cancers.
Preferably this treatment is accomplished by contacting bone marrow cells extracted from a patient ex vivo with a sufficient number of ribozymes, or vectors carrying ribozymes, for a time sufficient to effect cleavage of the oncogene present in the cells. Alternatively, the method may employ contacting the cells in vivo, for example, by administration directly into the bone marrow of a leukemic patient of vectors carrying the RNA molecule of the invention. When either method is applied to the cells of CML patients, the RNA molecule of this invention causes the specific destruction of the bcr-abl mRNA, resulting in the loss of synthesis of the tumorigenic BCR-ABL protein.
Once transmitted into the cellular environment via a vector, the ribozyme is expected to survive within the cell for a short period of time. Since there is not necessarily only a one to one relationship between the ribozyme and the target oncogene, a single ribozyme is expected to bind and cleave a number of oncogenic transcripts before being degraded or destroyed by the natural enzymes in the cells and/or the natural functions of the immune system.
The patient may be treated with conventional chemotherapy or radiation to substantially destroy the remaining bone marrow cells carrying the bcr-abl oncogene, and the treated cells are then returned to the patient. The treated cells, when returned to the patient may then be stimulated by various known hematopoietic growth factors to repopulate the bone marrow with cells which do not carry the oncogenic transcript.
This method has the advantage over conventional cancer or leukemia treatments, such as bone marrow transplant, of avoiding complications caused by lack of compatibility and rejection because in the present method only the patient's own cells are involved. Further, it is expected that many of the side effects associated with conventional chemotherapy may be avoided because the treatment takes place essentially ex vivo. However, this method may also be used in connection with other treatments, such as radiation or chemotherapy.
The in vitro reaction depicted in FIG. 3 indicates the applicability of the reaction to the in vivo conditions. The reaction was performed at 37� C. under physiological pH of 7.5 with the presence of the Mg++ cofactor. Under these conditions enzymatic activity will occur until the elimination of either the substrate or degradation of the ribozyme.
The number of ribozymes which are required can be determined in vitro by titration of a known substrate with known riboxyme until no activity is observed.
The following examples illustrate the compositions and methods of this invention.
The ribozyme was synthesized as an oligonucleotide on an Applied Biosystems DNA synthesizer. The 40 mer ribozyme was purified by isolation from 20% polyacrylamide-7 M urea gels. The products are located by either autoradiography or UV shadowing. The resultant products band is crushed, and soaked for between 1 hour and overnight in 2 volumes of 0.5M NaOAc pH 7.0. The extracted RNA is concentrated by ethanol precipitation and resuspended in H2 O. Purified RNAs are stored in H2 O at -20� C.
The resulting ribozyme was 40 nucleotides in length with the following sequence: ##STR2## wherein U is Uridine, C is Cytosine, G is Guanidine, and A is Adenine.
The 5' end of bcr-abl RNA containing the bcr-abl breakpoint was expressed by inserting a 420 bp fragment of bcr-abl cDNA, which was constructed from a library constructed from K562 mRNA, into the plasmid vector pGEM5 (Promega). This sequence is transcribed in vitro using T7 RNA polymerase in the presence of 32 P-rCTP. The resulting labelled RNA was isolated and purified.
The vector containing the BCR-ABL fragment was linearized by NdeI digestion and transcribed in vitro using T7 RNA polymerase in the presence of = P-rCTP. The reaction was stopped after one hour at 37� C. by the addition of DNASE. Following digestion of the plasmid template, labelled RNA transcripts were loaded onto a 4% PAGE-7M urea gel and isolated by elution of the band from the gel slice. The purified RNA transcript was resuspended in H2 O and stored at -20� C. until use.
The T7 polymerase generated RNA transcript was 499 bases in length; with 73 bases of pGEM 5 polylinker sequence prior to the 420 bases of BCR/ABL substrate and 6 bases from the polylinker restriction linearization site. The GUU cleavage site is located 140 bases from the 5' end of the BCR/ABL specific sequences.
Analysis of the RNA transcript was used to characterize the cleavage products which would be expected if the assay described below in Example 3 proved the efficacy of the ribozyme. The 5' cleavage product should be 140+73=213 nucleotides and the 3' cleavage product should be 280+6=286 nucleotides. The intact transcript is 73+420+6=499 nucleotides. In the absence of cleavage, one specie is expected: an intact 499 nucleotide fragment extending from the T7 polymerase start site, to the end of the linearized plasmid. This includes the BCR/ABL segment as well as sequences from the pGEM5 expression plasmid. If cleavage of the bcr-abl RNA occurs, the 499 fragment is split into two fragments 213 and 286 nucleotides in length.
From this it was determined that the uncleaved bcr-abl gene transcript was 499 nucleotides in length. This RNA was used as a substrate in the test of Example 3 below.
To assess whether the synthetic ribozyme of Example 1 can cleave the bcr-abl mRNA substrate, the ribozyme of Example 1 and the RNA substrate of Example 2 (1 pmol of each) were mixed in a 10-μl reaction volume containing 50 mM Tris-HCl, pH 7.5. This resembles the physiologic pH of 7.4. As a control the MgCl2 is omitted and 10 mM EDTA is added as the typical ribozyme-mediated cleavage is dependent on metal ions such as Mg++. The mixture is heated to 95� C. for 2 minutes and quick-cooled on ice. 10 mM MgCl2 is added and then the mixture is incubated at 37� C. for 14 hours.
Following the incubation, the reaction products were analyzed on a 4% polyacrylamide gel under denaturing conditions. The results presented in FIG. 3 show that the synthetic hammerhead cleaves the substrate RNA containing the bcr-abl junction, in the expected manner.
After cleavage, the bcr-abl fragment sizes were 290 nucleotides and 160 nucleotides. [See lanes 5 and 6 in the gel of FIG. 3]. These results also show that the cleavage occurs very efficiently in the presence of Mg++ ions. In contrast, this cleavage reaction was inhibited by EDTA. These results indicate that the introduction of this synthetic RNA ribozyme into leukemic cells synthesizing bcr-abl gene transcripts will result in the specific degradation of bcr-abl RNA which, in turn, prevents the synthesis of the oncogene BCR-ABL. Thus, this treatment is expected to result in the reversal of the leukemic process.
To deliver the ribozyme to a patient's leukemic cells, the ribozyme is inserted as a DNA fragment into a retroviral expression vector. A synthesized DNA fragment, such that its expression will result in the active ribozyme molecule, is cloned into a retroviral vector by standard methods (T. Maniatis et al, cited above). The retroviral vector, pC-1, contains the Moloney murine leukemia virus LTRs and a selectable neo gene. The crippled vector allows packaging and infection of the inserted gene. However, because the pathogenic portions of the parent virus have been removed, the pathogenicity of the parental viral infection has been eliminated. The recombinant virus containing the ribozyme DNA sequence is transfected into a packaging cell-line, such as PA31I7 or ψ2, to generate a producer cell line.
Bone marrow cells from a leukemic patient are infected either by co-cultivation with the producer cell-line or by incubation with cell-free virus containing supernatant. Following overnite infection, the bone marrow cells are washed in PBS and grow in vitro for a period of 14-21 days. Successfully infected cells are selected for by the inclusion of G418 (Gibco) in the medium at two days post-infection. The presence of the neo gene in the ribozyme-containing retrovirus allows for growth in the presence of this compound. Therefore cells which were not infected die. The population of infected bone marrow cells are transplanted into the patient. Bone marrow cells and/or peripheral blood samples are monitored by the PCR-RT technique using BCR-ABL specific primers to show the presence or absence of BCR/ABL transcripts and the success of the treatment.
Numerous modifications and variations of the methods of this invention are expected to occur to those of skill in the art. For example, the methods described above may be employed to design other ribozymes suitable for the treatment of other leukemias. Similarly, other recombinant techniques, vectors and methods for assembling the ribozymes may be selected by one of skill in the art without departing from this invention. Thus, the invention and such modifications are encompassed by the appended claims.
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Some people who went to an annual festival in Saint Jo that's dedicated to celebrating self-proclaimed rednecks took their fun a little too far this weekend.
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