Nanoparticles Home in on Brain Cancer

Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.

The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.

Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."

To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.

Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy." --Nikhil Swaminathan

British soldiers kill white rhino

British troops training in northern Kenya have shot dead a white rhinoceros after it charged at them.

The four soldiers were confronted by the adult male after they got lost at night on an exercise in the bush.

The shooting happened on Friday evening in Laikipia, north of the capital Nairobi. The area is popular for wildlife viewing.

White rhinos are killed by poachers who want their horns for use in traditional Chinese medicine or as ornaments.

Laikipia conservancy senior game warden Dickson Too said the soldiers had been "forced to shoot at it".

"We don't consider it a deliberate act of killing, they were just acting in self-defence," he said.

Mr Too added the rhino had been found the following day and the Kenya Wildlife Service had removed its horn.

Kenya Wildlife Service spokeswoman Connie Maina said British troops had a base near Laikipia and regularly underwent training in the area.

Inventor of a DNA Sequencing Technique Is Disputed

A small biotechnology company has emerged to claim that it invented a seminal technique crucial to biotechnology research. And the government says it will consider, nearly a quarter-century after the invention was made, whether it awarded the patent to the wrong party.

The United States Patent and Trademark Office has started a proceeding to determine the rightful inventor of the technique, automated DNA sequencing: scientists at the California Institute of Technology, who hold the patent, or those at Enzo Biochem, the small company.

If Enzo were to win the patent rights it could mean significant revenue for the company and could hurt Applied Biosystems, which licenses the patent in question from Caltech and dominates the DNA sequencing business. Applied Biosystems machines were the main ones used in the Human Genome Project to determine man’s genetic blueprint.

Applied Biosystems, a unit of Applera, recorded $540 million in sales of DNA sequencing machines and chemicals in the fiscal year ended June 30, accounting for 29 percent of its revenue. Caltech is estimated to have earned tens of millions of dollars from that and related patents.

Executives at Enzo, which is based in New York, say the company filed for a patent in June 1982, a few months before the Caltech scientists said they conceived of their invention. But Enzo’s application was continually rejected, delayed and amended in the patent office and remained unknown until now.

“We had to fight and fight with them,” said Eugene C. Rzucidlo, a New York patent lawyer who represents Enzo. “It’s only now that the patent office granted our claims and set up a proceeding to find who the real first inventor is.”

Patent law was changed in the 1990s to eliminate such “submarine patents,” which can lead to infringement by companies that develop a product on their own, never knowing about a patent that suddenly surfaces. But Enzo’s application is old enough to fall under the old rules.

If it were to get a patent it would last for 17 years from the date it is issued. Caltech’s patent was issued in 1998 and expires in 2015.

Spokeswomen for Caltech and Applied Biosystems said their organizations did not know enough yet to comment. But Edward R. Reines, a Silicon Valley patent lawyer who has represented Applied Biosystems, accused Enzo of trying to mine the patent system for money.

“Enzo appears to be attempting to claim credit for the invention of modern DNA sequencing 25 years after the fact when they have not brought a meaningful DNA sequencing product to market,” said Mr. Reines, who is with Weil, Gotshal & Manges.

Enzo executives disputed that, saying the company, founded in 1976, had long sold reagents for use in genetic analysis, though not sequencing machines. Enzo reported a net loss of $15.7 million in its last fiscal year on revenue of $39.8 million.

The Caltech sequencer attached a different color of fluorescent dye to each of the four chemical units of DNA, allowing the DNA sequence to be read by a machine. It made sequencing faster and set the stage for the Human Genome Project. The inventors include Leroy E. Hood, a biologist, and Michael W. Hunkapiller, who later ran Applied Biosystems.

The Caltech patents have withstood challenges before. A whistleblower lawsuit filed by a competitor of Applied Biosystems, said federal funds had been used in the invention, entitling the government to certain discounts and other rights. The government declined to pursue the lawsuit. And a former Caltech scientist filed a lawsuit claiming to be one of the inventors but lost in court.

R. Danny Huntington, a Washington lawyer who specializes in interference proceedings, said there were only about 100 such cases a year and they could take one or two years to resolve. The party with the earlier patent application date wins about two times out of three, he said.

While that would seem to favor Enzo, the patent office declaration of the interference criticizes Enzo’s patent claims for being unusually numerous, “erratically numbered” and “extraordinary in their flagrant disregard” of certain rules. The application is still not public, but lawyers said it contained about 1,200 claims.

Disease Detectives

Anytown, U.S.A., has a serious problem. One of its residents is very sick. Doctors suspect avian influenza. The disease, also called bird flu, can be devastating.

"If we do nothing," says Taylor Jones, the freckle-faced mayor of Anytown, "most likely, 70 percent of people in this town will die."

In a lab at the National Institutes of Health, student scientists Jack Grundy (left) and Erin Edwards tackle a make-believe avian-flu epidemic at this year's Discovery Channel Young Scientist Challenge.

While Jones and an epidemiologist use computer models to assess the town's risk, a virologist scans mucus samples to prepare a diagnosis. The patient, a 33-year-old named Joe Plastic, lies in a hospital isolation unit. He's struggling to breathe.

"He's starting to die," says Dr. Jayne Thompson.

The virologist, Kushal Naik, has more bad news.

"Joe is positive for avian flu, but that's not the worst part," Naik says. "We have nine specimens from other hospitals that are also positive. It's spreading."

Jayne Thompson and William Pete take a mucus sample from Joe Plastic's nose.

This crisis ends quickly, however, mainly because it's fictional. The team, ranging in age from 11 to 15, is tackling one of six 90-minute challenges at this year's Discovery Channel Young Scientist Challenge (DCYSC).

Each fall, DCYSC brings 40 middle school science fair champs to Washington, D.C., to compete for more than $100,000 in scholarships, prizes, and the honor of being named "America's Top Young Scientist of the Year." Winners must combine problem solving with quick thinking, teamwork, and the ability to explain complicated ideas clearly.

Gut navigation

This year's team competition, which had a medical theme, took place at the National Institutes of Health (NIH) in Bethesda, Md. Most challenges involved real-world medical problems. And cutting-edge NIH researchers were there to help.

"We try to deal with issues in the news," says Steve "Jake" Jacobs, head DCYSC judge. "NIH provided us with an opportunity available nowhere else on the planet."

NIH radiologist Ronald Summers explains the basics of reading a computerized tomography scan.

NIH researcher Ronald Summers, for example, studies virtual colonoscopy, a new way to screen for cancer of the colon (or large intestine). The technique combines X-ray–like computerized tomography (CT) scans with computer software to create three-dimensional videos of the inside of the colon. Doctors can then check the images for polyps, mushroomlike growths that can become cancerous.

The new diagnostic method is more comfortable for patients than the standard procedure. In that procedure, "you insert the scope into the patient's bottom and thread it through," Summers says. "A light and digital camera show you everything."

To compare the standard and new methods, students tried out each one. To perform a mock CT exam, they navigated through virtual images of five colons to spot the polyps in each. For the standard method, students threaded a 63-inch-long scope through a plastic model of a human colon. A screen displayed what was inside.

Steering the probe through the twists and folds of the colon was difficult. "I have no idea what I'm looking at," Otana Jakpor, 12, admitted at one point. Teammate Jack Grundy, 13, punctured the fake patient's intestinal wall by mistake.

Nolan Kamitaki and Anthony Hennig separate zebrafish embryos in a petri dish in the NIH labs.

Before the challenge ended, the colon explorers regrouped with teammates who had been injecting glowing proteins into see-through fish embryos. Together, the team needed to make a 3-minute, kid-to-kid video about new ways to look inside organisms.

Lunchtime

Downstairs, a different group of finalists battled another public health crisis: obesity (see "Packing Fat").

First, the team had to assemble a 500-calorie lunch from a selection of foods whose nutritional labels were hidden. The team picked a chicken wrap, a banana, carrot sticks, Fig Newtons, and milk.

The students were dismayed to learn that they'd overshot their mark: The lunch they'd assembled packed a walloping 885 calories.

Jayleen McAlpine demonstrates on a treadmill how much effort it takes to burn calories while her teammates look on.

Next, they used a chart, a treadmill, and their mathematics skills to figure out how much exercise it would take for a 125-pound person to burn off such a lunch.

After arguing about who would actually do so much exercise, they settled on four choices: an hour of basketball, an hour of tennis, 30 minutes of walking, and 30 minutes of lawn mowing.

Finally, the team created a podcast about energy balance and weight control.

"If people realized they had to do all that [exercise to burn off the calories in] a cookie, they might change their minds," Joseph Church, 14, said.

Collin McAliley, 13, was unconvinced. "It's such a good cookie, though," he said.

Grand prize

DCYSC involved more than challenges, dinners, meeting people, and having fun. On the final morning, the finalists visited an elementary school in Washington, D.C. They fielded questions, demonstrated science experiments, and helped kids with their science projects.

DCYSC competitor Joel Tinker demonstrates an experiment to two students at a Washington, D.C., school.

At the awards ceremony, the grand prize, a $20,000 scholarship, went to Nolan Kamitaki, 14, of Waiakea Intermediate School in Hilo, Hawaii.

Jacob "Pi" Hurwitz, 14, of Robert Frost Middle School in Rockville, Md., received a $10,000 scholarship. His nickname reflects his ability to recite 320 decimal digits of the number pi.

Amy David, 15, of Pinedale Middle School in Wyo., won third place and a $5,000 scholarship.

"One reason we're happy to have such bright, energetic people getting into science is that you are the next generation of leaders," NIH's Anthony Fauci told the finalists. "You are choosing a life of discovery and a probing of the unknown. It's a most unusual and extraordinary life."

Sharp Eye on the Sun

The sun is hotter than anything you can probably imagine, but that may not be the most striking thing about our closest star. The real surprise is that the sun's thin outer atmosphere, or corona, is much, much hotter than the sun's surface.

That's like the air high above a flame being hotter than the flame itself. The temperature should fall as you move away from a heat source.

A new spacecraft called Hinode has just started collecting data that might help explain this solar oddity.

The Earth-orbiting Hinode spacecraft, shown in this illustration, has telescopes and instruments for studying the sun.

cently launched through a collaboration involving Japan, Great Britain, and the United States, Hinode can collect two kinds of information about the sun. With a half-meter-wide visible-light telescope, it takes pictures of the sun's surface. It's the largest solar telescope that has ever flown into space.

Hinode's visible-light telescope shows details of the sun's turbulent surface, where great plumes of hot gas rise and fall to give the surface a speckled appearance.

Hinode also carries an X-ray telescope that detects hot gases in the sun's corona.

Hinode's X-ray telescope can record emissions that range between about 1 million and 4 million kelvins (273.15 kelvins equals 0°C or 32°F). This is an unusually wide temperature range for a detector, and it gives Hinode the power to sense the corona's calm, quiet features as well as its hot, explosive ones. Until now, scientists have been unable to study the corona in such detail.

New X-ray images of the sun reveal features known as X-ray bright points. Two examples are visible in the box.

The portrait (shown above) taken by Hinode's X-ray telescope on Oct. 28 shows features called X-ray bright points. These features, it appears, are magnetic loops that trap hot gas.

By monitoring X-ray bright points, scientists hope to better understand how the sun's corona becomes so hot. They should also get a clearer picture of how magnetic fields affect the corona.

Hinode, which means "sunrise" in Japanese, is still undergoing tests. In December, the spacecraft will officially begin a 3-year mission to unravel the sun's secrets.