Imaging technique could enable surgeons to see and remove malignant tumours with ease

Researchers have developed a new imagining technique that could enable surgeons to clearly see malignant growth that is often difficult to completely eliminate. The technique uses a synthetic version of a compound found in scorpion venom.

The new imagining technique uses a special high-sensitivity near-infrared camera, along with the imaging agent tozuleristide or BLZ-100. The agent contains a synthetic version of an amino acid compound found in scorpion venom.

Like the natural form of the compound, the synthetic version is not toxic and binds to tumour cells. It is attached to a fluorescent dye that glows when stimulated by a near-infrared laser.

Viewed through the cameras, the imaging agent might allow neurosurgeons to detect the boundaries between tumours and healthy brain tissue during surgery, improving the opportunity for surgeons to remove tumour cells while sparing normal brain tissue.

With this fluorescence, you see the tumour so much clearer because it lights up like a Christmas tree, said senior author of the study.

This is important because of the sprawling nature of gliomas, the type of brain tumours imaged during the trial. Gliomas are highly lethal and comprise about 33 % of all brain tumours.

They fan infiltrate brain tissue with tentacle-like structures, making them difficult to distinguish from normal brain tissue. They typically do not respond to traditional therapies such as chemotherapy and radiation. The key to extending patient survival depends on a surgeon's ability to detect and remove all parts of the tumour.

In the clinical trial, 17 adult patients with brain tumours were given varying doses of BLZ-100 before surgery. Despite the varying amounts of the drug given, the majority of tumours fluoresced, including both high-and-low-grade gliomas.

After surgery, patients were monitored for 30 days. Investigators found that none of the patients had any serious adverse responses to the drug and that the imaging system was safe and could be useful for imaging the brain tumours during surgery.

More clinical trials are needed to further evaluate the safety of the imaging system and demonstrate the system's effectiveness before BLZ-100 can gain approval from the givernment, and the camera used in the trial must be refined before it can be used seamlessly in an operating room. But the researcher said the clinical trial results were promising.

For a surgeon, this seamless integration of fluorescence imaging into the surgical microscope is very appealing, he said.

Unlike other experimental systems that are bulkier or rely on multiple cameras, the new imaging system uses a single camera that takes both near-infrared and while-light images by alternating between a laser and normal white lights at very high speeds. This technology enables surgeons to easily switch back and forth between normal vision using a surgical microscope and fluorescent super-vision on a nearby monitor, in real time.

The next phase of this research, already underway, is a clinical trial involving paediatric brain tumours. This trial will serve as a data set for potential government approval. A similar adult clinical trial is also being planned.

This technique in this study holds great promise not only for brain tumours but for many other cancer types in which we need to identify the margins of cancers. The ultimate goal is to bring greater precision to the surgical care we provide to our patients, said the doctor.

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Artificial Intelligence can help treat brain tumours

Researchers have developed an artificial intelligence-based (AI) method for analysis of brain tumours, paving the way for individualised treatment of tumours.

According to the study, AI machine learning methods, carefully trained on standard magnetic resonance imaging (MRI), are more reliable and precise than established radiological methods in the treatment of gliomas.

Glioma, a type of tumour that occurs in the brain and spinal cord, is common and most malignant of brain tumours in adults.

“With this study, we were able to demonstrate the potential of artificial neural networks in radiological diagnostics,” said a researcher.
 
For the study, the team included 500 brain tumour patients. Using a reference database with MRI scans of patients, the algorithms automatically recognised and localised brain tumours using artificial neural networks.

The algorithms were also enabled to volumetrically measure the individual areas (contrast medium-absorbing tumour portion, peritumoral edema).

“We want to advance the technology for automated high-throughput analysis of medical image data and transfer it not only to brain tumours but also to other diseases like brain metastases or multiple sclerosis,” said a researcher.

Glioma tumours often cannot be completely removed by surgery. Chemotherapy or radiotherapy are only effective to a limited extent because tumours are highly resistant. Therefore, new and precisely validated treatment approaches are urgently needed, the team noted.

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Brain tumors may respond to immunotherapy

According to a recent study, a slow-growing brain tumor in patients affected by neurofibromatosis type 1 (NF1) may be vulnerable to immunotherapy, which helps to boost the immune system in fighting cancer. The study, showed that a lot of have NF1, a hereditary disease that can lead to the development of tumors throughout the nervous system, including a type of brain tumor called a glioma.

Gliomas are most highly resistant to chemotherapy, and radiotherapy aggravates, rather than relieve, symptoms, such as headaches and seizures. Since the tumors typically engulf delicate brain regions, surgery is rarely an option.

Immunotherapy has been successful for some patients with melanoma, lymphoma, and a few other types of cancer. But some clinical trials have shown that it is ineffective for brain cancers in general. In this study, researchers performed an in-depth analysis of tumor samples from 56 patients to create the first comprehensive inventory of the genetic, epigenetic, and immune alterations in NF1 gliomas.

"This inventory will give us a much better idea of how to design individualised treatments," said a researcher. Immunotherapy is ineffective for most brain tumors because the tumors are infiltrated with large numbers of cells called macrophages that thwart the immune system's attack.

The study revealed that many slow-growing NF1 gliomas contain few macrophages and produce proteins, called neoantigens, that can trigger an immune system attack.

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This Virus Could Help Treat Cancer

A study which attempted to show that viruses could be delivered to brain tumors has delivered that and more. 

Not only did the particular virus in question reach its target, but it also stimulated the patient's own immune system - which then went on to attack the tumor as well. 
 

Pre-clinical trials in mice, followed by window-of-opportunity trials in nine human patients, showed that this naturally occurring virus offers potential for a new type of cancer therapy that could be used alongside other treatments. 
 
The virus that they used is one that has previously shown potential for cancer treatment. It's called the mammalian orthoreovirus type 3, and it has already been shown to kill tumor cells, but leave healthy cells alone. 

Previous experiments have demonstrated this, but these researchers are the first to successfully direct it at brain tumors. This is because, until now, it was thought unlikely that it was possible that the virus could cross the blood-brain barrier - a membrane that protects the brain from pathogens. 

Co-lead says that "this is the first time it has been shown that a therapeutic virus is able to pass through the brain-blood barrier, and that opens up the possibility that this type of immunotherapy could be used to treat more people with aggressive brain cancers."

Nine patients were selected to be injected with the virus. All either had brain tumors that had spread to other parts of the body, or fast-growing gliomas - a type of brain tumor that is hard to treat and has a poor prognosis. All were scheduled to have their brain tumors surgically removed following the reovirus experiment. 

The researchers took samples from the tumors after they had been removed, and compared them to the tumors of patients who had had brain surgery, but not the reovirus beforehand. They found the virus in the tumor samples of the trial patients, clearly proving that the virus had been able to reach the cancer. 

However, they also found an increased level of interferons, the proteins that activate our immune system. They team says that these interferons were attracting white blood cells to the site to fight the tumor. 

Co-lead author says that "our immune systems aren't very good at seeing cancers - partly because cancer cells look like our body's own cells, and partly because cancers are good at telling immune cells to turn a blind eye. But the immune system is very good at seeing viruses. In our study, we were able to show that reovirus could infect cancer cells in the brain. And, importantly, brain tumors infected with reovirus became much more visible to the immune system."

These findings are now being applied in a clinical trial, where patients are being given the reovirus treatment in addition to chemotherapy and radiotherapy. One patient's treatment is already underway - he is being given 16 doses of the reovirus to treat his gliobastoma.

The reason why he is being given multiple doses is because of the way the virus activates the immune system. This clinical trial will determine how well cancer patients can tolerate the treatment, since the virus can cause flu-like symptoms, and whether it makes the standard treatment more effective.

An oncologist, who is also leading the clinical trial, says that "the presence of cancer in the brain dampers the body's own immune system. The presence of the reovirus counteracts this and stimulates the defense system into action. Our hope is that the additional effect of the virus on enhancing the body's immune response to the tumor will increase the amount of tumor cells that are killed by the standard treatment, radiotherapy and chemotherapy."

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New blood test can detect blood cancer five years earlier than symptoms surface

Doctors would be able to diagnose blood  cancer from blood itself and that too five years before. American researchers have found out that changes in immune system can tell us a lot about growing brain  tumour five years before the symptoms of the life-threatening symptoms actually surface. The interactions among proteins that transfer information from immune cell to another are compromised in the blood of a brain cancer patients five years before the diagnosis of cancer. This research was carried out by a team. 

This breakthrough in medical sciences can lead to earlier diagnosis of brain cancer which can make the treatment a lot easier. The study was published in the journal , focused on gliomas, which make up about 80 percent of brain cancer diagnoses. Average survival time for the most common type of glioma is 14 months.

Symptoms include headaches, memory loss, personality changes, blurred vision and difficulty in speaking. Usually, the cancer is diagnosed three months after the symptoms become visible and when the tumours are typically advanced. 

"It's important to identify the early stages of tumor development if we hope to intervene more effectively," she said.

This research can pave the way for novel techniques to diagnose brain cancer earlier and allow a more efficient treatment. The researchers evaluated blood samples from 974 people, half of whom went on to receive a brain-cancer diagnosis in the years after their blood was drawn. They studied 277 cytokines in the blood samples and found less cytokine interaction in the blood of people who developed cancer.

"There was a clear weakening of those interactions in the group who developed brain cancer and it's possible this plays a role in tumor growth and development," she stated.
 
Cytokine activity in cancer is especially important to understand because it can play a good-guy role in terms of fighting tumor development, but it also can play a villain and support a tumor by suppressing the immune system, she said.

In addition to discovering the weakening of cytokine interactions in the blood of future cancer patients, the researchers found a handful of cytokines that appear to play an especially important role in glioma development.

"It's possible this could also happen with other tumors - that this is a general sign of tumor development," she noted.  

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Tumour-seeking salmonella may combat deadly brain cancer

Scientists have genetically modified salmonella – a strain of bacteria that causes food poisoning – to make them seek and destroy tumours, an advance that may help fight the deadliest form of brain cancer. Clinicians sorely need new treatment approaches for glioblastoma, the most aggressive form of brain cancer. The blood-brain barrier – a protective sheath separating brain tissue from its blood vessels – makes it difficult to attack the disease with drugs. It is also difficult to completely remove through surgery, as even tiny remnants inevitably spawn new tumours.

Even with the best care currently available, median survival time is a dire 15 months, and only 10 per cent of patients survive five years once diagnosed. Researchers at Duke University in the US decided to pursue an aggressive treatment option to match its opponent, turning to the bacterium Salmonella typhimurium. With a few genetic tweaks, scientists turned the bacterium into a cancer-seeking missile that produces self-destruct orders deep within tumours.

Tests in rat models with extreme cases of the disease showed a remarkable 20 per cent survival rate over 100 days -roughly equivalent to 10 human years – with the tumours going into complete remission. Previous studies have shown, quite accidentally, that the presence of bacteria can cause the immune system to recognise and begin attacking tumours.

However, follow-up clinical trials with genetically 0detoxified strains of S typhimurium have since proven ineffective by themselves. To use these common intestinal bacteria as tumour-seeking missiles, researchers including Nalini Mehta and Ravi Bellamkonda, selected a detoxified strain of S typhimurium that was also deficient in a crucial enzyme called purine, forcing the bacteria to seek supplies elsewhere.

Tumours just so happen to be an excellent source of purine, causing the bacteria to flock to them in droves. Then, scientists made a series of genetic tweaks so that the bacteria would produce two compounds called Azurin and p53 that instruct cells to commit suicide – but only in the presence of low levels of oxygen.

Since cancerous cells multiply energetically, the environment around tumours has unusually low oxygen. “A major challenge in treating gliomas is that the tumour is dispersed with no clear edge, making them difficult to completely surgically remove,” said Bellamkonda. “So designing bacteria to actively move and seek out these distributed tumours, and express their anti-tumour proteins only in hypoxic, purine rich tumour regions is exciting,” he said.

“At the doses we used in the experiments, they were naturally cleared once they’d killed the tumours, effectively destroying their own food source,” he added. The results appeared in the journal Molecular Therapy -Oncolytics.

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Hopes rise for brain tumour cure

Genes responsible for gliomas identified; targeted therapeutics are next step

Scientists have identified a family of genes responsible for the growth of a spectrum of hard-to-treat brain tumours, known as gliomas. “With these new genetic findings, our group of researchers plan to develop targeted therapeutics that we hope will one day be used to treat patients with high-grade brain tumours and increase their survival,” said lead author Joshua Breunig, a research scientist in the Brain Programme at the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the U.S.

Mutation combinations

“Any given tumour can harbour a variety of different combinations of mutations,” said Moise Danielpour, director of the Paediatric Neurosurgery Programme and the Centre for Paediatric Neurosciences in the Maxine Dunitz Children’s Health Centre.

“Despite advances in radiation and chemotherapy, there are currently no effective curative regimens for treatment for these diverse tumours,” Danielpour said.

Researchers first modelled high-grade brain tumours from resident stem cells inside the brain, using a cutting-edge method of rapid modelling that can create up to five distinct tumour models within 45 minutes. After modelling high-grade brain tumours, researchers identified the Ets family of genes as contributors to tumours. The Ets factors regulate the behaviour of tumour cells by controlling expression of genes necessary for tumour growth. When expression of the Ets genes is blocked, researchers can identify and strategise novel therapies.

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