FLASH Radiation Treatment for Tumours a Step Closer

Heavy ion bombardment in FLASH radiation treatment could be the future of radiotherapy, with encouraging findings from a German lab.

The GSI Helmholtzzentrum für Schwerionenforschung and the future accelerator centre FAIR succeeded in performing a carbon ion FLASH experiment for the first time in their Phase 0 experiment. 

The scientists involved were able to achieve the very high dose rates required to irradiate tumours. The success was a collective effort of the GSI Biophysics Department and the accelerator crew on the GSI/FAIR campus in close collaboration with the German Cancer Research Center DKFZ and the Heidelberg Ion Therapy (HIT) center.

FLASH irradiation involves utra-short and ultra-high radiation, delivering the treatment dose in fractions of a second. Traditional radiation therapy, as well as proton or ion therapy, deliver smaller doses of radiation to a patient over an extended time period, whereas FLASH radiotherapy is thought to require only a few short irradiations, all lasting less than 100 milliseconds.

In the field of electron radiation, recent in vivo investigations have shown that the FLASH method’s ultra-high dose rate is less harmful to healthy tissue, but just as efficient as conventional dose-rate radiation to inhibit tumour growth. Such an effect has not yet been demonstrated for proton and for ion beam irradiation, which is the basis of the tumour therapy with carbon ions developed at GSI. There is still a lot of research to be done here. The results of the current experiment at GSI are now being evaluated and will contribute to new knowledge.

There have also been technical barriers to FLASH radiation. Until now, FLASH technique has only been applicable using electron and proton accelerators. While the required dose rates for electrons and protons can be achieved with a cyclotron (circular accelerator), this is more difficult with the synchrotrons required in heavy ion therapy, such as the SIS18 at GSI.

That is why the current FAIR Phase 0 experiment is a very crucial step: Thanks to the improvements at the existing GSI accelerator facility as part of the preparations for FAIR, the necessary dose rate in millisecond range can now also be achieved for carbon ions. However,  much development work remains to be done before this procedure is mature enough to be routinely used on patients in the field of electron radiation.

Professor Marco Durante, Head of the GSI Biophysics Research Department, was very pleased with this important milestone in  the development of FLASH irradiation:

“It is a forward-looking method that could significantly increase the therapeutic window in radiotherapy. I am very happy that the researchers and the accelerator team were able to demonstrate the possibility to create conditions with carbon beams that are necessary for FLASH therapy of tumors. If we can combine the great effect and precision of heavy ion therapy with FLASH irradiation while maintaining efficacy and causing little damage to healthy tissue, this could pave the way of a future radiation therapy several years from now.”

Professor Paolo Giubellino, The Scientific Managing Director of GSI and FAIR, expressed his delight at the results: “The combination of expertise in biophysics and medicine as well as engineering excellence allows the first world-class experiments FLASH irradiation with ion beams to be performed. This could result in important complements to existing radiation therapies. Applications in tumour therapy are one of the research areas that can benefit from the recent increased intensities of GSI accelerators. However, modern radiobiology will substantially benefit from beams with even higher intensities, such as we will have at the FAIR facility currently under construction. FLASH is a first example of these future directions of work”.

Source: GSI Helmholtzzentrum für Schwerionenforschung GmbH

Tech Transfer for Local mRNA Vaccine Production

South Africa is planning to make vaccines locally using messenger RNA, the breakthrough technology of the global COVID vaccination effort – and once nearly consigned to the dustbin of medical research history.

The World Health Organization (WHO) and its COVAX partners are working with a South African consortium comprising Biovac, Afrigen Biologics and Vaccines, a network of universities and the Africa Centres for Disease Control and Prevention (CDC) to establish its first COVID mRNA vaccine technology transfer hub.

This follows WHO’s global call for Expression of Interest to establish COVID mRNA vaccine technology transfer hubs to scale up production and access to COVID vaccines. The partners will negotiate details with the South African government and public and private partners both local and international.

South African President Cyril Ramaphosa said: “The COVID pandemic has revealed the full extent of the vaccine gap between developed and developing economies, and how that gap can severely undermine global health security. This landmark initiative is a major advance in the international effort to build vaccine development and manufacturing capacity that will put Africa on a path to self determination. South Africa welcomes the opportunity to host a vaccine technology transfer hub and to build on the capacity and expertise that already exists on the continent to contribute to this effort.”

“This is great news, particularly for Africa, which has the least access to vaccines,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “COVID has highlighted the importance of local production to address health emergencies, strengthen regional health security and expand sustainable access to health products.”

The announcement follows the recent visit to South Africa by French President Emmanuel Macron, who gave his country’s commitment to aiding local vaccine production.

“Today is a great day for Africa. It is also a great day for all those who work towards a more equitable access to health products. I am proud for Biovac and our South African partners to have been selected by WHO, as France has been supporting them for years,” said President Macron. “This initiative is the first of a long list to come, that we will keep supporting, with our partners, united in the belief that acting for global public goods is the fight of the century and that it cannot wait.”

Technology transfer hubs are training facilities where the technology is established at industrial scale and clinical development performed. Interested manufacturers from low- and middle-income countries can receive training and any necessary licences to the technology, assisted by the WHO and partners.

Biovac is a bio-pharmaceutical company resulting from a partnership formed with the South African government in 2003 to establish local vaccine manufacturing capability for the provision of vaccines for national health management and security.

Afrigen Biologics and Vaccines is a biotechnology company focuses on product development, bulk adjuvant manufacturing and supply and distribution of key biologicals to address unmet healthcare needs.

The organisations complement one another, and can each take on different roles within the proposed collaboration: Biovac will be the developer while Afrigen is the manufacturer, with a consortium of universities as academic supporters providing mRNA know-how. Africa CDC will provide technical and regional support.

The South African consortium has existing operating facilities with available capacity and experience in technology transfers. It is also a global hub that can start training technology recipients immediately.

The WHO is speaking to a number of pharmaceutical manufacturers about establishing the hub, though the talks are so far mainly with “smaller companies,” said Soumya Swaminathan, WHO’s chief scientist. “We are having discussions with the larger companies with proven mRNA technology,” she added.

The mRNA vaccines may be produced in South Africa within 9 to 12 months, she said. WHO’s call for expressions of interest has so far generated 28 offers to either provide technology for mRNA vaccines or to host a technology hub or both. 

It is the first time that messenger RNA technology has been used to make vaccines, which has been used by Moderna and Pfizer/BioNTech. They have proven very effective against the original SARS-CoV-2 strains and even against its more recent variants.

Source: World Health Organization

‘Windscreen Wiper’ Tool for Laparoscopes Allows Uninterrupted View

Photo by Charlie Deets on Unsplash

A Brigham Young University student has developed a ‘windscreen wiper’ tool for laparoscopes that continuously keeps the camera end clean.

The laparoscope, a slender rod with a camera tip, allows doctors to see inside a body during surgery. Laparoscopes have made surgery less invasive and easier for surgeons and patients, but the device does have a problematic drawback: it must be removed, cleaned, and reinserted multiple times during surgery.

Engineering graduate student Jacob Sheffield has developed a tiny origami-based device that serves as a miniature windshield wiper for laparoscope camera lenses. When installed, the device eliminates the need to remove and reinsert laparoscopes every five or so minutes during surgery, which would allow surgeons to focus on the patient without disruptions.

“It’s like driving the car in the rain,” Sheffield explained. “If you can focus on driving and not on reaching out the window to wipe off the windshield with your hand, you can keep your focus on what’s important.”

His technology, developed with mentoring from BYU professor Larry Howell in the Compliant Mechanisms Research Lab and help from ME undergrad Amanda Lytle, is called LaparoVision. The disposable mechanism snaps on to existing laparoscopes and features a one-piece curved wiper that conforms to the cylindrical walls of the medical tool. The wiper, which is so small it can rest on the end of a finger, is actuated by a trigger outside of the body.

The innovative concept was impressive enough to earn Sheffield the title of 2021 Student Innovator of the Year at BYU, an award which also provides kickstarter money to develop a project.

“It’s extremely helpful to get that funding through BYU awards programs and the feedback you get from judges is invaluable,” Sheffield said. “My advice for future applicants is even if you don’t win or get money out of it, use the deadline of the competitions to drive progress for your idea.”

For Sheffield, the idea came about when he was meeting with surgeons across the country on other medical technologies being tested in the CMR lab. The issue of laparoscope removal and cleaning kept coming up in their conversations. The tool is used in 5 million surgeries every year in the US alone, and in roughly 90% of those procedures, the device must be removed.

Sheffield said that, according to many surgeons and studies, every five to eight minutes the device has to be pulled out and the lens wiped clean. With operating rooms costing $62 a minute, those fairly regular removals prove costly and frustrating. However, even more importantly, withdrawal of the scope at a critical time can cause serious risks for the patient.

“There is a high correlation in keeping the scope clean, maintaining surgical focus and ensuring timely and safe patient outcomes,” Sheffield said. “But it’s not just about improving efficiency during surgery; every time you lose vision it could be a critical part in the surgery where you make an incision and get blood on the lens and you can’t see what’s going on.”

Sheffield is currently in talks to license the technology and has now formed a startup (Bloom Surgical) to bring the device to market. Currently he is focusing on showing that the device is reliable and sage, and working towards getting FDA clearance for the tool.

Source: Brigham Young University

Bias Against Both Sexes Found in Clinical Trials

Photo by Tim Mossholder on Unsplash

Though evenly split overall, research shows that women and men in disease trials are not represented according to the population affected.

Clinical trial sample populations should be proportionate to the population affected by the disease, as some diseases are more prevalent or manifest differently in one sex versus the other. Neglecting one sex in clinical trials can skew medical evidence toward therapies for the neglected population.
The study cross-analysed over 20 000 US clinical trials between 2000-2020, and found that women are underrepresented in clinical trials in cardiology, oncology, neurology, immunology and haematology. Meanwhile, men are underrepresented in clinical trials in musculoskeletal disease and trauma, psychiatry and preventive medicine. 

This study, published JAMA Network Open, is the first to examine sex bias in all US human clinical trials relative to disease burden (which is the prevalence of disease based on factors such as sex and ethnicity).

“Sex bias in clinical trials can negatively impact both men and women by creating gendered data gaps that then drive clinical practice,” said first study author Dr Jecca Steinberg, a medical resident in the department of obstetrics and gynecology at Northwestern University Feinberg School of Medicine. “Neglecting one sex in clinical trials — the gold standard scientific exploration and discovery — excludes them from health innovation and skews medical evidence toward therapies with worse efficacy in that sex.”

Underrepresentating either sex in clinical trials can lead to less optimal health outcomes; differences exist for women and men in medical test results, disease progression, treatment response, drug metabolism and surgical outcomes, Dr Steinberg said.

These differences stem from variations in body size, composition, and hormones. Women’s smaller body sizes and higher fat contents typically result in varied drug responses. One study showed that aspirin has differential effects on the sexes with regard to primary protection against strokes and heart attacks. Aspirin only lowered women’s risk of stroke but had no effect on the risk of myocardial infarction or death.

“Identifying areas of research in which sex bias disadvantages males is important to improving population health,” Dr Steinberg said. “Our novel finding that men are underrepresented in trials related to mental health and trauma assumes greater urgency in American society where suicide, violence and substance use increasingly contribute to growing morbidity and premature male mortality in the US.”

Clinical trials for preventative medicine are more likely to have greater enrollment of women, the study found, adding credence to the notion that women, more than men, seek out preventive services and access to health care.  

Women-specific underrepresentation remains
“One of the top reasons for Food and Drug Administration drug recall is adverse effects in women,” Dr Steinberg said. “Millions and millions of dollars go into these trials, so to relatively neglect women in the trial population is a waste.

“A greater allocation of resources for female-focused trials could be critical to improving care for women and discerning the heterogenous manifestations of diseases within the female population.”

For example, women with heart disease often have different reactions to medications and experience different symptoms from men, such as feeling abdominal pain rather than their left arm. If a clinical trial implements its intervention based on symptoms predominantly exhibited by the male population, it could miss testing interventions in women with cardiac arrest. 

The reduced representation of women relative to disease burden specifically in oncology and cardiology clinical trials is especially troubling, said Steinberf, because cardiologic and oncologic diseases are among the leading causes of death among women in the US.

Participating in clinical trials is also one of the only ways to access cutting edge therapies, especially oncology, so the relative deficiency of one sex contributes to disparities in health outcomes, Steinberg said.  

“One of our hopes from this study is that scientists and physicians will read about our findings and be inspired to say, ‘Why is that happening in my field?’ and then address it,” Dr Steinberg said.

Source: Northwestern University

Common Gut Bacteria Could Inhibit SARS-CoV-2

Bifidobacterium eriksonii, stained with fluorescent antibodies. Source: Public Health Image Library

South Korean researchers have found that certain common gut bacteria produce compounds that inhibit SARS-CoV-2. 

The research was presented on June 20 at World Microbe Forum, an online meeting of the American Society for Microbiology (ASM), the Federation of European Microbiological Societies (FEMS), and several other societies that taking place online June 20-24.

Previous clinical findings had shown that some patients with moderate to severe COVID experience gastrointestinal symptoms, while others show signs of infection in the lungs only.

“We wondered whether gut resident bacteria could protect the intestine from invasion of the virus,” said Mohammed Ali, a PhD student in Medicine at Yonsei University in South Korea.

To investigate this hypothesis, the researchers screened dominant bacteria inhabiting the gut for activity against SARS-CoV-2. Their efforts revealed that Bifidobacteria, already shown to suppress other bacteria such as H. pylori and have proven active against irritable bowel syndrome, had such activity, said Ali. Bifidobacteria are common in the guts of breast fed infants, which is partly driven by the bifidogenic activities of specific mother milk-derived oligosaccharides

The researchers also searched for potential illness-fighting compounds in databases containing microbially produced molecules, and discovered some that might also be useful against SARS-CoV-2. “To train our model we leveraged previous coronavirus datasets in which several compounds were tested against targets from coronaviruses,” explained Ali. “This approach seems to be significant as those targets share features in common with SARS-CoV-2.”

Ali emphasised the ecological nature of his approach to this work, pointing out that numerous existing antibiotics and cancer therapies are themselves compounds that bacteria use to compete with each other within the gastrointestinal tract, and that these were initially purified from microbial secretions.

“Finding microbes that secrete anti-coronavirus molecules will be a promising method to develop natural or engineered probiotics to expand our therapeutics prevention techniques, to provide a more sustainable way to combat the viral infection,” said Ali.

Source: American Society for Microbiology

Brazil COVID Deaths Pass Half a Million

Brazil’s COVID deaths passed 500 000 in Brazil, days after the US reported passing 600 000 deaths. Experts warn of a worsening outbreak amid slow vaccination and the onset of winter.

President Jair Bolsonaro refuses to back measures like social distancing even as the virus continues to take its toll. With only 11% of adults vaccinated, Brazil’s health institute Fiocruz says the situation is “critical”.

Heavy criticism has been directed at President Bolsonaro for not implementing a co-ordinated national response and for his vaccine scepticism, lockdowns and mask-wearing requirements, which he has sought to loosen.

The country has reported, on average, 70 000 cases and 2 000 deaths daily in the past week. Most new cases were among those aged 20-59, Fiocruz said, warning that the start of winter in the southern hemisphere this week could result in more infections.

Yet governors and mayors have already relaxed nonpharmaceutical interventions. Restaurants, bars and shops have reopened in many cities, while many people in the streets are not wearing face masks or following social distancing.

“People in Brazil are tired and they normalise death now,” Dr Natalia Pasternak Taschner, a microbiologist at the Question of Science Institute, told the BBC, adding that they have a long way to go.

“If we’re not successful in changing the behaviour of people and if we don’t have campaigns for mask wearing, social distancing and vaccinations coming directly from the central government we’re not going to be able to control it.”

On Saturday, protests against President Bolsonaro were held in cities across the country, with demonstrators accusing him of delaying the purchase of vaccines yet prioritising unproven treatments, such as hydroxychloroquine.

More transmissible variants of the virus have driven Brazil’s outbreak, including the one first identified in the Amazon region which is now known as Gamma. Occupancy rate for intensive care unit beds remains at or above 80% in most states, while cities struggle with vaccine supplies.

Faced with a crumbling healthcare system without the relief of lockdowns, a ‘Covid Kit‘ of ivermectin and azithromycin has been touted by the government, and which is widely prescribed. Ironically, its creator, a doctor in Mato Grosso state, died of COVID last September. In a country notorious for its excessive pill-taking, doctors are finding it difficult to recruit people into trials who have not taken ivermectin.

The Brazilian Senate is looking into President Bolsonaro’s handling of the pandemic. The opposition is accusing him of delaying vaccine orders for political reasons, as he has consistently downplayed the pandemic’s severity.

But President Bolsonaro maintains he has done all he can to buy vaccines from several countries, and insists the impacts of a lockdown would be worse than the pandemic.

The president has not commented on the 500 000 deaths although on Twitter, Health Minister Marcelo Queiroga expressed solidarity with relatives of those who had died.

Source: BBC News

Disarming a Common Pathogenic Bacterium

Pseudomonas aeruginosa bacteria. Source: Public Health Imagery Library

Scientists have discovered a gene regulator in a common pathogenic bacterium that can be exploited to drastically reduce its virulence.

Pseudomonas aeruginosa is a gram-negative, aerobic, opportunistic, pathogenic bacterium found in a variety of ecological niches, such as plant roots, stagnant water or even plumbing. Naturally extremely versatile, it can cause acute and chronic infections that are potentially fatal for immunocompromised hosts. P. aeruginosa poses a serious threat in clinical settings, where it can colonise respirators and catheters. Additionally, its adaptability and resistance to many antibiotics make P. aeruginosa infections steadily more difficult to treat. Therefore new antibacterials are urgently needed. 

Scientists from the University of Geneva (UNIGE) in Switzerland have identified a previously unknown regulator of gene expression in this bacterium, without which the infectious power of P. aeruginosa is diminished. This discovery may unlock new developmental pathways to treat this bacteria.

RNA helicases perform essential regulatory functions by binding and unwinding various RNA molecules to perform their functions. RNA helicases are present in the genomes of almost all known living organisms, including bacteria, yeast, plants, and humans; however, they have acquired specific properties depending on the organism in which they are found. “Pseudomonas aeruginosa has an RNA helicase whose function was unknown, but which was found in other pathogens”, explained Martina Valentini,  a researcher leading this research in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine. “We wanted to understand what its role was, in particular in relation to the pathogenesis of the bacteria and their environmental adaptation.”

A severely reduced virulence

To accomplish this, the researchers took a combined biochemical and molecular genetic approach. “In the absence of this RNA helicase, P. aeruginosa multiplies normally in vitro, both in a liquid medium and on a semi-solid medium at 37°C”, reported Stéphane Hausmann, a researcher associate in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine and first author of this study. “To determine whether the infection capacity of the bacteria was affected, we had to observe it in vivo in a living organism.”

The scientists then continued their research using Galleria mellonella larvae, a model insect for studying host-pathogen interactions.These larvae can live at temperatures between 5°C and 45°C, which makes it possible to study bacterial growth at different temperatures, including that of the human body. Three groups of larvae were observed, including a control group injected with saline. In the presence of a normal strain of P. aeruginosa, less than 20% survived at 20 hours after infection. In contrast, when P. aeruginosa lacked the RNA helicase gene, over 90% of the larvae remained alive. “The modified bacteria became almost harmless, while remaining very much alive,” says Stéphane Hausmann.

Inhibiting instead of killing

The findings demonstrated that the regulator affects production of several virulence factors in the bacteria. “In fact, this protein controls the degradation of numerous messenger RNAs coding for virulence factors”, summarised Martina Valentini. “From an antimicrobial drug strategy point of view, switching off the pathogen’s virulence factors rather than trying to eliminate the pathogen completely, means allowing the host immune system to naturally neutralise the bacterium and potentially reduces the risk for the development of resistance. Indeed, if we try to kill the bacteria at all costs, the bacteria will adapt to survive, which favours the appearance of resistant strains.”

The Geneva team is continuing its investigations by screening drug molecules to see if any of them can selectively block this protein, and also performing a detailed study in detail on the inhibition mechanisms on which could be based the development of an effective therapeutic strategy.

Source: University of Geneva

Journal reference: Hausmann, S., et al. (2021) The DEAD-box RNA helicase RhlE2 is a global regulator of Pseudomonas aeruginosa lifestyle and pathogenesis. Nucleic Acid Research. doi.org/10.1093/nar/gkab503.

High Burden of Uncontrolled Disease in KwaZulu-Natal

Photo by Hush Naidoo on Unsplash

A comprehensive health-screening program has found a high burden of poorly controlled or uncontrolled disease KwaZulu-Natal, along with a high incidence of undiagnosed diseases.

The study, published in The Lancet Global Health, found that four out of five women over 30 had a chronic health condition, and that the HIV-negative population and older people had the highest burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension. The study was conducted at the Africa Health Research Institute (AHRI).

Study co-leader Emily Wong, MD, at AHRI in Durban, said: “The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed,” Dr Wong said. “The research was done before COVID, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases — given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID.” 

HIV-associated tuberculosis infections are particularly prevalent in Durban. Dr Wong of the University of Alabama works there to understand the impact of HIV infection on tuberculosis pathogenesis, immunity and epidemiology. In sub-Saharan Africa, 15 years of intense public health efforts that increased access to antiretroviral therapy has resulted in decreased AIDS mortality and raised life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

Over 18 months, health workers screened 17 118 people aged 15 years and older via mobile camps within 1 kilometre of each participant’s home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were largely well diagnosed and treated, some demographic groups  still had high rates of undiagnosed and untreated HIV, such as men in their 20s and 30s. In contrast, the majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Of particular concern was the high rates of undiagnosed and asymptomatic tuberculosis discovered, as it remains one of the leading causes of death in South Africa.

“Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease,” Dr Wong said. “But in that process, we may have neglected some of the other important diseases that are highly prevalent.”

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was combined with 20 years of population data from AHRI’s health and demographic surveillance research. Using a sophisticated data system combined with artificial intelligence to interpret the chest X-rays, AHRI’s clinical team examined the information in real time, referring people to the public health system as needed.

The study found that: 

  • Half of the participants had at least one active disease, and 12 percent had two or more diseases. Diabetes and hypertension incidences were 8.5 percent and 23 percent, respectively.
  • One-third of the people were living with HIV, but this was mostly well diagnosed and treated. A particularly high burden of HIV, high blood pressure and diabetes was seen in women.
  • For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, with higher rates of active tuberculosis seen in men.
  • Several disease patterns varied by geographical location — eg, the highest HIV burden was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Source: University of Alabama at Birmingham

Journal information: Wong, E. B., et al. (2021) Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study. The Lancet Global Health. doi.org/10.1016/S2214-109X(21)00176-5.

New Printable Biosensor Could Guide Surgery

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Surgeons may soon be able to pinpoint critical regions in tissues during surgery without interruption thanks to a new, 3D-printable biosensor.

Associate Professor Chi Hwan Lee created the biosensor, which enables both recording and imaging of tissues and organs during a surgical operation. Research on the biosensor was published in Nature Communications.

Prof Lee explained the benefits of such devices: “Simultaneous recording and imaging could be useful during heart surgery in localising critical regions and guiding surgical interventions such as a procedure for restoring normal heart rhythm.”

Existing methods to simultaneously record and image tissues and organs have proven challenging because other sensors used for recording typically interrupt the imaging process.

“To this end, we have developed an ultra-soft, thin and stretchable biosensor that is capable of seamlessly interfacing with the curvilinear surface of organs; for example the heart, even under large mechanical deformations, for example cardiac cycles,” Prof Lee said. “This unique feature enables the simultaneous recording and imaging, which allows us to accurately indicate the origin of disease conditions: in this example, real-time observations on the propagation of myocardial infarction in 3D.”

The biosensors are made of soft bio-inks and are rapid-prototyped to a custom-fit design, fitting a variety of sizes and shapes of an organ. The bio-inks used are softer than tissue, and can stretch without experiencing sensor degradation but also have reliable natural adhesion to the wet surface of organs without needing extra adhesives. The formulation and synthesis of the bio-inks was thanks to Kwan-Soo Lee’s research group in Los Alamos National Laboratory.

The researchers have produced a number of prototype biosensors using different shapes, sizes and configurations. Craig Goergen, the Leslie A Geddes Associate Professor of Biomedical Engineering in Purdue’s Weldon School of Biomedical Engineering, and his laboratory group have tested the prototypes in mice and pigs in vivo.

“Professor Goergen and his team were successfully able to identify the exact location of myocardial infarctions over time using the prototype biosensors,” Prof Lee said. “In addition to these tests, they also evaluated the biocompatibility and anti-biofouling properties of the biosensors, as well as the effects of the biosensors on cardiac function. They have shown no significant adverse effects.”

Source: Purdue University

Journal information: Kim, B., et al. (2021) Rapid custom prototyping of soft poroelastic biosensor for simultaneous epicardial recording and imaging. Nature Communications. doi.org/10.1038/s41467-021-23959-3.

In Vitro Cancer Cells Differ to Those in Body

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A new study has shown that most cancer cells grown in vitro have little in common genetically with cancer cells in humans.

Human cancer cells grown in culture dishes have the least genetic similarity to their human sources, according to a new computer-based technique developed by researchers at John Hopkins.

According to the researchers, the finding should help shift more resources to cancer research models such as genetically engineered mice and balls of human tissue known as ‘tumouroids’ to better evaluate human cancer biology and treatments, and the genetic errors responsible for cancer growth and progress.

“It may not be a surprise to scientists that cancer cell lines are genetically inferior to other models, but we were surprised that genetically engineered mice and tumouroids performed so very well by comparison,” says Patrick Cahan, PhD, associate professor of biomedical engineering at The Johns Hopkins University and the Johns Hopkins University School of Medicine and lead investigator of the new study.

The new computer modelling technique, CancerCellNet, compares the RNA sequences of a research model with data from a cancer genome atlas to see how closely the two sets match up.

On average, genetically engineered mice and tumouroids have RNA sequences most closely aligned with the genome atlas baseline data in 4 out of every 5 tumour types they tested, including breast, lung and ovarian cancers.

This adds to evidence that cancer cell lines grown in the laboratory have less parity with their human source due to the many differences between a human cell’s natural environment and a laboratory growth environment, the researchers said. “Once you take tumours out of their natural environment, cell lines start to change,” said Prof Cahan.

Around the world, scientists depend on a range of research models to enhance their understanding of cancer and other disease biology, and to develop treatments for conditions. Of these, one of the most widely used is cell lines created by extracting cells from human tumours and growing them with various nutrients in laboratory flasks.

Other methods involve mice that have been genetically engineered to develop cancer, or implanting human tumours into mice, known as xenografting, or use tumouroids.

To investigate the accuracy of these models, scientists often transplant lab-cultured cells or cells from tumouroids or xenografts into mice and see if the cells behave as they should — that is, grow and spread, retaining the genetic hallmarks of cancer. However, the researchers contend that this process is expensive, time-consuming and scientifically challenging and so they developed a more streamlined method. The new technique is based on genetic information about cellular RNA.

“RNA is a pretty good surrogate for cell type and cell identity, which are key to determining whether lab-developed cells resemble their human counterparts,” said Prof Cahan. “RNA expression data is very standardised and available to researchers, and less subject to technical variation that can confound a study’s results.”

To start, Prof Cahan and his team had to choose a standard set of data that acted as a baseline to compare the research models. They used data from The Cancer Genome Atlas as ‘training’ data, which includes RNA expression information of hundreds of patient tumour samples, and other information on the tumour.

They also tested their CancerCellNet tool by applying it to data where the tumour type was already known, such as from the International Human Genome Sequencing Consortium.

The John Hopkins researchers combed through The Cancer Genome Atlas data to select 22 types of tumours for study, and used that data as the baseline for comparing RNA expression data from cancer cell lines, xenografts, genetically engineered mouse models and tumouroids.

Some differences observed included prostate cancer cells from a line called PC3 that started to look genetically more like bladder cancer, Prof Cahan noted. It’s also possible, he said, that originally  the cell line was simply labelled incorrectly, or else it could have in fact been derived from bladder cancer. But, from a genetic standpoint, the prostate cancer cell line was not a representative surrogate for what happens in a typical human with prostate cancer.

According to a 0-1 scoring method, cell lines had, on average, lower scoring alignment to atlas data than tumouroids and xenografts.

Prof Cahan said he and his team will be improving the reliability of CancerCellNet by adding additional RNA sequencing data.

Source: John Hopkins Medicine

Journal information: Da Peng et al, Evaluating the transcriptional fidelity of cancer models, Genome Medicine (2021). DOI: 10.1186/s13073-021-00888-w