#New analysis reveals tumor weaknesses Scientists have known for decades that cancer can be caused by genetic mutations
but more recently they have discovered that chemical modifications of a gene can also contribute to cancer.
Analyzing these modifications can provide important clues to the type of tumor a patient has
For example patients with glioblastoma a type of brain tumor respond well to a certain class of drugs known as alkylating agents
In some cancers the MGMT gene is turned off when methyl groups attach to specific locations in the DNA sequence namely cytosine bases that are adjacent to guanine bases.
This technique which cuts the amount of time required to analyze epigenetic modifications could be a valuable research tool as well as a diagnostic device for cancer patients says Andrea Armani a professor of chemical engineering
The MIT team is now adapting the device to detect methylation of other cancer-linked genes by changing the DNA sequences of the biochip probes.
#A new way to model cancer Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer.
They have shown that a gene-editing system called CRISPR can introduce cancer-causing mutations into the livers of adult mice enabling scientists to screen these mutations much more quickly.
In a study appearing in the Aug 6 issue of Nature the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten.
They are now working on ways to deliver the necessary CRISPR components to other organs allowing them to investigate mutations found in other types of cancer.
The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations.
Tyler Jacks director of MIT s Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology is the paper s senior author.
To investigate the potential usefulness of CRISPR for creating mouse models of cancer the researchers first used it to knock out p53 and pten
Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.
and pten the researchers were able to disrupt those two genes in about 3 percent of liver cells enough to produce liver tumors within three months.
Using CRISPR to generate tumors should allow scientists to more rapidly study how different genetic mutations interact to produce cancers as well as the effects of potential drugs on tumors with a specific genetic profile.
This is a game-changer for the production of engineered strains of human cancer says Ronald Depinho director of the University of Texas MD Anderson Cancer Center who was not part of the research team.
Enhanced potential of this powerful technology will be realized with improved delivery methods the testing of#CRISPR/Cas9 efficiency in other organs and tissues and the use of CRISPR/Cas9 in tumor-prone backgrounds.
The research was funded by the National institutes of health and the National Cancer Institute u
#New material structures bend like microscopic hair MIT engineers have fabricated a new elastic material coated with microscopic hairlike structures that tilt in response to a magnetic field.
When Edward Scolnick met the Stanleys he had had a stellar career first in cancer research in the 1970s and then as one of the most respected scientists in the pharmaceutical industry.
the first vaccine against cervical cancer; and many other breakthroughs. Instead of retiring Scolnick took on a new challenge:
Early in his career Scolnick had helped launch a revolution in cancer research based on the discovery of the first cancer genes.
Beth Israel Deaconess Medical center Boston Children s Hospital Brigham and Women s Hospital Dana-Farber Cancer Institute and Massachusetts General Hospital.
They have discovered several hundred genes that are mutated in cancer and applied this knowledge to begin to invent new targeted forms of therapy.
In contrast to researchers studying cancer or diabetes researchers studying psychiatric disorders have been unable to identify animal models that correctly capture important biological aspects of the disorders
including cancer and cardiovascular disease, the researchers say. here been a growing amount of excitement about delivery to the liver in particular,
says Daniel Anderson, the Samuel A. Goldblith Associate professor of Chemical engineering, a member of MIT Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science,
400 variants of their particles in cervical cancer cells by measuring whether they could turn off a gene coding for a fluorescent protein that had been added to the cells.
which promote the growth of blood vessels that feed tumors. By blocking these in lung endothelial cells,
the researchers were able to slow lung tumor growth in mice and also reduce the spread of metastatic tumors.
The researchers plan to test additional potential targets in hopes that these particles could eventually be deployed to treat cancer, atherosclerosis,
which was funded by a National Defense Science and Engineering Fellowship, the National Science Foundation, MIT Presidential Fellowships, the National institutes of health, the Stop and Shop Pediatric Brain tumor Fund,
#Chemotherapy timing is key to success MIT researchers have devised a novel cancer treatment that destroys tumor cells by first disarming their defenses,
dramatically shrinks lung and breast tumors. The MIT team, led by Michael Yaffe, the David H. Koch Professor in Science,
who is a member of MIT Koch Institute for Integrative Cancer Research. ee moving from the simplest model of the nanoparticle just getting the drug in there
and targeting it to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumor.
Doctors routinely give cancer patients two or more different chemotherapy drugs in hopes that a multipronged attack will be more successful than a single drug.
which shuts down one of the pathways that promote uncontrolled tumor growth. These pretreated tumor cells were much more susceptible to treatment with a DNA-damaging drug called doxorubicin than cells given the two drugs simultaneously. t like rewiring a circuit,
says Yaffe, who is also a member of the Koch Institute. hen you give the first drug,
found on tumor cell surfaces, has been approved by the Food and Drug Administration to treat pancreatic cancer and some types of lung cancer.
Doxorubicin is used to treat many cancers, including leukemia, lymphoma, and bladder, breast, lung, and ovarian tumors.
Staggering these drugs proved particularly powerful against a type of breast cancer cell known as triple-negative,
which doesn have overactive estrogen, progesterone, or HER2 receptors. Triple-negative tumors, which account for about 16 percent of breast cancer cases,
are much more aggressive than other types and tend to strike younger women. That was an exciting finding
ow do you translate that into something you can actually give a cancer patient? From lab result to drug delivery To approach this problem,
folate, helps direct the particles to tumor cells, which express high quantities of folate receptors.
Once the particles reach a tumor and are taken up by cells, the particles start to break down.
The researchers tested the particles in mice implanted with two types of human tumors: triple-negative breast tumors and non-small-cell lung tumors.
Both types shrank significantly. Furthermore, packaging the two drugs in liposome nanoparticles made them much more effective than the traditional forms of the drugs,
even when those drugs were given in a time-staggered order. his particle delivery system not only provides a platform for time-staggered treatment strategies in cancer,
but also for delivering the drugs more directly to the tumor tissue itself, says Rune Linding,
As a next step before possible clinical trials in human patients, the researchers are now testing the particles in mice that are programmed genetically to develop tumors on their own,
instead of having human tumor cells implanted in them. The researchers believe that time-staggered delivery could also improve other types of chemotherapy.
and ovarian cancers. At the same time, Hammond lab is working on more complex nanoparticles that would allow for more precise loading of the drugs
The work was funded by the National institutes of health, the Center for Cancer Nanotechnology Excellence, the Koch Institute Frontier Research Program supported by the Kathy and Curt Marble Fund for Cancer Research,
and a Breast cancer Alliance Exceptional Project Grant
#Getting more electricity out of solar cells When sunlight shines on today solar cells, much of the incoming energy is given off as waste heat rather than electrical current.
which may lead to cancer and other diseases if not mended. The effectiveness of these repair systems varies greatly from person to person;
scientists believe that this variability may explain why some people get cancer while others exposed to similar DNA-damaging agents do not.
which could help determine individualsrisk of developing cancer and help doctors predict how a given patient will respond to chemotherapy drugs.
who is the Uncas and Helen Whitaker Professor, an American Cancer Society Professor, and a member of MIT departments of biological engineering and of biology, Center for Environmental Health Sciences,
and Koch Institute for Integrative Cancer Research. Measuring repair With the new test, the MIT team can measure how well cells repair the most common DNA lesions,
Some of these differences have been linked with cancer vulnerability; for example, a genetic defect in a type of DNA repair called nucleotide excision repair often leads to a condition called xeroderma pigmentosum, in
Such a test could also be used to predict patientsresponse to chemotherapy drugs, which often work by damaging cancer cellsdna,
Inhibitors could be targeted to tumors to make them more susceptible to chemotherapy, while enhancers could help protect people who have been exposed accidentally to DNA-damaging agents,
Tumors in low-oxygen environments tend to be more resistant to therapy and spread more aggressively to other parts of the body.
Measuring tumors oxygen levels could help doctors make decisions about treatments but there s currently no reliable noninvasive way to make such measurements.
In cases where you are trying to make therapeutic decisions you want to have some numbers that you can fall back on says Vincent Liu a graduate student in Cima s lab at MIT s Koch Institute for Integrative Cancer Research
Doctors often use MRI to diagnose tumors but currently MRI can only reveal the size and location of a tumor.
With the new MIT sensor doctors could track the state of the tumor and predict how it might respond to radiation treatment according to the researchers.
Radiation kills tumors by initiating DNA damage but oxygen is required to help finish the job.
An accurate reading of how much oxygen is present would help doctors calculate how much radiation might be necessary.
Measuring oxygen levels could also reveal the metastatic potential of a tumor: Those with lower oxygen levels tend to spread more aggressively.
Ralph Weissleder a professor at Harvard Medical school and director of the Massachusetts General Hospital Center for Molecular Imaging Research says this type of sensor is a novel way to potentially track how cancer patients
The cancer field certainly needs something like this says Weissleder who was not part of the research team.
What s happening in a tumor This type of sensor could also be useful for monitoring blood flow in diabetic patients who often experience restricted circulation in their extremities
The researchers also anticipate that it could help scientists learn more about tumor biology. As opposed to just studying the genetic profile of tumor cells this could also reveal how they re interacting with the stroma that surrounds the tumor.
Oxygen tension as simple as it sounds is a good measure of what s happening in a tumor Cima says.
The researchers are now working on sensors that could be used to monitor other biological properties such as ph. We hope this is the first of many types of solid-state contrast agents where the material responds to its chemical environment in such a way that we can detect it by MRI Cima says.
The research was funded by the National Cancer Institute Centers of Cancer Nanotechnology Excellence and the U s army Research Office e
What s exciting about this approach is that we can actually correct a defective gene in a living adult animal says Daniel Anderson the Samuel A. Goldblith Associate professor of Chemical engineering at MIT a member of the Koch Institute for Integrative Cancer Research
The research was funded by the National Cancer Institute the National institutes of health and the Marie D. and Pierre Casimir-Lambert Fund u
Theye also used as biological probes to image cancer and to study processes inside cells,
and rapidly test new peptides to treat cancer and other diseases, as well as more effective variants of existing peptides, such as insulin, Pentelute says.
#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,
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.
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
Many of the proteins overexpressed in the more aggressive tumors are activated by the same cellular signaling pathways,
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.
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,
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,
The researchers are now seeking extracellular matrix proteins that are overexpressed in other metastatic cancers, including colon and pancreatic cancers.
which escaped tumor cells often metastasize such as the bone, liver, and lungs make them more receptive to invading cancer cells.
#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
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.
and Howard Hughes Medical Institute investigator Sangeeta Bhatia relies on nanoparticles that interact with tumor proteins called proteases each
Bhatia who is also a member of MIT s Koch Institute for Integrative Cancer Research
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.
These particles congregate at tumor sites where MMPS cleave hundreds of peptides which accumulate in the kidneys
In tests in mice the researchers were able to accurately identify colon tumors as well as blood clots.
Bhatia says the technology would likely first be applied to high-risk populations such as people who have had cancer previously
I think it would be great to bring it back to this setting where point-of-care image-free cancer detection
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 Burroughs Wellcome Fund the National Cancer Institute and the Howard Hughes Medical Institute u
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 determine the extent of cancer metastasis after removing a tumor. The dye used for this imaging binds tightly to albumin,
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,
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.
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.
and could be used to create sensors to monitor diseases such as cancer, inflammation, or diabetes in living systems. his new technique gives us an unprecedented ability to recognize any target molecule by screening nanotube-polymer complexes to create synthetic analogs to antibody function,
#Biologists ID new cancer weakness About half of all cancer patients have a mutation in a gene called p53
which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA.
A new study from MIT biologists has found that tumor cells with mutated p53 can be made much more vulnerable to chemotherapy by blocking another gene called MK2.
In a study of mice tumors lacking both p53 and MK2 shrank dramatically when treated with the drug cisplatin while tumors with functional MK2 kept growing after treatment.
The findings suggest that giving cancer patients a combination of a DNA-damaging drug and an MK2 inhibitor could be very effective says Michael Yaffe the David H. Koch Professor in Science
and senior author of a paper describing the research in the Nov 14 issue of the journal Cell Reports.
and colitis but the drugs have never been tested as possible cancer treatments. What our study really says is that these drugs could have an entirely new second life in combination with chemotherapy says Yaffe who is a member of MIT s Koch Institute for Integrative Cancer Research.
We re very much hoping it will go into clinical trials for cancer. Sandra Morandell a postdoc at the Koch Institute is the paper s lead author.
To kill a tumorp53 is a tumor suppressor-protein protein that controls cell division. Before cell division begins p53 checks the cell s DNA
or apoptosis. Tumors that lack p53 can avoid this fate. Usually p53 is the main driver of cell death
if you block the MK2 pathway tumor cells wouldn t recognize that they had DNA damage
if this would hold true in tumors in living animals as well as cells grown in a lab dish.
To do that they used a strain of mice that are programmed genetically to develop non-small-cell lung tumors.
or off allowing them to study tumors with and without MK2 in the same animal.
This new approach allows them for the first time to compare different types of tumors in the same mice where all genetic factors are identical except for MK2 expression.
Using these mice the researchers found that before treatment tumors lacking both MK2 and p53 grow faster than tumors that have MK2.
This suggests that treating tumors with an MK2 inhibitor alone would actually do more harm than good possibly increasing the tumor s growth rate by taking the brake off the cell cycle.
However when these tumors are treated with cisplatin the tumors lacking MK2 shrink dramatically while those with MK2 continue growing.
A nonobvious combination The potential combination of cisplatin and MK2 inhibitors is unlike other chemotherapy combinations that have been approved by the Food
While this study focused on non-small-cell lung tumors the researchers have gotten similar results in cancer cells grown in the lab from bone cervical and ovarian tumors.
They are now studying mouse models of colon and ovarian cancer. The research was funded by the Austrian Science Fund the National institutes of health Janssen Pharmaceuticals Inc. the Koch Institute MIT s Center for Environmental Health Sciences the Volkswagenstiftung the Deutsche Forschungsgemeinschaft the German
which hold potential as portable diagnostic devices for cancer and other diseases. These devices consist of microfluidic channels engraved on tiny chips,
This type of particle can be useful for diagnosing cancer and other diseases, following customization to detect proteins
#Resistance is futile Cisplatin is given a chemotherapy drug to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA but if tumors become resistant to cisplatin they often grow back.
A new study from MIT and the University of Toronto offers a possible way to overcome that resistance.
Senior authors of the new paper are Stephen Lippard the Arthur Amos Noyes Professor of Chemistry at MIT and a member of MIT's Koch Institute for Integrative Cancer Research and Shana
which contains the metal platinum was approved to treat ovarian and testicular tumors in 1978 and is used now for many other cancers including lung and bladder.
The drug forms crosslinks in DNA creating blockages that interfere with a cell s ability to read
The research was funded by the National Cancer Institute the Canadian Institute of Health and a David H. Koch Graduate Fellowship s
but existing blood tests are not consistently able to detect the formation of new clots says Bhatia who is also a senior associate member of the Broad Institute and a member of MIT s Koch Institute for Integrative Cancer Research
Bhatia and her colleagues developed their new test based on a technology they first reported last year for early detection of colorectal cancer.
and diagnosing cancer. It could also be adapted to track liver pulmonary and kidney fibrosis Bhatia says.
The research was funded by the Koch Institute Frontier Research Fund the Kathy and Curt Marble Cancer Research Fund the Mazumdar-Shaw International Oncology Fellows Program the Burroughs Wellcome
They found many patients suffering from chronic diseases such as diabetes, cancer, and heart disease and a lack of permanent oatingsfor medical implants that might help these patients.
for example, diabetes, cancer, multiple sclerosis, and osteoporosis. Now Microchips Biotech will begin co-developing microchips with Teva Pharmaceutical, the world largest producer of generic drugs,
the two lead authors, are former postdocs in the laboratory of Robert Langer, the David H. Koch Institute Professor at MIT Koch Institute for Integrative Cancer Research.
and identify the boundaries of tumors.""This nanoparticle may open the door for new'hypermodal'imaging systems that allow a lot of new information to be obtained using just one contrast agent,
This would enable doctors to better see where tumors begin and end, Lovell says. Explore further:
#A speedy test for bladder cancer A fast and accurate urine test for bladder cancer developed by A*STAR researchers has the potential to replace the currently used invasive physical probe.
Cystoscopy clinical procedure that uses a narrow, tubular optical instrument called a cystoscope to view inside the bladders currently the gold standard for detecting cancer in this organ.
a recently discovered urinary antigen and a potential biomarker for bladder cancer. The new tool could be used as a high-throughput screening platform to identify patients at risk of developing the urologic condition.
They found significantly elevated levels of A1at in bladder cancer patients. There was also a marked difference in the A1at concentrations of cancer and non-cancer patients,
which suggests that the technique is highly discriminative, specific and accurate. Importantly, only tiny amounts of sample were required:
"We have developed a smart SERS biosensor for the rapid screening of bladder cancer, "says Olivo."
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011