Culture

(Vienna, October 12, 2020) Weight loss surgery significantly cuts the risk of developing pancreatic cancer in people who are obese with diabetes, a new 20-year analysis has found.

The study, presented today at UEG Week 2020 Virtual, analysed 1,435,350 patients with concurrent diabetes and obesity over a 20-year period. A total of 10,620 patients within the study had undergone bariatric (weight loss) surgery, an operation that helps patients lose weight by making changes to the digestive system.

The research found that obese patients with diabetes were significantly less likely to develop pancreatic cancer if they had undergone bariatric surgery (prevalence of 0.32% vs 0.19%, p

Lead author Dr Aslam Syed, from the Allegheny Health Network, Division of Gastroenterology in Pittsburgh, USA, commented, "Obesity and diabetes are well-known risk factors for pancreatic cancer via chronic inflammation, excess hormones and growth factors released by body fat. Previously, bariatric surgery has been shown to improve high blood sugar levels in diabetic patients and our research shows that this surgery is a viable way in reducing the risk of pancreatic cancer in this growing, at-risk group."

The findings are particularly timely, with rates of diabetes, obesity and pancreatic cancer all on the rise.

For pancreatic cancer, cases in the EU increased by 5% between 1990 and 2016 - the highest increase in the EU's top five cancers - with the disease expected to be the second leading cause of cancer death in the near future. A total of 46,200 people are estimated to die from the disease in Europe in 2020, compared to 42,200 deaths recorded in 2015. The increase in cases is believed to be fuelled by rising rates of obesity and type 2 diabetes.

Obesity rates continue to increase at a rapid and concerning pace across Europe, with little expectation that these figures will decrease or plateau. Over half (52%) of the adult EU population is either overweight or obese, with growing rates also prevalent in children.

Dr Syed explains how preventing pancreatic cancer is crucial, with a lack of improvements in the survival of the disease for four decades. "The average survival time at diagnosis is particularly bleak for this silent killer, at just 4.6 months, with patients losing 98% of their healthy life expectancy. Only 3% of patients survive more than five years."

Often referred to as the 'silent killer', symptoms of pancreatic cancer - which include pain in the back or stomach, jaundice and unexplained weight loss - can be hard to identify which adds difficulties in diagnosing patients early.

"Clinicians should consider bariatric surgery in patients with metabolic disorders, such as diabetes and obesity, to help reduce the risk and burden of pancreatic cancer," adds Dr Syed.

Researchers at CSIRO, Australia's national science agency, have found that SARS-CoV-2, the virus responsible for COVID-19, can survive for up to 28 days on common surfaces including banknotes, glass - such as that found on mobile phone screens - and stainless steel.

The research, undertaken at the Australian Centre for Disease Preparedness (ACDP) in Geelong, found that SARS-CoV-2:

survived longer at lower temperatures

tended to survive longer on non-porous or smooth surfaces such as glass, stainless steel and vinyl, compared to porous complex surfaces such as cotton

survived longer on paper banknotes than plastic banknotes.

Results from the study The effect of temperature on persistence of SARS-CoV-2 on common surfaces was published in Virology Journal.

CSIRO Chief Executive Dr Larry Marshall said surface survivability research builds on the national science agency's other COVID-19 work, including vaccine testing, wastewater testing, Personal Protective Equipment (PPE) manufacture and accreditation, and big data dashboards supporting each state.

"Establishing how long the virus really remains viable on surfaces enables us to more accurately predict and mitigate its spread, and do a better job of protecting our people," Dr Marshall said.

"Together, we hope this suite of solutions from science will break down the barriers between us, and shift focus to dealing with specific virus hotspots so we can get the economy back on track.

"We can only defeat this virus as Team Australia with the best Australian science, working alongside industry, government, research and the Australian community."

Dr Debbie Eagles is Deputy Director of ACDP, which has been working on both understanding the virus and testing a potential vaccine.

"Our results show that SARS-CoV-2 can remain infectious on surfaces for long periods of time, reinforcing the need for good practices such as regular handwashing and cleaning surfaces," Dr Eagles said.

"At 20 degrees Celsius, which is about room temperature, we found that the virus was extremely robust, surviving for 28 days on smooth surfaces such as glass found on mobile phone screens and plastic banknotes.

"For context, similar experiments for Influenza A have found that it survived on surfaces for 17 days, which highlights just how resilient SARS-CoV-2 is."

The research involved drying virus in an artificial mucus on different surfaces, at concentrations similar to those reported in samples from infected patients and then re-isolating the virus over a month.

Further experiments were carried out at 30 and 40 degrees Celsius, with survival times decreasing as the temperature increased.

The study was also carried out in the dark, to remove the effect of UV light as research has demonstrated direct sunlight can rapidly inactivate the virus.

"While the precise role of surface transmission, the degree of surface contact and the amount of virus required for infection is yet to be determined, establishing how long this virus remains viable on surfaces is critical for developing risk mitigation strategies in high contact areas," Dr Eagles said.

Director of ACDP Professor Trevor Drew said many viruses remained viable on surfaces outside their host.

"How long they can survive and remain infectious depends on the type of virus, quantity, the surface, environmental conditions and how it's deposited - for example touch vs droplets emitted by coughing," Professor Drew said.

"Proteins and fats in body fluids can also significantly increase virus survival times.

"The research may also help to explain the apparent persistence and spread of SARS-CoV-2 in cool environments with high lipid or protein contamination, such as meat processing facilities and how we might better address that risk."

Volume 11, Issue 28 of Oncotarget features "Genetic analysis of the cooperative tumorigenic effects of targeted deletions of tumor suppressors Rb1, Trp53, Men1, and Pten in neuroendocrine tumors in mice" by Xu et, al. which reported that the authors examined whether the TSGs Rb1, Trp53, Pten, and Men1 have cooperative effects in suppressing neuroendocrine tumors in mice.

By monitoring growth and examining the histopathology of the pituitary and pancreas in these mice, the authors demonstrated that pRB had the strongest cooperative function with PTEN in suppressing Pit NETs and had strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs. TRP53 had weak cooperative function with PTEN in suppressing pituitary lesions.

Collectively, the data indicated that pRB and PTEN pathways play significant roles in suppressing Pit NETs, while the Menin-mediated pathway plays a significant role in suppressing Pan NETs. Understanding the molecular mechanisms of these genes and pathways on NETs will help us understand the molecular mechanisms of neuroendocrine tumorigenesis and develop effective preclinical murine models for NET therapeutics to improve clinical outcomes in humans.

Dr. Eugenia Y. Xu from Rutgers and Princeton University as well as Dr. Daniel A. Notterman from Princeton University said, "Human pituitary neuroendocrine tumors (PitNETs) are the third most common intracranial neoplasms and represent approximately 10–25% of all primary intracranial tumors."

Additionally, in rare cases, RB1 has been found with epigenetic mutations in the promoter region in Pit NETs suggesting that inactivation of the RB pathway contributes to the development of Pit NETs. Compound mice with concomitant deletions of Men1 and Pten develop Pit NETs and Pan NETs and mice with p18–/– Pten+/– mutations develop Pit NETs, suggesting that PTEN plays a role in pituitary and pancreatic islet tumorigenesis.

However, Men1 deletion mice develop pars distalis prolactinomas and Rb1 deletion mice develop pars intermedia tumors of the pituitary, suggesting that the functions of Menin and pRB may not fully overlap.

Here they investigate the question of whether Men1 and Rb1 have cooperative tumorigenic effects on NETs using tissue-specific double homozygous deletions of Men1 and Rb1 in mice.

The Oncotarget authors report that the characterization of Pit NETs and Pan NETs with double homozygous deletions of TSGs and illustrate that pRB has the strongest cooperative function with PTEN in suppressing Pit NETs and has a strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs in mice.

"The Oncotarget authors report that the characterization of Pit NETs and Pan NETs with double homozygous deletions of TSGs and illustrate that pRB has the strongest cooperative function with PTEN in suppressing Pit NETs and has a strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs in mice."

The Xu/Notterman Research Team concluded in their Oncotarget Research Paper, "our data clearly demonstrate that TSGs Rb1, Pten, Men1, and Trp53 have distinct tissue specificity in neuroendocrine tumorigenesis in mouse and likely in man. The mouse models here and deletion of these TSGs in MIP-Cre mice will help further our understanding the molecular function of these TSGs and their pathways in PitNET and PanNET pathogenesis, which will help develop targeted novel therapeutic options in treating human patients."

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27660

Full text - https://www.oncotarget.com/article/27660/text/

Correspondence to - Eugenia Y. Xu - exu@princeton.edu and Daniel A. Notterman - dan1@princeton.edu

Keywords -
neuroendocrine tumors,
RB1,
Trp53,
PTEN,
Men1

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Journal

Oncotarget

DOI

10.18632/oncotarget.27660

Volume 11, Issue 28 of Oncotarget features "Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation" by Gaba et, al. which reported that reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs.

Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug-metabolizing enzyme expression.

The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous injection into immunodeficient mice and Oncopigs.

Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers.

Finally, Oncopig HCC cells are amenable to gene editing for the development of personalized HCC tumors.

Dr. Kyle M. Schachtschneider from The Department of Radiology and The Biological Resources Laboratory at The University of Illinois at Chicago as well as The National Center for Supercomputing Application at The University of Illinois at Urbana-Champaign said, "Hepatocellular carcinoma (HCC)–the most common type of primary liver cancer–is an aggressive cancer that spans more than 850,000 new yearly diagnoses and causes 800,000 annual deaths, representing the fifth most common cancer globally and the second most common cause of cancer-related death worldwide."

The rabbit VX2 model has been considered the most relevant and widely used model to test HCC LRTs to date.

As such, there is a crucial need for more clinically relevant large animal models that faithfully recapitulate human HCC to address unmet clinical needs and serve as a bridge between murine studies and clinical practice.

This study describes the utilization of the Oncopig Cancer Model for the development of a clinically relevant, translational porcine HCC model.

The Oncopig Cancer Model is a transgenic pig model that develops site and cell-specific tumors following Cre recombinase induced expression of heterozygous KRASG12D and TP53R167H transgenes.

The large size of the pig and its similarities with humans in terms of anatomy, physiology, metabolism, immunity, and genetics make it an ideal model species for the development of a large animal cancer model.

Development of Oncopig HCC cell lines has been previously described, however, prior work was limited to characterization of HCC cell lines derived from three Oncopigs, minimal in vitro and in vivo profiling, and no description of intrahepatic tumors.

As such, this study was undertaken to test the hypothesis that phenotypically consistent Oncopig HCC cells that faithfully recapitulate the in vitro features of human HCC can be developed across a large Oncopig cohort and that these cells can be utilized to develop clinically relevant intrahepatic HCC tumors in Oncopigs.

The Schachtschneider Research Team concluded in their Oncotarget Research Paper, "the Oncopig HCC model offers a novel, physiologically and anatomically relevant cancer model for which a multitude of innovative therapeutic modalities can be applied and tested while significantly reducing the costs, confounding variables seen in human subjects, and lengthy conduct of human clinical trials. Importantly, the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies. Its size allows for utilization of the same methods and instruments used in human clinical practice, including CT and magnetic resonance imaging technologies. This model is thus amenable to developing and establishing medical imaging standards related to diagnosing HCC tumors and tracking treatment response using accepted radiologic criteria, a critical facet of therapeutic discovery and validation. Importantly, the Oncopig is also immunocompetent, lending itself to investigation of immunotherapies [32]. Therefore, the Oncopig fulfills the currently unmet clinical modeling needs for HCC, particularly for pilot investigations of experimental therapies or experimental therapeutic combinations not feasible in human subjects."

"The Oncopig HCC model offers a novel, physiologically and anatomically relevant cancer model for which a multitude of innovative therapeutic modalities can be applied and tested while significantly reducing the costs, confounding variables seen in human subjects, and lengthy conduct of human clinical trials. Importantly, the Oncopig can be utilized to conduct correlative studies for more efficient and consistent investigation of new therapies. Its size allows for utilization of the same methods and instruments used in human clinical practice, including CT and magnetic resonance imaging technologies. This model is thus amenable to developing and establishing medical imaging standards related to diagnosing HCC tumors and tracking treatment response using accepted radiologic criteria, a critical facet of therapeutic discovery and validation. Importantly, the Oncopig is also immunocompetent, lending itself to investigation of immunotherapies [32]. Therefore, the Oncopig fulfills the currently unmet clinical modeling needs for HCC, particularly for pilot investigations of experimental therapies or experimental therapeutic combinations not feasible in human subjects."

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27647

Full text - https://www.oncotarget.com/article/27647/text/

Correspondence to - Kyle M. Schachtschneider - kschach2@uic.edu

Keywords -
liver cancer,
transgenic pigs,
large animal model,
interventional radiology,
personalized medicine

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Journal

Oncotarget

DOI

10.18632/oncotarget.27647

The same stem cells that heal broken bones can also generate arthritic bone spurs called osteophytes, according to a new study in the Annals of the Rheumatic Diseases.

"Although these stem and progenitor cells promote healthy bone repair in other contexts, they are inappropriately activated to cause a pathological bony protuberance in the context of arthritis," said Gage Crump, a professor of stem cell biology and regenerative medicine at USC. Crump is the paper's co-corresponding author, along with Cosimo de Bari from the University of Aberdeen in the UK.

Led by Crump and de Bari, an international team of scientists made this discovery by studying mice that had sustained a type of knee injury that causes arthritis. In these mice, a different colored fluorescent protein labeled each of eight distinct cell populations. This allowed the scientists to view the fluorescent labels under a microscope and trace how the various cell populations contribute to the formation of arthritic bone spurs.

The major culprit turned out to be a type of stem cell with activity in a gene called Sox9, which is also involved in bone repair. At the edge of the arthritic joint, these cells contributed to cartilage outgrowths that later turned into pathological bone spurs. These cartilage outgrowths had many of the distinctive hallmarks of the cartilage seen during bone regeneration, suggesting further parallels between pathological bone spur formation and normal bone repair.

"By resolving the cellular origins of osteophytes, our work provides clues for how to target these painful bone spurs that develop at the edge of joints in many arthritis patients," Crump said.

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of immune cells, resembling acute flares of systemic lupus erythematosus (SLE), an autoimmune disease.

Their findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. They also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes.

The results were published online on Oct. 7 in Nature Immunology.

The Emory team's results converge with recent findings by other investigators, who found that high inflammation in COVID-19 may disrupt the formation of germinal centers, structures in lymph nodes where antibody-producing cells are trained. The Emory group observed that B cell activation is moving ahead along an "extrafollicular" pathway outside germinal centers - looking similar to they had observed in SLE.

B cells represent a library of blueprints for antibodies, which the immune system can tap to fight infection. In severe COVID-19, the immune system is, in effect, pulling library books off the shelves and throwing them into a disorganized heap.

Before the COVID-19 pandemic, co-senior author Ignacio (Iñaki) Sanz, MD and his lab were focused on studying SLE and how the disease perturbs the development of B cells.

Sanz is head of the division of rheumatology in the Department of Medicine, director of the Lowance Center for Human Immunology, and a Georgia Research Alliance Eminent Scholar. Co-senior author Frances Eun-Hyung Lee, MD is associate professor of medicine and director of Emory's Asthma/Allergy Immunology program.

"We came in pretty unbiased," Sanz says. "It wasn't until the third or fourth ICU patient whose cells we analyzed, that we realized that we were seeing patterns highly reminiscent of acute flares in SLE."

In people with SLE, B cells are abnormally activated and avoid the checks and balances that usually constrain them. That often leads to production of "autoantibodies" that react against cells in the body, causing symptoms such as fatigue, joint pain, skin rashes and kidney problems. Flares are times when the symptoms are worse.

Whether severe COVID-19 leads to autoantibody production with clinical consequences is currently under investigation by the Emory team. Sanz notes that other investigators have observed autoantibodies in the acute phase of the disease, and it will be important to understand whether long-term autoimmune responses may be related to the fatigue, joint pain and other symptoms experienced by some survivors.

"It's an important question that we need to address through careful long-term follow-up," he says. "Not all severe infections do this. Sepsis doesn't look like this."

In lupus, extrafollicular B cell responses are characteristic of African-American patients with severe disease, he adds. In the new study, the majority of patients with severe infection were African-American. It will be important to understand how underlying conditions and health-related disparities drive the intensity and quality of B cell responses in both autoimmune diseases and COVID-19, Sanz says.

The study compared 10 critically ill COVID-19 patients (4 of whom died) admitted to intensive care units at Emory hospitals to 7 people with COVID-19 who were treated as outpatients and 37 healthy controls.

People in the critically ill group tended to have higher levels of antibody-secreting cells early on their infection. In addition, the B cells and the antibodies they made displayed characteristics suggesting that the cells were being activated in an extrafollicular pathway. In particular, the cells underwent fewer mutations in their antibody genes than seen in a focused immune response, which is typically honed within germinal centers.

The Nature Immunology paper was the result of a collaboration across Emory. The co-first authors are Matthew Woodruff, PhD, an instructor in Sanz's lab, and Richard Ramonell, MD, a fellow in pulmonary and critical care medicine at Emory University Hospital.

Ramonell notes that the patients studied were treated early during the COVID-19 pandemic. It was before the widespread introduction of the anti-inflammatory corticosteroid dexamethasone, which has been shown to reduce mortality.

The team's findings could inform the debate about which COVID-19 patients should be given immunomodulatory treatments, such as dexamethasone or anti-IL-6 drugs. Patients with a greater expansion of B cells undergoing extrafollicular activation also had higher levels of inflammatory cytokines, such as IL-6.

Some COVID-19 patients have been given drugs that push back against IL-6, but results have been mixed in clinical trials. Patients with markers of unregulated immune responses may be appropriate candidates for treatment with anti-inflammatory drugs that target the corresponding pathways, Sanz suggests.

The American Medical Association has joined the African American Tobacco Control Leadership Council in suing the Food and Drug Administration on their inaction to ban menthol-flavored tobacco products which have been heavily marketed by cigarette companies to Black communities for decades.

Cristine Delnevo, director of the Rutgers Center for Tobacco Studies and a professor at the Rutgers School of Public Health, recently published three studies showing that menthol cigarette smoking persists in the United States, particularly among vulnerable populations, despite population-level cigarette declines. Another co-authored paper with Ollie Ganz, an instructor at the Rutgers School of Public Health and a researcher at the tobacco center, called for a ban of menthol cigarettes, saying banning the product should be considered a social justice issue. They both discuss why actions at the state and federal level need to be taken to make the ban a reality.

Why should menthol cigarettes concern public health officials?

Delnevo: The FDA's Tobacco Product Scientific Advisory Committee (TPSAC) was tasked by Congress to review the scientific evidence of menthol cigarette use among specific groups given the high use rates among youth smokers and Black smokers. It concluded that menthol in cigarettes reduced the harshness of smoking and was associated with increased initiation, higher dependence and had lower quit success.

The continued availability of menthol cigarettes in the U.S. should be viewed as a social justice issue. The majority of Black smokers in the U.S. smoke menthol cigarettes and there is extensive research showing that the tobacco industry has targeted these African American communities with advertising for menthol cigarettes for decades.

Additionally, as TPSAC pointed out, menthol cigarettes are particularly appealing to the youth, especially minorities. In the past, the industry manipulated menthol levels in cigarettes to be more appealing to young smokers. Even data from the National Youth Tobacco Survey reported that while menthol use declined overall among youth from 2011-2018, there was no decline among Black and Hispanic students.

Our study, published in the journal Nicotine & Tobacco Research draws attention to other populations for which menthol use is high, including sexual minorities, pregnant women and those with mental health problems.

How has the consumption of cigarettes, especially menthol cigarettes, changed over the years following Congress' Passage of the Family Smoking Prevention and Tobacco Control Act which banned flavored cigarettes, but exempted menthol?

Delnevo: Our study, published in JAMA Network Open, which analyzed cigarette consumption data in the U.S. between 2000 to 2018, found there was a 46 percent decline in cigarette consumption during this period. However, 85 percent of that decline was attributed to non-menthol cigarettes. During this time, menthol consumption was fairly stable and the market share of menthol cigarettes increased by nearly 10 percent. This pattern is consistent with scientific evidence that menthol in cigarettes increases initiation and progression to regular smoking and decreases smoking cessation success.

Additionally, we found that although consumption for non-menthol cigarettes declined 33.1 percent since the passage of the Tobacco Control Act in 2009, but there was only an 8.2 percent decline for menthol cigarettes, with 91 percent of that decline attributed to non-menthol cigarettes between 2009 and 2018.

Why is it important to ban menthol cigarettes and why has it been difficult to enact a nationwide ban? Why have other products like flavored vapes been banned and not menthol cigarettes?

Ganz: Research shows that a ban on menthol cigarettes would significantly impact public health and positively impact the African American community. A 2011 study modeling the effects of a menthol ban in the U.S. estimated that 633,252 deaths could have been averted and that one of three of these lives lost would be a Black person. Our youth and other vulnerable communities like pregnant women and Hispanic and Black populations are also at risk if this issue continues.

Delnevo: Our paper, published in the journal Nicotine & Tobacco Research, questioned if menthol cigarettes would have been banned by now if the typical consumer was young, white and upper-middle class. It is fascinating to consider how quickly flavored e-cigarettes were banned in numerous locations spurred on by the efforts of Parents against Vaping E-cigs -- an advocacy group created in 2018 led by three white mothers. Contrast this with the battle to ban menthol cigarettes for over a decade by numerous advocacy groups and organizations, including the African American Tobacco Control Leadership Council and the National African American Tobacco Prevention Network, to protect their communities, but had no meaningful action taken.

What can be done to enact a ban on menthol cigarettes?

Ganz: We urge policymakers in other states across the country to take action and follow the lead of California and Massachusetts, who banned menthol cigarettes just this year.

Delnevo: Our research has also found that local bans at the city level are likely insufficient to reduce menthol cigarette availability. That isn't to say local bans are a bad idea. They aren't. A local movement can grow to a statewide campaign, just like it did in California. But ideally, we should be addressing this at a national level. The Senate should step up and pass HR 2339, also known as the "Reversing the Youth Tobacco Epidemic Act of 2019"--which would ban menthol cigarettes nationwide and be an important step in protecting public health and achieve health equity in the U.S.

In a groundbreaking new study, researchers at the University of Minnesota, in collaboration with the U.S. Army Combat Capabilities Development Command Soldier Center, have 3D printed unique fluid channels at the micron scale that could automate production of diagnostics, sensors, and assays used for a variety of medical tests and other applications.

The team is the first to 3D print these structures on a curved surface, providing the initial step for someday printing them directly on the skin for real-time sensing of bodily fluids. The research is published in Science Advances, a peer-reviewed scientific journal published by the American Association for the Advancement of Science (AAAS).

Microfluidics is a rapidly growing field involving the control of fluid flows at the micron scale (one millionth of a meter). Microfluidics are used in a wide range of application areas including environmental sensing, medical diagnostics (such as COVID-19 and cancer), pregnancy testing, drug screening and delivery, and other biological assays.

The global microfluidics market value is currently estimated in the billions of dollars. Microfluidic devices are typically fabricated in a controlled-environment cleanroom using a complex, multi-step technique called photolithography. The fabrication process involves a silicone liquid that is flowed over a patterned surface and then cured so that the patterns form channels in the solidified silicone slab.

In this new study, the microfluidic channels are created in a single step using 3D printing. The team used a custom-built 3D printer to directly print the microfluidic channels on a surface in an open lab environment. The channels are about 300 microns in diameter--about three times the size of a human hair (one one-hundredth of an inch). The team showed that the fluid flow through the channels could be controlled, pumped, and re-directed using a series of valves.

Printing these microfluidic channels outside of a cleanroom setting could provide for robotic-based automation and portability in producing these devices. For the first time, the researchers were also able to print microfluidics directly onto a curved surface. In addition, they integrated them with electronic sensors for lab-on-a-chip sensing capabilities.

"This new effort opens up numerous future possibilities for microfluidic devices," said Michael McAlpine, a University of Minnesota mechanical engineering professor and senior researcher on the study. "Being able to 3D print these devices without a cleanroom means that diagnostic tools could be printed by a doctor right in their office or printed remotely by soldiers in the field."

But McAlpine said the future is even more compelling.

"Being able to print on a curved surface also opens up many new possibilities and uses for the devices, including printing microfluidics directly on the skin for real-time sensing of bodily fluids and functions," said McAlpine, who holds the Kuhrmeyer Family Chair Professorship in the Department of Mechanical Engineering.

A research team at LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered that exosomes derived from Vδ2-T cells (Vδ2-T-Exos) can effectively control Epstein-Barr virus-associated tumours and induce T-cell anti-tumour immunity. The novel findings of Vδ2-T-Exos provide insights into new therapeutic approach for Epstein-Barr virus (EBV)-associated tumours. The ground-breaking findings have been published in the leading academic journal, Science Translational Medicine. [Link to the publication]

Background

EBV infects about 95% of the human population and causes more than 200,000 cases of cancer each year and that around 2% of all cancer deaths are due to EBV-attributable malignancies. EBV-associated tumours include Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric tumour and post-transplant lymphoproliferative disease, etc. Current treatment options for EBV-associated tumours are limited with considerably unwanted off-target toxicities and incomplete effectiveness for relapsed or refractory disease. Vδ2-T cells are innate-like T cells with anti-tumour potentials against EBV-associated tumours. Unfortunately, its clinical translation is limited because Vδ2-T cells from some cancer patients are difficult to be expanded. Exosomes are endosome-originated small extracellular vesicles that mediate intercellular communication. Compared with cell-based therapy, cell-free exosomes have advantages with higher safety, easier storage, and lower costs. However, the anti-tumour activity of exosomes derived from Vδ2-T cells (Vδ2-T-Exos) remains unknown.

Research findings

Herein, the team found that Vδ2-T-Exos contained death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules (CD80, CD86, MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumour cells through FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumours in immunodeficient and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, the team further explored the anti-tumour activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Interestingly, the team found that allogeneic Vδ2-T-Exos had more effective anti-tumour activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumour tissues and induced more robust CD4 and CD8 T cells-mediated anti-tumour immunity. Compared with exosomes derived from NK cells with direct cytotoxic anti-tumour activity or dendritic cells that induced T-cell anti-tumour responses, Vδ2-T-Exos have dual anti-tumour activities by directly killing tumour cells and indirectly inducing T cells-mediated anti-tumour responses, thus resulting in more effective control of EBV-associated tumours.

"Our study provides the first evidence about the anti-tumour activities of Vδ2-T-Exos against EBV-associated tumours. These exosomes could effectively control EBV-associated cancers in multiple mouse models. More importantly, allogeneic Vδ2-T-Exos had higher therapeutic efficacy than autologous Vδ2-T-Exos to control EBV-associated tumours. Therefore, the Vδ2-T-Exos prepared from healthy donors can be used to treat patients with EBV-associated tumours, which is highly beneficial to the clinical application of this novel approach," said Professor Tu Wen-wei, Antony and Nina Chan professor in Paediatric Immunology, Department of Paediatrics and Adolescent Medicine, HKUMed, who led the research.

Significance of the study

The findings of the study have significant implications in cancer immunotherapy. Firstly, the identification that Vδ2-T-Exos has potent immunostimulatory property suggests that they could be designed as a cancer vaccine by serving as immune adjuvant and delivering immunogens. Secondly, the Vδ2-T-Exos has advantages over other exosome-based therapies (e.g. NK-Exos and DC-Exos) by displaying dual anti-tumour activities and are easier in preparation. Thirdly, the results that allogeneic Vδ2-T-Exos have higher anti-tumour efficacies than autologous Vδ2-T-Exos can greatly enhance the clinical feasibility of Vδ2-T-Exos, because the preparation of allogeneic exosomes does not require personalized procedures and is easier in quality control, standardization and centralization for clinical application.

A research collaboration between Queen Mary University of London, the University of Cambridge and the Institute for High Pressure Physics in Troitsk has discovered the fastest possible speed of sound.

The result- about 36 km per second - is around twice as fast as the speed of sound in diamond, the hardest known material in the world.

Waves, such as sound or light waves, are disturbances that move energy from one place to another. Sound waves can travel through different mediums, such as air or water, and move at different speeds depending on what they're travelling through. For example, they move through solids much faster than they would through liquids or gases, which is why you're able to hear an approaching train much faster if you listen to the sound propagating in the rail track rather than through the air.

Einstein's theory of special relativity sets the absolute speed limit at which a wave can travel which is the speed of light, and is equal to about 300,000 km per second. However until now it was not known whether sound waves also have an upper speed limit when travelling through solids or liquids.

The study, published in the journal Science Advances, shows that predicting the upper limit of the speed of sound is dependent on two dimensionless fundamental constants: the fine structure constant and the proton-to-electron mass ratio.

These two numbers are already known to play an important role in understanding our Universe. Their finely-tuned values govern nuclear reactions such as proton decay and nuclear synthesis in stars and the balance between the two numbers provides a narrow 'habitable zone' where stars and planets can form and life-supporting molecular structures can emerge. However, the new findings suggest that these two fundamental constants can also influence other scientific fields, such as materials science and condensed matter physics, by setting limits to specific material properties such as the speed of sound.

The scientists tested their theoretical prediction on a wide range of materials and addressed one specific prediction of their theory that the speed of sound should decrease with the mass of the atom. This prediction implies that the sound is the fastest in solid atomic hydrogen. However, hydrogen is an atomic solid at very high pressure above 1 million atmospheres only, pressure comparable to those in the core of gas giants like Jupiter. At those pressures, hydrogen becomes a fascinating metallic solid conducting electricity just like copper and is predicted to be a room temperature superconductor. Therefore, researchers performed state-of-the-art quantum mechanical calculations to test this prediction and found that the speed of sound in solid atomic hydrogen is close to the theoretical fundamental limit.

Professor Chris Pickard, Professor of Materials Science at the University of Cambridge, said: "Soundwaves in solids are already hugely important across many scientific fields. For example, seismologists use sound waves initiated by earthquakes deep in the Earth interior to understand the nature of seismic events and the properties of Earth composition. They're also of interest to materials scientists because sound waves are related to important elastic properties including the ability to resist stress."

Seismic waves, commonly associated with earthquakes, have been used by scientists to develop a universal scaling law for the sense of touch. A team, led by researchers at the University of Birmingham, used Rayleigh waves to create the first scaling law for touch sensitivity. The results are published in Science Advances.

The researchers are part of a European consortium (H-Reality) that are already using the theory to develop new Virtual Reality technologies that incorporate the sense of touch.

Rayleigh waves are created by impact between objects and are commonly thought to travel only along surfaces. The team discovered that, when it comes to touch, the waves also travel through layers of skin and bone and are picked up by the body's touch receptor cells.

Using mathematical modelling of these touch receptors the researchers showed how the receptors were located at depths that allowed them to respond to Rayleigh waves. The interaction of these receptors with the Rayleigh waves will vary across species, but the ratio of receptor depth vs wavelength remains the same, enabling the universal law to be defined.

The mathematics used by the researchers to develop the law is based on approaches first developed over a hundred years ago to model earthquakes. The law supports predictions made by the Nobel-Prize-winning physicist Georg von Békésy who first suggested the mathematics of earthquakes could be used to explore connections between Rayleigh waves and touch.

The team also found that the interaction of the waves and receptors remained even when the stiffness of the outermost layer of skin changed. The ability of the receptors to respond to Rayleigh waves remained unchanged despite the many variations in this outer layer caused by, age, gender, profession, or even hydration.

Dr Tom Montenegro-Johnson, of the University of Birmingham's School of Mathematics, led the research. He explains: "Touch is a primordial sense, as important to our ancient ancestors as it is to modern day mammals, but it's also one of the most complex and therefore least understood. While we have universal laws to explain sight and hearing, for example, this is the first time that we've been able to explain touch in this way."

James Andrews, co-author of the study at the University of Birmingham, adds: "The principles we've defined enable us to better understand the different experiences of touch among a wide range of species. For example, if you indent the skin of a rhinoceros by 5mm, they would have the same sensation as a human with a similar indentation - it's just that the forces required to produce the indentation would be different. This makes a lot of sense in evolutionary terms, since it's connected to relative danger and potential damage."

By applying natural language processing tools to the movements of protein molecules, University of Maryland scientists created an abstract language that describes the multiple shapes a protein molecule can take and how and when it transitions from one shape to another.

A protein molecule's function is often determined by its shape and structure, so understanding the dynamics that control shape and structure can open a door to understanding everything from how a protein works to the causes of disease and the best way to design targeted drug therapies. This is the first time a machine learning algorithm has been applied to biomolecular dynamics in this way, and the method's success provides insights that can also help advance artificial intelligence (AI). A research paper on this work was published on October 9, 2020, in the journal Nature Communications.

"Here we show the same AI architectures used to complete sentences when writing emails can be used to uncover a language spoken by the molecules of life," said the paper's senior author, Pratyush Tiwary, an assistant professor in UMD's Department of Chemistry and Biochemistry and Institute for Physical Science and Technology. "We show that the movement of these molecules can be mapped into an abstract language, and that AI techniques can be used to generate biologically truthful stories out of the resulting abstract words."

Biological molecules are constantly in motion, jiggling around in their environment. Their shape is determined by how they are folded and twisted. They may remain in a given shape for seconds or days before suddenly springing open and refolding into a different shape or structure. The transition from one shape to another occurs much like the stretching of a tangled coil that opens in stages. As different parts of the coil release and unfold, the molecule assumes different intermediary conformations.

But the transition from one form to another occurs in picoseconds (trillionths of a second) or faster, which makes it difficult for experimental methods such as high-powered microscopes and spectroscopy to capture exactly how the unfolding happens, what parameters affect the unfolding and what different shapes are possible. The answers to those questions form the biological story that Tiwary's new method can reveal.

Tiwary and his team applied Newton's laws of motion--which can predict the movement of atoms within a molecule--with powerful supercomputers, including UMD's Deepthought2, to develop statistical physics models that simulate the shape, movement and trajectory of individual molecules.

Then they fed those models into a machine learning algorithm, like the one Gmail uses to automatically complete sentences as you type. The algorithm approached the simulations as a language in which each molecular movement forms a letter that can be strung together with other movements to make words and sentences. By learning the rules of syntax and grammar that determine which shapes and movements follow one another and which don't, the algorithm predicts how the protein untangles as it changes shape and the variety of forms it takes along the way.

To demonstrate that their method works, the team applied it to a small biomolecule called riboswitch, which had been previously analyzed using spectroscopy. The results, which revealed the various forms the riboswitch could take as it was stretched, matched the results of the spectroscopy studies.

"One of the most important uses of this, I hope, is to develop drugs that are very targeted," Tiwary said. "You want to have potent drugs that bind very strongly, but only to the thing that you want them to bind to. We can achieve that if we can understand the different forms that a given biomolecule of interest can take, because we can make drugs that bind only to one of those specific forms at the appropriate time and only for as long as we want."

An equally important part of this research is the knowledge gained about the language processing system Tiwary and his team used, which is generally called a recurrent neural network, and in this specific instance a long short-term memory network. The researchers analyzed the mathematics underpinning the network as it learned the language of molecular motion. They found that the network used a kind of logic that was similar to an important concept from statistical physics called path entropy. Understanding this opens opportunities for improving recurrent neural networks in the future.

"It is natural to ask if there are governing physical principles making AI tools successful," Tiwary said. "Here we discover that, indeed, it is because the AI is learning path entropy. Now that we know this, it opens up more knobs and gears we can tune to do better AI for biology and perhaps, ambitiously, even improve AI itself. Anytime you understand a complex system such as AI, it becomes less of a black-box and gives you new tools for using it more effectively and reliably."

Bottom Line: Analysis of DNA copy number variants (CNVs) in the cells exfoliated in urine showed better sensitivity and similar specificity in detecting urothelial carcinoma compared with urine cytology.

Journal in Which the Study was Published:
Clinical Cancer Research, a journal of the American Association for Cancer Research

Authors: Chuan-Liang Xu, MD, PhD, urologist at Changhai Hospital in Shanghai; and Jia-Tao Ji, MD, PhD, urologist at Shanghai Hudong Hospital

Background: "Urine cytology, which is widely used to screen for bladder cancer, has high specificity but lacks sensitivity, especially for low-grade cancers," said Xu. "Cystoscopy, while more accurate than cytology, is an invasive procedure with added costs and potential complications for the patient," he added. "Therefore, an inexpensive, non-invasive test for the detection and monitoring of bladder cancer is an unmet clinical need."

"The DNA isolated from urine exfoliated cells, a complex cell mixture that potentially includes tumor cells shed from the lining of the bladder, can provide clues to the presence of bladder cancer," said Ji. "Because CNVs are a hallmark of many cancers, we developed an assay to detect CNV burden in the DNA from urine exfoliated cells."

How the Study was Conducted & Results: The assay, called UroCAD, begins with a urine sample. Following urine sedimentation and DNA extraction, the sample is analyzed using low-coverage whole-genome sequencing (LC-WGS). Because the assay relies on the detection of overall CNV burden, and not on the identification of specific genetic alterations, this cost-effective sequencing method is an ideal technique for sample analysis, noted Xu.

The researchers used samples from patients enrolled in an observational clinical trial in Shanghai that is evaluating the UroCAD assay. A total of 190 patients (126 with urothelial carcinoma, 64 without cancer) participated in the discovery phase; no significant CNV burden was detected in those without cancer. The researchers then developed a diagnostic model which incorporated all autosomal chromosomal changes in urine exfoliated cells. In the discovery cohort, UroCAD identified urothelial carcinoma with a sensitivity and specificity of 82.5 percent and 96.9 percent, respectively.

The UroCAD assay was then evaluated in a validation cohort comprising 95 patients (56 with urothelial carcinoma, 39 without cancer). When compared with urine cytology, the researchers found that UroCAD had significantly higher sensitivity (80.4 percent versus 33.9 percent) and comparable specificity (94.9 percent versus 100 percent) for the detection of urothelial carcinoma. Further, in the seven patients whose low-grade tumors were confined to the epithelial layer of the bladder (pTa tumors), UroCAD had a sensitivity of 71.4 percent, while urine cytology had a sensitivity of 0 percent.

The sensitivity of UroCAD corresponded with tumor grade, as it could detect low-grade and high-grade urothelial carcinoma with a sensitivity of 60 percent and 86.6 percent, respectively. Further, the sensitivity of the test correlated with tumor size; the sensitivity of detection for tumors of 1 cm or less, tumors between 1 and 3 cm, and tumors greater than 3 cm was 66.7 percent, 72 percent, and 95.5 percent, respectively.

Authors' Comments: "The relatively lower sensitivity of UroCAD for the detection of lower grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations," said Xu. "Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination, but not to replace it."

"For patients with hematuria or who have suspected urothelial carcinoma, UroCAD is a promising way to replace cytology and to reduce repeated cystoscopy examinations," Ji said. The use of UroCAD for the surveillance of urothelial carcinoma is currently being evaluated in a clinical trial.

Study Limitations: The detection of CNV burden was correlated with the amount of epithelial cells present, suggesting that a lack of sufficient exfoliated cells may limit the assay, Xu noted.

The COVID-19 pandemic provides an opportunity to reset the global economy and reverse decades of ecosystem and species losses, but most countries are failing to invest in nature-related economic reforms or investments, according to a Rutgers-led paper.

Indeed, some countries, including the United States, Brazil and Australia, are back-tracking on existing laws and relaxing regulations and enforcement actions aimed at protecting nature, according to lead author Pamela McElwee, an associate professor in the Department of Human Ecology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick.

"Just last week at the United Nations, more than 60 heads of state spoke at a virtual summit and pledged their support to tackle the biodiversity crisis. But when we look at what countries are doing, either in their prior budget and policies or especially in their post-COVID planning and recovery packages, very few governments are putting their money where their mouths are," McElwee said. "We still see huge amounts of financial support for harmful practices, such as subsidizing overfishing or fossil fuel production or building infrastructure that will harm ecological integrity. Only a small number of countries are addressing the biodiversity crisis in the serious manner it deserves."

The paper, by economists, anthropologists and environmental scientists at many institutions on three continents, is published in the journal One Earth. It explores the changes in global economic systems - including incentives, regulations, fiscal policy and employment programs - that are necessary to shift away from activities that damage biodiversity and move toward those supporting ecosystem resilience.

Unless action is taken, around 1 million species face extinction, many within decades, and the global rate of species extinction will accelerate, according to the 2019 Global Assessment Report on Biodiversity and Ecosystem Services from the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). That report noted the extinction rate is "already at least tens to hundreds of times higher than it has averaged over the past 10 million years." The authors of this new paper were all contributors to the 2019 IPBES report.

The new paper spells out the actions governments should be taking in their stimulus and recovery plans that would prioritize nature, provide immediate employment benefits and lead to longer-term transformations in the global economy. Examples include shifting from harmful fossil fuel subsidies to beneficial ones, including those that encourage environmentally friendly farming; carbon taxes that could support forest protection programs; and work programs that focus on ecological restoration and green infrastructure.

While many scientists and politicians have promoted a COVID-19 recovery that is low carbon, how to include biodiversity and ecosystems in economic plans has received much less attention. Discussions of nature-related actions have largely focused on closing wildlife markets as a potential source of novel viruses, expanding protected natural areas or reducing tropical deforestation. While these can be important, they do not necessarily address the root causes of ecological disruptions, the authors say.

A number of countries, including the United States and China, have allocated essentially zero stimulus funding to biodiversity or ecosystems. Only the European Union and member countries are making substantial financial investments in biodiversity for post-COVID planning. Other nations, including New Zealand, India and Pakistan, are proposing investments in nature-based jobs like ecological restoration, but at only modest levels.

"Governments are falling short of their stated promises and they need to do more - immediately," McElwee said. "We will continue to monitor proposed recovery packages, stimulus measures and financial pledges for how they address the biodiversity crises going forward, particularly in light of the mega-summit on biodiversity to be held in China next May."

Could something as simple as a certain type of sugar water be medicine for perforated bones, and even bone marrow cancer itself?

Inside our bodies are some jellyfish-like cells that actually eat away at our bones. Every year, they eat about ten per cent of the bone mass in our body. Fortunately, other cells usually follow and build up new bone.

We undergo a kind of continuous remodelling and repair that enables most of us to traipse around with steel in our legs and arms.

In people with bone marrow cancer, the bone-eating cells run amok. They become too numerous and eat too much. The bone-building gang doesn't have time to rebuild the bone mass, despite overtime and long shifts. Bone tissue gets gobbled up.

Many people with bone marrow cancer often end up with perforated bones, a condition that is very painful to live with. They sometimes experience collapsed vertebrae or suffer broken bones just by turning in bed.

For decades, scientists around the world have been scratching their heads and wondering what the cause could be. Various theories have been launched, but researchers have not reached a consensus on the main cause.

Bone marrow cancer remains an incurable disease so far. Available treatments can prolong life, but not cure the disease.

Now Standal and her research group at the Centre of Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology (NTNU) have discovered a piece of the puzzle that looks very promising.

They have come to the conclusion that the cause of the bone destruction is too little sugar. We're not talking about the sugar we eat in our cakes and biscuits, but sugar that resides in a substance that is important for the immune system.

To get to the bottom of how sugar is related to bone loss, we need to get into the bone marrow. This is the soft cavity that inside all our bones.

Within the bones are plasma cells. When bacteria or viruses enter the body, the plasma cells begin their job of getting rid of the invaders. Antibodies are produced which are sent via the blood, ready to do battle.

So far so good, but in people with bone marrow cancer, far too much of one type of antibody is produced. It's going amok here, too. The antibody that the cancer makes is also completely useless. It doesn't knock out either the cold or the flu but just takes up too much space and displaces other types of antibodies.

"I thought simply. If people with bone marrow cancer have too much of the antibody and too many bone-eating cells, then they must be connected," Standal says.

The search for an answer gobbled a lot of her working hours for almost five years. The hard work was fortunately not in vain, and has led to a completely new and fundamental understanding.

The finding has now been published in Blood, the highest ranked blood disease journal in in the world.

This is how Standal arrived at the answer:

The vast majority of patients with bone marrow cancer develop perforated bones, but not all. Standal asked nicely, and received samples from patients with bone loss. She also took samples from patients without this kind of bone loss.

The researchers extracted antibodies from the samples and cultured bone-eating cells in the laboratory.

When Standal placed the bone-eating cells into the antibody of the patients with bone perforations, she discovered that the number of bone-eating cells increased.

When she put the bone-eating cells into the antibody of the patients without bone perforations, she discovered that the number of bone-eating cells did not increase.

"Why that was the case became the next interesting thing to figure out," Standal says.

The antibody carries a type of sugar that "decorates" it, in a way. The sugar has an effect on how the antibody works. Standal found her way to Manfred Wuhrer at the Center for Proteomics and Metabolomics of the Leiden University Medical Center in the Netherlands. He is a specialist in this type of sugar, and Standal sent the samples to him.

He found that individuals with bone loss were missing two sugar molecules at the end of a long chain inside the antibody.

"There was too little sugar," says Standal.

But this answer wasn't sufficient, either.

Although a difference was detected between the two groups, the researchers could not confirm that the missing sugar molecules were the reason patients developed more bone-eating cells. Several further experiments had to be conducted.

The research team went to the lab and put more sugar on the antibody. This did not lead to more bone-eating cells. Standal also did the opposite, removing sugar from the antibody. This did lead to more bone-eating cells.

The researchers then had sufficient test results to show that too little sugar can be decisive for the number of bone-eating cells. But this is not enough in medical research - at least not if the goal is to use the knowledge to make medicine for humans.

The next step involved animal experiments with mice that have bone marrow cancer. The mice were divided into two groups and were given two different types of sugar water. In theory, one type of sugar water would lead to more sugar on the antibody.

"The theory actually worked. The mice that received this type of sugar water had smaller perforations in their bone tissue. They also developed less cancer," says Standal.

Now she has to carry out more animal experiments to move forward on the path towards a treatment that can give patients with bone marrow cancer a better life.

"I think it might be realistic to try this on a small group of patients in four to five years," says Standal.