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By Michael Greenwood, M.Sc. Reviewed by Danielle Ellis, B.Sc.

Enzymes in cancer diagnosis
Enzymes in cancer therapy
References
Further reading

Enzymes are proteins that facilitate biochemical reactions by acting as a catalyst, and thus, their expression and activity have a strong influence on the reactions taking place within cells. As enzymes are involved at every stage of cell regulation, a better understanding of their role and function allows them to be exploited in the clinic, both as diagnostic and therapeutic agents.

Image Credit: Design_Cells/Shutterstock.com Enzymes in cancer diagnosis

Metabolic changes within cells are a hallmark of cancer, where genetic aberrations reduce or enhance the generation of enzymes and their metabolic products. This has allowed enzymes to be utilized as cancer biomarkers, providing a diagnostic and prognostic marker that clinicians may use to characterize a tumor.

Enzymes were among the first biomolecules utilized as cancer biomarkers, with the serine protease prostate-specific antigen (PSA) identified as a prognostic tool for prostate cancer in the 1980s. PSA is produced by the secretory cells that line the prostate glands and eventually reach the sera. Higher PSA in the blood is a result of greater numbers of more densely packed cells in the prostate, indicative of malignant cancer.

Similarly, numerous enzyme-related biomarkers for ovarian cancer have also been identified, such as the downregulation of apolipoprotein A1 and the downregulation and truncation of transthyretin.

The protein products of enzyme interactions can also be used in cancer diagnosis in the study of the proteome. The proteome consists of a large number of low and ultra-low molecular-weight protein fragments and is a rich source of information regarding the state of the cell. The proportion of specific low-molecular-weight proteins in a cell can be used to infer the activity and number of enzymes, which might otherwise be hard to distinguish from the many other proteins in the cell.

Enzymes are additionally useful in biomolecule identification and cancer diagnosis as an analytical tool in the form of the enzyme-linked immunosorbent assay (ELISA). ELISA can indicate the bonding of a target molecule colorimetrically or fluorimetrically, exploiting the highly specific binding of enzymes. Enzymes in cancer therapy

Besides their use in cancer diagnosis, enzymes are also involved in cancer therapy, both as targets of therapeutic methods and as a therapeutic tool. For example, where an abundance of enzymes induced by dysregulated genetic transcription is causing the cancer cell to proliferate more quickly, drugs can be used to target and thus regulate the population of this enzyme, slowing the spread of cancer. Alternatively, where the absence of a particular enzyme is encouraging cancer-like behavior, introducing therapeutic enzymes can help control the proliferation of a tumor. Related StoriesMetabolic syndrome linked to higher pancreatic cancer risk, study showsNew drug combo shows promise in targeting RAS-mutant multiple myelomaNew study challenges "gold standard" opioid treatment for cancer pain

Administration of pro-enzymes trypsinogen and chymotrypsinogen A have demonstrated potent anti-tumor effects against a range of cell lines while limiting angiogenesis, growth, and migration. It is thought that the primary influence of these pro-enzymes is to encourage the breakdown of filamentous protein structures that grow quickly to supply the tumor with blood. Enzymes have also been used to enhance the effect of other therapeutic efforts. For example, uridine diphospho-glucuronosyltransferase (UGT) enzymes are found in the cytosol and are involved in the glucuronidation reaction, often used to remove cellular pollutants from the cytosol.

In various cancer states, upregulation of UGT is observed, which can limit the function of the anti-cancer drug irinotecan. UGT enzyme inhibitor drugs (vorinostat) have been applied to patients exhibiting high levels of UGT enzymes, demonstrating a return of efficacy of chemotherapy.

The manipulation of metabolic pathways by the inhibition of enzymes is the goal of numerous therapeutic strategies. One pathway of particular interest to cancer treatment is the management of reactive oxygen species (ROS). ROS are essential to multiple cell signaling pathways, but high concentrations of ROS can be damaging to surrounding biomolecules and induce genetic mutation and apoptosis.

Poor blood flow and acidic conditions within tumors promote the generation of ROS, and many chemo- and radiotherapeutic approaches directly induce the generation of ROS in both target and non-target cells, causing the death of cancer cells but also severe side effects. Cellular antioxidant and ROS-generating enzymes can also be damaged by the cancer therapy applied or the resulting increase in ROS concentration, further destabilizing the dynamics of ROS control within cells.

The Monoamine oxidase A (MAO-A) enzyme is involved in ROS regulation and is commonly up or downregulated in tumors. High expression of the MAO-A has been associated with poor clinical outcomes in prostate cancer patients, associated with excessive ROS concentrations. Drug inhibition of MAO-A has been found to eliminate tumor growth and metastasis in some mouse models, limiting the spread of cancer by modulating ROS generation. References Liang and Chan (2007) Enzymes and Related Proteins as Cancer Biomarkers: a Proteomic Approach. Clin Chim Acta.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104743/ Wu and Qu (2012) Cancer Biomarker Detection: Recent Achievements and Challenges. RSC.
https://pubs.rsc.org/en/content/getauthorversionpdf/c4cs00370e Peran et al. (2017) A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer. Scientific reports.
https://www.nature.com/articles/s41598-017-14571-x Pathania et al. (2018) Drug metabolizing enzymes and their inhibitors' role in cancer resistance. Biomedicine & pharmacotherapy.
https://www.sciencedirect.com/science/article/pii/S0753332218317050 Liu et al. (2018) Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer. Oncology letters.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778774/

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Last Updated: Dec 14, 2023

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Entertainment

BBC and Channel 4 should ‘merge’ to survive, Sir Phil Redmond says

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BBC and Channel 4 should 'merge' to survive, Sir Phil Redmond says

One of Britain’s most legendary TV dramatists, Sir Phil Redmond, is no stranger to tackling difficult issues on screen.

Courting controversy famously with his hard-hitting storylines on his children’s show Grange Hill for the BBC in 1978, before he switched over to Channel 4 to give it its two most prominent soaps, Brookside (1982) and later Hollyoaks (1995).

He’s been a pivotal figure at Channel 4 from its inception, widely considered to be a father to the channel.

Sir Phil Redmond says the BBC and Channel 4 should team up to survive
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Sir Phil Redmond says the BBC and Channel 4 should team up to survive

While he’s been responsible for putting some of TV’s most impactful storylines to air for them – from the first lesbian kiss, to bodies buried under patios – off-screen nowadays, he’s equally radical about what should happen.

“Channel 4’s job in 1980 was to provide a platform for the voices, ideas, and people that weren’t able to break through into television. They did a fantastic job. I was part of that, and now it’s done.”

It’s not that he wants to kill off Channel 4 but – as broadcasting bosses gather for Edinburgh’s annual TV Festival – he believes they urgently should be talking about mergers.

A suggestion which goes down about as well as you might imagine, he says, when he brings it up with those at the top.

He laughs: “The people with the brains think it’s a good idea, the people who’ve got the expense accounts think it’s horrendous.”

Some of the original Grange Hill cast collecting a BAFTA special award in 2001. Pic: Shutterstock
Image:
Some of the original Grange Hill cast collecting a BAFTA special award in 2001. Pic: Shutterstock

A ‘struggling’ BBC trying to ‘survive’

With charter renewal talks under way to determine the BBC’s future funding, Sir Phil says “there’s only one question, and that is what’s going to happen to the BBC?”

“We’ve got two public sector broadcasters – the BBC and Channel 4 – both owned by the government, by us as the taxpayers, and what they’re trying to do now is survive, right?

“No bureaucracy ever deconstructs itself… the BBC is struggling… Channel 4 has got about a billion quid coming in a year. If you mix that, all the transmissions, all the back office stuff, all the technical stuff, all that cash… you can keep that kind of coterie of expertise on youth programming and then say ‘don’t worry about the money, just go out and do what you used to do, upset people!’.”

Brookside's lesbian kiss between Margaret and Beth (L-R Nicola Stapleton and Anna Friel) was groundbreaking TV. Pic: Shutterstock
Image:
Brookside’s lesbian kiss between Margaret and Beth (L-R Nicola Stapleton and Anna Friel) was groundbreaking TV. Pic: Shutterstock

How feasible would that be?

Redmond claims, practically, you could pull it off in a week – “we could do it now, it’s very simple, it’s all about keyboards and switches”.

But the screenwriter admits that winning people over mentally to his way of thinking would take a few years of persuading.

As for his thoughts on what could replace the BBC licence fee, he says charging people to download BBC apps on their phones seems like an obvious source of income.

“There are 25 million licences and roughly 90 million mobile phones. If you put a small levy on each mobile phone, you could reduce the actual cost of the licence fee right down, and then it could just be tagged on to VAT.

“Those parts are just moving the tax system around a bit. [then] you wouldn’t have to worry about all the criminality and single mothers being thrown in jail, all this kind of nonsense.”

Original Brookside stars at BAFTA - L:R: Michael Starke, Dean Sullivan, Claire Sweeney and Sue Jenkins. Pic: PA
Image:
Original Brookside stars at BAFTA – L:R: Michael Starke, Dean Sullivan, Claire Sweeney and Sue Jenkins. Pic: PA

‘Subsidising through streaming is not the answer’

Earlier this year, Peter Kosminsky, the director of historical drama Wolf Hall, suggested a levy on UK streaming revenues could fund more high-end British TV on the BBC.

Sir Phil describes that as “a sign of desperation”.

“If you can’t actually survive within your own economic basis, you shouldn’t be doing it.

“I don’t think top slicing or subsidising one aspect of the business is the answer, you have to just look at the whole thing as a totality.”

Mark Rylance (L) and Damian Lewis in Wolf Hall: The Mirror And The Light. Pic: BBC
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Mark Rylance (L) and Damian Lewis in Wolf Hall: The Mirror And The Light. Pic: BBC

Since selling his production company, Mersey Television, two decades ago, much of his current work has focused on acting as an ambassador for the culture and creative industries.

Although he’s taken a step away from television, he admits he’s disappointed by how risk-averse programme makers appear to have become.

“Dare I say it? There needs to be an intellectual foundation to it all.”

The Hollyoaks cast in 1995. Pic: Shutterstock
Image:
The Hollyoaks cast in 1995. Pic: Shutterstock

TV’s ‘missing a trick’

He believes TV bosses are too scared of being fined by Ofcom, and that’s meant soaps are not going as far as they should.

“The benefits [system], you know, immigration, all these things are really relevant subjects for drama to bring out all the arguments, the conflicts.

“The majority of the people know the benefits system is broken, that it needs to be fixed because they see themselves living on their estate with a 10 or 12-year-old car and then there’s someone else down the road who knows how to fill a form in, and he’s driving around in a £65k BMW, right? Those debates would be really great to bring out on TV, they’re missing a trick.”

While some of TV’s biggest executives are slated to speak at the Edinburgh Television Festival, Redmond is not convinced they will be open to listening.

“They will go where the perceived wisdom is as to where the industry is going. The fact that the industry is taking a wrong turn, we really need somebody else to come along and go ‘Oi!'”

When I ask if that could be him, he laughs. Cue dramatic music and closing credits. As plot twists go, the idea of one of TV’s most radical voices making a boardroom comeback to stir the pot, realistic or not, is at the very least food for thought for the industry.

Edinburgh TV Festival runs from 19 – 22 August.

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Noel Gallagher praises ‘amazing’ Liam for Oasis reunion tour

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Noel Gallagher praises 'amazing' Liam for Oasis reunion tour

Noel Gallagher has said he is “proud” of his brother Liam after the pair reunited for this summer’s Oasis Live ’25 tour.

The highly anticipated reunion was announced in August last year, after the brothers seemingly put the feud which led to their split in 2009 behind them.

At the time, Noel said he “simply could not go on working with Liam”, but having just completed the UK-leg of their comeback tour, he has nothing but praise for his younger sibling.

“Liam’s smashing it. I’m proud of him,” Noel told talkSport in his first interview since the tour began.

“I couldn’t do the stadium thing like he does it, it’s not in my nature. But I’ve got to say, I kind of look and I think ‘good for you, mate’. He’s been amazing.

“It’s great just to be back with Bonehead [Paul Arthurs] and Liam and just be doing it again.”

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‘We need each other’: Oasis back on stage

When asked if he has felt emotional during the tour, Noel added: “I guess when it’s all said and done we will sit and reflect on it, but it’s great being back in the band with Liam, I forgot how funny he was.”

He went on to say he was “completely blown away” after the band’s opening night in Cardiff, and “grossly underestimated” what he was getting himself into when first signing up for the shows.

Fans in Manchester don Oasis merch. Pic: Reuters
Image:
Fans in Manchester don Oasis merch. Pic: Reuters

The brothers at Wembley, London. Pic: Lewis Evans
Image:
The brothers at Wembley, London. Pic: Lewis Evans

He said: “It was kind of after about five minutes, I was like, ‘all right, can I just go back to the dressing room and start this again?’

“I’ve done stadiums before and all that, but I don’t mind telling you, my legs had turned to jelly after about halfway through the second song.”

Pic: Big Brother Recordings
Image:
Pic: Big Brother Recordings

“Every night is the crowd’s first night, you know what I mean?” he continued. “So every night’s got that kind of same energy to it, but it’s been truly amazing. I’m not usually short for words, but I can’t really articulate it.”

Having played to packed crowds in Cardiff, London, Manchester, Dublin and Edinburgh, Oasis have scheduled dates around the world including in major cities across the US, Canada, Mexico, Australia, and Japan.

Read more:
Oasis photographers remember the early days
Wembley investigating smuggling claims at Oasis gig

It’s rumoured the band will continue their run of shows next year, when it marks 30 years since they played two sell-out nights at Knebworth Park to an estimated 250,000 people.

When quizzed on the rumours on talkSport, Noel quickly changed the subject, saying: “Right, let’s talk about football.”

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Labour smell dirty tricks over asylum hotel court ruling – but the risks are clear

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Labour smell dirty tricks over asylum hotel court ruling - but the risks are clear

“It’s an interesting moment,” was how one government source described the High Court ruling that will force an Essex hotel to be emptied of asylum seekers within weeks.

That may prove to be the understatement of the summer.

For clues as to why, just take a glance at what the Home Office’s own lawyer told the court on Tuesday.

Granting the injunction “runs the risk of acting as an impetus for further violent protests”, the barrister said – pointing out that similar legal claims by other councils would “aggravate pressures on the asylum estate”.

Right on cue and just hours after the ruling came in, Broxbourne Council – over the border in Hertfordshire – posted online that it was urgently seeking legal advice with a view to taking similar court action.

The risks here are clear.

Police officers ahead of a demonstration outside The Bell Hotel. Pic: PA
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Police officers ahead of a demonstration outside The Bell Hotel. Pic: PA

Recent figures show just over 30,000 asylum seekers being housed in hotels across the country.

If they start to empty out following a string of court claims, the Home Office will struggle to find alternative options.

After all, they are only in hotels because of a lack of other types of accommodation.

There are several caveats though.

This is just an interim injunction that will be heard in full in the autumn.

So the court could swing back in favour of the hotel chain – and by extension the Home Office.

Read more:
Who says what on asylum hotels?

Protesters in Epping on 8 August. Pic: Reuters
Image:
Protesters in Epping on 8 August. Pic: Reuters

We have been here before

Remember, this isn’t the first legal claim of this kind.

Other councils have tried to leverage the power of the courts to shut down asylum hotels, with varying degrees of success.

In 2022, Ipswich Borough Council failed to get an extension to an interim injunction to prevent migrants being sent to a Novotel in the town.

As in Epping, lawyers argued there had been a change in use under planning rules.

The hotel has been the scene of regular protests. Pic: PA
Image:
The hotel has been the scene of regular protests. Pic: PA

But the judge eventually decided that the legal duty the Home Office has to provide accommodation for asylum seekers was more important.

So there may not be a direct read across from this case to other councils.

Home Office officials are emphasising this injunction was won on the grounds of planning laws rather than national issues such as public order, and as such, each case will be different.

Failing Labour approach or Tory tricks?

But government sources also smell dirty tricks from Epping Council and are suggesting that the Tory-led local authority made the legal claim for political reasons.

Pointing to the presence of several prominent Tory MPs in the Essex area – as well as the threat posed by Reform in the county – the question being posed is why this legal challenge was not brought when asylum seekers first started being sent to the hotel in 2020 during the Conservatives‘ time in government.

Epping Council would no doubt reject that and say recent disorder prompted them to act.

But that won’t stop the Tories and Reform of seizing on this as evidence of a failing approach from Labour.

So there are political risks for the government, yes, but it’s the practicalities that could flow from this ruling that pose the bigger danger.

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