#How tumors escape About 90 percent of cancer deaths are caused by tumors that have spread from their original locations.
MIT cancer biologists have discovered now that certain proteins in this structure, known as the extracellular matrix, help cancer cells make their escape.
but not less aggressive tumors, and found that four of those proteins are critical to metastasis. The findings could lead to new tests that predict which tumors are most likely to metastasize,
and may also help to identify new therapeutic targets for metastatic tumors, which are extremely difficult to treat. he problem is,
all the current drugs are targeted to primary tumors. Once a metastasis appears, in many cases, there nothing you can do about it,
says Richard Hynes, leader of the research team and a member of MIT Koch Institute for Integrative Cancer Research. n principle,
one could imagine interfering with some of these extracellular proteins and blocking metastasis in a patient.
Other authors are Steven Carr, director of the Proteomics Platform at the Broad Institute; Karl Clauser, a research scientist at the Broad Institute;
Patients whose tumors have a greater abundance of extracellular matrix proteins have a poorer prognosis, but until now, scientists did not know why. he matrix has really been understudied,
the Daniel K. Ludwig Professor for Cancer Research in MIT Department of biology. his study couldn have been done five to 10 years ago.
It dependent on modern technology having the genome sequences, having mass spectrometry machines that are really good,
Researchers in Hyneslab previously developed a method for identifying extracellular matrix proteins by enriching them from tumors
To compare the extracellular matrix proteins found in different tumor types, the researchers implanted metastatic and nonmetastatic human breast cancer cells into mice.
They identified 118 extracellular matrix proteins that were found in both types of tumors. However, there were also several dozen proteins that were abundant in either metastatic or nonmetastatic tumors,
but not both. Manipulating the environment It appears that metastatic tumors as well as the supportive cells that surround them, secrete certain proteins into the extracellular matrix to make it easier for them to escape
and survive at a distant site, the researchers say. Many of the proteins overexpressed in the more aggressive tumors are activated by the same cellular signaling pathways,
including one controlled by a growth factor called TGF beta, which controls cell proliferation and is elevated often in cancer cells.
Other matrix-associated proteins were controlled by pathways stimulated by low concentrations of oxygen a condition known to make cancer cells more aggressive.
the researchers analyzed five of the proteins that are elevated in highly aggressive tumors and found that four of them are necessary for metastasis to occur.
tumors failed to spread. his elegant study sheds new light into the extracellular matrix proteins involved in various steps of the metastatic cascade,
a professor of radiation oncology at Harvard Medical school and Massachusetts General Hospital. ur knowledge about the abundance of extracellular matrix proteins in tumors has been limited.
This study utilizes the power of proteomics to identify extracellular matrix proteins critical in metastasis. Many of the proteins identified interact with cancer cells by binding to proteins called integrins that are found on cell surfaces,
The researchers also compared their results with human tumor samples and found that when the proteins they had identified in mice were overexpressed in human tumors,
the patients had lower survival rates. It would be impractical to do this kind of large-scale protein screen in patients,
but it could be possible to test samples for certain proteins using antibodies, say the researchers,
who are now developing such antibodies. hat could become part of a kit that doctors would use to distinguish a patient who has a tumor that going to metastasize,
so they would follow the patient differently from a patient with a tumor they know won metastasize,
Naba says. The researchers are now seeking extracellular matrix proteins that are overexpressed in other metastatic cancers,
including colon and pancreatic cancers. They are also studying whether extracellular matrix proteins in tissues to which escaped tumor cells often metastasize such as the bone, liver,
and lungs make them more receptive to invading cancer cells. If such proteins could be identified they could also be good drug targets b
Despite their potential to reduce carbon dioxide (CO2 EMISSIONS and fuel consumption electric and hybrid cars and trucks struggled for years to find a solid customer base.
Much of the reason came down to cost and convenience: Electric car batteries are expensive and charging them requires plug-in infrastructure that s still sparse in the United states. Now MIT spinout XL Hybrids is upfitting (and retrofitting) gas and diesel commercial vans and trucks with fuel-saving add-on electric powertrains
whose batteries are charged through energy generated by braking. According to tests conducted by the startup the $8000 system which has been incorporated into hundreds of vans in the commercial fleets of Coca-cola
and Fedex among others can provide a 20 percent reduction in fuel consumption and CO2 EMISSIONS. The goal is to reduce oil consumption with cost-effective electric drive technology where fleets don t need additional infrastructure
and don t need a large battery says Tod Hynes 02 co-founding president of XL Hybrids and a lecturer at the MIT Sloan School of management.
The system s powertrain includes an electric traction motor a lithium-ion battery advanced power converters
and other connecting components that attach to the powertrains of traditional General motors and Ford cargo delivery and shuttle vans as well as cutaway trucks.
When the vehicles brake a process known as regenerative braking captures the kinetic energy (usually dissipated as heat through friction) and converts it into electricity that charges the battery
which in turn releases the energy to the electric motor during acceleration. Custom software reads the driver s braking habits
and optimizes the system. The startup also collects operational data from the vehicles to inform fleet managers of the best vehicles for the technology usually ones traveling in the stop
-and-go traffic of urban areas. Over the past year XL Hybrids co-founded by Clay Siegert SM 09
and Justin Ashton GM 08 who Hynes met through MIT s entrepreneurial network has seen its revenue grow twentyfold.
Last month Fast Company ranked the startup No. 35 on its list of the world s 50 most innovative companies and third in energy-specific companies trailing only Tesla motors and General electric.
This week the company was named an Energy Innovation Pioneer by the global analytics company IHS at CERAWEEK a leading international energy conference.
Benefits by the numbershybrids themselves have been around for decades and other companies have started retrofitting vehicles with electric powertrains.
But XL Hybrids innovation comes from targeting commercial fleet vehicles with a good value proposition all around Hynes says offering low-cost equipment quick installation savings on gas and oil and easy integration.
At the end of the day it s about making the economics work to compete against the price of fuel Hynes says adding We re able to do a lot with a little.
Electric or hybrid fleet vehicles traditionally run on large batteries sometimes more than 100 kilowatt-hours (kwh) in capacity that cost upward of $40000.
XL Hybrids installs small 1. 8-kwh lithium-ion batteries that provide a 20 percent fuel savings Hynes says.
To determine the extent of the savings XL Hybrids conducted a dynamometer test which involves running a vehicle on treadmill-like rollers to estimate fuel mileage in urban driving.
They first ran a 5-ton vehicle through the test without XL Hybrids system and then with the system observing a 21 percent savings.
With this savings companies can expect to save 4000 gallons of fuel over the life of an XL Hybrids system Hynes says.
Since the system costs $8000 companies essentially pay $2 for each gallon saved. Why pay $3 or $4 for a gallon when you can pay $2 to save a gallon?
Hynes says. Additional benefits to the system Hynes says include reducing brake wear and maintenance and the time employees spend filling up at gas stations.
Also downsizing engines: An XL Hybrids electric motor adds torque to an existing powertrain meaning a customer can reduce the size of the engine from say a 6-liter to a 4. 8-liter
and get better acceleration which can save hundreds or thousands of dollars upfront Hynes says.
When a fleet customer looks at the numbers they want to see benefits based on fuel savings
and engine downsizing Hynes says. These other benefits are just gravy. While the system can be added as a retrofit it s generally installed as part of the modifications that most commercial fleet vehicles go through.
This ease of integration helps set the company apart from the competition Hynes says. The vehicles literally roll of the line
and go to facilities where they ll be modified anyway he says. Manufacturers don t need to change their manufacturing processes.
Renewed energyfor Hynes the path to entrepreneurship alternative energy and XL Hybrids revolves around his alma mater.
As an MIT undergraduate in management in the late 1990s and early 2000s Hynes became very passionate about startups.
With the Internet boom in full swing he co-founded a couple of dot-coms but began viewing climate change and energy as the real challenges of my generation.
After graduating he co-founded the consulting and engineering services firm Strategic Energy systems with two MIT alumni before taking a position as director of alternative energy at Citizens Energy in Boston.
Over five years a few things came together: Alternative energy became a focus at MIT which had launched among other things the MIT Energy Club (2004) and the MIT Energy Initiative (2006) both
of which Hynes became involved with. I got more engaged with MIT as MIT got more engaged with energy he says.
At the same time across the nation clean energy ventures became much more profitable: For example the wind industry grew from a $500 million industry to a $15 billion industry in five years.
But Hynes noticed that the nation didn t have an electricity problem. It has an oil problem he says.
We re very dependent on oil: We rely on imports and more than 95 percent of transportation fuel is oil.
So he quit his job in 2008 with the aim of starting a company to cut oil consumption.
With rising innovations in batteries and advanced power inverters and motors Hynes backed into a technological solution with retrofitted electric powertrains.
Reconnecting with former mentor Bill Aulet now managing director of the Martin Trust Center for MIT Entrepreneurship Hynes put the final pieces into place.
Hynes and Aulet co-founded MIT s Clean energy Prize in 2008; via the competition Hynes met Ashton his XL Hybrids cofounder.
The trio began grinding away in a garage in Somerville Mass. conducting early trials on the Ford Crown Victoria
and incorporate it onto other vehicle makes and models and rapidly scale across the industry Hynes says.
Coming full circle Hynes now teaches at MIT helping to walk students through the process of launching alternative-energy startups.
Back on campus he says the energy landscape has expanded certainly since he was an undergraduate
and even since he started XL Hybrids. MIT has done a tremendous job at becoming a world center for energy innovation he says e
#A paper diagnostic for cancer Cancer rates in developing nations have climbed sharply in recent years
and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes
but screening approaches such as mammograms and colonoscopy used in the developed world are too costly to be implemented in settings with little medical infrastructure.
To address this gap MIT engineers have developed a simple cheap paper test that could improve diagnosis rates
and help people get treated earlier. The diagnostic which works much like a pregnancy test could reveal within minutes based on a urine sample
whether a person has cancer. This approach has helped detect infectious diseases and the new technology allows noncommunicable diseases to be detected using the same strategy.
The technology developed by MIT professor and Howard hughes medical institute investigator Sangeeta Bhatia relies on nanoparticles that interact with tumor proteins called proteases each
of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient s urine.
When we invented this new class of synthetic biomarker we used a highly specialized instrument to do the analysis says Bhatia the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical engineering and Computer science.
For the developing world we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting without the need for any specialized equipment.
The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.
Bhatia who is also a member of MIT s Koch Institute for Integrative Cancer Research
and Institute for Medical Engineering and Science is the senior author of a paper describing the particles in the Proceedings of the National Academy of Sciences the week of Feb 24.
The paper s lead authors are graduate student Andrew Warren postdoc Gabriel Kwong and former postdoc David wood.
Amplifying cancer signalsin 2012 Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumor proteins that would be hard to detect on their own.
These proteins known as matrix metalloproteinases (MMPS) help cancer cells escape their original locations by cutting through proteins of the extracellular matrix which normally holds cells in place.
The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPS. These particles congregate at tumor sites where MMPS cleave hundreds of peptides
which accumulate in the kidneys and are excreted in the urine. In the original version of the technology these peptides were detected using an instrument called a mass spectrometer
which analyzes the molecular makeup of a sample. However these instruments are not readily available in the developing world so the researchers adapted the particles
so they could be analyzed on paper using an approach known as a lateral flow assay the same technology used in pregnancy tests.
To create the test strips the researchers first coated nitrocellulose paper with antibodies that can capture the peptides.
Once the peptides are captured they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides.
If one of these lines becomes visible it means the target peptide is present in the sample.
The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.
This is a clever and inspired technology to develop new exogenous compounds that can detect clinical conditions with aberrantly high protease concentrations says Samuel Sia an associate professor of biological engineering at Columbia University who was involved not in the research.
Extending this technology to detection by strip tests is a big leap forward in bringing its use to outpatient clinics and decentralized health settings.
In tests in mice the researchers were able to accurately identify colon tumors as well as blood clots.
This is a new idea to create an excreted biomarker instead of relying on what the body gives you she says.
Bhatia says the technology would likely first be applied to high-risk populations such as people who have had cancer previously
or had a family member with the disease. Eventually she would like to see it used for early detection throughout developing nations.
I think it would be great to bring it back to this setting where point-of-care image-free cancer detection
whether it s in your home or in a pharmacy clinic could really be transformative Bhatia says.
With the current version of the technology patients would first receive an injection of the nanoparticles then urinate onto the paper test strip.
To make the process more convenient the researchers are now working on a nanoparticle formulation that could be implanted under the skin for longer-term monitoring.
The team is also working to identify signatures of MMPS that could be exploited as biomarkers for other types of cancer as well as for tumors that have metastasized.
The research was funded by a National Science Foundation Graduate Research Fellowship a Mazumdar-Shaw International Oncology Fellowship the Ruth L. Kirschstein National Research Service Award from the National institutes of health
the Burroughs Wellcome Fund the National Cancer Institute and the Howard hughes medical institute u
#Researchers find that going with the flow makes bacteria Stick in a surprising new finding researchers have discovered that bacterial movement is impeded in flowing water enhancing the likelihood that the microbes will attach to surfaces.
The new work could have implications for the study of marine ecosystems and for our understanding of how infections take hold in medical devices.
The findings the result of microscopic analysis of bacteria inside microfluidic devices were made by MIT postdoc Roberto Rusconi former MIT postdoc Jeffrey Guasto (now an assistant professor of mechanical engineering at Tufts
University) and Roman Stocker an associate professor of civil and environmental engineering at MIT. Their results are published in the journal Nature Physics.
The study which combined experimental observations with mathematical modeling showed that the flow of liquid can have two significant effects on microbes:
Stocker says in some cases that phenomenon could lead to new approaches to tuning flow rates to prevent fouling of surfaces by microbes potentially averting everything from bacteria getting a toehold on medical equipment to biofilms causing drag on ship hulls.
Microbiologists have taken rarely into account fluid flow as an ecological parameter whereas physicists have started just recently to pay attention to microbes he says adding:
One prominent location is near the walls of tubes where the result is a strong enhancement of the bacteria s tendency to adhere to those walls and form biofilms.
But this effect varies greatly depending on the speed of the flow opening the possibility that the rate of biofilm formation can be tweaked by increasing or decreasing flow rates.
Guasto says the new understanding could help in the design of medical equipment to reduce such infections:
Since the phenomenon peaks at particular rates of shear he says Our results might suggest additional design criteria for biomedical devices which should operate outside this range of shear rates when possible either faster or slower.
Biofilms are found everywhere Rusconi says adding that the majority of bacteria spend significant fractions of their lives adhering to surfaces.
Bacteria concentrated in biofilms are up to 1000 times more resistant to antibiotics than those suspended in liquid.
and there is no preferential accumulation Rusconi says. The new findings could also be important for studies of microbial marine ecosystems by affecting how bacteria move in search of nutrients
Howard A. Stone a professor of mechanical and aerospace engineering at Princeton university who was involved not in this research calls this a very interesting paper
and idea owing to the major importance of bacterial biofilms The research was supported by the National Science Foundation and by a Gordon and Betty Moore Marine Microbial Initiative Investigator award to Stocker r
#Hitchhiking vaccines boost immunity Many vaccines, including those for influenza, polio, and measles, consist of a killed or disabled version of a virus. However, for certain diseases,
this type of vaccine is ineffective, or just too risky. An alternative, safer approach is made a vaccine of small fragments of proteins produced by a disease-causing virus or bacterium.
This has worked for some diseases, but in many cases these vaccines don provoke a strong enough response.
Now a team of engineers at MIT has developed a new way to deliver such vaccines directly to the lymph nodes
where huge populations of immune cells reside: These vaccines hitch a ride to the lymph nodes by latching on to the protein albumin, found in the bloodstream.
In tests with mice, such vaccines produced very strong immune responses, the researchers report in the Feb 16 online edition of Nature. he lymph nodes are where all the action happens in a primary immune response.
T cells and B cells reside there, and that where you need to get the vaccine to get an immune response.
The more material you can get there, the better, says Darrell Irvine, a professor of biological engineering and of materials science and engineering,
and the senior author of the paper. This approach could be especially useful for delivering HIV vaccines
and for stimulating the body immune system to attack tumors, says Irvine, who is also a member of MIT Koch Institute for Integrative Cancer Research.
Free ride Vaccines made of protein or sugar fragments, also known as subunit vaccines, have been successful against a few diseases, such as hepatitis and diphtheria.
To develop subunit vaccines for other diseases, scientists have tried targeting them to lymph nodes using nanoparticles to deliver them,
or tagging them with antibodies specific to immune cells in the lymph nodes. However these strategies have had limited only success,
because it is difficult to get all of the vaccine to the lymph nodes without some escaping to the rest of the body,
which can cause unwanted side effects. Irvine team took a new approach, based on an existing procedure for targeting imaging dyes to the lymph nodes.
Surgeons use this procedure, known as entinel lymph node mapping, to determine the extent of cancer metastasis after removing a tumor.
The dye used for this imaging binds tightly to albumin, allowing it to accumulate in the lymph nodes.
Previous studies have revealed that when foreign particles such as the dye bind to albumin immune cells in the lymph nodes efficiently capture the albumin. e realized that might be an approach that you could try to copy in a vaccine design a vaccine molecule that binds to albumin
and hitchhikes to the lymph node, Irvine says. To get protein fragments, known as peptides, to bind to albumin,
the researchers took advantage of albumin function as a transporter of molecules called fatty acids. Albumin has binding pockets that can capture fatty, hydrophobic molecules,
so the researchers added a fatty tail called a lipid to their vaccine peptides. They created a few different vaccines
targeting HIV, melanoma, and cervical cancer, and tested them in mice. Each one generated a large population of memory T cells specific to the viral
or tumor peptide. e knew we were on the right track because we saw you could get immune responses that were just tremendous,
Irvine says. hen you look in the blood, one in three T cells in the blood was a vaccine-specific T cell,
which is something you usually only see with vaccines delivered by viruses. The albumin-targeted vaccines provoked immune responses five to 10 times stronger than those generated by the peptide antigens alone.
The melanoma vaccine slowed cancer growth and the cervical cancer vaccine shrank tumors. t certainly is an interesting approach,
and the results are very convincing, says Pal Johansen, a professor of dermatology at University Hospital Zurich who was not part of the research team. oth the effect on the stimulated immune responses
and the consequential suppression of tumor growth are results that would suggest further development and clinical testing.
Controlled inflammation The researchers also tested this delivery strategy with an adjuvant a molecule that enhances the immune responses of vaccines.
Targeting a commonly used adjuvant called Cpg to albumin dramatically boosted the resulting inflammatory response.
This delivery method could also improve the safety of adjuvants by confining their effects to the lymph nodes.
Otherwise, the adjuvant could spread through the bloodstream and provoke inflammation in other parts of the body. his lymph-node-targeting modification causes pretty much all of the material to get caught in the draining lymph nodes,
so that means it more potent because it getting concentrated in the lymph nodes, and it also makes it more safe
because it not getting into the systemic circulation, Irvine says. The researchers are planning to test this method to deliver HIV vaccines in nonhuman primates,
and they are also working on further developing cancer vaccines, including one for lung cancer. The research was funded by the Koch Institute Support Grant from the National Cancer Institute, the National institutes of health, the U s. Department of defense,
and the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard university l
#Boosting science math technology and ethics in Tibetan communities To many Westerners science monks and technology may not be an obvious trio.
But to Tenzin Priyadarshi and others at MIT s Dalai lama Center for Ethics and Transformative Values they are a means of improving the lives of Tibetans dispersed throughout India and elsewhere.
The program called the Science Monks and Technology Leadership Program was launched a year ago to help members of the Tibetan diaspora find solutions to the challenges they face in some of India s poorest regions.
For example the program has produced the first of a planned series of science centers a simple concrete building outfitted with computers
and online access in an area where most people lack electricity or piped water. There students and monks will be able to learn from materials such as lectures on MIT s Opencourseware (with added Tibetan subtitles.
The center is expected to reach full operation by this summer. We ll be using that as a hub for testing out some of the models Priyadarshi says efforts such as solar
-or bicycle-powered electricity and creating awareness about sustainable farming and improved water systems. Besides encouraging the development of locally useful technologies the program aims to improve the teaching of math and science.
Science teachers in rural India have a very basic education and no way to continue that education Priyadarshi says.
And often in India he says Once they become teachers they re shy of going back to education.
We re trying to break that paradigm and the idea has gained already traction. The centers will provide courses serve as hubs where people can try out things Priyadarshi says
and provide continuing education to science teachers with each center serving 30 to 40 nearby schools he says.
In addition Priyadarshi says A lot of young monks are interested in science but there s not many resources. Since monks are respected highly they can provide good role models
and mentors in both technology and community leadership he adds. One resource that Priyadarshi s team hopes to develop is a basic glossary of math terms translated from English to Tibetan something that he says does not currently exist.
This project is led by now a team of Tibetan high school students mentored by volunteers and is advanced in an stage of development.
The program links MIT teachers and mentors to Tibetan community programs through Skype supplemented by regular travel by Dalai lama Center staff alumni and students who among other work teach weeklong leadership
classes to groups of Tibetan students and monks. Some team members will travel to India this spring to work on ongoing projects including a rainwater harvesting system
and a bicycle-powered charging system for cellphones and lanterns. Davide Zaccagnini a vascular surgeon and program manager for the Science Monks and Technology Leadership Program says he was motivated to join because
I wanted to be involved in something beyond just my own career. This program he says is not only Buddhism not only science not only leadership but the three things together.
I believe that mix itself provides the highest value for all the stakeholders. The education is a two-way street Zaccagnini says with the MIT students
and alumni bringing their technological knowledge while gaining exposure to the culture and mentality of the young Tibetans and monks who see things a different way.
The program emphasizes leadership and community building Zaccagnini says rather than a simple transfer of knowledge.
The selection of projects is driven by the Tibetans based on their sense of the challenges they face.
and spread information about those that work well so that others can benefit from the lessons learned.
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011