Human Memory’s brain yields new evidence

Source: Neuroscience News

3D model of famous amnesiac’s brain helps illuminate human memory.

During his lifetime, Henry G. Molaison (H.M.) was the best-known and possibly the most-studied patient of modern neuroscience. Now, thanks to the postmortem study of his brain, based on histological sectioning and digital three-dimensional construction led by Jacopo Annese, PhD, at the University of California, San Diego, scientists around the globe will finally have insight into the neurological basis of the case that defined modern studies of human memory.

Jacopo Annese examines final brain tissue slides, which were also digitized for study by researchers worldwide. Credit UCSD.
The microscopic anatomical model of the whole brain and detailed 3D measurements of the medial temporal lobe (MTL) region are described in a paper to be published online in Nature Communications on January 28.

H.M. was an epileptic patient whose severe and almost total amnesia was the unexpected result of a bilateral surgical ablation of the MTL, including the hippocampus, in 1953. Until his death in 2008, the purity and severity of H.M.’s memory impairment, along with his willingness to participate in continual testing, made his case uniquely influential.

While his intellectual abilities, personality, language and perceptual skills remained intact, he was unable to store information in long-term memory. After his brain operation, H.M. was profoundly impaired in forming new declarative memories. This unfortunate outcome became the catalyst for over 50 years of scientific discoveries (and thousands of publications) that have radically changed scientists’ basic understanding of memory function. His case was significant because it provided the first conclusive evidence for the involvement of the hippocampus in forming new memories.

In December 2009, Annese and his team dissected H.M.’s brain into 2,401 thin tissue slices that were then preserved cryogenically in serial order. While the brain was being sliced, the researchers collected an unabridged series of digital images of the surface of the block, corresponding to each tissue section. These images were archived and used to create a three-dimensional microscopic model of the whole brain. The model of H.M.’s brain contains clues to help understand the surgery performed in 1953, and the level of sampling and image quality afforded by this study represents a significant advance over the MRI scans performed with H.M. when he was alive.

“Our goal was to create this 3D model so we could revisit, by virtual dissection, the original surgical procedure and support retrospective studies by providing clear anatomical verification of the original brain lesion and the pathological state of the surround areas of H.M.’s brain,” Annese said. But the study reveals a small, circumscribed lesion in the left orbitofrontal cortex that had been previously undiscovered, showing the power of the technique. Based on the 3D geometry of the lesion and the type of the lobectomy that was performed in 1953, Annese thinks this lesion was very likely created by Scoville during the surgery.

The findings reported in Nature Communications constitute new evidence that may help scientists today understand more fully the consequences of H.M.’s operation in the context of modern knowledge on memory of the functional anatomy of the hippocampus.

Annese and his team at UCSD also created a web-based atlas of H.M.’s brain, meant to support collaboration and preserve an archive of anatomical images relative to the case. The atlas contains structural delineations and digitized versions of the stained histological slides that can be viewed at the cellular-level using Google maps, a level of detail not seen before.

Notes about this memory and neuroscience research

For more information on the H.M. project and the Brain Observatory, visit: To view a Google maps version of the slice featured in the paper (Fig. 5), go to:

Funding for the study was provided by grants from the National Science Foundation (NSF-SGER 0714660), the Dana Foundation Brain and Immuno-Imaging Award, and by private contributions from viewers of the web broadcast of the dissection. In the course of the study, Annese was supported in part by research grants from the National Eye Institute, R01EY018359–02 and ARRA R01 EY018359–02S1 and the National Institute of Mental Health, R01MH084756.

PEOPLE at high risk of bowel and womb cancer will receive a more accurate diagnosis


New hopes for cancer prediction

PEOPLE at high risk of bowel and womb cancer will receive a more accurate diagnosis due to a new model that can turn “previously uninterpretable DNA data into usable knowledge”, scientists say.

A scientist from Cardiff University is part of an international research team that claims to have developed a new way of identifying people at high risk of cancer.

The study focuses on the genes responsible for Lynch Syndrome, which is a rare condition that runs in families and is the most common form of hereditary bowel cancer.

People with the syndrome also have an increased risk of developing other cancers, including womb cancer.

It is hoped the research will enable doctors to give patients a more accurate picture of their familial risk.

“In the UK, bowel cancer kills about 16,000 people each year, and womb cancer – the commonest gynaecological cancer – about 2000 women a year, with Wales having the highest rate,” said Dr Ian Frayling, from Cardiff University’s Institute of Medical Genetics and a member of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT), which organised the research.

“What we have been able to do is effectively refine genetic information in the InSiGHT database and provide a more accurate answer of the risk of getting cancer,” he said.

As a result of this study, published in the journal Nature Genetics, doctors will be able to say “much more confidently” whether patients have Lynch Syndrome, and therefore whether they are at a higher risk of cancer, Dr Frayling said.

“This will help to save more lives, because by giving a definite answer to more patients they will be able to access the specialist screening that they need,” he said.

Ice cream hits the spot at CanTeen

Source: Sunshinecoast

THE daily stresses of living with cancer were washed away with a scoop of ice cream by the beach for a group young people visiting the Sunshine Coast.

Wendy’s Ice Cream brought a sweet treat to 65 children and teenagers having a break at Dicky Beach as part of the annual CanTeen Summer Program yesterday.

Smooth and creamy ice cream was taken from the freezer, across the sand to the group in a surprise delivery.

The children spent the warm summer’s day at the Caloundra beach playing games and swimming on the second last day of the camp.

CanTeen is an organisation which supports, develops and empowers young people living with cancer.

The organisation runs the five-day overnight programs to provide much-needed relief for these young Australians.

An extra 23,000 young people every year have to face the challenge of dealing with cancer – whether they’ve been diagnosed themselves or a parent, brother or sister has the disease.

“A cancer diagnosis threatens the security of a young person’s world, leaving them feeling vulnerable, frightened and confused,” CanTeen programs officer Jaimie Trotter said.

“Attending a CanTeen program gives our members the chance to meet other young people who truly understand what they’re going through while also having some fun.

“The programs are free to attend and that’s why we’re so grateful for every donation we receive from the community and our corporate supporters such as Wendy’s.

“The programs wouldn’t be possible without them.”

Unprecedented success in trialling new adult leukaemia therapy

Source: ACRF

A new, potentially life-saving drug has raised new hope for patients in advanced stages of chronic lymphocytic leukaemia – one of the most common types of adult leukaemia in Australia.

In many cases this cancer becomes resistant to traditional treatment methods such as chemotherapy. This is because of its high levels of a “pro-survival” protein called BCL-2 that render cancer cells, according to Walter and Eliza Hall Institute haematologist Prof. Andrew Roberts “basically indestructible”.

This new drug, currently in phase one clinical trials, targets this BCL-2 protein and breaks down the leukaemia cancer cells with-in the patient’s body creating a positive outlook for many patients battling the advanced stages of this disease.

Results from the trial reveal the cancer has become completely undetectable in almost a quarter of patients and in 61 per cent of cases the patient has gone into partial remission.

Peter MacCallum Cancer Centre chair of haematology, Professor John Seymour, said while trials were at an early stage, the drug’s success was unprecedented. “Patients on the trial were typically incurable, with an average life expectancy of up to 18 months, so to see complete clearance of cancer in nearly one quarter of these patients after taking this single therapy is incredibly encouraging,” he said.

The protein and its significance in leukaemia – as well as several other cancers including some lymphomas, breast and prostate, was first identified by scientists at the Walter and Eliza Hall Institute (WEHI) in 1988. Professor Andrew Roberts said it had long been a target of scientists trying to develop anti-cancer drugs.

The drug, taken as a pill, also shows promise for the treatment of these other types of cancer, which are also reliant on the BCL-2 protein.

Melbourne patients with advanced stages of chronic lymphocytic leukaemia were the first in the world to receive this new therapy developed in partnership with the WEHI. Trials have been run by the Royal Melbourne Hospital and the Peter MacCallum Cancer Centre. The ACRF is very proud to have provided significant funding to each of these three research centres in Melbourne.

A phase two trial to establish the drug’s safety and effectiveness in a larger group of patients in Australia, the US and Europe is under way and could lead to approval for wider use by regulatory authorities within three years.

World-first Melbourne-led clinical trial reports stunning results in people with advanced leukaemia

Source: PeterMac

Researchers and clinicians from the Peter MacCallum Cancer Centre, The Royal Melbourne Hospital and the Walter and Eliza Hall Institute for Medical Research are leading an international trial of a new therapy, for people with advanced leukaemia for whom no conventional treatment options are available, which has completely cleared cancer in 23 per cent of patients.

Reporting preliminary results of the ongoing first-in-human clinical trial of the novel compound to treat chronic lymphocytic leukaemia (CLL) at the American Society of Hematology Annual Meeting in New Orleans today, Professor John Seymour: Chair of the Haematology Service at Peter Mac, revealed 84 per cent of patients experienced remission, despite participants’ disease having failed an average of four prior treatment regimes.

Professor Seymour says the results of the trial are unprecedented in the quality of the disease responses.

‘Patients on the trial were typically incurable, with an average life expectancy of up to 18 months, so to see complete clearance of cancer in nearly one quarter of these patients, after taking this single therapy, is incredibly encouraging.’

‘By comparison, the phase I study of ibrutinib, now hailed as a game-changer in CLL, reported cleared disease in only two per cent of a similar group of patients.’

Professor Andrew Roberts: head of clinical translation at the Walter and Eliza Hall Institute and the Metcalf Chair of Leukaemia Research at The University of Melbourne and The Royal Melbourne Hospital, says the therapy works by overcoming the action of a key survival signal within leukaemia cells which allows them to avoid dying.

‘Although CLL cells are slow to proliferate, they accumulate inexorably because they fail to die, creating large tumours that standard treatments have not been able to adequately combat.

‘This novel compound selectively targets the protein-to-protein interaction responsible for keeping the leukaemia cells alive and, in many cases, we’ve seen the number of cancerous lymphocytes simply melt away.’

To date, the phase I study has involved 67 patients, whose cancer was resistant to up to eleven cancer treatment regimens.

Professor Seymour says a further promising aspect of the phase I results is the presence of the same survival instinct in malignant cells of other cancer types.

‘Pre-clinical studies at Peter Mac and the Walter and Eliza Hall Institute have shown this protein interaction can keep cancer cells alive in other haematological malignancies and breast, lung and prostate cancers — and we have already seen extremely exciting effectiveness of this compound in laboratory models, when combined with other anti-cancer treatments.

‘We certainly feel there is potential for therapies similar to this to enter clinical development as complementary therapies for these diseases.’

The final phase of this study in leukaemia is expected to complete accrual around the end of the year.



Harmless lung cancer? A provocative study found that nearly 1 in 5 lung tumors detected on CT scans are probably so slow-growing that they would never cause problems.

The analysis suggests the world’s No. 1 cause of cancer deaths isn’t as lethal as doctors once thought.

In the study, these were not false-positives — suspicious results that turn out upon further testing not to be cancer. These were indeed cancerous tumors, but ones that caused no symptoms and were unlikely ever to become deadly, the researchers said.

Still, the results are not likely to change how doctors treat lung cancer.

For one thing, the disease is usually diagnosed after symptoms develop, when tumors show up on an ordinary chest X-ray and are potentially life-threatening.

Also, doctors don’t know yet how to determine which symptomless tumors found on CT scans might become dangerous, so they automatically treat the cancer aggressively.

The findings underscore the need to identify biological markers that would help doctors determine which tumors are harmless and which ones require treatment, said Dr. Edward Patz, Jr., lead author and a radiologist at Duke University Medical Center. He is among researchers working to do just that.

Patz said patients who seek lung cancer screening should be told about the study results.

“People have to understand that we’re going to find some cancers which if we’d never looked, we never would have had to treat,” he said. Among patients and even many doctors, “it’s not something that is commonly known with lung cancer.”

A leader of an influential government-appointed health panel agreed.

“Putting the word ‘harmless’ next to cancer is such a foreign concept to people,” said Dr. Michael LeFevre, co-chairman of the U.S. Preventive Services Task Force.

The panel recently issued a draft proposal recommending annual CT scans for high-risk current and former heavy smokers — echoing advice from the American Cancer Society. A final recommendation is pending, but LeFevre said the panel had already assumed that screening might lead to overdiagnosis.

“The more we bring public awareness of this, then the more informed decisions might be when people decide to screen or not,” LeFevre said. He called the study “a very important contribution,” but said doctors will face a challenge in trying to explain the results to patients.

In testimonials, patients often say lung cancer screening via CT scans cured them, but the study suggests that in many cases, “we cured them of a disease we didn’t need to find in the first place,” LeFevre said.

The study was published Monday in the journal JAMA Internal Medicine.

More than 200,000 Americans are diagnosed with lung cancer each year, and more than half of them die. Worldwide, there are about 1.5 million lung cancer deaths annually.

The new study is an analysis of data from the National Lung Cancer Screening Trial — National Cancer Institute research involving 53,452 people at high risk for lung cancer who were followed for about six years.

Half of them got three annual low-dose CT scans — a type of X-ray that is much more sensitive than the ordinary variety — and half got three annual conventional chest X-rays. During six years of follow-up, 1,089 lung cancers were diagnosed in CT scan patients, versus 969 in those who got chest X-rays.

That would suggest CT scans are finding many early cases of lung cancer that may never advance to the point where they could be spotted on an ordinary chest X-ray.

An earlier report on the study found that 320 patients would need to get CT screening to prevent one lung cancer death.

The new analysis suggests that for every 10 lives saved by CT lung cancer screening, almost 14 people will have been diagnosed with a lung cancer that would never have caused any harm, said Dr. Len Lichtenfeld, the cancer society’s deputy chief medical officer.

He said that is a higher rate of overdiagnosis than he would have predicted, but that the study shows how much understanding of cancer has evolved. Decades ago, “every cancer was a bad cancer,” he said.

Now it’s known that certain cancers, including many prostate cancers, grow so slowly that they never need treatment.

The American College of Radiology said in statement Monday that the earlier study showed lung cancer screening significantly reduces lung cancer deaths in high-risk patients and that the benefit “significantly outweighs the comparatively modest rate of overdiagnosis” found in the new analysis.

Low-dose CT scans are the only test shown to reduce lung cancer deaths in high-risk smokers, the radiology group said, adding, “Overdiagnosis is an expected part of any screening program and does not alter these facts.”

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