Saturday, September 14, 2019

Nano-sized cells of body may help in fighting cancer

The nano-sized cells that transfer genetic material to other cells in our body may turn into mini treatment to kill cancer cells, suggests a study.

What we've done is improve a therapeutic approach to delivering enzyme-producing genes that can convert certain drugs into toxic agents and target tumors, said the lead author of the study.


These drugs, or pro-drugs, start out as inactive compounds. But once they metabolise in the body, they're immediately activated and can get to work in fighting everything from cancer to headache. Aspirin is an example of pro-drug.


In this case, researchers used extracellular vesicles, or EVs, to deliver the enzyme-producing genes that could activate a prodrug combination therapy of ganciclovir and CB1954 in breast cancer cells.
Mini circle DNA and regular plasmid-- 2 different gene vectors that act as additional delivery mechanisms for DNA--were loaded into the vesicles to see which was better at helping transport treatment. This is known as a gene-directed enzyme, pro-drug therapy.


They found that the mini circle DNA was 14 times more effective at delivery and even more successful at killing the cancerous tumour.


Interestingly, the plasmid delivery method didn't show any tumour cell killing, the Dr. said. Yet the mini circle DNA therapy killed more than half of the breast cancer cells in the mice.


According to the researcher, this new approach could effectively become a better cancer treatment option than chemotherapy down the road.


Conventional chemotherapy isn't able to differentiate between tumours and normal tissue, so it attacks it all, he said. This non-specificity can cause severe side effects and insufficient drug concentration in tumours.


With EVs, treatment can be targeted and because of their compatibility with the human body, this type of delivery could minimise the risk of unwanted immune responses that can come with other gene therapies.


If EVs prove to be effective in humans, it would be an ideal platform for gene delivery and it could be used in humans sooner than we expect, the researcher said.


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Tuesday, September 03, 2019

Breast cancer drugs may put some cells into 'sleeper mode'

Breast cancer drugs may force some cancer cells into 'sleeper mode', allowing them to potentially come back to life years after initial treatment.

The research could open avenues for finding ways of keeping the cancer cells dormant for longer, or even potentially finding a way of awakening the cells so they can then be killed by the treatment.

The team studied human breast cancer cells in the laboratory and examined the effects of a group of breast cancer drugs called hormone treatments.

"For a long time scientists have debated whether hormone therapies - which are a very effective treatment and save millions of lives - work by killing breast cancer cells or whether the drugs flip them into a dormant 'sleeper' state," said the lead author of the study.

"This is an important question as hormone treatments are used on the majority of breast cancers. Our findings suggest the drugs may actually kill some cells and switch others into this sleeper state," she added.

"If we can unlock the secrets of these dormant cells, we may be able to find a way of preventing cancer coming back, either by holding the cells in permanent sleep mode, or be waking them up and killing them," she said.

In the study, the team studied around 50,000 human breast cancer single cells in the lab, and found that treating them with hormone treatment exposed a small proportion of them as being in a dormant state.



The 'sleeper cells' may also provide clues as to why some breast cancer cells become resistant to treatment, causing a patient's drugs to stop working, and their cancer to return, the researchers said.

Hormone therapies are used to treat a type of breast cancer called estrogen-receptor positive. These make up over 70 per cent of all breast cancers, and are fuelled by the hormone estrogen.

These cancers are usually treated with surgery to remove the tumour, followed by a course of targeted hormone therapy - usually either aromatase inhibitors or tamoxifen, which target estrogen receptors.

However, around 30 per cent of breast cancer patients taking hormone therapies see their cancer eventually return - sometimes as long as 20 years after treatment.

This returning cancer is usually metastatic, meaning it has spread around the body, and the tumours are often now resistant to medication.


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Thursday, June 02, 2016

New protein can help treat cancer, other diseases

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 Researchers have designed a new protein that can effectively kill cells linked to the development and progression of cancer and a number of other diseases.

ProAgio, which is created from a human protein, targets the cell surface receptor integrin v3 at a novel site that has not been targeted by other scientists.

The researchers from Georgia State University in the US found ProAgio induces apoptosis, or programmed cell death, of cells that express integrin v3.

This integrin has been a focus for drug development because abnormal expression of v3 and is linked to the development and progression of a number of diseases.

"This integrin pair, v3, is not expressed in high levels in normal tissue," said Zhi-Ren Liu, lead author of the study and professor at Georgia State.

"In most cases, it's associated with a number of different pathological conditions. Therefore, it constitutes a very good target for multiple disease treatment," said Liu. Integrins are cell surface receptors that play a critical role in cells that attach to the extracellular matrix.

They are composed of different combinations and subunits. Different types of cells have different pairs of subunits. Integrin v3 has been studied by many scientists as a potential target for drugs that prevent inflammation and the growth of new blood vessels.

This integrin is expressed in the cells of new blood vessels, activated macrophages (immune cells that are involved in the first defence against infection), some cancer cells that metastasise or spread to other parts of the body and bone cells that are critical to maintenance and repair.

Previous approaches to targeting this integrin have focused on ligand binding, or attaching a molecule to the active site, which has not been effective.

There is an urgent need to develop agents that target this integrin at sites other than the ligand-binding site, Liu said.

"We designed a protein that binds to a different site. Once the protein binds to the site, it directly triggers cell death. When we're able to kill pathological cells, then we're able to kill the disease," Lui said.

Researchers, including Ravi Turaga of Georgia State, performed extensive cell and molecular testing that confirmed ProAgio interacts and binds well with integrin v3.

They found ProAgio induces apoptosis by recruiting caspase 8, an enzyme that plays an essential role in programmed cell death, to the cytoplasmic area of integrin v3. ProAgio was much more effective in inducing cell death than other agents tested.

In addition, tests with mouse models of cancer showed ProAgio strongly inhibits tumour growth. Tissue analyses indicated the protein effectively prevents the growth of tumour blood vessels, while existing blood vessels were not affected.

The findings were published in the journal Nature Communications.

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