Uncovering cancer's inner workings by capturing live images of growing tumors

Sep. 17, 2013 — Scientists seeking new ways to fight cancer often try to understand the subtle, often invisible, changes to DNA, proteins, cells, and tissue that alter the body's normal biology and cause disease. Now, to aid in that fight, a team of researchers has developed a sophisticated new optical imaging tool that enables scientists to look deep within tumors and uncover their inner workings. In experiments that will be described at Frontiers in Optics (FiO), The Optical Society's (OSA) Annual Meeting, Dai Fukumura and his colleagues will present new optical imaging techniques to track the movement of molecules, cells, and fluids within tumors; examine abnormalities in the blood vessel network inside them; and observe how the tumors were affected by treatments.

These techniques, created by Fukumura and his long-term collaborators at Massachusetts General Hospital and Harvard Medical School, combine two different high-tech optical imaging methods that were custom-built for the research. One is called multiphoton laser-scanning microscopy (MPLSM), which is an advanced fluorescence imaging technology that is now commercially available at the high end of the microscope market. The other is called optical frequency domain imaging (OFDI), which images tissues by their light scattering properties. According to Fukumura, OFDI is gaining popularity in the optical imaging field but has yet to become commercially available.

"MPLSM overcomes many of the limitations from which conventional microscopy and confocal microscopy suffer, and OFDI provides robust large volume imaging data," Fukumura said.

Fukumura will present their research at FiO 2013, taking place Oct. 6-10 in Orlando, Fla. There, he will describe how his unique technique can image tumors inside and out, and show detailed pictures of live tumors -- images that he and colleagues call "astonishing."

He added that while the new combined approach would be too expensive to be used for routine diagnostic purposes, it promises to help researchers better understand the intricate workings of human cancer and aid in drug discovery to treat cancer. "These optical imaging approaches can provide unprecedented insights in the biology and mechanisms of cancer," he said.

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Inner ear 'link to hyperactivity '

5 September 2013 Last updated at 23:10 GMT Problems in the inner ear can be genetic, or caused by illness or injury Inner-ear problems could be a cause of hyperactive behaviour, research suggests.

A study on mice, published in Science, said such problems caused changes in the brain that led to hyperactivity.

It could lead to the development of new targets for behaviour disorder treatments, the US team says.

A UK expert said the study's findings were "intriguing" and should be investigated further.

Behavioural problems such as ADHD are usually thought to originate in the brain.

But scientists have observed that children and teenagers with inner-ear disorders - especially those that affect hearing and balance - often have behavioural problems.

However, no causal link has been found.

The researchers in this study suggest inner-ear disorders lead to problems in the brain which then also affect behaviour.

Gene mutation

The team from the Albert Einstein College of Medicine of Yeshiva University in New York noticed some mice in the lab were particularly active - constantly chasing their tails.

They were found to be profoundly deaf and have disorders of the inner ear - of both the cochlea, which is responsible for hearing, and the vestibular system, which is responsible for balance.

The researchers found a mutation in the Slc12a2 gene, also found in humans.

Blocking the gene's activity in the inner ears of healthy mice caused them to become increasingly active.

The researchers then examined the striatum, an area in the centre of the brain area that controls movement.

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Attention deficit hyperactivity disorder is thought to affect 2-5% of children and young people.

Common symptoms include inattentiveness, hyperactivity and impulsiveness.

Symptoms tend to be first noticed at an early age and it is normally diagnosed between the ages of three and seven.

Recent evidence showed a 50% rise in the use of drugs for the condition in England, with 657,000 prescriptions issued for drugs including Ritalin.

They found higher-than-normal levels of two proteins, pERK and pCREB.

Mice with the gene flaw were given injections of haloperidol, a medicine already used to treat tics - uncontrollable movement - in humans.

It was seen to counteract the high protein levels, and mouse activity patterns returned to normal.

The researchers suggest the same process could be targeted in people, and that medications could be developed to help manage hyperactivity in children with inner-ear disorders.

Prof Jean Hebert, the lead scientist, said: "Our study provides the first evidence that a sensory impairment, such as inner-ear dysfunction, can induce specific molecular changes in the brain that cause maladaptive [counterproductive] behaviours traditionally considered to originate exclusively in the brain."

Anita Thapar, professor of child and adolescent psychiatry at Cardiff University's Institute of Psychological Medicine and Clinical Neurosciences, said it was an "intriguing study and set of findings".

Prof Thapar, whose research has suggested there could be a genetic link to attention deficit hyperactivity disorder (ADHD), added: "It certainly raises the issue that we ought to critically consider what contributes to the links between sensory impairments and specific behaviours/disorders."

But she added there should be caution about directly extrapolating the findings to humans.

"ADHD, like most neuropsychiatric and medical disorders, is not caused by a single mutation.

"On the other hand animal models allow for experimental manipulation in a way that cannot be achieved in humans and the results can help shape hypotheses to test in humans."

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