Tag: cancer

Categories : Cancer GenderTags :

Stronger Immune Systems in Women Protect against Skin Cancer

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Photo by rfstudio on Pexels

Women may have a stronger immune response to a common form of skin cancer than men, according to a preliminary study on mice and human cells.

Men develop more skin squamous cell carcinoma (cSCC) than females and their tumours are more aggressive, though it is not clear if this is related to sunlight exposure. Using mouse models to answer the question, they found that male mice developed more aggressive tumours than females, despite receiving identical treatments.

In female mouse skin and tumours, the immune cell infiltration and gene expression related to the anti-cancer immune system were increased, suggesting a protective effect of the immune system.

In keeping with the animal study, 931 patient records collected from four hospitals in Manchester, London and France, the researchers identified that while women commonly have a more mild form of cSCC compared to men, immunocompromised women developed cSCC in a way more similar to men

That suggests the protective effect of their immune system may have been compromised.

These results were confirmed in a further cohort of sun-damaged skin from the US. In this cohort, human epidermal cells confirmed women’s skin activated immune-cancer fighting pathways and immune cells at sites damaged by sunlight.

The US cohort also that showed CD4 and CD8 T cells, which are important in our immune response to skin cancer, were twice as abundant in women as in men.

The researchers used RNA sequencing to examine differences in male and female immunosuppressed mice and human skin cells.

“It has long been assumed that men are at higher risk of getting non-melanoma skin cancer than women” said Dr Amaya Viros, from The University of Manchester.

“Other life-style and behavioural differences between men, such as the type of work or exposure to the sun are likely to be significant.

“However, we also identify for the first time the possible biological reasons, rooted in the immune system, which explains why men may have more severe disease.

“Although this is early research, we believe the immune response is sex-biased in the most common form of skin cancer, and highlights that female immunity may offer greater protection than male immunity.”

Dr Viros added: “We can’t yet explain why women have a more nuanced immune system than men.

“But perhaps it’s reasonable to speculate that women’s evolutionary ability to carry an unborn child of foreign genetic material may require their immunological system to be very finely tuned and have unique skills.

“Very little is known about how sex differences affect incidence and outcome in infectious diseases, autoimmune disorders and cancer. More work needs to be done. But we feel this study has opened a window into this area, and could one day have important implications on other types of immunologically based diseases.

“And it suggests if doctors are to offer personalised treatment of cancer, then biological sex should be one of the factors they take into account.”

Commenting on the study, Dr Samuel Godfrey, Research Information Manager at Cancer Research UK said: “Research like this chips away at the huge question of why people respond to cancer differently. Knowing more about what drives immune responses to cancer could give rise to new treatment options and show us a different perspective on preventing skin cancer.”

Source: Medical Xpress

Journal information: Timothy Budden et al, Female Immunity Protects from Cutaneous Squamous Cell Carcinoma, Clinical Cancer Research (2021). DOI: 10.1158/1078-0432.CCR-20-4261

Categories : Cancer Immune SystemTags :

Study Reveals Natural Killer Cells’ Fuel Source

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Pictured is a false-colour scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Photo by National Cancer Institute on Unsplash

Scientists have discovered how natural killer (NK) cells fuel their activities when fighting infections, which will in turn help inform the development of immune therapies.

When it comes to dealing with infections and cancer, if T cells are like a team of specialist doctors in an emergency room, then NK cells are the paramedics: They arrive first on the scene and perform damage control until reinforcements arrive. Their existence was revealed in the 1970s when scientists were trying to characterise T cell cytotoxicity.

NK cells belong to our innate immune system, which dispatches these first responders, and they come with a built-in ability to recognise and respond to danger. Learning what powers NK cells is an ongoing area of immunology research, with important clinical implications.

“There’s a lot of interest right now in NK cells as a potential target of immunotherapy,” said Joseph Sun, an immunologist in the Sloan Kettering Institute. “The more we can understand what drives these cells, the better we can program them to fight disease.”

First responders

Previous studies have shown that aerobic glycolysis provides the energy for T cells to carry out their protective activities. But it was not known whether NK cells use this form of metabolism in performing their functions.

Dr Sun and his colleagues studied NK cells in animal models instead of in vitro, in order to find out, in a natural setting, what type of metabolism NK cells use and compare it to T cells. They discovered that NK cells increase aerobic glycolysis about five days before T cells respond with their own glycolytic surge.

“This fits with the idea that NK cells are innate immune cells that are really critical for mounting a rapid response,” said Research Fellow Sam Sheppard.

The findings are relevant to ongoing efforts to use NK cells as immunotherapy in people with cancer and other conditions. These are particularly relevant for procedures that make use of NK cells as a form of cell therapy—when cells are grown outside the body and then introduced back into the patient.

Finding a delicate balance

“If you’re growing these cells in a dish and you push them to divide too rapidly, they may not have as much potential to undergo aerobic glycolysis when you put them into a patient,” Dr Sheppard explained.

For researchers designing clinical trials, the goal is to find a balance between encouraging NK cells to multiply and preserving their stamina. These NK cells are the paramedics of our immune system, so it’s important to keep them speedy and responsive.

The findings were reported June 1, 2021, in the journal Cell Reports.

Source: Eureka Alert

Categories : Cancer Immune SystemTags :

Surprising Mechanism of Action Discovered for Stem Cell Drugs

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Two cytotoxic T cells (red) attacking an oral squamous cancer cell. Photo by National Cancer Institute on Unsplash

A new study revealed surprising insights into how specialised drugs that regenerate immune cells lost to chemotherapy actually work. 

In cancer patients following chemotherapy, there is a decrease in immune cells because chemotherapy also impacts the stem cells in bone marrow, which were meant to develop into new immune cells. This means that the immune system is then left short of immune cells to fight new infections.

Certain drugs exist, such as plerixafor, that can stimulate the release of stem cells from the bone marrow into the blood stream, so that they can be harvested and then reintroduced into the patients after treatment. These stem cells develop into new immune cells, bolstering the immune system. However, there was a lack of detailed knowledge of how these drugs actually worked.

Now, a study conducted in mice by researchers at the University of Copenhagen demonstrates how the medicine works at the cell level—and, surprisingly, how plerixafor, one of the two applied and tested drugs, is more effective than the other, despite the fact that the other drug, on paper, appears to be the most effective of the two. This discovery may not just help improve stem cell transplantation; it may also lead to improved drugs in the future.

“We have tested two drugs for stem cell transplantation which appear to have the same effect. What they do is block a receptor, causing the bone marrow to release stem cells into the blood. What the new study shows, though, is that they do not just block the receptor; one of the two drugs also affects other signaling pathways in the cell. And in short, that makes it more effective than the other of the two drugs,” explained PhD student Astrid Sissel Jørgensen from the Department of Biomedical Sciences at the University of Copenhagen.

“We used to believe that all we had to do was block the receptor, and that the two drugs had the same effect. It now appears that there is more to it,” she said.

The drugs tested by the researchers mobilise stem cells by acting as CXCR4 receptor antagonists. There are several drugs that target this receptor, including drugs inhibiting HIV replication.

“The drugs not only block the receptor’s normal signaling. One of the two drugs we have tested also affect some of the other cell pathways and even make the receptor withdraw into the cell and disappear from the surface,” explained corresponding author Professor Mette Rosenkilde. The study results revealed that one of the two drugs makes the bone marrow release more stem cells into the blood.

These findings on how the drugs affect cell pathways differently is also known as biased signalling. Mechanisms like these are what make the one drug more effective in practice than on paper, and they challenge the current view of these drugs.

“The results of our study directly influence our view of drugs used for stem cell transplantation. In the long term, though, it may also affect our view of future drugs, and how new drugs should be designed to have the best possible effect, both in connection with stem cell mobilisation, but also for treating HIV infections, where this particular receptor also plays a main role,” said Prof Rosenkilde.

Source: Medical Xpress

Journal information: Astrid S. Jørgensen et al, Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization, Communications Biology (2021). DOI: 10.1038/s42003-021-02070-9

Categories : Cancer GeneticsTags :

New Study Finds Genetic Switch Role in Melanoma

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The ability of cancer cells to move and spread depends on actin-rich core structures such as the podosomes (yellow) shown here in melanoma cells. Cell nuclei (blue), actin (red), and an actin regulator (green) are also shown. Source: National Cancer Institute
Metastatic melanoma cells

A study published in the journal Cell Reports reveals that a genetic switch that could potentially be targeted to develop new treatments for melanoma by keeping the switch turned off.

Melanoma causes the majority of skin cancer-related deaths, despite only making up roughly 1 percent of skin cancers. The incidence of malignant melanoma is rapidly increasing around the world, and this increase is occurring at a faster rate than that of any other cancer except lung cancer in women. Treatments exist for this serious disease, but the effectiveness of these drugs can vary depending on the individual.

“We’ve been able to correlate the activity of this genetic switch to melanin production and cancer,” said Salk study corresponding author Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology.

Melanoma develops when melanocytes, the pigment-producing skins in the cell, mutate and begin to multiply out of control. These mutations can cause proteins such as CRTC3 to prompt the cell to produce an abnormal amount of pigment, or to migrate and be more invasive.

While it was known that the CRTC family of proteins (CRTC1, CRTC2, and CRTC3) is involved in pigmentation and melanoma, obtaining precise details about the individual proteins has proven difficult. “This is a really interesting situation where different behaviours of these proteins, or genetic switches, can actually give us specificity when we start thinking about therapies down the road,” said first author Jelena Ostojic, a former Salk staff scientist and now a principal scientist at DermTech.

When the researchers deleted the CRTC3 gene in mice caused a color change in the animal’s coat color, demonstrating that the protein is needed for melanin production. They also found that when melanoma cells lacked the protein, they migrated and invaded less, meaning they were less aggressive, suggesting that inhibiting the protein could help treat the disease.

The team also described the connection between two cellular signalling systems that work on the CRTC3 protein in melanocytes. These two systems tell the cell to either proliferate or make the pigment melanin. Montminy likens this process to a relay race: essentially, a baton (chemical message) is passed from one protein to another until it reaches the CRTC3 switch, either turning it on or off.

“The fact that CRTC3 was an integration site for two signaling pathways—the relay race—was most surprising,” says Montminy, who holds the J.W. Kieckhefer Foundation Chair. “CRTC3 makes a point of contact between them that increases specificity of the signal.”

Next, the team plans to further investigate the mechanism of how CTRC3 impacts the balance of melanocyte differentiation to develop a better understanding of its role in cancer.

Source: Salk Institute

Categories : CancerTags :

Cells in the Centres of Kidney Tumours are The Most Aggressive

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Researchers have found that cells from different parts of kidney tumours behave differently, and cells within the centre of a tumour are the most aggressive and most likely to spread around the body.

Metastasis, where cancer cells from tumours spread to other parts of the body, is the main cause of death in cancer patients. 

In this multidisciplinary study published in Nature Ecology and Evolution, scientists analysed 756 cancer biopsy samples from different regions within tumours from the TRACERx Renal study.

They discovered that, in contrast to the cells at the outside of tumours, the cells in the centres of tumours have more unstable genomes, and a higher potential for metastasis. The cells on the outside had lower growth rates and had less genetic damage.

“Cancer cells in the central zone of the tumour face harsh environmental conditions, as there’s a lack of blood supply and oxygen. They have to adapt to survive, which makes them stronger and more aggressive. This also means they are more likely to successfully evolve into cells that can disseminate and take hold in distant organs,” explained Kevin Litchfield, paper author and group leader at the UCL Cancer Institute.

These findings show that it is important to focus on the tumour centre for a better understanding of how cancer spreads, and identify the most dangerous cells. Also, in order to wipe out the most aggressive tumour cells, treatment development must target the unique environmental conditions found within the tumour core.

The scientists also examined how genetically different populations of cancer cells grow within a tumour. With a unique mapping tall that reconstructed the growth of tumour cells, they discovered that, while tumours tend to follow a pattern where populations of cells grow in the local area, in two cases, cells took hold in a new region of the tumour by seemingly ‘jumping’ over other populations of tumour cells.

For their next steps, the researchers aim to reconstruct 3D tumour maps, providing even better visualisation of the tumours’ internal structure.

Samra Turajlic, head of the Crick’s Cancer Dynamics Laboratory, Consultant Medical Oncologist at the Royal Marsden NHS Foundation Trust and the Chief Investigator of TRACERx Renal, said: “Cancer spread is one of the biggest barriers to improving survival rates. In the context of the TRACERx Renal study we previously resolved the genetic make up of different tumour areas, but until now, there has been no understanding of how these differences relate spatially. The most critical question is the part of the tumour from which cancer cells break away and migrate making cancer incurable.

“Using this unique clinical cohort and a multidisciplinary approach, including mathematical modeling, we identified with precision the place in the tumour where genetic chaos emerges to give rise to metastases. Our observations shed light on the sort of environmental conditions that would foster emergence of aggressive behaviour. These findings are a critical foundation for considering how we target or even prevent distinct populations of cells that pose the biggest threat.”

Source: Francis Crick Institute

Categories : Cancer Metabolic DisordersTags :

Rise in Obesity Impeding Cancer Fight

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Though cancer death rates have fallen dramatically in the United States, those from obesity-related cancers are falling much more slowly.

In a study published this week in JAMA Network Open, researchers found that obesity-related cancer deaths are improving, but at a slowing pace.

Researchers at the University of North Carolina Gillings School of Global Public Health drew on mortality data for 50 million people, cancer deaths not associated with obesity — such as lung or skin cancer – are declining at a rate almost three times faster than obesity-related cancers, such as stomach, colorectal, uterine, thyroid and postmenopausal breast cancer.

“These are cancers where we could see even larger mortality improvements with creative and practical tools to combat obesity,” said study senior author Hazel B Nichols, PhD, associate professor in the Department of Epidemiology at the UNC Gillings School.

Most Americans are over the recommended body weight, and being overweight or obese puts them at risk for certain cancers.  

Extra body fat can lead to changes in the body that can contribute to cancer development, such as long-lasting inflammation and higher than normal levels of insulin and hormones that can fuel cell growth, according to the U.S. Centers for Disease Control and Prevention.

Discordant progress

Researchers use cancer death rates to track progress against cancer over time. The study authors set out to find out if obesity was stalling progress against cancer the way it did against heart disease. After 2011, heart disease mortality rates slowed their decline, a phenomenon which may be due to obesity.

“What was puzzling was that we didn’t see the same pattern of slower improvements when looking at cancer overall, which is surprising because obesity contributes to both cancer risk and heart disease risk,” said Dr Nichols. “When we focused on the differences between obesity-related cancers and non-obesity related cancers, we saw that improvements for obesity cancers were not as impressive — consistent with the pattern for heart disease.”

For example, the study showed that in 2011, 110 people out of 100 000 died from cancers not related to obesity. In 2018, the mortality rate for those cancers fell to 93.8 deaths per 100 00 people — a 2.29% annual decline.

During the same period, the decline for obesity-related cancers was much slower, changing from 58.4 to 54.9 deaths per 100 000 people, a rate of .83% — a rate one-third the decrease in non-obesity related cancers.

Obesity may also be contributing to more of the cancer deaths in the US. The study found that cancers not associated with obesity accounted for 66.8% of cancer deaths in 1999, decreasing to 62.6% in 2018.
The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation. Christy Leigh Avery, PhD

Falls in cancer deaths are the result of fewer smokers, along with better screening and treatments, according to the American Cancer Society.

But the findings by UNC researchers reinforce the impact of obesity on cancer. 

“Obesity is a risk factor for many, but not all, types of cancer,” Nichols Dr said. “We need to make maintaining a healthy weight an obtainable goal for everyone in terms of safe public spaces, the availability and affordability of nutritious foods, and other structural factors. The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation.”

Source: University of North Carolina

Journal information: Avery CL, Howard AG, Nichols HB. Comparison of 20-Year Obesity-Associated Cancer Mortality Trends With Heart Disease Mortality Trends in the US. JAMA Netw Open. 2021;4(5):e218356. doi:10.1001/jamanetworkopen.2021.8356

Categories : Cancer GeneticsTags :

Oesophageal Cancer Unleashes ‘Fossil Viruses’ Hidden in Human DNA

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Colorectal cancer cells. Photo by National Cancer Institute on Unsplash.

Scientists have discovered that many oesophageal cancers turn on ancient viral DNA that was embedded in our genome hundreds of millions of years ago.

“It was surprising,” said principal investigator Adam Bass, MD, the Herbert and Florence Irving Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center. 

“We weren’t specifically searching for the viral elements, but the finding opens up a huge new array of potential cancer targets that I think will be extremely exciting as ways to enhance immunotherapy.”

The idea that bits of ancient retroviruses within the human genome—known as endogenous retroviral elements, or ERVs—play a role in cancer is not new. About 8% of our genome is made up of these remnants of viral infections that have accumulated over the last 100 million years. While ERV sequences have degraded over the aeons and cannot produce viral particles, the viral fossils sometimes wind up inside other genes, disrupting their normal activities, or act as switches that turn on cancer-causing genes.

Recent research however shows that ERVs may also have a cancer fighting role if they are transcribed into strands of RNA.

“When cells activate lots of ERVs, a lot of double-stranded RNA is made and gets into the cell cytoplasm,” Dr Bass explained. “That creates a state that’s like a viral infection and can cause an inflammatory response. In that way, ERVs may make the cancer more susceptible to immunotherapy, and many researchers are working on ways to trick cancer cells into activating ERVs.”

In the new study, Bass and colleagues created organoids of oesophageal mouse tissue to follow the development of cancer from normal cells to malignancy.

With these organoids, Bass discovered that a specific cancer-promoting gene in oesophageal cancers called SOX2 triggers the expression of many ERVs.  

As ERV expression and the accumulation of double-stranded RNAs that can result can be toxic to cells, the researchers found that there is a specific enzyme called ADAR1 that rapidly degrades these double-stranded RNAs.

ADAR1 has been implicated in oesophageal cancer by other researchers, although its role had been unclear. Levels of ADAR1 are known to correlate with poor survival. “The cancers are dependent on ADAR1 to prevent an immune reaction that can be very toxic to the cells,” Bass says.

Some patients with oesophageal cancer are currently treated with immunotherapy, which has been shown to increase survival by several months. “We have a lot of enthusiasm that blocking ADAR1 may both have direct efficacy for oesophageal cancers and that ADAR1 inhibition may have even great effects by enhancing the efficacy of cancer immunotherapy in patients with oesophageal cancer,” Bass said.

Beyond the results regarding ADAR1 and ERVs, the process of modelling the development of oesophageal cancer via genomic engineering of organoids also uncovered a variety of other processes in oesophageal cancer that could help develop new therapies.

“The way we used organoids to build cancers up from the normal cell is a powerful system for uncovering cancer-causing activities and testing therapeutic targets,” said Bass. “By making individual genome alterations in these models one at a time, we can see which combinations of genetic alterations lead to cancer and then determine specific mechanisms of tumor formation.”

In this study, the organoids started with overexpression of the SOX2 gene, a commonly amplified factor that promotes the development of squamous cancers.

In the study, Dr Bass’ team built a panel of organoids emulating conditions ranging from normal oesophagus to fully transformed cancer.

By comparing normal and cancerous organoids, the team could dissect how the activity of SOX2 differs in normal and cancerous tissues. “It’s important to understand the difference, since potential treatments need to target the cancer functions but have lesser impact upon normal tissue,” he says. “It’s relatively easy to kill cancer cells. The problem is, how do you kill cancer cells but spare other cells?”

Results from the organoids showed that when SOX2 is overactive—and two tumour suppressors are inactivated—SOX2 interacts with other factors, activating an array of cancer-causing genes in addition to their effects upon induction of ERVs.  

“These findings reveal new vulnerabilities in SOX2 oesophageal cancers,” Bass said, “that will now allow us to begin developing therapies that can precisely target the cancer cell and improve the treatment of patients.”

Source: Columbia University Irving Medical Center

Journal information: Zhong Wu, et al. Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nature Genetics, 2021; DOI: 10.1038/s41588-021-00859-2

Categories : Cancer New Compounds and TreatmentsTags :

Lenvatinib Produces Impressive Results Against Tough Tumours

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Image by doodlartdotcom from Pixabay

Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI) induced a strong tumour response in patients with advanced gastrointestinal or pancreatic tumours, according to results from a phase II trial.

The study focused on previously treated advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). An overall response rate (ORR) of 29.9% was seen in the trial, with a particularly high ORR — 44.2% — in patients with pancreatic NETs. 

“This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other targeted agents, suggesting the potential value in the treatment of advanced GEP-NETs,” wrote Jaume Capdevila, MD, PhD, of Vall Hebron University Hospital in Barcelona, and colleagues.

TKIs are a group of pharmacologic agents that disrupt the signal transduction pathways of protein kinases by several modes of inhibition. Since sunitinib maleate (Sutent), another multitargeted TKI, was approved ten years ago, investigators have been evaluating newer-generation TKIs that target VEGF receptors (VEGFRs), among other receptors, both in pancreatic and non-pancreatic NETs.

Lenvatinib targets VEGFR 1-3, fibroblast growth factor receptors (FGFR) 1-4, and platelet-derived growth factor receptor alpha.

The researchers noted that studies have demonstrated its particular effectiveness against FGFR-1, which is a key driver of resistance to antiangiogenic drugs, “suggesting that it could potentially also reverse primary and acquired resistance to anti-VEGFR treatments or to other targeted agents.”

A total of 111 patients were enrolled in the study; 55 had histologically confirmed grade 1-2 pancreatic NETs, while 56 had gastrointestinal NETs. Patients were administered 24-mg lenvatinib once daily until disease progression or treatment intolerance. Median follow-up was 23 months.

The ORR was 16.4% for patients with gastrointestinal NETs, and median duration of response was 19.9 months for patients with pancreatic NETs and 33 months for gastrointestinal NETs. The median progression-free survival (PFS) for both groups was 15.7 months.

These results compare well with PFS outcomes reported in phase III trials, including those evaluating sunitinib and surufatinib, the authors noted.

“Interestingly, the ORR in pancreatic NETs was 44%, a rate not seen before with targeted agents,” Jonathan Strosberg, MD, head of the neuroendocrine tumor division at Moffitt Cancer Center in Tampa, told MedPage Today.

Dr Strosberg, who was not involved with this research, noted that the study group had been heavily treated beforehand, and that 29% had received prior sunitinib. “In contrast, the response rates with other TKIs have been <20% in this population, even in less heavily treated populations. The ORR for gastrointestinal NETs was more modest, but still impressive,” he added.

The most common grade 3/4 adverse events was hypertension (22.7%), while a majority of patients needed either a dose reduction or a pause.

“This suggests that lower starting doses might be considered in this population, and that particularly close monitoring of blood pressure is necessary,” said Dr Strosberg.

The study results “suggest that lenvatinib is more than just a ‘me-too’ competitor to sunitinib,” he noted. “It actually seems to have superior activity, potentially due to its ability to target both the VEGF and FGF receptors. Moreover, it appears to have activity in patients who have progressed on sunitinib. Randomized phase III studies with this drug are warranted, both for pancreatic and GI/lung NETs.”

Source: MedPage Today

Journal information: Capdevila J, et al “Lenvatinib in patients with advanced grade 1/2 pancreatic and gastrointestinal neuroendocrine tumors: results of the phase II TALENT trial (GETNE1509)” J Clin Oncol 2021; DOI: 10.1200/JCO.20.03368.

Categories : Cancer Diet and NutritionTags :

Could Cutting Sugary Drinks Reduce Cancer Risk in Women?

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A higher intake of sugar-sweetened beverages (SSBs) in adulthood and adolescence was linked to an increased risk of early-onset colorectal cancer (CRC) in women, according to data from a large prospective study.

The Nurses’ Health Study II followed over 95 000 registered nurses from 1991 to 2015. Those consuming at least two SSB servings a day in adulthood had more than double the early-onset CRC risk of those consuming less than one serving a week. This rose by 16% with each extra serving per day.

In the adolescent years of ages 13 to 18, each serving-per-day increment was associated with a 32% higher risk of early-onset CRC. Meanwhile, replacing each SSB serving per day for adults with a serving of a non-SSB drink was associated with a 17-36% lower risk.

“Considering the well-established, adverse health consequences of SSBs and the highest consumption being characterized in adolescents and young adults under age 50 years, our findings reinforce the public health importance of limiting SSB intake for better health outcomes,” Yin Cao, ScD, MPH, of Washington University in St. Louis, and co-researchers wrote.

Although CRC has been on the decline, the age of early onset — that is, diagnosed before age 50 — has been increasing the past two decades. In comparison to adults born around 1950, those born around 1990 had twice the colon cancer risk and four times the rectal cancer risk.

An estimated 12% of the US population currently consume more than three SSB servings per day, as shown by National Health and Nutrition Examination Survey data. SSBs in the US are often include high fructose corn syrup as an ingredient, as opposed to South Africa which uses cane sugar.

In this study, the population consisted overwhelmingly of white females, ages 25 to 42, with an average age of approximately 42 at enrollment. Over up to 24-plus years of follow-up, 109 cases of early-onset CRC were recorded.

The researchers found that those with higher SSB intakes in adulthood tended to be less physically active and more likely to have a lower endoscopy history, to use non-steroidal anti-inflammatory drugs, and consume red and processed meats. They were also less likely to take multivitamins and to have a reduced intake of alcohol, fibre, folate, and calcium, and to have a poorer diet overall.

No association was found between intake of artificially sweetened beverages or fruit juice in adulthood and risk of early-onset CRC, mirroring past research.

The investigators listed a number of possible pathways for the effect of SSBs on early-onset CRC. 

For example, compared with isocaloric solid foods, energy-containing beverages do not create a feeling of satiation, leading to weight gain. SSBs also initiate rapid blood glucose response and insulin secretion, possibly leading to insulin resistance, inflammation, obesity, and type 2 diabetes — metabolic conditions which are linked to heightened CRC risk.

Other possibilities include intestinal dysbiosis and endotoxemia caused by high fructose levels , the principal sweetener in SSBs in the US and certain other countries, which can impair gut barrier function, increasing gut permeability, and possibly promote cancer formation. A recent experimental study suggested that the high-fructose corn syrup in SSBs from the US enhanced the growth of aggressive tumours in mice, regardless of weight and metabolic syndrome.

High-fructose corn syrup has also been linked to metabolic dysregulation, regardless of obesity.

Fortunately, overall SSB intake has been trending downward in recent years, and Dr Cao and co-authors concluded that further limiting consumption may be “an actionable strategy to curb the rising incidence of [early-onset] CRC.”

Study limitations, the researchers said, included possible unknown confounding variables, the few early-onset CRC cases prevented pinpointing the window of exposure, and there weren’t enough diabetic participants to stratify by a personal history of diabetes. Since the participants were mostly white women, the results were not readily generalisable to other ethnic groups or to men.

Source: MedPage Today

Source Reference: Hur J, et al “Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women” Gut 2021; DOI: 10.1136/gutjnl-2020-323450.

Categories : CancerTags :

Nanoparticles Deliver Chemotherapy to Cancer Cell’s Doorsteps

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Fanciful depiction of nanoparticles. Photo by Landon Arnold on Unsplash

New research has developed a nanoparticle system that can deliver large, unwieldy protein-based chemotherapy drugs right to the doorsteps of cancer cells.

Some cancer treatments make use of antibodies’ ability to recognise specific cancer cells in order to target those cells with small active agents, but have not been able to deliver larger protein-based drugs.

Research published in the journal Angewandte Chemie shows how, using a new protein transport system, proteins can arrive at their target intact, protected from destructive proteases by polymer brushes.

Two problems keep coming up when scientists try to develop new anticancer drugs. Firstly, an active agent needs to be able to kill the body’s cells at the root of the cancer, and secondly it should be active in target cancer cells rather than in healthy cells. To this end, some medical researchers are  trying to implement a cargo package as a method of delivery. The active agent stays protected and packaged until it reaches the target location, while antibodies that only attach to cancer cells help with “finding the right address”. 

These antibodies recognise specific receptor structures on the outer membrane of cancer cells, attaching to these structures with the cell absorbing the active agent. However, this strategy is unsuccessful when the active agents are large proteins. 

These large proteins are usually water soluble, and unable to penetrate the cell membrane. The body’s own protease enzymes throw in another complication, because they break down the protein cargoes before they can reach their target location.

Sankaran Thayumanavan and colleagues at the University of Massachusetts in Amherst, USA, have now developed a protected nanosized cargo package, which meets both requirements of targeted delivery and keeping the cargo intact. For the container, they use miniscule beads made of silicon dioxide with a diameter of just 200 nanometres. The surface of these beads is coated with brush-like polymer strands made of polyethylene glycol (PEG) that can be doubly functionalised, giving tiny “brush beads”. This is termed a protein-antibody conjugate (PAC).

With simple click chemistry, the researchers attach the desired active-agent protein and antibodies to the polymer bristles. The finished bead-shaped packages have antibodies on the outermost layer, with the proteins safely concealed in the forest of polymer strands.

Besides the ability to transport water-soluble proteins, this PAC also possessed another advantage: a possible high protein-antibody ratio. The researchers said that, at least in theory, over 10 000 proteins could be transported per (expensive) antibody using the researchers’ PACs, compared to the maximum of four active agents per antibody in previous antibody-drug combinations.

The team tested their system on various cell cultures with different antibodies and test proteins. The test was a success; the PACs delivered their deadly cargoes to their cellular targets as planned.
The team is now going to figure out if and how the packages can be shielded from macrophages. They are optimistic about this because the PEG functionalities and the surface antibodies are designed for a quick delivery while minimising clearance by macrophages.

Source: News-Medical.Net

Journal information: Liu, B., et al. (2021) Protein–Antibody Conjugates (PACs): A Plug‐and‐Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins. Angewandte Chemie International Edition. doi.org/10.1002/anie.202103106.