High hormone levels in blood raise prostate cancer risk

Men with higher levels of testosterone and a growth hormone in their blood are more likely to be diagnosed with prostate cancer, according to a new study.

A research of more than 200,000 men is one of the first to show strong evidence of two factors that could possibly be modified to reduce prostate cancer risk.

"Prostate cancer is the second most commonly diagnosed cancer in men worldwide after lung cancer and a leading cause of cancer deaths. But, there is no evidence-based advice that we can give to men to reduce their risk," said the study's lead author.

"We were interested in studying the levels of two hormones circulating in the blood because previous research suggests they could be linked with prostate cancer and because these are factors that could potentially be altered in an attempt to reduce prostate cancer risk," he added.

The researchers studied 200,452 men who are part of the UK Biobank project. All were free of cancer when they joined the study and were not taking any hormone therapy.

The men gave blood samples that were tested for their levels of testosterone and a growth hormone called insulin-like growth factor-I (IGF-I).

The researchers calculated the levels of free testosterone which is circulating in the blood and not bound to any other molecule and can therefore have an effect in the body.

A subset of 9,000 men gave a second blood sample at a later date, to help the researchers account for natural fluctuations in the hormone levels.

The men were followed for an average of six to seven years to see if they went on to develop prostate cancer. Within the group, there were 5,412 cases and 296 deaths from the disease.

The researchers found that men with higher concentrations of the two hormones in their blood were more likely to be diagnosed with prostate cancer.

For every increase of five nanomoles in the concentration of IGF-I per litre of blood (5 nmol/L), men were nine per cent more likely to develop prostate cancer.

For every increase of 50 picomoles of testosterone per litre of blood (50 pmol/L), there was a 10 per cent increase in prostate cancer risk.

According to the researchers, 25 per cent greater risk in men who have the highest levels of IGF-I, compared to those with the lowest.

Men with the highest testosterone levels face an 18 per cent greater risk of prostate cancer, compared to those with the lowest levels.

"This type of study can't tell us why these factors are linked, but we know that testosterone plays a role in the normal growth and function of the prostate and that IGF-I has a role in stimulating the growth of cells in our bodies," the author said. The study was presented at 2019 NCRI Cancer Conference in London.

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Modified radiotherapy less likely to damage healthy cells: Experts

A modified way of concentrating radiotherapy dose in tumour while minimising damage to healthy cells has been proposed in a recent research.

The study —proposes that focusing high-energy particle beams on a small spot deep inside the body could potentially enable clinicians to target cancerous tumour precisely.

External beam radiotherapy involves treating patients with either high energy X-rays or particle beams. Tumour cells are killed by the radiation, which is usually administered in multiple fractions, which are applied daily over several weeks.

The lead of the project, said: “Around half of the population will suffer from cancer at some time in their lives. Of these people, half will be treated using radiotherapy or a combination of radiotherapy and chemotherapy.”

One of the challenges in radiotherapy is to deposit a high radiation dose in a way that the dose fully ‘conforms’ to the tumour to ensure that all cancerous cells are killed while preventing damage to healthy cells. Our study showed that we can very simply focus radiation onto a tumour to irradiate it while reducing the dose in surrounding healthy tissue.”

One of the disadvantages of using X-rays in radiotherapy is that these are absorbed in the body and their effects diminish, resulting in a high entrance dose. Proximal and distal doses before and after the tumour can also be as high as, or higher than, the radiation dose in the tumour.

To eradicate the tumour precisely with sufficient radiation to kill all tumour cells, the X-ray beam is often rotated while pointing at the tumour from different directions, while the patient remains stationary.

An effective radiotherapy modality uses heavier particles such as protons and ions. These have the advantage of radiation doses that can be confined to a small region called the “Bragg peak.”

“This work presents a comprehensive numerical study of fundamental issues encountered in cancer treatment with very high energy electrons for a wide range of geometries. Results suggest that technology and beam transport systems routinely employed in high-energy particle accelerators could find direct application in this field, expanding the range of tools available for radiotherapy,” said  one of the researchers of the study.

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Gene therapy first to halt most common cause of blindness

Researchers claim to have carried out the world's first gene therapy operation to halt age-related macular degeneration (AMD), the leading cause of untreatable blindness in the developed world.

Dry AMD is a slow deterioration of the cells of the macula.

It affects the central part of a patient's vision with gaps or 'smudges', making everyday activities like reading and recognising faces difficult.

If successful, the treatment could have a beneficial impact of patients' quality of life and their ability to remain independent.

"A genetic treatment administered early on to preserve the vision in patients who would otherwise lose their sight would be a tremendous breakthrough and certainly something I hope to see in the near future," said a Prof.

The first person to undergo the procedure was  a lady, said  the Prof., who carried out the procedure.

Like many people with AMD,she has the condition in both eyes, but it is more advanced in her left eye.

As is typical with this condition, the central vision in her left eye has deteriorated and is very hazy, although her peripheral vision is better. 

The operation involves detaching the retina and injecting a solution containing a virus underneath.

The virus contains a modified DNA sequence, which infects cells, called the retinal pigment epithelium (RPE), and corrects a genetic defect that causes AMD.

Ideally if successful, gene therapy would only need to be performed once, as the effects are thought to be long-lasting.

A key factor in AMD is the complement system, a system of proteins in our immune system that fights bacteria.

In macular degeneration, these proteins are over-active and start to attack the retinal cells, in a similar way to how they would attack bacteria.

"We are harnessing the power of the virus, a naturally occurring organism, to deliver the DNA into the patient's cells," the Prof. said.

"When the virus opens up inside the retinal cell it releases the DNA of the gene we have cloned, and the cell starts making a protein that we think can modify the disease, correcting the imbalance of the inflammation caused by the complement system," he said.

"The idea of this gene therapy is to 'deactivate' the complement system, but at a very specific point at the back of the eye, so the patient would otherwise be unaffected by it, and we hope that in future it will slow down the progression of macular degeneration," he said .

"We have a better understanding now on the relationship between the complement system and the AMD disease which lead us to the discovery that restoring the balance of a hyperactive complement system could be a potential therapeutic approach in dry AMD," he said.

The aim of the therapy is to halt the progress of the condition and preserve what vision patients have remaining.

It is hoped that gene therapy can be used in the future on patients with early AMD and so halt the disease before their vision has started to deteriorate.

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This plant can clean indoor air

Researchers have genetically modified a common indoor plant -- pothos ivy -- to remove pollutants inside the house including chloroform and benzene that have been linked to cancer, according to a new study.

The modified plants express a protein, called P450 2E1 or 2E1, that transforms these compounds into molecules that the plants can then use to support their own growth. 

"People have not really been talking about these hazardous organic compounds in homes, and I think that is because we could not do anything about them," said a Prof.
 
For the study, the team tested how well their modified plants could remove the pollutants from air compared to normal pothos ivy. 

They put both types of plants in glass tubes and then added either benzene or chloroform gas into each tube. Over 11 days, they tracked how the concentration of each pollutant changed in each tube.

Findings showed that for the unmodified plants, the concentration of either gas did not change over time. 

However, for the modified plants, the concentration of chloroform dropped by 82 per cent after three days, and it was almost undetectable by day six. 

In addition, the concentration of benzene also decreased in the modified plant vials by about 75 per cent.

"If you had a plant growing in the corner of a room, it will have some effect in that room. But without air flow, it will take a long time for a molecule on the other end of the house to reach the plant," the Prof. noted. 

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Scientists may have found potential treatment for leukaemia

Some scientists have identified a molecule that can be targeted to cure leukaemia -the most common form of cancer in childhood.

The therapy is similar to but distinct from CD19-targeted chimeric antigen receptor T-cell therapy, or CAR T-cell therapy, in which a patient's T cells are genetically modified to target a molecule called CD19 on the surface of the cancer cells.

This therapy was recently approved by the govenment for the treatment of some types of blood cancers, according to a study.

The therapy genetically modifies a patient's T cells to target a different molecule called CD22, scientists  said.

The approach is helpful because the cancer cells of some patients who undergo CD19-targeted CAR T-cell therapy stop expressing the CD19 molecule on their cell surfaces.

CAR T-cell therapy relies on a patient's own T cells – a type of immune cell that can be a powerful killing machine.

Fifteen of the 21 patients in the study had previously either relapsed or failed to respond to anti-CD19 CAR T-cell treatment.

At the lowest dose level, one in six patients achieved complete remission after treatment with the anti-CD22 CAR T cells.

However, when the researchers escalated the dose to the next level in the study, 11 of 15 patients, or 73 per cent, entered remission.

They hope that targeting CD19 and CD22 simultaneously may result in a powerful therapy - one that cancer cells are unable to evade.

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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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