WASHINGTON (AP) ? Congressman Paul Ryan's plan for Medicare gets all the attention, but the GOP vice presidential candidate has proposed even bigger changes to medical care for the poor and disabled.
The Wisconsin congressman is calling for states to take over the Medicaid program.
At the same time, Ryan's budget would reduce projected federal spending on Medicaid by about $800 billion over 10 years, shrinking the program as a share of the overall national economy.
Ryan is in sync with his new boss, Republican presidential candidate Mitt Romney.
Advocates for the poor and nonpartisan analysts say cuts would result in millions of vulnerable people losing health insurance. Republicans say that won't happen if states can make the program more efficient.
New nanoparticles shrink tumors in micePublic release date: 15-Aug-2012 [ | E-mail | Share ]
Contact: Sarah McDonnell s_mcd@mit.edu 617-253-8923 Massachusetts Institute of Technology
Particles that shut off cancer genes could also allow researchers to screen potential drug targets more rapidly
CAMBRIDGE, MA -- By sequencing cancer-cell genomes, scientists have discovered vast numbers of genes that are mutated, deleted or copied in cancer cells. This treasure trove is a boon for researchers seeking new drug targets, but it is nearly impossible to test them all in a timely fashion.
To help speed up the process, MIT researchers have developed RNA-delivering nanoparticles that allow for rapid screening of new drug targets in mice. In their first mouse study, done with researchers at Dana-Farber Cancer Institute and the Broad Institute, they showed that nanoparticles that target a protein known as ID4 can shrink ovarian tumors.
The nanoparticle system, described in the Aug. 15 online edition of Science Translational Medicine, could relieve a significant bottleneck in cancer-drug development, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of the David H. Koch Institute for Integrative Cancer Research at MIT.
"What we did was try to set forth a pipeline where you start with all of the targets that are pouring out of genomics, and you sequentially filter them through a mouse model to figure out which ones are important. By doing that, you can prioritize the ones you want to target clinically using RNA interference, or develop drugs against," says Bhatia, one of the paper's senior authors.
William Hahn, an associate professor of medicine at Harvard Medical School and the paper's other senior author, is the leader of Project Achilles, a collaborative effort to identify promising new targets for cancer drugs from the flood of data coming from the National Cancer Institute's cancer-genome-sequencing project.
Among those potential targets are many considered to be "undruggable," meaning that the proteins don't have any pockets where a traditional drug could bind to them. The new nanoparticles, which deliver short strands of RNA that can shut off a particular gene, may help scientists go after those undruggable proteins.
"If we could figure out how to make this work [in humans], it would open up a whole new class of targets that hadn't been available," says Hahn, who is also director of the Center for Cancer Genome Discovery at Dana-Farber and a senior associate member of the Broad Institute.
Lead authors of the paper are Yin Ren, an MD/PhD student in Bhatia's lab, and Hiu Wing Cheung, a postdoc in Hahn's lab.
An abundance of targets
Through Project Achilles, Hahn and his colleagues have been testing the functions of many of the genes disrupted in ovarian cancer cells. By revealing genes critical to cancer-cell survival, this approach has narrowed the list of potential targets to several dozen.
Typically, the next step in identifying a good drug target would be to genetically engineer a strain of mice that are missing (or overexpressing) the gene in question, to see how they respond when tumors develop. However, this normally takes two to four years. A much faster way to study these genes would be simply to turn them off after a tumor appears.
RNA interference (RNAi) offers a promising way to do that. During this naturally occurring phenomenon, short strands of RNA bind to the messenger RNA (mRNA) that delivers protein-building instructions from the cell's nucleus to the rest of the cell. Once bound, the mRNA molecules are destroyed and their corresponding proteins never get made.
Scientists have been pursuing RNAi as a cancer treatment since its discovery in the late 1990s, but have had trouble finding a way to safely and effectively target tumors with this therapy. Of particular difficulty was finding a way to get RNA to penetrate tumors.
Bhatia's lab, which has been working on RNAi delivery for several years, joined forces with Hahn's group to identify and test new drug targets. Their goal was to create a "mix and dose" technique that would allow researchers to mix up RNA-delivery particles that target a particular gene, inject them into mice and see what happens.
Shrinking tumors
In their first effort, the researchers decided to focus on the ID4 protein because it is overexpressed in about a third of high-grade ovarian tumors (the most aggressive kind), but not in other cancer types. The gene, which codes for a transcription factor, appears to be involved in embryonic development: It gets shut down early in life, then somehow reactivates in ovarian tumors.
To target ID4, Bhatia and her students designed a new type of RNA-delivering nanoparticle. Their particles can both target and penetrate tumors, something that had never before been achieved with RNA interference.
On their surface, the particles are tagged with a short protein fragment that allows them to enter tumor cells. Those fragments are also drawn to a protein found on tumor cells, known as p32. This fragment and many similar ones were discovered by Erkki Ruoslahti, a professor at the Sanford-Burnham Medical Research Institute at the University of California at Santa Barbara, who is also an author of the new paper.
Within the nanoparticles, strands of RNA are mixed with a protein that further helps them along their journey: When the particles enter a cell, they are encapsulated in membranes known as endosomes. The protein-RNA mixture can cross the endosomal membrane, allowing the particles to get into the cell's main compartment and start breaking down mRNA.
In a study of mice with ovarian tumors, the researchers found that treatment with the RNAi nanoparticles eliminated most of the tumors.
The researchers are now using the particles to test other potential targets for ovarian cancer as well as other types of cancer, including pancreatic cancer. They are also looking into the possibility of developing the ID4-targeting particles as a treatment for ovarian cancer.
###
The research was funded by the Howard Hughes Medical Institute, the National Cancer Institute, the National Institutes of Health, the Mary Kay Foundation, the Sandy Rollman Ovarian Cancer Foundation, the Canadian Institutes of Health Research and the H.L. Snyder Medical Foundation.
Written by Anne Trafton, MIT News Office
[ | 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.
New nanoparticles shrink tumors in micePublic release date: 15-Aug-2012 [ | E-mail | Share ]
Contact: Sarah McDonnell s_mcd@mit.edu 617-253-8923 Massachusetts Institute of Technology
Particles that shut off cancer genes could also allow researchers to screen potential drug targets more rapidly
CAMBRIDGE, MA -- By sequencing cancer-cell genomes, scientists have discovered vast numbers of genes that are mutated, deleted or copied in cancer cells. This treasure trove is a boon for researchers seeking new drug targets, but it is nearly impossible to test them all in a timely fashion.
To help speed up the process, MIT researchers have developed RNA-delivering nanoparticles that allow for rapid screening of new drug targets in mice. In their first mouse study, done with researchers at Dana-Farber Cancer Institute and the Broad Institute, they showed that nanoparticles that target a protein known as ID4 can shrink ovarian tumors.
The nanoparticle system, described in the Aug. 15 online edition of Science Translational Medicine, could relieve a significant bottleneck in cancer-drug development, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of the David H. Koch Institute for Integrative Cancer Research at MIT.
"What we did was try to set forth a pipeline where you start with all of the targets that are pouring out of genomics, and you sequentially filter them through a mouse model to figure out which ones are important. By doing that, you can prioritize the ones you want to target clinically using RNA interference, or develop drugs against," says Bhatia, one of the paper's senior authors.
William Hahn, an associate professor of medicine at Harvard Medical School and the paper's other senior author, is the leader of Project Achilles, a collaborative effort to identify promising new targets for cancer drugs from the flood of data coming from the National Cancer Institute's cancer-genome-sequencing project.
Among those potential targets are many considered to be "undruggable," meaning that the proteins don't have any pockets where a traditional drug could bind to them. The new nanoparticles, which deliver short strands of RNA that can shut off a particular gene, may help scientists go after those undruggable proteins.
"If we could figure out how to make this work [in humans], it would open up a whole new class of targets that hadn't been available," says Hahn, who is also director of the Center for Cancer Genome Discovery at Dana-Farber and a senior associate member of the Broad Institute.
Lead authors of the paper are Yin Ren, an MD/PhD student in Bhatia's lab, and Hiu Wing Cheung, a postdoc in Hahn's lab.
An abundance of targets
Through Project Achilles, Hahn and his colleagues have been testing the functions of many of the genes disrupted in ovarian cancer cells. By revealing genes critical to cancer-cell survival, this approach has narrowed the list of potential targets to several dozen.
Typically, the next step in identifying a good drug target would be to genetically engineer a strain of mice that are missing (or overexpressing) the gene in question, to see how they respond when tumors develop. However, this normally takes two to four years. A much faster way to study these genes would be simply to turn them off after a tumor appears.
RNA interference (RNAi) offers a promising way to do that. During this naturally occurring phenomenon, short strands of RNA bind to the messenger RNA (mRNA) that delivers protein-building instructions from the cell's nucleus to the rest of the cell. Once bound, the mRNA molecules are destroyed and their corresponding proteins never get made.
Scientists have been pursuing RNAi as a cancer treatment since its discovery in the late 1990s, but have had trouble finding a way to safely and effectively target tumors with this therapy. Of particular difficulty was finding a way to get RNA to penetrate tumors.
Bhatia's lab, which has been working on RNAi delivery for several years, joined forces with Hahn's group to identify and test new drug targets. Their goal was to create a "mix and dose" technique that would allow researchers to mix up RNA-delivery particles that target a particular gene, inject them into mice and see what happens.
Shrinking tumors
In their first effort, the researchers decided to focus on the ID4 protein because it is overexpressed in about a third of high-grade ovarian tumors (the most aggressive kind), but not in other cancer types. The gene, which codes for a transcription factor, appears to be involved in embryonic development: It gets shut down early in life, then somehow reactivates in ovarian tumors.
To target ID4, Bhatia and her students designed a new type of RNA-delivering nanoparticle. Their particles can both target and penetrate tumors, something that had never before been achieved with RNA interference.
On their surface, the particles are tagged with a short protein fragment that allows them to enter tumor cells. Those fragments are also drawn to a protein found on tumor cells, known as p32. This fragment and many similar ones were discovered by Erkki Ruoslahti, a professor at the Sanford-Burnham Medical Research Institute at the University of California at Santa Barbara, who is also an author of the new paper.
Within the nanoparticles, strands of RNA are mixed with a protein that further helps them along their journey: When the particles enter a cell, they are encapsulated in membranes known as endosomes. The protein-RNA mixture can cross the endosomal membrane, allowing the particles to get into the cell's main compartment and start breaking down mRNA.
In a study of mice with ovarian tumors, the researchers found that treatment with the RNAi nanoparticles eliminated most of the tumors.
The researchers are now using the particles to test other potential targets for ovarian cancer as well as other types of cancer, including pancreatic cancer. They are also looking into the possibility of developing the ID4-targeting particles as a treatment for ovarian cancer.
###
The research was funded by the Howard Hughes Medical Institute, the National Cancer Institute, the National Institutes of Health, the Mary Kay Foundation, the Sandy Rollman Ovarian Cancer Foundation, the Canadian Institutes of Health Research and the H.L. Snyder Medical Foundation.
Written by Anne Trafton, MIT News Office
[ | 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.
NEW YORK (Reuters) - In David Cronenberg's philosophical new film, "Cosmopolis," Robert Pattinson plays a young, emotionless, obscenely rich financial visionary who rides around New York in a limousine as he slowly becomes unraveled.
For the "Twilight" star, who became one of Hollywood's highest earning actors and biggest heart-throbs, his new role may be the greatest test yet of whether he can carry over his young vampire romance fans to the R-rated indie film.
Pattinson, 26, stepped out in New York this week to promote the film in his first public appearances since his "Twilight" co-star and girlfriend, Kristen Stewart, admitted cheating on him with a married British film director and issued an unusual public apology.
But the break-up with Stewart, 22, was getting just as much attention as "Cosmopolis," if far fewer answers.
Asked how he was coping, the British actor told Reuters at a press event for the movie: "There is this whole thing about wanting to know more and more about celebrities. But really, all that everyone wants to do, is they want them to be celebrities again. However ridiculous that is to say, no one really wants to know."
And in giggly television interviews this week with "The Daily Show" and "Good Morning America," Pattinson repeatedly dodged the topic that made world headlines and shocked millions of "Twilight" fans.
"I've never been interested in trying to sell my personal life and that's really the only reason people bring it up. The reason you go on to TV is to promote movies. That's the only way to do it," he told "Good Morning America" on Wednesday.
He went on to describe his life as "like being on the craziest theme park ride."
That isn't far off the surreal scenario of "Cosmopolis," in which Pattinson plays the all-knowing Eric Packer. Packer shoots off enigmatic lines such as "life is too contemporary" straight from Don DeLillo's book of the same name in a story that has been interpreted as a warning against the dominance of capitalism and technology in society.
"UNREALITY BUBBLE"
Pattinson as Packer encounters figures from his life, including his art dealer (Juliette Binoche) and his similarly cold wife (Sarah Gordon), all the while knowing that his life is under threat from an unknown man (Paul Giamatti) as the city at times comes to a halt or crumbles around him.
The London-born actor, who Cronenberg said was in part chosen for his "star power" to help gain financing for the movie, says his performance, like previous ones, is influenced by events in his real life.
"Every film I did, thinking about it now, no matter what the character is, is just what you were at that time and how you interpret it," Pattinson told Reuters.
"I think every one of the 'Twilight' movies is kind of different. It's not the same character in every one. But obviously, like, once your life suddenly changes - in a lot of ways my life got a lot smaller - after I got famous. And so all the characters, every movie I did, has got bits and pieces of that."
Pattinson hopes "Twilight" fans will crossover to see "Cosmopolis," which was made on a small 15 million euro ($18 million) budget.
"I don't think people realize that the 'Twilight' audience is actually older. There are not very many who are even under 18," he said. "Hopefully, they will be the ones who like it."
Early reviews have been mixed, with The Hollywood Reporter saying the film was "lacking a palpable subversive pulse" and "will initially attract some Robert Pattinson fans but will be met with audience indifference."
The story, including scenes of anarchic protests against capitalism, has drawn some easy parallels with the 2008 financial crisis and Occupy Wall Street protests.
But Cronenberg told Reuters he decided to adapt DeLillo's 2003 novel more due to the "resonance of the dialogue and the wit and the humor."
Still, many people had connected to the anti-capitalist tone, including a French billionaire who invested in the film.
"He felt that he worked with many people who were in a bubble, an unreality bubble, like Eric Packer, and that they had created this virtual world for themselves, which was very strange," he said. "Very alive and familiar to them, but really quite strange and quite disconnected from human life, basically, and that it has ultimately destructive potential. As it does for Eric."
(Reporting By Christine Kearney. Editing by Jill Serjeant and Andre Grenon)
To be more precise, according to one recent study, areas of social deprivation have an equal supply of cancer care services as more well-to-do areas.
Elizabeth Lamont and colleagues, of Harvard Medical School, set out to determine ?whether area social factors are associated with the area health care supply,? according to the abstract of their report, published in the Journal of Clinical Oncology. Using Census Bureau records, the authors noted the social factors at play in 3,096 urban zip codes, and checked the health care supply in the 465 hospital service areas that corresponded to those zip codes. Focusing specifically on breast cancer and colorectal cancer, the authors cross-checked the data to see if social factors were associated with the supply of health care services, namely screening, treatment, and post-treatment surveillance.
The authors found no such association. The supply of physicians conducting these three areas of care was no different for disadvantaged neighborhoods than it was for more advantaged neighborhoods.
In the quest to understand why health outcomes are worse among people living in poor areas, this study is a small step that rules out one potential variable. Okay, so, the number of people providing important services isn?t the problem. So if there is an adequate supply, then what?s the problem?
As Sandra Swain notes in a http://www.reuters.com/article/2012/08/08/us-cancer-care-services-idUSBRE8771GZ20120808 on the study, insurance, money, medical literacy and transportation may all be contributing to the difference in outcomes.
Though the causes remain unclear, the link between social deprivation (is that a euphemism or a more nuanced and accurate way to speak about poverty?) and worse outcomes among people with cancer is undeniable. A few startling findings:
Among 7290 colorectal cancer patients in the UK who underwent surgery, social deprivation was associated with higher postoperative mortality (death after surgery) and a longer hospital stay ? and that difference was on a sliding scale; as deprivation worsened, so did outcomes.
This report from Cancer Research UK notes that unskilled workers are more likely to die from cancer than are professionals, and cancer mortality rates, though varying widely across geographic areas in the country, are highest in areas with dramatic levels of social deprivation. Interestingly, the report authors assert that much of this difference can be chalked up to smoking prevalence.
But smoking can?t be the only factor. Another study of 762 women with breast cancer (also in England) found that wealthier women were less likely to be diagnosed with invasive ductal tumors, high-grade tumors, and estrogen receptor-negative tumors. That study also found that poorer women may have been having more potentially unnecessary mastectomies.
This report presents a more global view of the socioeconomic determinants of cancer, with an emphasis of the problem in developing countries.
The connection with social deprivation and race has also come under some scrutiny. As this report (albeit from several years ago) highlights, breast cancer incidence may not be that different among white women and black women, but breast cancer mortality is higher among the latter.
It?s true that most of the reports noted above are not from the United States, and perhaps the supply of services is an issue in other countries. My guess would be not, that the issues linking social deprivation to cancer in developed countries are, by and large, the same. But what are they?
As part of their ongoing campaign to dehumanize sex workers as much as possible, The New York Post?ran a story today that breathlessly chronicles the improbable continued employment of ?prosti-teacher? Melissa Petro as?get this?something other than a prostitute. WHAT THE WHAT?
Yes, that?s right. Despite once having done sex work to make a living, and subsequently being fired from her teaching job as a result of said fact, the resilient young teacher/writer/human fallen woman is now teaching adults at Gotham Writing Workshops, as well as ?teaching hookers? at the Red Umbrella Project, an organization that helps sex workers write and share their stories. Adults and hookers? She?s so versatile.
The actual content of the article is not that damning, because there were no damning facts to report; Petro?s employers were aware of her past when they hired her. But the way the article is framed is a study in sensationalistic, ?once a hooker, always a hooker? language, from the lede (?She?s a working girl once again!?), to the reference to exposed flesh (?Petro, wearing a sleeveless dress that showed off her tattooed arm??What a harlot, showing off one of her arms) to the continued insistence on referring to people who?ve done sex work as ?hookers,? as though once you accept money for sex, you are forever defined by it.
They had to take a quote blatantly out of context to make it sound like even one of her students was upset to be enrolled in a class taught by the ?prosti-teacher:?
Two Department of Education employees who enrolled unaware of her background had mixed reviews of their bad-girl teacher when they learned about her past.
?As a teacher, yes, it concerns me,? said a GED teacher on Staten Island who asked not to be identified.
?She?s probably better suited to teach adults. You literally have to kill someone to get fired from the DOE.?
And this line, Petro explained to me by email, is a mischaracterization of how she feels about what happened to her:
Petro, who has an MFA from The New School, said she regrets advocating for sex-worker rights while she was working for the Education Department.
?What happened to me was terrible, and I regret the pain it caused my family and my former colleagues,? she writes. ??But I?ve said explicitly again and again that I have no regrets- not about my past, not about coming forward. Knowing what I do now- that is, the way it all turned out- I certainly would have done some things differently, but regret? No. I try to learn from things, rather than regret them.?
Petro has a great response to the piece on Jezebel today which is certainly worth a read, in which she talks about the dangers of reducing a human being down to an archetype:
In real life, I teach my students, none of us are caricatures. That is to say that characters are never entirely villainous nor heroic. Main characters, especially, must be portrayed as real. Whether prostitute or public school teacher, each character is an individual, unique and complex. I teach my students to look for the plot. Even real life, and, accordingly nonfiction, sometimes follows this formula: there is a protagonist, she has a goal, she encounters a conflict. As a result of conflict, there?s change.
That said, she?s in a pretty good place these days, so she seems more amused than anything by the Post?s continued obsession with her:
Sex work, I can see more than ever, is only a part of my past ? and when it comes to being the ?hooker teacher,? that story is written and I have moved on.?I wish the?Post?would, too. If not, hopefully that reporter learned something from my class.
ScienceDaily (Aug. 13, 2012) ? Both heredity and environment play a role in congenital heart defects, but exactly how various risk factors influence the development of the heart during pregnancy has been a mystery -- until now.
With the aid of a supercomputer, an international, interdisciplinary research team has analysed millions of data points. This has allowed the scientists to show that a huge number of different risk factors -- for example in the form of genetic defects -- influence the molecular biology of heart development.
"The discovery of a biological common denominator among many thousands of risk factors is an important step in health research, which in time can improve the prevention and diagnosis of congenital heart defects," explains Professor Lars Allan Larsen from the Department of Cellular and Molecular Medicine, University of Copenhagen.
Research results have recently been published in the Proceedings of the National Academy of Sciences. The project was supported by the Danish Heart Association, Novo Nordisk Foundation and Danish National Research Foundation, among others.
Tailored treatment in future
Scientists have analysed several thousand genetic mutations and environmental risk factors associated with heart malformations in the hope of finding a pattern or common factor.
"Our investigations show that many different genetic factors together with environmental factors can influence the same biological system and cause disease. The results are also interesting in a broader perspective, because it is probable that similar interactions are also valid for diseases such as schizophrenia, autism, diabetes and cancer," says Kasper Lage, Director of Bioinformatics at Harvard University.
Thus the results of the study give scientists an idea of how different combinations of variations in hereditary material can dispose the individual to disease: "This is interesting if we want to make treatment more efficient by tailoring an optimal approach for each individual patient," adds Professor S?ren Brunak from the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.
Complex pattern creation provides new knowledge
When the international research team brought a systems biology perspective to bear on the huge data mass, they could see previously unknown and complex correlations between known risk factors and heart biology:
"Systems biology is a relatively new and holistic research field that uses bioinformatics and supercomputers to investigate highly complex biological problems. For example, we know of a number of genetic mutations that cause heart defects -- but it is first now we have been able to show which biological systems in the heart are influenced by the mutations in question," explains Professor Lars Allan Larsen.
The research approach of systems biology can lead to surprising and pioneering conclusions, but the work is difficult and requires a great degree of interdisciplinary collaboration. In this case team members include genetic scientists, cardiac specialists and experts in bioinformatics from universities, hospitals and industry.
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A DSLR camera in the $1,000 range isn't usually as quick and rugged Pentax K-30. That solid performance inside a well-built shell has had us excited since we first got our hands on its weather-sealed body. This camera is clearly the competitor to Canon's new T4i—can its photos and videos hold up? More »
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