Cancer genomes sequenced - The Scientist

scientists have charted the most complete cancer genomes to date, according to two studies published in Nature this week, providing a catalog of some 90% of all the somatic mutations in melanoma and a type of lung cancer, as well as a starting point for identifying potentially causal mutations common to these types of cancer.

"For the first time we have a really quite comprehensive view of two different common tumor types," said Bert Vogelstein of Johns Hopkins Medicine, who was not involved in the research. "That information will form the foundation for subsequent studies."

Previously, scientists studying cancer genomes had identified a handful of so-called driver mutations -- those that have a causative effect on the cancerous growth. But these two papers are the first to also analyze the noncoding regions of the genome, which may also contain driver mutations that could act by altering gene expression, Vogelstein said.

Using shotgun sequencing techniques, Michael Stratton of the Wellcome Trust Sanger Institute and the Institute of Cancer Research in the UK and his colleagues compiled a list of more than 50,000 somatic mutations in a small-cell lung cancer metastasis and a malignant melanoma cell line. Comparing them to known mutations in these cancer types, the researchers determined they had identified approximately 90% of all the mutations in the cancer cell lines, Stratton said. Finally, using traditional PCR techniques to search the genomes for newly identified mutations, the shotgun sequencing appeared to result in only about a 3% false positive rate. "That's a high quality catalog," Stratton said.

From these catalogs, the researchers further identified the types of mutations that were most prominent in each cancer type and found them to be consistent with their known causes of ultraviolet light and tobacco carcinogens. The lung cancer genome, for example, was riddled with G to T substitutions, while the melanoma cell line carried predominately C to T mutations.

Gerd Pfeifer, a molecular biologist at the City of Hope clinical research hospital in California, found the similarity among the mutation types within a particular cancer genome "quite surprising." While scientists had previously identified a handful of mutations found in these particular cancer types, "people thought that was maybe a unique situation," said Pfeifer, who was not involved in the research. "But it seems to be a much more general phenomenon that affects the entire genome."

Thus, by knowing the complete genomes of a variety of cancer types, Pfeifer added, "we might understand [something] about the etiology of these cancers." For melanoma and lung cancer, scientists have a pretty good understanding of what causes the mutations, but for many other cancer types, such as breast or pancreatic cancer, the "mutational signatures" revealed by these types of sequencing studies may get scientists "closer to understanding the origin of the tumors," he said.

"I think over the next year you can be absolutely confident there will be dozens if not hundreds of different tumors looked at," Vogelstein said.

In addition to sequencing more different kinds of cancers, there will be a "profound benefit" of sequencing more cell lines from the same tumor type, said Stratton. By identifying mutations that show up consistently in hundreds of different tumors of the same type, he said, scientists will be able to pinpoint additional driver mutations of specific cancers. These genes may present new drug targets for cancer therapies.

A complete list of the driver mutations in any particular cancer type can then serve as the ultimate diagnostic tool, Stratton added. Looking at a particular tumor in a particular patient and being able to identify which driver mutations it carries "will give us a good indication of which drugs the patient will respond to," he said, "[giving] us a much more refined way of applying cancer therapy to the benefit of patients."

"This is a landmark moment in cancer research," Stratton said. "From this moment on, this is going to be our expectation for what we want to know about individual cancers -- it resets our ambitions for cancer."

Desert Spider Discovery on Jordan-Israel Border

One benefit of the Israel-Jordan peace treaty, signed 15 years ago, was that it allowed for scientific cooperation and exchanges between the countries.

Among the more recent cooperative efforts is a cross-border study in the Arava Valley involving biologists at the University of Haifa and colleagues from Jordan. “We were very happy finally to be able to see what kind of diversity there is on the other side of the border,” said Uri Shanas, a biologist at the university’s Oranim campus. They are looking, in part, at ecological differences between the Israeli side, with its more Western-style agricultural economy, and the nomadic land management on the Jordanian side.

But in the process, the researchers discovered something else: a new species of desert spider.

The spider, Cerbalus aravensis, was collected in the Sands of Samar, a dune area on the Jordanian border. C. aravensis is large by spider standards — up to five inches across — and lives in a small burrow in the sand, reinforcing the walls with silk. The spider covers the burrow with a door of sorts, made of sand-encrusted silk. “It completely conceals the entrance,” Dr. Shanas said.

The scientists have yet to learn much about the spider’s habits, though presumably it consumes insects and, given its size, perhaps small geckos. But Dr. Shanas said time might be running out as its habitat was endangered. The dunes are being quarried for construction material. “They’re really under great threat,” he said. “There’s almost nothing left.”

Courtesy: Newyork times

Shedding New Light On Walking

Researchers at the medical university Karolinska Institutet have created a genetically modified mouse in which certain neurons can be activated by blue light. Shining blue light on brainstems or spinal cords isolated from these mice produces walking-like motor activity. The findings, which are published in the scientific journal Nature Neuroscience, are of potential significance to the recovery of walking after spinal cord injury.

"This new mouse model will impact the way in which future studies examining the organization of neurons involved in walking are performed. We hope that our findings can provide insight that eventually will contribute to treatments for spinal cord injured patients"", says Professor Ole Kiehn, who lead the study.

Excitatory neurons have been suggested to play an important role for the initiation and maintenance of locomotion, or walking. However, this has not been demonstrated directly. In order to test the hypothesis that activation of excitatory neurons is essential to locomotion, a research team at the Department of Neuroscience, Karolinska Institutet, created a genetically modified mouse which expresses a light sensitive protein in excitatory neurons.

The light sensitive protein, Channelrhodopsin2 (ChR2), is normally found in algae and activates the cell it is expressed in when exposed to blue light. ChR2 has previously been introduced into rodent cells by viral infection, but this can be problematic due to exposure and replication demands. The researchers circumvented the problems by creating the first genetically modified mouse to successfully express ChR2 in a specific set of neurons.

By inserting ChR2 into nerve cells expressing Vglut2 - a transporter found in most excitatory neurons in the brainstem and spinal cord as well as many excitatory neurons in other regions of the brain - they created a Vglut2-ChR2 mouse . The reason for doing this was to be able to selectively activate excitatory neurons in specific regions of the brainstem and spinal cord, as the excitatory neurons are believed to be important for initiating locomotion, or walking.

The researchers then recorded from motor nerves leaving the spinal cord. When blue light was shined directly on the spinal cord, walking-like activity began and was maintained for the duration of the light pulse. This proved that activation of Vglut2-expressing excitatory neurons in the spinal cord is sufficient for walking. Walking-like activity could also be initiated by exposing the lower brainstem to blue light, demonstrating that excitatory cells in the brainstem provide a sufficient 'go' signal to the spinal neurons involved in walking.

All the experiments were made in vitro in the laboratory and not in living animals.

Source: Katarina Sternudd
Karolinska Institutet


Courtesy: Medical News today

Human Brain Uses a Grid to Represent Space

'Grid cells' that act like a spatial map in the brain have been identified for the first time in humans, according to new research by UCL scientists which may help to explain how we create internal maps of new environments.

The study is by a team from the UCL Institute of Cognitive Neuroscience and was funded by the Medical Research Council and the European Union. Published in Nature, it uses brain imaging and virtual reality techniques to try to identify grid cells in the human brain. These specialised neurons are thought to be involved in spatial memory and have previously been identified in rodent brains, but evidence of them in humans has not been documented until now.

Grid cells represent where an animal is located within its environment, which the researchers liken to having a satnav in the brain. They fire in patterns that show up as geometrically regular, triangular grids when plotted on a map of a navigated surface. They were discovered by a Norwegian lab in 2005 whose research suggested that rats create virtual grids to help them orient themselves in their surroundings, and remember new locations in unfamiliar territory.

Study co-author Dr Caswell Barry said: "It is as if grid cells provide a cognitive map of space. In fact, these cells are very much like the longitude and latitude lines we're all familiar with on normal maps, but instead of using square grid lines it seems the brain uses triangles.

Lead author Dr Christian Doeller added: "Although we can't see the grid cells directly in the brain scanner, we can pick up the regular six-fold symmetry that is a signature of this type of firing pattern. Interestingly, the study participants with the clearest signs of grid cells were those who performed best in the virtual reality spatial memory task, suggesting that the grid cells help us to remember the locations of objects."

Professor Neil Burgess, who leads the team, commented: "The parts of the brain which show signs of grid cells -- the hippocampal formation and associated brain areas -- are already known to help us navigate our environment and are also critical for autobiographical memory. This means that grid cells may help us to find our way to the right memory as well as finding our way through our environment. These brain areas are also amongst the first to be affected by Alzheimer's disease which may explain why getting lost is one of the most common early symptoms of this disease."

Courtesy: ScienceDaily

Deciphering the Chatter of Monkeys and Chimps

Walking through the Tai forest of Ivory Coast, Klaus Zuberbühler could hear the calls of the Diana monkeys, but the babble held no meaning for him.

That was in 1990. Today, after nearly 20 years of studying animal communication, he can translate the forest’s sounds. This call means a Diana monkey has seen a leopard. That one means it has sighted another predator, the crowned eagle. “In our experience time and again, it’s a humbling experience to realize there is so much more information being passed in ways which hadn’t been noticed before,” said Dr. Zuberbühler, a psychologist at the University of St. Andrews in Scotland.

Do apes and monkeys have a secret language that has not yet been decrypted? And if so, will it resolve the mystery of how the human faculty for language evolved? Biologists have approached the issue in two ways, by trying to teach human language to chimpanzees and other species, and by listening to animals in the wild.

The first approach has been propelled by people’s intense desire — perhaps reinforced by childhood exposure to the loquacious animals in cartoons — to communicate with other species. Scientists have invested enormous effort in teaching chimpanzees language, whether in the form of speech or signs. A New York Times reporter who understands sign language, Boyce Rensberger, was able in 1974 to conduct what may be the first newspaper interview with another species when he conversed with Lucy, a signing chimp. She invited him up her tree, a proposal he declined, said Mr. Rensberger, who is now at M.I.T.

But with a few exceptions, teaching animals human language has proved to be a dead end. They should speak, perhaps, but they do not. They can communicate very expressively — think how definitely dogs can make their desires known — but they do not link symbolic sounds together in sentences or have anything close to language.

Better insights have come from listening to the sounds made by animals in the wild. Vervet monkeys were found in 1980 to have specific alarm calls for their most serious predators. If the calls were recorded and played back to them, the monkeys would respond appropriately. They jumped into bushes on hearing the leopard call, scanned the ground at the snake call, and looked up when played the eagle call.

It is tempting to think of the vervet calls as words for “leopard,” “snake” or “eagle,” but that is not really so. The vervets do not combine the calls with other sounds to make new meanings. They do not modulate them, so far as is known, to convey that a leopard is 10, or 100, feet away. Their alarm calls seem less like words and more like a person saying “Ouch!” — a vocal representation of an inner mental state rather than an attempt to convey exact information.

But the calls do have specific meaning, which is a start. And the biologists who analyzed the vervet calls, Robert Seyfarth and Dorothy Cheney of the University of Pennsylvania, detected another significant element in primates’ communication when they moved on to study baboons. Baboons are very sensitive to who stands where in their society’s hierarchy. If played a recording of a superior baboon threatening an inferior, and the latter screaming in terror, baboons will pay no attention — this is business as usual in baboon affairs. But when researchers concoct a recording in which an inferior’s threat grunt precedes a superior’s scream, baboons will look in amazement toward the loudspeaker broadcasting this apparent revolution in their social order.

Baboons evidently recognize the order in which two sounds are heard, and attach different meanings to each sequence. They and other species thus seem much closer to people in their understanding of sound sequences than in their production of them. “The ability to think in sentences does not lead them to speak in sentences,” Drs. Seyfarth and Cheney wrote in their book “Baboon Metaphysics.”

Some species may be able to produce sounds in ways that are a step or two closer to human language. Dr. Zuberbühler reported last month that Campbell’s monkeys, which live in the forests of the Ivory Coast, can vary individual calls by adding suffixes, just as a speaker of English changes a verb’s present tense to past by adding an “-ed.”

The Campbell’s monkeys give a “krak” alarm call when they see a leopard. But adding an “-oo” changes it to a generic warning of predators. One context for the krak-oo sound is when they hear the leopard alarm calls of another species, the Diana monkey. The Campbell’s monkeys would evidently make good reporters since they distinguish between leopards they have observed directly (krak) and those they have heard others observe (krak-oo).

Even more remarkably, the Campbell’s monkeys can combine two calls to generate a third with a different meaning. The males have a “Boom boom” call, which means “I’m here, come to me.” When booms are followed by a series of krak-oos, the meaning is quite different, Dr. Zuberbühler says. The sequence means “Timber! Falling tree!”

Dr. Zuberbühler has observed a similar achievement among putty-nosed monkeys that combine their “pyow” call (warning of a leopard) with their “hack” call (warning of a crowned eagle) into a sequence that means “Let’s get out of here in a real hurry.”

Apes have larger brains than monkeys and might be expected to produce more calls. But if there is an elaborate code of chimpanzee communication, their human cousins have not yet cracked it. Chimps make a food call that seems to have a lot of variation, perhaps depending on the perceived quality of the food. How many different meanings can the call assume? “You would need the animals themselves to decide how many meaningful calls they can discriminate,” Dr. Zuberbühler said. Such a project, he estimates, could take a lifetime of research.

Monkeys and apes possess many of the faculties that underlie language. They hear and interpret sequences of sounds much like people do. They have good control over their vocal tract and could produce much the same range of sounds as humans. But they cannot bring it all together.

This is particularly surprising because language is so useful to a social species. Once the infrastructure of language is in place, as is almost the case with monkeys and apes, the faculty might be expected to develop very quickly by evolutionary standards. Yet monkeys have been around for 30 million years without saying a single sentence. Chimps, too, have nothing resembling language, though they shared a common ancestor with humans just five million years ago. What is it that has kept all other primates locked in the prison of their own thoughts?

Drs. Seyfarth and Cheney believe that one reason may be that they lack a “theory of mind”; the recognition that others have thoughts. Since a baboon does not know or worry about what another baboon knows, it has no urge to share its knowledge. Dr. Zuberbühler stresses an intention to communicate as the missing factor. Children from the youngest ages have a great desire to share information with others, even though they gain no immediate benefit in doing so. Not so with other primates.

“In principle, a chimp could produce all the sounds a human produces, but they don’t do so because there has been no evolutionary pressure in this direction,” Dr. Zuberbühler said. “There is nothing to talk about for a chimp because he has no interest in talking about it.” At some point in human evolution, on the other hand, people developed the desire to share thoughts, Dr. Zuberbühler notes. Luckily for them, all the underlying systems of perceiving and producing sounds were already in place as part of the primate heritage, and natural selection had only to find a way of connecting these systems with thought.

Yet it is this step that seems the most mysterious of all. Marc D. Hauser, an expert on animal communication at Harvard, sees the uninhibited interaction between different neural systems as critical to the development of language. “For whatever reason, maybe accident, our brains are promiscuous in a way that animal brains are not, and once this emerges it’s explosive,” he said.

In animal brains, by contrast, each neural system seems to be locked in place and cannot interact freely with others. “Chimps have tons to say but can’t say it,” Dr. Hauser said. Chimpanzees can read each other’s goals and intentions, and do lots of political strategizing, for which language would be very useful. But the neural systems that compute these complex social interactions have not been married to language.

Dr. Hauser is trying to find out whether animals can appreciate some of the critical aspects of language, even if they cannot produce it. He and Ansgar Endress reported last year that cotton-top tamarins can distinguish a word added in front of another word from the same word added at the end. This may seem like the syntactical ability to recognize a suffix or prefix, but Dr. Hauser thinks it is just the ability to recognize when one thing comes before another and has little to do with real syntax.

“I’m becoming pessimistic,” he said of the efforts to explore whether animals have a form of language. “I conclude that the methods we have are just impoverished and won’t get us to where we want to be as far as demonstrating anything like semantics or syntax.”

Yet, as is evident from Dr. Zuberbühler’s research, there are many seemingly meaningless sounds in the forest that convey information in ways perhaps akin to language.

Courtesy: NewYork Times

Breast Cancer Multigene Test Helping Patients Avoid Chemotherapy

A 21-gene test that predicts whether early stage breast cancer patients will benefit from chemotherapy is having a big impact on treatment decisions by patients and doctors alike.

The test caused doctors to change their treatment recommendations in 31.5 percent of cases, while 27 percent of patients changed their treatment decisions. In most such cases, the change by both doctors and patients was to avoid chemotherapy.

The study, lead by Loyola University Health System Medical oncologist Dr. Shelly Lo, is published in the Journal of Clinical Oncology.

The multigene test, Oncotype DX®, is made by Genomic Health Inc. The test examines 21 genes from a tumor sample to determine how active they are. A test score between 0 and 100 predicts how likely the cancer is to recur. For women with low scores, chemotherapy is not recommended.

More than 120,000 breast cancer patients have undergone the test since it became commercially available in 2004. The test is intended for patients who have a type of breast cancer, called estrogen receptor-positive that has not spread to the lymph nodes. About 100,000 such cases are diagnosed each year.

"The trend in oncology is towards personalized medicine," Lo said. "We likely will see more tests similar to this one in the future."

The study included 89 breast cancer patients who received the gene test. They were treated by 17 medical oncologists at Loyola, University of Michigan, University of California at Davis and Edward Hospital in Naperville, Il.

Doctors changed treatment decisions for 28 patients. In 20 of these cases, they changed their decision from hormone therapy plus chemotherapy to hormone therapy alone. Twenty-four patients changed their treatment decisions, including nine who dropped chemotherapy.

"This is the first study to show that results from this test simultaneously impact decisions by physicians as well as patients," Lo said. Lo is an assistant professor in the Department of Medicine, Loyola University Chicago Stritch School of Medicine.

Doctors said the test increased their confidence in their treatment recommendations in 76 percent of cases. And in 97 percent of cases, doctors said they would order the test again.

After receiving test results, patients reported they were significantly less conflicted about their decision and felt significantly less anxiety about their situation.

"This test of patients' own breast cancer provides us with greater certainty of who derives benefit from chemotherapy and who can safely avoid it," said senior author Dr. Kathy Albain, professor in the Department of Medicine, Division of Hematology/Oncology, Stritch School of Medicine.

The test costs $3,910, and generally is covered by insurance. Researchers said the test might lower overall costs by avoiding the expense of chemotherapy in some patients.

Insect Cells Provide the Key to Alternative Swine Flu Vaccination

Scientists in Vienna have developed a new technique for producing vaccines for H1N1 -- so-called swine flu -- based on insect cells. The research, published in the Biotechnology Journal, reveals how influenza vaccines can be produced faster than through the traditional method of egg-based production, revealing a new strategy for the fight against influenza pandemics.

"Recent outbreaks of influenza highlight the importance of a rapid and sufficient vaccine supply for pandemic and inter pandemic strains," said co-author Florian Krammer from the University of Natural Resources and Applied Life Science in Vienna. "However, classical manufacturing methods for vaccines fail to satisfy this demand."

Traditional influenza vaccines, which are produced in embryonated chicken eggs, can be manufactured in the quantities needed for seasonal strains of influenza. Yet because of limited egg supply this method may be insufficient in a pandemic scenario, such as the current H1N1 'swine flu' pandemic.

The team's new method turns to insect cell based technology to create recombinant influenza virus-like particles (VLPs), which resemble virus particles but lack the viral nucleic acid, so they are not infectious.

The Austrian team took just ten weeks to produce swine-origin pandemic H1N1 influenza VLPs for immunological study in mice. This shows that production of a mock-up vaccine is feasible in this time range, outcompeting conventional production methods which take months.

Using insect cells also bypasses the disadvantages of egg-based production, such as limited production capacity, allergic reactions to egg proteins and biosafety issues.

"Our work demonstrates that recombinant influenza virus-like particles are a very fast, safe and efficient alternative to conventional influenza vaccines and represents a significant new approach for newly emerging influenza strains like swine-origin H1N1 or H5N1," concluded Krammer.

"Virus-like particles will be one solution to tackle the biological variability of influenza pandemics," said journal editor Professor Alois Jungbauer. "Mutated strains can be quickly engineered. So in this respect the teams' work is an extremely valuable contribution to modern vaccine production."

Courtesy: ScienceDaily

Sedentary TV Time May Cut Life Short

Couch potatoes beware: every hour of television watched per day may increase the risk of dying earlier from cardiovascular disease, according to research reported in Circulation: Journal of the American Heart Association.

Australian researchers tracked the lifestyle habits of 8,800 adults and found that each hour spent in front of the television daily was associated with: • an 11 percent increased risk of death from all causes, • a 9 percent increased risk of cancer death; and • an 18 percent increased risk of cardiovascular disease (CVD)-related death.

Compared with people who watched less than two hours of television daily, those who watched more than four hours a day had a 46 percent higher risk of death from all causes and an 80 percent increased risk for CVD-related death. This association held regardless of other independent and common cardiovascular disease risk factors, including smoking, high blood pressure, high blood cholesterol, unhealthy diet, excessive waist circumference, and leisure-time exercises.

While the study focused specifically on television watching, the findings suggest that any prolonged sedentary behavior, such as sitting at a desk or in front of a computer, may pose a risk to one's health. The human body was designed to move, not sit for extended periods of time, said David Dunstan, Ph.D., the study's lead author and professor and Head of the Physical Activity Laboratory in the Division of Metabolism and Obesity at the Baker IDI Heart and Diabetes Institute in Victoria, Australia.

"What has happened is that a lot of the normal activities of daily living that involved standing up and moving the muscles in the body have been converted to sitting," Dunstan said. "Technological, social, and economic changes mean that people don't move their muscles as much as they used to -- consequently the levels of energy expenditure as people go about their lives continue to shrink. For many people, on a daily basis they simply shift from one chair to another -- from the chair in the car to the chair in the office to the chair in front of the television."

Dunstan said the findings apply not only to individuals who are overweight and obese, but also those who have a healthy weight. "Even if someone has a healthy body weight, sitting for long periods of time still has an unhealthy influence on their blood sugar and blood fats," he said.

Although the study was conducted in Australia, Dunstan said the findings are certainly applicable to Americans. Average daily television watching is approximately three hours in Australia and the United Kingdom, and up to eight hours in the United States, where two-thirds of all adults are either overweight or obese.

The benefits of exercise have been long established, but researchers wanted to know what happens when people sit too much. Television-watching is the most common sedentary activity carried out in the home.

Researchers interviewed 3,846 men and 4,954 women age 25 and older who underwent oral glucose-tolerance tests and provided blood samples so researchers could measure biomarkers such as cholesterol and blood sugar levels. Participants were enrolled from 1999-2000 and followed through 2006. They reported their television-viewing habits for the previous seven days and were grouped into one of three categories: those who watched less than two hours per day; those who watched between two and four hours daily; and those who watched more than four hours.

People with a history of CVD were excluded from the study. During the more than six-year follow-up, there were 284 deaths -- 87 due to CVD and 125 due to cancer.

The association between cancer and television viewing was only modest, researchers reported. However, there was a direct association between the amount of television watched and elevated CVD death as well as death from all causes even after accounting for typical CVD risk factors and other lifestyle factors. The implications are simple, Dunstan said. "In addition to doing regular exercise, avoid sitting for prolonged periods and keep in mind to 'move more, more often'. Too much sitting is bad for health."

Co-authors are: E. L. M. Barr, Ph.D.; G. N. Healy, Ph.D.; J. Salmon, Ph.D.; J. E. Shaw, M.D.; B. Balkau, Ph.D.; D. J. Magliano, Ph.D.; A. J. Cameron, Ph.D.; P. Z. Zimmet, Ph.D. and N. Owen, Ph.D. Author disclosures and funding sources are on the manuscript.

Courtesy: ScienceDaily

'Nano Cocktail' to Target and Kill Tumors

A team of researchers in California and Massachusetts has developed a "cocktail" of different nanometer-sized particles that work in concert within the bloodstream to locate, adhere to and kill cancerous tumors.

"This study represents the first example of the benefits of employing a cooperative nanosystem to fight cancer," said Michael Sailor, a professor of chemistry and biochemistry at the University of California, San Diego and the primary author of a paper describing the results, which is being published in a forthcoming issue of the Proceedings of the National Academy of Sciences.

In their study, the UC San Diego chemists, bioengineers at MIT and cell biologists at UC Santa Barbara developed a system containing two different nanomaterials the size of only a few nanometers, or a thousand times smaller than the diameter of a human hair, that can be injected into the bloodstream. One nanomaterial was designed to find and adhere to tumors in mice, while the second nanomaterial was fabricated to kill those tumors.

These scientists and others had previously designed nanometer-sized devices to attach to diseased cells or deliver drugs specifically to the diseased cells while ignoring healthy cells. But the functions of those devices, the researchers discovered, often conflicted with one another.

"For example, a nanoparticle that is engineered to circulate through a cancer patient's body for a long period of time is more likely to encounter a tumor," said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at the Koch Institute for Integrative Cancer Research at MIT and a coauthor of the study. "However, that nanoparticle may not be able to stick to tumor cells once it finds them. Likewise, a particle that is engineered to adhere tightly to tumors may not be able to circulate in the body long enough to encounter one in the first place."

When a single drug does not work in a patient, a doctor will commonly administer a cocktail containing several drug molecules. That strategy can be very effective in the treatment of cancer, where the rationale is to attack the disease on as many fronts as possible. Drugs may sometimes work together on a single aspect of the disease, or they may attack separate functions. In either case, drug combinations can provide a greater effect than either drug alone.

Treating tumors with nanoparticles has been challenging because immune cells called mononuclear phagocytes identify them and yank them from circulation, preventing the nanomaterials from reaching their target.

Ji-Ho Park, a graduate student in Sailor's UC San Diego laboratory, and Geoffrey von Maltzahn, a graduate student in Bhatia's MIT laboratory, headed the effort to develop two distinct nanomaterials that would work in concert to overcome that obstacle and others. The first particle is a gold nanorod "activator' that accumulates in tumors by seeping through its leaky blood vessels. The gold particles cover the whole tumor and behave like an antenna by absorbing otherwise benign infrared laser irradiation, which then heats up the tumor.

After the nanorods had circulated in the bloodstream of mice that had epithelial tumors for three days, the researchers used a weak laser beam to heat the rods that attached to the tumors. This sensitized the tumors, and the researchers then sent in a second nanoparticle type, composed of either iron oxide nanoworms or doxorubicin-loaded liposomes. This "responder" nanoparticle was coated with a special targeting molecule specific for the heat-treated tumor. Much of that work was done in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara, and another co-author of the study.

"Think of them like soldiers attacking an enemy base," said Sailor. "The gold nanorods are the Special Forces, who come in first to mark the target. Then the Air Force flies in to deliver the laser-guided bomb. The devices are designed to minimize collateral damage to the rest of the body."

While one type of nanoparticle improves detection of the tumor, he said, the other is designed to kill the tumor. The researchers designed one type of responder particle with strings of iron oxide, which they called "nanoworms," that show up brightly in a medical magnetic resonance imaging, or MRI, system. The second type is a hollow nanoparticle loaded with the anti-cancer drug doxorubicin. With the drug-loaded responder, the scientists demonstrated in their experiments that a tumor growing in a mouse can be arrested and then shrunk. "The nanoworms would be useful to help the medical team identify the size and shape of a tumor in a patient before surgery, while the hollow nanoparticles might be used to kill the tumor without the need for surgery," said Sailor.

"This study is important because it is the first example of a combined, two-part nanosystem that can produce sustained reduction in tumor volume in live animals," said Sailor.

The project was funded by grants from the National Cancer Institute of the National Institutes of Health. Bhatia is a Howard Hughes Medical Institute Investigator.

Courtesy to ScieneDaily