Nanotech system, cellular heating may improve treatment of ovarian cancer

PUBLIC RELEASE DATE:

17-Oct-2013

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Contact: Oleh Taratula
oleh.taratula@oregonstate.edu
541-737-5785
Oregon State University

CORVALLIS, Ore. The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancer while reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer one of the leading causes of cancer-related deaths in women often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

"Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery," said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. "It's essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that."

It's known that elevated temperatures can help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size neither too big nor too small so the immune system will not reject it. A special polyethylene glycol coating further adds to the "stealth" effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

"The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field," said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. "The nanoparticles absorb energy from the oscillating field and heat up."

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin, the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

"I'm very excited about this delivery system," Taratula said. "Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We're not trying to kill the cell with heat, but using it to improve the function of the drug."

Iron oxide particles had been used before in some medical treatments, researchers said, but not with the complete system developed at OSU. Animal tests, and ultimately human trials, will be necessary before the new system is available for use.

Drug delivery systems such as this may later be applied to other forms of cancer, such as prostate or pancreatic cancer, to help improve the efficacy of chemotherapy in those conditions, Taratula said.

###

Editor's Notes: A graphic to illustrate this drug delivery system is available online: http://bit.ly/15omJcP

The study this story is based on is available online: http://bit.ly/18PLoY4

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

PUBLIC RELEASE DATE:

17-Oct-2013

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]

Contact: Oleh Taratula
oleh.taratula@oregonstate.edu
541-737-5785
Oregon State University

CORVALLIS, Ore. The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancer while reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer one of the leading causes of cancer-related deaths in women often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

"Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery," said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. "It's essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that."

It's known that elevated temperatures can help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size neither too big nor too small so the immune system will not reject it. A special polyethylene glycol coating further adds to the "stealth" effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

"The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field," said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. "The nanoparticles absorb energy from the oscillating field and heat up."

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin, the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

"I'm very excited about this delivery system," Taratula said. "Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We're not trying to kill the cell with heat, but using it to improve the function of the drug."

Iron oxide particles had been used before in some medical treatments, researchers said, but not with the complete system developed at OSU. Animal tests, and ultimately human trials, will be necessary before the new system is available for use.

Drug delivery systems such as this may later be applied to other forms of cancer, such as prostate or pancreatic cancer, to help improve the efficacy of chemotherapy in those conditions, Taratula said.

###

Editor's Notes: A graphic to illustrate this drug delivery system is available online: http://bit.ly/15omJcP

The study this story is based on is available online: http://bit.ly/18PLoY4

---

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-10/osu-nsc101713.php
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Afghan insurgents hit convoy by foreigner compound

KABUL, Afghanistan (AP) — A suicide car bomber attacked a small convoy of vehicles Friday near a heavily fortified private residential compound used by hundreds of foreigners on the outskirts of Kabul, killing two passers-by, Afghan officials said.

Inferior Ministry spokesman Sediq Sediqi said a suicide car bomber attacked two vehicles used "by foreigners" near the Green Village compound. There were no reports that the people in the vehicles were injured.

A police official said two civilians passing by the site of the explosion were killed by the blast. He spoke on condition of anonymity because he was not authorized to speak to the media.

Taliban spokesman Zabihullah Mujahid claimed responsibility for the car bombing and said Green Village was the intended target.

The NATO-led International Security Assistance Force confirmed that a car bomb attack had occurred in Kabul and that "there was one enemy killed as a result of the attack."

"We have no operational reports of ISAF personnel fatalities," it said in a statement.

Small arms fire could be heard after the initial blast, apparently as guards in the industrial zone where the blast occurred started shooting. An Associated Press reporter there saw fire trucks move to extinguish a blaze started by the blast.

Police initially reported that the residential compound was the target of the attack. The camp houses contractors from various countries, European diplomatic personnel and United Nations employees.

It is located on the main highway connecting Kabul to the eastern city of Jalalabad and is surrounded by layers of blast walls and has dozens of armed guards.

Green Village was last attacked by a suicide car bomber and armed attackers on May 2, 2012, and a number of Afghan guards were killed. None of its residents was injured in that assault.

___

Associated Press writer Patrick Quinn contributed to this report.

Source: http://news.yahoo.com/afghan-insurgents-hit-convoy-foreigner-compound-144636951.html
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'Matilda' and 'Betrayal' enjoy good Broadway week

NEW YORK (AP) — Two Broadway shows with very different audiences broke box office records last week — the kid-friendly "Matilda the Musical" and the very adult revival of Harold Pinter's "Betrayal."

Data released Tuesday from The Broadway League shows that the sold-out revival of the Harold Pinter play starring Daniel Craig and Rachel Weisz in a crumbling marriage took in $1,112,027 over seven performances ending Sunday, breaking the Barrymore Theatre's weekly box office record. It had set the record the week before with $1,100,818. It opens Oct. 27.

On the other end of the entertainment spectrum, "Matilda" had its best week ever, pulling in $1,430,085 and creating a new record at the Shubert Theatre for the sixth time. The English hit opened April 11 and has been an instant draw, regularly grossing over $1 million a week.

Michael David, a "Matilda" producer and president of the partnership Dodger Properties, credited his show's surge to the Columbus Day holiday weekend and the decision last week to scrap the Wednesday night performance of "Matilda" in favor of two shows on Sunday. He said Broadway is enjoying a robust October after a slow September. "For a lot of shows, this was a breath of fresh air. Everything worked together, if you planned it right, to make healthy box office business."

David, who also produced "Jersey Boys," has watched as early curiosity in "Matilda," a witty musical adaptation of the beloved novel by Roald Dahl, has led to strong ongoing interest in America, no sure thing. "That ongoing interest accounts for, after six months, the capability of the show to do as well as it is doing."

Not to be outdone, "The Book of Mormon" broke the Eugene O'Neill Theatre's box office record — for the 45th time. The show's grosses were $1,844,549 for the week ending Sunday with a top premium ticket going for $477. Unsurprisingly, the musical also had the highest average paid admission at $210.

And "Kinky Boots," the reigning Tony Award-winning musical, earned $1,810,202, its biggest haul so far and marking a new record for an eight-show week at the Al Hirschfeld Theatre.

Overall, Broadway box offices are ahead of where they were last season at this time. Last week's 28 shows grossed $24,614,027, ahead of the same week in 2012 in which 26 shows pulled in $20,614,956. Four shows are still in previews this time, including a play based on John Grisham's "A Time To Kill."

"Soul Doctor," the musical about the life and music of Rabbi Shlomo Carlebach, bowed out Sunday after playing 32 previews and 66 regular performances. It was critically savaged and was earning less than 20 percent of its box office potential. The week also bid farewell to "The Trip to Bountiful," a well-regarded revival of Horton Foote's play that starred Cicely Tyson.

___

Mark Kennedy can be reached at http://twitter.com/KennedyTwits

Source: http://news.yahoo.com/matilda-betrayal-enjoy-good-broadway-week-175259228.html
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Five Songs By The 'Rhodes Scholar' Keyboardist Of Hip-Hop

Keyboardist and producer Bob James' 1970s work helped to establish the sound of smooth jazz — and lives on in hip-hop samples galore.

Courtesy of the artist

Keyboardist and producer Bob James' 1970s work helped to establish the sound of smooth jazz — and lives on in hip-hop samples galore.

Courtesy of the artist

Professing love for Bob James' music can yield a side-eye in some circles. Jazz purists routinely view the keyboardist's 1970s period as a progenitor to smooth jazz — an idiom they frequently react to as if it were a sign of the apocalypse.

Nevertheless, James knows his way around the keyboards, and has demonstrated a keen gift for concocting catchy melodies and funky grooves, enticing many R&B and funk fans. His music also seduced legions of hip-hop and deep house producers such as DJ Jazzy Jeff, Q-Tip, Pete Rock, Dr. Dre and Kenny "Dope" Gonzalez. In fact, James' output on the CTI and (his own) Tappan Zee labels is some of the most sampled music in hip-hop.

That's one of the reasons why the new two-disc compilation, Rhodes Scholar: Jazz-Funk Classics 1974-1982, is a motherlode for any DJ looking for jams with a deeper sense of music history that will still ignite dance floors. And don't be surprised if you hear some of today's funk-informed jazz stars such as Robert Glasper, Karriem Riggins and Ben Williams drop a Bob James quote or two in their live performances.

Source: http://www.npr.org/blogs/ablogsupreme/2013/10/17/236231843/five-songs-by-the-rhodes-scholar-keyboardist-of-hip-hop?ft=1&f=1039
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Nexus 5 makes a brief appearance on Google Play, listed at $349

The link is dead(ish) now, but there it is, folks. The Nexus 5, for $349.

Source: http://feedproxy.google.com/~r/androidcentral/~3/Rj_ytXjbvWY/story01.htm
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Zimbabwe diamonds: Where has all the money gone?

File - in this file photo taken Wednesday, Nov. 1, 2006 gangs of illegal miners dig for diamonds in Marange, eastern Zimbabwe. The wealth enjoyed by just a few comes, at least in part, from the vast Marange diamond field that was exposed by an earth tremor in 2006. The Marange deposit is the biggest diamond field found in Africa for a century, estimated to be worth some billions of dollars, but as most Zimbabweans remain mired in poverty, questions are being asked about where all the money went and who benefited. (AP Photo/Tsvangirayi Mukwazhi, FILE)

File - in this file photo taken Wednesday, Nov. 1, 2006 gangs of illegal miners dig for diamonds in Marange, eastern Zimbabwe. The wealth enjoyed by just a few comes, at least in part, from the vast Marange diamond field that was exposed by an earth tremor in 2006. The Marange deposit is the biggest diamond field found in Africa for a century, estimated to be worth some billions of dollars, but as most Zimbabweans remain mired in poverty, questions are being asked about where all the money went and who benefited. (AP Photo/Tsvangirayi Mukwazhi, FILE)

FILE - in this file photo taken Wednesday, Nov. 1, 2006, illegal miners dig for diamonds in Marange, Zimbabwe. The wealth enjoyed by just a few comes, at least in part, from the vast Marange diamond field that was exposed by an earth tremor in 2006. The Marange deposit is the biggest diamond field found in Africa for a century, estimated to be worth some billions of dollars, but as most Zimbabweans remain mired in poverty, questions are being asked about where all the money went and who benefited. (AP Photo/Tsvangirayi Mukwazhi, FILE)

File - in this file photo taken Wednesday, Nov. 1, 2006, gangs of illegal miners dig for diamonds in Marange, eastern Zimbabwe. The wealth enjoyed by just a few comes, at least in part, from the vast Marange diamond field that was exposed by an earth tremor in 2006. The Marange deposit is the biggest diamond field found in Africa for a century, estimated to be worth some billions of dollars, but as most Zimbabweans remain mired in poverty, questions are being asked about where all the money went and who benefited. (AP Photo/Tsvangirayi Mukwazhi, FILE)

HARARE, Zimbabwe (AP) — Despite living in an impoverished country under sanctions, some in Zimbabwe seem awash in money, judging by the Mercedes-Benzes parked at a country club and the private woodland estate with artificial lake and mansion built by the nation's police chief.

The wealth enjoyed by just a few comes, at least in part, from the vast Marange diamond field that was exposed by an earth tremor in 2006. The deposit in eastern Zimbabwe is the biggest diamond field found in Africa for a century, worth billions of dollars.

Now, as most Zimbabweans remain mired in poverty, with government coffers short on funds to build and maintain the nation's roads, clinics, utility services and schools, questions are being asked as to where all the money went and who benefited.

A recent bipartisan parliamentary investigation concluded that tens of millions of dollars in diamond earnings are missing from 2012 alone. The lawmakers who wrote the unprecedented and unusually candid report said their "worst fears were confirmed" by evidence of "underhand dealings" and diamond smuggling since 2009.

In a speech opening parliament on Sept. 17, President Robert Mugabe took the rare step of accusing one top mining official and ruling party loyalist of accepting a $6 million bribe from Ghanaian investors to obtain diamond mining rights in Marange. Mugabe said Godwills Masimirembwa took the bribe when he was head of the state Zimbabwe Mining Development Corporation which is in charge of mining concessions.

Masimirembwa quit that post to contest the July 31 national election as a candidate for Mugabe's ZANU-PF party but failed to win a parliament seat. Masimirembwa denies any wrongdoing.

The parliamentary report and a human rights group say diamond mining has led to serious human rights abuses and that diamond concessions were awarded by government officials to enrich top members of the ZANU-PF party, of the security forces and Chinese allies.

In declaring his innocence, Masimirembwa said the purported deal with the Ghanaian investors was discussed with national Police Chief Augustine Chihuri and then Mines Minister Obert Mpofu, a longtime business associate of Masimirembwa who is also one of the nation's wealthiest businessmen.

Chihuri and Mpofu have frequently insisted in the state media that their wealth comes from legitimate business empires to make up for poor salaries paid for full-time government duties.

Expected revenues from the Marange diamond fields have scarcely materialized.

Former Zimbabwe Finance Minister Tendai Biti says he was promised $600 million for economic and development projects from diamond revenues last year but only received $41 million. Nothing was paid into the national treasury up to the disputed July elections that the ZANU-PF won, a vote result that caused the end of a coalition government with the MDC party that Biti belonged to, and the loss of his Cabinet seat.

Some $2 billion in Zimbabwe's diamond revenues have been unaccounted for since 2008, according to Global Witness, which campaigns against natural resource-related conflict and corruption and associated environmental and human rights abuses. Zimbabwe is the world's fourth-largest diamond miner, producing an estimated 17 million carats this year, according to the Kimberley Process which is charged with ensuring that gems reaching world markets don't bear the taint of being "blood diamonds." Marange diamonds have been declared conflict free.

But controversy and secrecy have swirled around Marange since the earth opened up and exposed its riches.

The discovery lured thousands of impoverished Zimbabweans to dig in the alluvial deposit. In 2008, the Zimbabwean army sealed off the 60,000 hectare (130,000 acre) area to take control of the mining. At least 200 people died in a mass expulsion of people living in the closed area, Global Witness and other rights groups have alleged.

Chinese construction contractors built an airfield at the Marange diamond fields. Executive planes arrive there and at a bonded warehouse alongside the runway at Harare's main airport, without traceable flight plans or having to go through customs and immigration formalities, say commercial pilots who say they have complained of the irregularities to aviation authorities. They insisted on anonymity because of fears for their safety.

Some are living high from diamond deals.

As children begged in the street a block away, Zimbabwean diamond company executives accompanied by elegant young women arrived at a popular Harare nightclub last year, ordered drinks for about 120 patrons and picked up the $ 4,000 tab, said a person who witnessed the scene and who demanded anonymity to prevent reprisals.

The identities of owners, directors and shareholders in diamond enterprises have never been officially disclosed, though the Zimbabwe Republic Police Trust, a business enterprise of the police force, is publicly listed as holding a 20 percent stake in the Ghanaian diamond investment project.

The parliamentary panel's report said powerful officials, politicians and police and army commanders repeatedly tried to thwart the probe into diamond dealings. The chairman of the 22-member panel, Edward Chindori-Chininga, a former Mugabe mines minister, died in a car crash just days after he signed the report in June.

Police said Chindori-Chininga's death was accidental and that his car had veered off the highway and slammed into trees.

Car wrecks or mysterious accidents have taken the lives of 12 senior politicians, all of whom were believed to have bucked official policy, in the past two decades, according to local press reports.

The parliamentary committee's report said several officials lied while giving evidence under subpoena and that diamond earnings are not only shielded from scrutiny but are not channeled into the state coffers. It said the Marange fields in particular are a no-go area, shrouded in secrecy and deception. The mining companies don't even buy food or services from surrounding communities, the report said.

Mugabe's government and ZANU-PF have repeatedly denied diamond revenues have been siphoned off.

But Global Witness says otherwise.

"Our research has exposed links between Zimbabwe's two largest diamond mining companies and the Zimbabwean military and other ZANU-PF insiders," said Emily Armistead, senior campaigner for Global Witness.

"It is not clear where the money is going," she added. "It appears there is a mixture of corruption enriching specific individuals and some funds going to security operations. Our concern is that it could be used to fund repression and human rights abuses."

The difficulty with monitoring diamond earnings lies in the "opaque" way the mining enterprises were formed and financed, said Zimbabwean economist John Robertson. Information on their expenditure, profits and staff levels have not been divulged, he said.

"You are not allowed to know what is going on and if you need to know that amounts to attempted espionage," Robertson said.

So far, no legal action has been taken against Masimirembwa, the man accused by Mugabe.

And despite widespread reports since September in the Zimbabwean press that other top political and military figures would likely be exposed, so far none has.

Associated PressSource: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-10-17-Zimbabwe-Diamonds/id-d187a6f1afd04bd9b8cfce2dceadc995
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Director Bay attacked on 'Transformers' set in HK

American film director Michael Bay, left, assists the cameraman as they are filming their latest film "Transformers Four" in Hong Kong Thursday, Oct. 17, 2013. Two men have been arrested after the American film director, Michael Bay, was allegedly assaulted in Quarry Bay while working on his latest film, "Transformers Four" as the two men demanding money from the film crew. (AP Photo)

American film director Michael Bay, left, assists the cameraman as they are filming their latest film "Transformers Four" in Hong Kong Thursday, Oct. 17, 2013. Two men have been arrested after the American film director, Michael Bay, was allegedly assaulted in Quarry Bay while working on his latest film, "Transformers Four" as the two men demanding money from the film crew. (AP Photo)

American film director Michael Bay, center, with members of his crew film his latest film "Transformers Four" in Hong Kong Thursday, Oct. 17, 2013. Two men have been arrested after the American film director, Michael Bay, was allegedly assaulted in Quarry Bay while working on his latest film, "Transformers Four" as the two men demanding money from the film crew. (AP Photo)

FILE - In this June 28, 2011 file photo, executive producer and director Michael Bay attends the "Transformers: Dark Of The Moon" premiere in Times Square in New York. Filming of Hollywood movie Transformers 4 in Hong Kong was briefly suspended after director Bay fell victim to an extortion attempt in which he was slightly injured, according to media reports and police Thursday, Oct. 17, 2013. (AP Photo/Evan Agostini, File)

HONG KONG (AP) — Hollywood director Michael Bay was attacked and slightly injured Thursday on the set of the fourth installment of the "Transformers" movie series currently filming in Hong Kong, police said.

A Hong Kong police spokeswoman said two brothers surnamed Mak who own a shop near the film set approached Bay and demanded 100,000 Hong Kong dollars ($13,000).

When Bay refused to pay, they assaulted him, she said. The brothers also allegedly assaulted three police officers who were called to the set.

The spokeswoman said Bay suffered a minor injury to his face but declined medical treatment. She spoke on customary condition of anonymity.

The two men, aged 27 and 28, were arrested and face charges of blackmail, assault and assaulting police officers, she said.

Paramount Pictures gave a somewhat different account of the incident, which it said occurred on the film's first day of production in Hong Kong.

It said in a statement that a man allegedly under the influence of a narcotic substance rushed onto the set wielding an air conditioning unit and swung it at Bay's head. It said Bay ducked and wrestled the air conditioning unit away from the man.

Police arrested the man and two companions, and no one on the set was injured, Paramount said.

"Transformers 4: Age of Extinction" is partly set in Hong Kong. It stars Mark Wahlberg and is to be released next June.

Associated PressSource: http://hosted2.ap.org/APDEFAULT/4e67281c3f754d0696fbfdee0f3f1469/Article_2013-10-17-Hong%20Kong-Transformers/id-420c6f8d86fc47cd886126ca73f29c13
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