Overcoming cancer drug resistance with nanoparticles
(Nanowerk News) One of the ways in which cancer cells evade anticancer therapy is by producing a protein that pumps drugs out of the cell before these compounds can exert their cell-killing effects. A research team at Northwestern University has found that biocompatible iron oxide-titanium dioxide nanoparticles can bypass this pump and enable DNA-damaging anticancer drugs to reach the cell nucleus.
Gayle Woloschak, a member of the Northwestern University Center for Cancer Nanotechnology Excellence, led the research team that developed this nanoparticle. She and her collaborators reported their findings in the journal Cancer Research ("Nanocarriers Enhance Doxorubicin Uptake in Drug-Resistant Ovarian Cancer Cells").
The goal of this work was two-fold: identify a nanoparticle that would overcome pump-related drug resistance which could simultaneously serve as a tumor imaging agent. The researchers chose a nanoparticle with an iron oxide core surrounded by a titanium dioxide shell. The iron oxide core serves as a powerful magnetic resonance imaging (MRI) contrast agent, while the titanium dioxide shell can bind to anticancer agents such as doxorubicin through a chemical bond that will break in the acidic conditions inside a cancer cell.
The investigators treated drug-resistant ovarian cancer cells with a doxorubicin-loaded nanoparticle and showed that the nanoparticle was readily transported into the cells. More importantly, the nanoparticles released their drug payload, enabling doxorubicin to reach the cell nucleus. Doxorubicin kills cells through a process that involves binding to DNA in the nucleus. When compared to doxorubicin alone, the resistant cells accumulated up to 6 times more drug then when administered using the nanoparticle-drug combination. Interestingly, the researchers found that when they co-administered even empty nanoparticles (no doxorubicin) with transferrin, a molecule involved in iron transport, they saw increased cell uptake of transferrin. This observation is important since many research groups are developing nanoparticles that incorporate transferrin on the surface to stimulate cell uptake. In this scenario, it could be beneficial to co-treat with this type of empty particle.
Image: Courtesy of Graham Snodgrass/U.S. Army Public Health Command
In Brief
After a decades-long reprieve, bed bugs have returned with a vengeance, plaguing rich and poor alike.
A confluence of factors ranging from the evolution of insecticide resistance to shifts in patterns of international travel seem to have fueled the parasite?s comeback.
Scientists have recently identified several aspects of bed bug biology and behavior that could lead to novel ways of detecting and eradicating the pests.
The elderly man lived by himself in a low-income apartment near Cincinnati. But he was not alone. After dark the bed bugs would emerge from his recliner and tattered box-spring mattress to feed on his blood. Judging from the thousands of insects I found in his home, I would venture that it had been this way for many months. Imprisoned by poverty and infirmity, the man had nourished generations of these pests, enduring their bites night after night while their numbers swelled.
NEW YORK ? Apple Inc. on Thursday launched its attempt to make the iPad a replacement for a satchel full of textbooks by starting to sell electronic versions of a handful of standard high-school books.
The electronic textbooks, which include "Biology" and "Environmental Science" from Pearson and "Algebra 1" and "Chemistry" from McGraw-Hill, contain videos and other interactive elements.
But it's far from clear that even a company with Apple's clout will be able to reform the primary and high-school textbook market. The printed books are bought by schools, not students, and are reused year after year, which isn't possible with the electronic versions. New books are subject to lengthy state approval processes, making the speed and ease with which ebooks can be published less of an advantage.
Major textbook publishers have been making electronic versions of their products for years, but until recently, there hasn't been any hardware suitable to display them. PCs are too expensive and cumbersome to be good e-book machines for students. Dedicated e-book readers like the Kindle have small screens and can't display color. IPads and other tablet computers work well, but iPads cost at least $499. Apple didn't reveal any new program to defray the cost of getting the tablet computers into the hands of students.
All this means textbooks have lagged the general adoption of e-books, even when counting college-level works that students buy themselves. Forrester Research said e-books accounted for only 2.8 percent of the $8 billion U.S. textbook market in 2010.
Pearson PLC of Britain and The McGraw-Hill Cos. of New York are two of the three big companies in the U.S. textbook market. The third, Boston-based Houghton Mifflin Harcourt, also plans to supply books to Apple's store, but none were immediately available.
The new textbooks are legible with a new version of the free iBooks application, which became available Thursday.
The textbooks will cost $15 or less, said Phil Schiller, Apple's head of marketing. He unveiled the books at an event at New York's Guggenheim Museum. Schools will be able to buy the books for its students and issue redemption codes to them, he said.
Albert Greco, a professor of marketing at Fordham University in New York and a former high-school principal, said schools would need to buy iPads for its students if it were to replace printed books.
It wouldn't work to let students who can afford to buy their own iPads use them in class with textbooks they buy themselves, alongside poorer students with printed books.
"The digital divide issue could be very embarrassing. Because if you don't have the iPad, you can't do the quiz, you don't get instant feedback ... that is an invitation for a lawsuit," Greco said. "I would be shocked if any principal or superintendent would let that system go forward."
Greco said hardback high-school textbooks cost an average of about $105, and a freshman might need five of them. However, they last for five years.
That means that even if an iPad were to last for five years in the hands of students, the e-books plus the iPad would cost more than the hardback textbooks.
At the private Xavier High School in New York, student Omar Soria welcomed the idea of getting rid of printed textbooks.
"They get pretty heavy, about maybe one pound per textbook. And depending on all the other books, which is binders and notebooks, it can get pretty heavy," he said.
Apple also released an app for iTunes U, which has been a channel for colleges to release video and audio from lectures, through iTunes. The app will open that channel to K-through-12 schools, and will let teachers present outlines, post notes and communicate with students in other ways.
Greco called the new app "a shot across the bow" of Blackboard Inc., a privately held company that provides similar electronic tools to teachers. It, too, has applications for cellphones and tablets.
Apple also revealed iBook Author, an application for Macs that lets people create electronic textbooks.
According to biographer Walter Isaacson, reforming the textbook market was a pet project of Apple co-founder Steve Jobs, even in the last year of his life. At a dinner in early 2011, Jobs told News Corp. chairman Rupert Murdoch that the paper textbooks could be made obsolete by the iPad. Jobs wanted to circumvent the state certification process for textbook sales by having Apple release textbooks for free on the tablet computer.
Jobs died in October after a long battle with cancer.
NICE, the healthcare guidance body, has today published final draft guidance not recommending cabazitaxel (Jevtana, Sanofi) in combination with prednisone or prednisolone as a second line treatment for prostate cancer.
Commenting onthe draft guidance published today Sir Andrew Dillon, Chief Executive of NICEsaid: "We need to be sure that new treatments provide sufficient benefits to patients to justify the significant resources the NHS would need to make available. Although cabazitaxel has been shown to be effective in extending life, it is also associated with a number of side effects [7]. The committee was concerned about the nature of the health-related quality of life information provided by the manufacturer.
"Once these factors had been taken into account, the independent Committee appraising this drug concluded that it would not provide enough health benefit to justify its cost, which means it would not be a cost effective use of limited NHS resources."
The draft guidance on cabazitaxel is now with consultees, who have the opportunity to appeal against it. Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments. This draft guidance does not mean that people currently taking cabazitaxel will stop receiving it. They have the option to continue treatment until they and their clinicians consider it appropriate to stop.
Ends
Notes to Editors
About cabazitaxel
1. The draft guidance will be available at http://guidance.nice.org.uk/TA/Wave23/31 from 12 January 2012.
2. The main treatment options for patients whose disease progresses after first line docetaxel include mitoxantrone and retreatment with docetaxel retreatment. Other chemotherapy regimens used in this setting were 5FU, cyclophosphamide and carboplatin/etoposide.
3. The Committee concluded that cabazitaxel resulted in a mean improvement of greater than 3 months in mean overall survival
4. If a drug meets the criteria to be considered under NICE's supplementary advice for end of life treatments, then a higher cost per QALY may be accepted. There is no set threshold cost per QALY for drugs that meet the end of life criteria, but since the supplementary advice was introduced, the highest cost per QALY of a recommended drug has been ?50,000 (TA169 - Sunitinib (first-line) for renal cell carcinoma).
The Committee considered that the most plausible ICER would be above ?87,500 per QALY gained.
5. The drug did meet the criteria to be considered under NICE's end of life considerations. However, the Committee considered that the additional weight needed to bring the Incremental Cost Effectiveness Ratio (ICER) into the range considered a cost-effective use of NHS resources was too great.
6. Each cycle of treatment with cabazitaxel costs approximately ?3,700. The median number of cycles received in the TROPIC study was 6; therefore cabazitaxel would cost a median of ?22,200 per patient.
7. Side effects: The most commonly occurring adverse reactions are related to bone marrow suppression which include anaemia, leukopenia, neutropenia, and thrombocytopenia and gastrointestinal events such as diarrhoea. Other very common adverse reactions include fatigue, nausea, vomiting, constipation, asthenia, haematuria, back pain, anorexia, pyrexia, dyspnoea, abdominal pain, dysgeusia, cough, arthralgia, and alopecia.
For the Committee, haematological adverse events and diarrhoea were major concerns. The Committee noted that the incidence of neutropenia was lower among participants recruited at European centres than other centres. The Committee was concerned that in TROPIC more participants in the cabazitaxel arm died from cardiac and renal complications than in the mitoxantrone arm.
Following consultation on the draft recommendations the Committee considered three sources of data presented by the manufacturer: the results of studies evaluating cardiac toxicity associated with cabazitaxel; the conclusions of a review by an expert panel of renal events observed with cabazitaxel; and post-marketing safety data. It concluded that there is no evidence of additional risk other than that included in the summary of product characteristics.
8. The SMC does not recommend cabazitaxel for this condition.
About NICE
9. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health
10. NICE produces guidance in three areas of health:
public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
11. NICE produces standards for patient care:
quality standards- these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients
12. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.
PORT-AU-PRINCE, Haiti ? A truck's brakes failed and it crashed a small bus then careened onto the sidewalk of one Port-au-Prince's busiest streets, killing 29 people and injuring 67, a Haitian official said Tuesday.
Nadia Lochard of Haiti's Civil Protection Office said the accident happened on Route Delmas in the capital when the driver lost control of his dump truck.
The press office of President Michel Martelly issued a statement saying the leader went to the site of the crash, which was in front of the national television headquarters.
The sidewalk outside the news station is often crowded with street vendors who sell their goods and motorcycle cabbies awaiting customers.
Power generation is blowing in the windPublic release date: 17-Jan-2012 [ | E-mail | Share ]
Contact: Anne Stark stark8@llnl.gov 925-422-9799 DOE/Lawrence Livermore National Laboratory
LIVERMORE, Calif. -- By looking at the stability of the atmosphere, wind farm operators could gain greater insight into the amount of power generated at any given time.
Power generated by a wind turbine largely depends on the wind speed. In a wind farm in which the turbines experience the same wind speeds but different shapes (such as turbulence) to the wind profile, a turbine will produce different amounts of power.
And this variable power can be predicted by looking at atmospheric stability, according to Lawrence Livermore National Laboratory scientist Sonia Wharton and colleague Julie Lundquist of the University of Colorado at Boulder and the National Renewable Energy Laboratory.
In a paper appearing in the Jan. 12 edition of the journal, Environmental Research Letters, Wharton and Lundquist examined turbine-generated power data, segregated by atmospheric stability, to figure out the power performance at a West Coast wind farm.
"The dependence of power on stability is clear, regardless of whether time periods are segregated by three-dimensional turbulence, turbulence intensity or wind shear," Wharton said.
The team found that power generated at a set wind speed is higher under stable conditions and lower under strongly unsteady conditions at that location. The average wind power output difference is as high as 15 percent less wind power generation when the atmosphere is unstable.
While turbulence is a relatively well-known term in assessing turbine efficiency, wind shear -- which is a difference in wind speed and direction over a relatively short distance in the atmosphere -- also plays an important role when assessing how much power a turbine generates over certain time scales.
Wharton and Lundquist said that wind farm operators could better estimate how much power is generated if the wind forecasts included atmospheric stability impact measurements.
Though earlier research looked at atmospheric stability effects on power output, few studies have analyzed power output from modern turbines with hub heights of more than 60 meters.
In the new research, Wharton and Lundquist gathered a year of power data from upwind modern turbines (80 meters high) at a multi-megawatt wind farm on the West Coast. They considered turbine power information as well as meteorological data from an 80-meter tall tower and a Sonic Detection and Ranging (SODAR), which provided wind profiles up to 200 meters above the surface, to look at turbulence and wind shear. Looking at upwind turbines removed any influence that turbine wakes may have on power performance.
The team found that wind speed and power production varied by season as well as from night to day. Wind speeds were higher at night (more power) than during the day (less power) and higher during the warm season (more power) than in the cool season (less power). For example, average power production was 43 percent of maximum generation capacity on summer days and peaked at 67 percent on summer nights.
"We found that wind turbines experienced stable, near-neutral and unstable conditions during the spring and summer," Wharton said. "But daytime hours were almost always unstable or neutral while nights were strongly stable."
"This work highlights the benefit of observing complete profiles of wind speed and turbulence across the turbine rotor disk, often available only with remote sensing technology like SODAR or LIDAR (Laser Detection and Ranging,)" Lundquist said. "Wind energy resource assessment and power forecasting would profit from this increased accuracy."
###
Founded in 1952, Lawrence Livermore National Laboratory (www.llnl.gov) provides solutions to our nation's most important national security challenges through innovative science, engineering and technology. Lawrence Livermore National Laboratory is managed by Lawrence Livermore National Security, LLC for the U.S. Department of Energy's National Nuclear Security Administration.
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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.
Power generation is blowing in the windPublic release date: 17-Jan-2012 [ | E-mail | Share ]
Contact: Anne Stark stark8@llnl.gov 925-422-9799 DOE/Lawrence Livermore National Laboratory
LIVERMORE, Calif. -- By looking at the stability of the atmosphere, wind farm operators could gain greater insight into the amount of power generated at any given time.
Power generated by a wind turbine largely depends on the wind speed. In a wind farm in which the turbines experience the same wind speeds but different shapes (such as turbulence) to the wind profile, a turbine will produce different amounts of power.
And this variable power can be predicted by looking at atmospheric stability, according to Lawrence Livermore National Laboratory scientist Sonia Wharton and colleague Julie Lundquist of the University of Colorado at Boulder and the National Renewable Energy Laboratory.
In a paper appearing in the Jan. 12 edition of the journal, Environmental Research Letters, Wharton and Lundquist examined turbine-generated power data, segregated by atmospheric stability, to figure out the power performance at a West Coast wind farm.
"The dependence of power on stability is clear, regardless of whether time periods are segregated by three-dimensional turbulence, turbulence intensity or wind shear," Wharton said.
The team found that power generated at a set wind speed is higher under stable conditions and lower under strongly unsteady conditions at that location. The average wind power output difference is as high as 15 percent less wind power generation when the atmosphere is unstable.
While turbulence is a relatively well-known term in assessing turbine efficiency, wind shear -- which is a difference in wind speed and direction over a relatively short distance in the atmosphere -- also plays an important role when assessing how much power a turbine generates over certain time scales.
Wharton and Lundquist said that wind farm operators could better estimate how much power is generated if the wind forecasts included atmospheric stability impact measurements.
Though earlier research looked at atmospheric stability effects on power output, few studies have analyzed power output from modern turbines with hub heights of more than 60 meters.
In the new research, Wharton and Lundquist gathered a year of power data from upwind modern turbines (80 meters high) at a multi-megawatt wind farm on the West Coast. They considered turbine power information as well as meteorological data from an 80-meter tall tower and a Sonic Detection and Ranging (SODAR), which provided wind profiles up to 200 meters above the surface, to look at turbulence and wind shear. Looking at upwind turbines removed any influence that turbine wakes may have on power performance.
The team found that wind speed and power production varied by season as well as from night to day. Wind speeds were higher at night (more power) than during the day (less power) and higher during the warm season (more power) than in the cool season (less power). For example, average power production was 43 percent of maximum generation capacity on summer days and peaked at 67 percent on summer nights.
"We found that wind turbines experienced stable, near-neutral and unstable conditions during the spring and summer," Wharton said. "But daytime hours were almost always unstable or neutral while nights were strongly stable."
"This work highlights the benefit of observing complete profiles of wind speed and turbulence across the turbine rotor disk, often available only with remote sensing technology like SODAR or LIDAR (Laser Detection and Ranging,)" Lundquist said. "Wind energy resource assessment and power forecasting would profit from this increased accuracy."
###
Founded in 1952, Lawrence Livermore National Laboratory (www.llnl.gov) provides solutions to our nation's most important national security challenges through innovative science, engineering and technology. Lawrence Livermore National Laboratory is managed by Lawrence Livermore National Security, LLC for the U.S. Department of Energy's National Nuclear Security Administration.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Ratings down a bit from last year's show. By Gil Kaufman
Ricky Gervais at the 2012 Golden Globes Photo: Getty Images
Ricky Gervais has said that his third go-round as host of the Golden Globes would be his last. And while his latest Hollywood-tweaking gig on Sunday night didn't draw the same headlines as last year's scorched-earth takedown of Tinsel Town pomposity, ratings for the broadcast were steady.
According to Nielsen figures, the 69th annual Globes was seen by 16.8 million viewers, which is just below the 17 million who tuned in last year. And though some critics dented Gervais for being more controlled than he was last year, the Globes has already set the high-water mark for awards programs so far this season, beating out both the American Music Awards and the Emmys.
MTV's Movies team gave Gervais both a thumbs up and down on his performance, praising him for "winning over Hollywood frenemies and delivering a very funny opening monologue." But there was some bad news as well: "The comedian might have talked a big game heading into the show, but Gervais' performance was a restrained one after last year's hullabaloo. What's great about the comedian is how he coats a witty mean-spiritedness with kindly, winking, you-know-I-still-love-you sugar. When your biggest dig is a fish-in-the-barrel attack on 'The Tourist,' you know you've caved to the worrywarts in the Hollywood Foreign Press Association."
With big wins for George Clooney for "The Descendants" and a boost for the silent film "The Artist," both movies solidified their spots as front-runners of the awards season.
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Public release date: 17-Jan-2012
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