Such particles could help scientists to track specific molecules produced in the body monitor a tumor s environment
These particles could also be used to evaluate the level of oxygen radicals in a patient s tumor which can reveal valuable information about how aggressive the tumor is.
We think we may be able to reveal information about the tumor environment with these kinds of probes
#Better chemotherapy through targeted delivery Every year about 100000 Americans are diagnosed with brain tumors that have spread from elsewhere in the body.
These tumors known as metastases are treated usually with surgery followed by chemotherapy but the cancer often returns.
A new study from MIT Brigham and Women s Hospital and Johns hopkins university suggests that delivering chemotherapy directly into the brain cavity may offer a better way to treat tumors that have metastasized to the brain.
We re showing we get much higher degrees of tumor cell death when we deliver the drug locally.
To make sure that enough reaches a tumor very large quantities must be given often producing side effects.
TMZ which is a first-line treatment for brain metastasis and gliomas and doxorubicin a common treatment for breast cancer
Zone of influenceworking with mice implanted with tumors similar to human brain metastases the researchers found that TMZ delivered directly to the brain prolonged survival by several days compared with TMZ administered by injection.
or programmed cell death in tumor cells near the capsules. However doxorubicin delivered to the brain did not perform as well as systemic injection of doxorubicin.
This could be valuable information in designing future versions of this treatment for brain tumors or other cancers he adds.
Michael Lim an associate professor of neurosurgery at Johns Hopkins says the new approach seems like a promising way to expand the range of treatments available for brain tumors
For example it could be developed as a method of locating tumor cells within the body by identifying their surface texture perhaps in combination with other characteristics.
#Fast modeling of cancer mutations Sequencing the genomes of tumor cells has revealed thousands of genetic mutations linked with cancer.
what their role is in tumor progression. If we can actually understand the biology we can then go in
In this study the researchers focused on a type of non-small cell lung cancer called lung adenocarcinoma
Jacks lab has engineered previously mice that conditionally express the Kras oncogene only in the lung leading them to develop lung adenocarcinoma.
The researchers administered these mice with lentiviruses targeting three different genes allowing them to see how each gene cooperates with Kras to influence tumor growth.
Once the tumors develop the researchers can study how aggressive they are how fast they grow
The researchers found that the mice in this study developed very similar tumors to those seen previously in mice with those genes deleted using traditional methods.
whose role in lung cancer is understood not as well revealed that APC loss also drives tumor progression.
Tumors without that gene became much less differentiated and more similar to embryonic cells. To verify these results the researchers also used mice with APC deleted by traditional methods
and found the same types of tumors. This is#a wonderful new example of the power of the CRISPR approach says Anton Berns a professor of molecular genetics at The netherlands Cancer Institute.
and brain to model tumors in those regions the researchers say. This method also offers new ways to seek personalized treatments for cancer patients depending on the types of mutations found in their tumors the researchers say.
They envision using this technique to create mice with tumors carrying the same genetic profile as a patient then testing different drugs on them to see which have the best effect.
This opens up a whole new field of being personalized able to do oncology where you can model human mutations
and start treating tumors based on these mutations Papagiannakopoulos says. The research was funded by the Howard hughes medical institute the Ludwig Center for Molecular Oncology at MIT and the National Cancer Institute u
and bind with particular molecules within the body such as markers for tumor cells or other disease agents.
For example the coating could have a molecule that binds to a specific type of tumor cells;
so you could see the spatial macroscopic outlines of a tumor he says. The next step for the team is to test the new nanoparticles in a variety of biological settings.
What that means for the tumor and what that means for the health of the patient those are long-term questions still to be answered says Matthew Vander Heiden an associate professor of biology a member of MIT s Koch Institute for Integrative Cancer Research
These findings led us to hypothesize that the increase in branched chain amino acids is due to the presence of an early pancreatic tumor.
They suspect that pancreatic tumors may be trying to feed their own appetite for amino acids that they need to build cancerous cells.
The findings may also allow scientists to pursue new treatments that would work by targeting tumor metabolism
and cutting off a tumor s nutrient supply Vander Heiden says. MIT s contribution to this research was funded by the Lustgarten Foundation the National institutes of health the Burroughs Wellcome Fund and the Damon Runyon Cancer Research Foundation n
Their device, about the size of a dime, could be used to detect the extremely rare tumor cells that circulate in cancer patientsblood,
whether a tumor is going to spread. Separating cells with sound offers a gentler alternative to existing cell-sorting technologies,
To test whether the device could be useful for detecting circulating tumor cells, the researchers tried to separate breast cancer cells known as MCF-7 cells from white blood cells.
the researchers plan to test it with blood samples from cancer patients to see how well it can detect circulating tumor cells in clinical settings.
A 1-milliliter sample of blood may contain only a few tumor cells. f you can detect these rare circulating tumor cells,
Dao says. his method is a step forward for detection of circulating tumor cells in the body.
However delivering these small RNAS to solid tumors remains a significant challenge as the RNAS must target the correct cells
and shrink tumor growth. Their research offers promise for personalized RNA combination therapies to improve therapeutic response.
and tumor-suppressor gene p53 is deleted researchers injected mice with RNA-carrying nanoparticles. This mouse model reflects many of the hallmarks of human lung cancer
They found that delivery of mir-34a a p53-regulated mirna slowed tumor growth as did delivery of sikras a KRAS-targeting sirna.
Instead of just slowing tumor growth this combination therapy caused tumors to regress and shrink to about 50 percent of their original size.
It is appreciated widely that the major hurdle in this field is efficient delivery to solid tumors outside of the liver
#New analysis reveals tumor weaknesses Scientists have known for decades that cancer can be caused by genetic mutations
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
#A new way to model cancer Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer.
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.
The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations.
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.
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.
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.
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,
and targeting it to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumor.
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.
and ovarian tumors. Staggering these drugs proved particularly powerful against a type of breast cancer cell known as triple-negative,
Triple-negative tumors, which account for about 16 percent of breast cancer cases, are much more aggressive than other types
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,
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.
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.
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.
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.
#How tumors escape About 90 percent of cancer deaths are caused by tumors that have spread from their original locations.
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,
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,
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,
which escaped tumor cells often metastasize such as the bone, liver, and lungs make them more receptive to invading cancer cells.
and Howard hughes medical institute investigator Sangeeta Bhatia relies on nanoparticles that interact with tumor proteins called proteases each
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 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.
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.
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.
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,
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.
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
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.
The drug kills cells very effectively by damaging nuclear DNA but if tumors become resistant to cisplatin they often grow back.
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.
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:
PTT uses the nanoparticles to focus light-induced heat energy only within the tumor harming no adjacent normal cells.
That means the photo-thermal effect of iron-oxide nanoparticles may show in the next decade a strong promise in human cancer therapy likely with localized tumors.
With this technology a low-power laser beam is directed at the tumor where a small amount of magnetic iron-oxide nanoparticles are present either by injecting the particles directly into the tumor
Sufficient heat is generated then locally by the laser light raising the tumor temperature rapidly to above 43 degrees Celsius
but only generates local heat within the tumor therefore posing much less side effects than the traditional chemo or radiation therapies.
because the tumors are usually stage three or four before they can be detected. He stated With nanomaterial technology we can detect the tumor early
and kill it on sight at the same time. Each tumor has a corresponding protein that is cancer specific called a tumor specific ligand
or an antibody antigen reaction that only has expression for that specific cancer such as breast or prostate cancer.
Scientists identify this certain biomarker that is specific to a certain tumor then conjugates this biomarker on the surface of the nanocarrier that only has the expression for that specific kind of cancer cell.
and biodegradable and can potentially stay in the tumor cells until its job is finished then dissolve
So far in vivo testing in mice has shown that this approach produces significant accumulation of drugs in tumor sites instead of healthy organs.
the combination of carrier and drug also dramatically reduced tumor growth compared with the drug alone.
A key challenge in chemotherapy is ensuring that the drugs are delivered only to the tumor
and filtered out of the body by the immune system before it reaches the tumor. Micellar nanocomplexes of less than 100 nanometers in dimension are formed from the OEGCG core
and renal clearance while providing for tumor targeting. The research team conducted animal studies to evaluate the performance of IBN's green tea-based protein delivery system.
The study revealed that IBN's green tea nanocomplex loaded with Herceptin reduced tumor growth much more effectively
Using the new nanocarrier twice as much drug accumulated in the cancer cells indicating an improved tumor targeting ability.
A nanosheet with a heat-sensitive polymer could burn surrounding tumors to destroy them functioning as a kind of super-specific chemotherapy.
#'Stealth'nanoparticles could improve cancer vaccines Cancer vaccines have emerged recently as a promising approach for killing tumor cells before they spread.
Now scientists have developed a new way to deliver vaccines that successfully stifled tumor growth when tested in laboratory mice.
Hiroshi Shiku Naozumi Harada and colleagues explain that most cancer vaccine candidates are designed to flag down immune cells called macrophages and dendritic cells that signal killer T cells to attack tumors.
When molecules for signaling killer T cells were put inside the nanoparticles they hindered tumor growth far better than existing vaccines.
The nanogel-based vaccine significantly inhibited in vivo tumor growth in the prophylactic and therapeutic settings compared to another vaccine formulation using a conventional delivery system incomplete Freund's adjuvant.
In a newly published article in the journal ACS Advanced Materials & Interfaces, researchers Ravi Saraf and Chieu Van Nguyen describe a thin-film sensor that can detect tumors too small and deep
the researchers ued the film to successfully detect tumors as small as 5 millimeters, hidden up to 20 millimeters deep.
when tumors are diagnosed at less than 10 millimeters. Saraf said the thin-film tool would have at least three advantages to a manual breast exam performed by a physician:
#Handheld scanner could make brain tumor removal more complete reducing recurrence Cancerous brain tumors are notorious for growing back
or none get left behind to form new tumors. The method reported in the journal ACS Nano could someday vastly improve the outlook for patients.
Moritz F. Kircher and colleagues at Memorial Sloan Kettering Cancer Center point out that malignant brain tumors particularly the kind known as glioblastoma multiforme (GBM) are among the toughest to beat.
Surgical removal is one of the main weapons doctors have to treat brain tumors. The problem is that currently there's no way to know
and go specifically to tumor cells and not to normal brain cells. Using a handheld Raman scanner in a mouse model that mimics human GBM the researchers successfully identified
Neuroscientists use lightwaves to improve brain tumor surgery More information: Guiding Brain tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-held Raman Scanner ACS Nano Article ASAPDOI:
10.1021/nn503948abstractthe current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients.
Here we evaluated the ability of a hand-held Raman scanner guided by surface-enhanced Raman scattering (SERS) nanoparticles to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model.
In a simulated intraoperative scenario we tested both a static Raman imaging device and a mobile hand-held Raman scanner.
and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors.
because it uses inert gold#silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room o
to heat up and destroy cancer cells in the lab. The team used the new photothermal delivery method in lab experiments to introduce impermeable dyes and small DNA molecules into human prostate cancer and fibroblast sarcoma cells."
So, they can be used to enhance contrast of optical imaging of tumors along with that of MRI I
when the tumor is composed already of millions of cancer cells and the disease is starting to advance into a more mature phase.
In 2010 they successfully obtained funding for the project called SPEDOC (Surface Plasmon Early Detection of Circulating Heat shock proteins and Tumor Cells) under the 7th Framework Program (FP7) of the European commission.
Tumors appeared accelerate the tissue aging process by 36 years and healthy breast tissue near breast tumors were an average of 12 years older than tissue elsewhere in the body.
In contrast transforming adult human cells into#pluripotent stem cells which reprograms them to act like embryonic stem cells effectively resets the cells'clock to zero Horvath says.#
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