Posts Tagged ‘team’

Invisible blood in urine may indicate bladder cancer

Scientists at the University of Exeter Medical School found that one in 60 people over the age of 60 who had invisible blood in their urine (identified by their GP testing their urine) transpired to have bladder cancer. The figure was around half those who had visible blood in their urine — the best known indicator of bladder cancer. However, it was still higher than figures for other potential symptoms of bladder cancer that warrant further investigation.

Lead author Sarah Price, a PhD student at the University of Exeter Medical School, led the first robust study to investigate whether invisible blood in urine can indicate bladder cancer. Speaking as the study is published in the British Journal of General Practice on September 1 2014, she said: “It is well known that if you see blood in your urine you should contact your GP, who is likely to refer you for tests. But there is no clear guidance for GPs on what to do if they detect blood that is not visible during routine tests. We are hopeful that our findings will now lead to robust guidance that it warrants further investigation. Early diagnosis is crucial to have the best chance of successfully treating bladder cancer. The three-quarters of patients who are diagnosed early have much better outcomes than those whose disease is diagnosed late. Anything we can do to boost early detection is crucial to help save lives.”

The study examined more than 26,000 people whose anonymized data contributed to the Clinical Practice Research Datalink; this is a large research database used by the Exeter team in several cancer studies. The team found that the risk of bladder cancer was 1.6 per cent in people over 60 who had invisible blood in their urine.

Around 10,000 people in the UK are diagnosed with bladder cancer each year. The condition is more common in men than women and in older people, with the average age of diagnosis at 68. Smoking is among the main causes.

source : http://www.sciencedaily.com/releases/2014/09/140901090731.htm

Introducing the multi-tasking nanoparticle

“These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors; apply light to make the nanoparticles release singlet oxygen (photodynamic therapy) or use a laser to heat them (photothermal therapy) — all proven ways to destroy tumors.”

Jessica Tucker, program director of Drug and Gene Delivery and Devices at the National Institute of Biomedical Imaging and Bioengineering, which is part of the National Institutes of Health, said the approach outlined in the study has the ability to combine both imaging and therapeutic applications in a single platform, which has been difficult to achieve, especially in an organic, and therefore biocompatible, vehicle.

“This is especially valuable in cancer treatment, where targeted treatment to tumor cells, and the reduction of lethal effects in normal cells, is so critical,” she added.

Though not the first nanoparticles, these may be the most versatile. Other particles are good at some tasks but not others. Non-organic particles, such as quantum dots or gold-based materials, work well as diagnostic tools but have safety issues. Organic probes are biocompatible and can deliver drugs but lack imaging or phototherapy applications.

Built on a porphyrin/cholic acid polymer, the nanoparticles are simple to make and perform well in the body. Porphyrins are common organic compounds. Cholic acid is produced by the liver. The basic nanoparticles are 21 nanometers wide (a nanometer is one-billionth of a meter).

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers. At 32 nanometers, CNPs are ideally sized to penetrate tumors, accumulating among cancer cells while sparing healthy tissue.

In the study, the team tested the nanoparticles, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, CNPs effectively transported anti-cancer drugs, such as doxorubicin. Even when kept in blood for many hours, CNPs only released small amounts of the drug; however, when exposed to light or agents such as glutathione, they readily released their payloads. The ability to precisely control chemotherapy release inside tumors could greatly reduce toxicity. CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

CNPs also can be configured to respond to light, producing singlet oxygen, reactive molecules that destroy tumor cells. They can also generate heat when hit with laser light. Significantly, CNPs can perform either task when exposed to a single wavelength of light.

CNPs offer a number of advantages to enhance imaging. They readily chelate imaging agents and can remain in the body for long periods. In animal studies, CNPs congregated in tumors, making them easier to read on an MRI. Because CNPs accumulated in tumors, and not so much in normal tissue, they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans.

This versatility provides multiple options for clinicians, as they mix and match applications.

“These particles can combine imaging and therapeutics,” said Li. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

“These particles can also be used as optical probes for image-guided surgery,” said Lam. “In addition, they can be used as highly potent photosensitizing agents for intraoperative phototherapy.”

While early results are promising, there is still a long way to go before CNPs can enter the clinic. The Lam lab and its collaborators will pursue preclinical studies and, if all goes well, proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” said Li. “From delivering chemo, photodynamic and photothermal therapies to enhancing diagnostic imaging, it’s the complete package.”

source : http://www.sciencedaily.com/releases/2014/08/140826112648.htm

Cancer-fighting drugs might also stop malaria early

Duke University assistant professor Emily Derbyshire and colleagues identified more than 30 enzyme-blocking molecules, called protein kinase inhibitors, that curb malaria before symptoms start.

By focusing on treatments that act early, before a person is infected and feels sick, the researchers hope to give malaria — especially drug-resistant strains — less time to spread.

The findings appear online and are scheduled to appear in a forthcoming issue of the journal ChemBioChem.

Malaria is caused by a single-celled parasite called Plasmodium that spreads from person to person through mosquito bites. When an infected mosquito bites, parasites in the mosquito’s saliva first make their way to the victim’s liver, where they silently grow and multiply into thousands of new parasites before invading red blood cells — the stage of the disease that triggers malaria’s characteristic fevers, headaches, chills and sweats.

Most efforts to find safe, effective, low-cost drugs for malaria have focused on the later stage of the infection when symptoms are the worst. But Derbyshire and her team are testing chemical compounds in the lab to see if they can identify ones that inhibit malaria during the short window when the parasite is still restricted to the liver, before symptoms start.

One of the advantages of her team’s approach is that focusing on the liver stage of the malaria lifecycle — before it has a chance to multiply — means there are fewer parasites to kill.

Using a strain of malaria that primarily infects rodents, Derbyshire and Jon Clardy of Harvard Medical School tested 1,358 compounds for their ability to keep parasites in the liver in check, both in test tubes and in mice.

“It used to be that researchers were lucky if they could identify one or two promising compounds at a time; now with advances in high-throughput screening technology we can explore thousands at once and identify many more,” said Derbyshire, an assistant professor in the Departments of Chemistry and Molecular Genetics and Microbiology at Duke.

Focusing on a particular group of enzyme-blocking compounds called protein kinase inhibitors, they identified 31 compounds that inhibit malaria growth without harming the host. Several of the compounds are currently in clinical trials to treat cancers like leukemia and myeloma.

The same compounds that stopped the stage of malaria that lurks in the liver also worked against the stage that lives in the blood.

Malaria-free mice that received a single dose before being bitten by infected mosquitos were able to avoid developing the disease altogether.

Medicines for malaria have been around for hundreds of years, yet the disease still afflicts more than 200 million people and claims hundreds of thousands of lives each year, particularly in Asia and Africa. Part of the reason is malaria’s ability to evade attack. One of the most deadly forms of the parasite, Plasmodium falciparum, has already started to outsmart the world’s most effective antimalarial drug, artemisinin, in much of southeast Asia. Infections that used to clear up in a single day of treatment now take several days.

Diversifying the antimalarial arsenal could also extend the lifespan of existing drugs, since relying less heavily on our most commonly used weapons gives the parasite fewer opportunities to develop resistance, Derbyshire said.

Another advantage is that the compounds they tested suppress multiple malaria proteins at once, which makes it harder for the parasites to develop ways around them.

“That makes them like a magic bullet,” she said.

source : http://www.sciencedaily.com/releases/2014/08/140825185840.htm