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Researchers at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center have identified a previously unrecognized form of hormone therapy-resistant prostate cancer, as well as a set of molecules that drive its growth. This discovery opens the door to the development of therapies that treat this specific disease.
In the study, published May 27 in Science, the researchers examined the molecular changes that occur within an advanced malignancy called castration-resistant prostate cancer, which arises when tumors evade treatment that deprives them of the hormones that drive their growth. Using samples derived from patients, they conducted a comprehensive survey of this cancer.
“Our data showed us that there are four groups of castration-resistant disease, two of which have not been defined before,” said co-senior author Dr. Ekta Khurana, WorldQuant Foundation Research Scholar and associate professor of physiology and biophysics at Weill Cornell Medicine.
One of these, which they call stem cell-like (SCL), accounts for approximately a quarter of castration-resistant prostate cancers, she and her collaborators estimated. Within SCL tumor cells, they identified a set of proteins that work together to fuel this treatment-resistant disease. Studies have shown that this same molecular pathway drives other solid tumors, including colorectal cancer and malignancies of the breast and lung, so scientists are already working to develop ways of interfering with their activity.
“For patients that fall into this SCL group, we have found very promising drug targets, which future studies will work to validate,” said Dr. Khurana, who is also co-leader of the Genetics and Epigenetics Program at the Sandra and Edward Meyer Cancer Center and a member of the Englander Institute for Precision Medicine at Weill Cornell Medicine. Dr. Khurana collaborated with co-senior author Dr. Yu Chen at Memorial Sloan Kettering Cancer Center on this study.
An estimated 268,000 men will develop prostate cancer this year. Researchers already knew that this type of cancer encompasses more than one disease. Some tumors may manage to resist the treatment, but still need testosterone and other hormones, which are called androgens collectively, to grow. Others, meanwhile, shed their dependence on androgens and take on an aggressive form known as neuroendocrine. The new study identified two additional types of this disease: SCL and WNT, named for the signaling pathways that is overactive in tumors of these types.
Scientists seeking to investigate castration-resistant prostate cancer have generally lacked enough cells derived from patients to capture its full diversity. For this study, however, the team had access to 40 tumor samples. Most of these came from a collection of organoids, which are tiny organ-like structures grown from tumor cells collected from patients at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center.
The researchers analyzed these cells’ DNA, RNA, and how compactly their DNA was packaged, a characteristic known as chromatin accessibility. Changes in this packaging contribute to cancer by altering genes’ availability for expression. The chromatin data led them to identify the four groups, including SCL and WNT.
To determine the proportion of cases they each may comprise, the researchers used RNA sequencing data to classify 100 patients from Weill Cornell Medicine and 266 from the organization Stand Up to Cancer. Depending on the set of patients, 22 to 30 percent fell into the SCL category, while WNT accounted for 5 or 7 percent.
Focusing on SCL, they used sophisticated computational tools to integrate the molecular data and identify the malfunctioning pathway at the heart of this cancer. These proteins, FOSL1, TEAD, YAP and TAZ, become overly active and alter chromatin accessibility to propel tumor growth. In experiments, the researchers found that two molecules known to interfere with these proteins slowed the growth of the SCL cells, but not that of androgen-dependent cells — a result that highlights the potential for a targeted treatment.
“Once you can identify which type of tumor patients have, that’s very powerful information,” Dr. Khurana said.

Dopamine is an important signalling molecule for nerve cells. Its concentration could not be precisely determined with both high spatial or temporal resolution until now. A new method has now made this possible: A research team from Bochum, Göttingen and Duisburg used modified carbon nanotubes that glow brighter in the presence of the messenger substance dopamine. These sensors visualise the release of dopamine from nerve cells with unprecedented resolution. The researchers headed by Professor Sebastian Kruss from the Physical Chemistry Department at Ruhr-Universität Bochum (RUB) and Dr. James Daniel as well as Professor Nils Brose from the Max Planck Institute for Multidisciplinary Sciences in Göttingen report on this in the journal PNAS from 25 May 2022.
Fluorescence changes in the presence of dopamine
The neurotransmitter dopamine controls the brain’s reward centre, among other things. If this signal transmission no longer functions, it can lead to disorders such as Parkinson’s disease. Moreover, the chemical signals are altered by drugs such as cocaine and play a role in substance abuse disorders. “However, until now there was no method that could simultaneously visualise the dopamine signals with high spatial and temporal resolution,” explains Sebastian Kruss, head of the Functional Interfaces and Biosystems Group at RUB and a member of the Ruhr Explores Solvation Cluster of Excellence (RESOLV) and the International Graduate School of Neuroscience (IGSN).
This is where the novel sensors come into play. They are based on ultra-thin carbon tubes, about 10,000 times thinner than a human hair. When irradiated with visible light, they glow in the near-infrared range with wavelengths of 1,000 nanometres and more. “This range of light is not visible to the human eye, but it can penetrate deeper into tissue and thus provide better and sharper images than visible light,” says Kruss. In addition, there are far fewer background signals in this range that can distort the result.
“We have systematically modified this property by binding various short nucleic acid sequences to the carbon nanotubes in such a way that they change their fluorescence when they come into contact with defined molecules,” explains Sebastian Kruss. This is how his research group has succeeded in turning carbon nanotubes into tiny nanosensors that specifically bind to dopamine and fluoresce more or less strongly depending on the dopamine concentration. “We immediately realised that such sensors would be interesting for neurobiology,” says Kruss.
Coating healthy nerve cells with a sensor layer
In order to do this, the sensors have to be moved into the vicinity of functioning neuronal networks. Dr. Sofia Elizarova and James Daniel from the Max Planck Institute for Multidisciplinary Sciences in Göttingen developed cell culture conditions for this, in which the nerve cells remain healthy and can be coated with an extremely thin layer of sensors. This allowed the researchers to visualise individual dopamine release events along neuronal structures for the first time and gain insights into the mechanisms of dopamine release.
Kruss, Elizarova and Daniel are confident that the new sensors have enormous potential: “They provide new insights into the plasticity and regulation of dopamine signals,” says Sofia Eizarova. “In the long term, they could also facilitate progress in the treatment of diseases such as Parkinson’s.” In addition, further sensors are currently being developed with which other signalling molecules can be made visible for example to identify pathogens.
Cooperation partners
The study was conducted by researchers from Physical Chemistry II at Ruhr-Universität Bochum and the Max Planck Institute for Multidisciplinary Sciences in Göttingen, teams from the Institute of Physical Chemistry at Göttingen University, the Centre for Integrative Physiology and Molecular Medicine at Saarland University and the Fraunhofer Institute for Microelectronic Circuits and Systems in Duisburg.
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen. Note: Content may be edited for style and length.

In today’s medicine, doctors define and diagnose most diseases on the basis of symptoms. However, that does not necessarily mean that the illnesses of patients with similar symptoms will have identical causes or demonstrate the same molecular changes. In biomedicine, one often speaks of the molecular mechanisms of a disease. This refers to changes in the regulation of genes, proteins or metabolic pathways at the onset of illness. The goal of stratified medicine is to classify patients into various subtypes at the molecular level in order to provide more targeted treatments.
To extract disease subtypes from large pools of patient data, new machine learning algorithms can help. They are designed to independently recognize patterns and correlations in extensive clinical measurements. The LipiTUM junior research group, headed by Dr. Josch Konstantin Pauling of the Chair for Experimental Bioinformatics has developed an algorithm for this purpose.
Complex analysis via automated web tool
Their method combines the results of existing algorithms to obtain more precise and robust predictions of clinical subtypes. This unifies the characteristics and advantages of each algorithm and eliminates their time-consuming adjustment. “This makes it much easier to apply the analysis in clinical research,” reports Dr. Pauling. “For that reason, we have developed a web-based tool that permits online analysis of molecular clinical data by practitioners without prior knowledge of bioinformatics.”
On the website (https://exbio.wzw.tum.de/mosbi/), researchers can submit their data for automated analysis and use the results to interpret their studies. “Another important aspect for us was the visualization of the results. Previous approaches were not capable of generating intuitive visualizations of relationships between patient groups, clinical factors and molecular signatures. This will change with the web-based visualization produced by our MoSBi tool,” says Tim Rose, a scientist at the TUM School of Life Sciences. MoSBi stands for “Molecular Signatures using Biclustering.” “Biclustering” is the name of the technology used by the algorithm.
Application for clinically relevant questions
With the tool, researchers can now, for example, represent data from cancer studies and simulations for various scenarios. They have already demonstrated the potential of their method in a large-scale clinical study. In a cooperative study conducted with researchers from the Max Planck Institute in Dresden, the Technical University of Dresden and the Kiel University Clinic, they studied the change in lipid metabolism in the liver of patients with non-alcoholic fatty liver disease (NAFLD).
This widespread disease is associated with obesity and diabetes. It develops from the non-alcoholic fatty liver (NAFL), in which lipids are deposited in liver cells, to non-alcoholic steatohepatitis (NASH), in which the liver becomes further inflamed, to liver cirrhosis and the formation of tumors. Apart from dietary adjustments, no treatments have been found to date. Because the disease is characterized and diagnosed by the accumulation of various lipids in the liver, it is important to understand their molecular composition.
Biomarkers for liver disease
Using the MoSBi methods, the researchers were able to demonstrate the heterogeneity of the livers of patients in the NAFL stage at the molecular level. “From a molecular standpoint, the liver cells of many NAFL patients were almost identical to those of NASH patients, while others were still largely similar to healthy patients. We could also confirm our predictions using clinical data,” says Dr. Pauling. “We were then able to identify two potential lipid biomarkers for disease progression.” This is important for early recognition of the disease and its progression and the development of targeted treatments.
The research group is already working on further applications of their method to gain a better understanding of other diseases. “In the future algorithms will play an even greater role in biomedical research than they already do today. They can make it significantly easier to detect complex mechanisms and find more targeted treatment approaches,” says Dr. Pauling.
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Materials provided by Technical University of Munich (TUM). Note: Content may be edited for style and length.

T cells, biology textbooks teach us, are the soldiers of the immune system, constantly on the ready to respond to a variety of threats, from viruses to tumors. However, without rest and maintenance T cells can die and leave their hosts more susceptible to pathogens, Yale scientists report May 27 in the journal Science.
“We may have to change how we teach T cell biology,” said Lieping Chen, the United Technologies Corporation Professor in Cancer Research at Yale and professor of immunobiology, of dermatology, and of medicine and senior author of the study.
Until pathogens are detected, T cells remain in a quiescent state. However, the molecular mechanisms that keep T cells inactive were previously unknown.
In the new study, Yale researchers show that a protein known as CD8a — which is found in a subset of T cells called CD8 cells — is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.
Further, they identified another protein, PILRa, that provides a biochemical signal to CD8a. By disrupting this protein pair, both “memory” CD8 cells — cells that previously had been exposed to pathogens — and naïve cells died because they lacked the ability to stay in a quiescent state.
The researchers hope that understanding why this resting state is crucial to maintenance and survival of T cells can lead to improved immune system function.
Chen noted that as people age they tend to lose both naïve and memory T cells, making older individuals more susceptible to infections. It is possible that the inability of T cells to remain in a quiescent state could lead to people becoming more susceptible to infections and cancer, the authors suggest.
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

While the U.S. spends twice as much on cancer care as the average high-income country, its cancer mortality rates are only slightly better than average, according to a new analysis by researchers at Yale University and Vassar College.
The results were published May 27 in JAMA Health Forum.
“There is a common perception that the U.S. offers the most advanced cancer care in the world,” said lead author Ryan Chow, an M.D./Ph.D. student at Yale. “Our system is touted for developing new treatments and getting them to patients more quickly than other countries. We were curious whether the substantial U.S. investment on cancer care is indeed associated with better cancer outcomes.”
Out of the 22 high-income countries included in the study, the United States had the highest spending rate.
“The U.S. is spending over $200 billion per year on cancer care — roughly $600 per person, in comparison to the average of $300 per person across other high-income countries,” said senior author Cary Gross, professor of medicine and director of the National Clinician Scholars Program at Yale. “This raises the key question: Are we getting our money’s worth?”
The researchers found that national cancer care spending showed no relationship to population-level cancer mortality rates. “In other words, countries that spend more on cancer care do not necessarily have better cancer outcomes,” said Chow.
In fact, six countries — Australia, Finland, Iceland, Japan, Korea, and Switzerland — had both lower cancer mortality and lower spending than the United States.
Smoking is the strongest risk factor for cancer mortality, and smoking rates have historically been lower in the United States, compared to other countries. When the researchers controlled for international variations in smoking rates, U.S. cancer mortality rates became no different than the average high-income country, with nine countries — Australia, Finland, Iceland, Japan, Korea, Luxembourg, Norway, Spain, and Switzerland — having lower smoking-adjusted cancer mortality than the United States.
“Adjusting for smoking shows the United States in an even less favorable light, because the low smoking rates in the U.S. had been protective against cancer mortality,” said Chow.
More research is needed to identify specific policy interventions that could meaningfully reform the United States cancer care system, the authors say. However, they point to lax regulation of cancer drug approvals and drug pricing as two key factors contributing to the high cost of U.S. cancer care.
“The pattern of spending more and getting less is well-documented in the U.S. healthcare system; now we see it in cancer care, too,” said co-author Elizabeth Bradley, president of Vassar College and professor of science, technology, and society. “Other countries and systems have much to teach the U.S. if we could be open to change.”
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Materials provided by Yale University. Note: Content may be edited for style and length.

Biological arms races are commonplace in nature. Cheetahs, for example, have evolved a sleek body form that lends itself to rapid running, enabling them to feast upon similarly speedy gazelles, the fastest of which may evade predation. On the molecular level, immune cells produce proteins to conquer pathogens, which may in turn evolve mutations to evade detection.
Though less well known, other games of one-upmanship unfold within the genome. In a new study, biologists at the University of Pennsylvania show, for the first time, evidence of a two-sided genomic arms race involving stretches of repetitive DNA called satellites. “Opposing” the rapidly evolving satellites in the arms race are similarly fast-evolving proteins that bind those satellites.
While satellite DNA does not encode genes, it can contribute to essential biological functions, such as formation of molecular machines that process and maintain chromosomes. When satellite repeats are improperly regulated, impairments to these crucial processes can result. Such disruptions are hallmarks of cancer and infertility.
Using two closely related species of fruit flies, researchers probed this arms race by purposefully introducing a species mismatch, pitting, for example, one species’ satellite DNA against the other species’ satellite-binding protein. Severe impairments to fertility were a result, underscoring evolution’s delicate balance, even at the level of a single genome.
“We typically think of our genome as a cohesive community of elements that make or regulate proteins to build a fertile and viable individual,” says Mia Levine, an assistant professor of biology in Penn’s School of Arts & Sciences and the senior author on the work, published in Current Biology. “This evokes the idea of a collaboration between our genomic elements, and that’s largely true.
“But some of these elements, we think, actually harm us,” she says. “This disquieting idea suggests that there needs to be a mechanism to keep them in check.”
The researchers’ findings, likely to also be relevant in humans, suggest that when satellite DNA occasionally escapes the management of satellite-binding proteins, significant costs to fitness can occur, including impacts on molecular pathways required for fertility and perhaps even those relevant in the development of cancer.

Using a next generation sequencing analysis to examine human endogenous retrovirus (HERV) integration sites, researchers from Kumamoto University, the National Institute of Genetics (Japan), and the University of Michigan (USA) have discovered that these ancient retroviruses can undergo retrotransposition (DNA sequence insertion with RNA mediation) into iPS cells. The team believes that their discovery places a spotlight on a possible risk that HERVs pose when using iPS cells in regenerative medicine.
The study of ancient retroviruses embedded in our genome requires knowledge about our coexistence with viral threats throughout history. We know that HERVs occupy approximately 8% of the human genome and obtain mutations and deletions over long periods. HERVs are also expressed in early embryos and play several physiological roles in human development. For example, HERV-W and HERV-FRD Env proteins are important for placental formation, and HERV-K is thought to protect host cells from exogenous retrovirus infection. However, uncontrollable HERV-K expression is also thought to be associated with various diseases, including various cancers and neurological diseases, but the details of this association is not well known in humans.
Since no one has yet discovered replication competent HERVs in our genome, it is thought that they are from an extinct (fossil) virus. In their current work, the research team from Japan and the US discovered that HERV-K is expressed in SOX2-expressing cells, such as those in early embryos, cancer stem cells and iPS cells. They also found that some HERV-K are newly integrated into the host genome in the absence of Env, the viral envelope glycoprotein. This integration was dependent on reverse transcriptase, integrase and protease, thus the researchers hypothesized that the HERV-K embedded in our genome is actually not from a fossil virus, but moves on the genome through the synthesis of proviral DNA reverse transcription. Interestingly, when the researchers compared the HERV-K integration sites between iPS and fibroblast cells from the same donor, they found new HERV-K integration sites in iPS cells. However, the new integration sites were rarely preserved and disappeared during long-term culturing. HERV-K is likely to be randomly integrated into genome, thus the possibility remains that HERV-K retrotransposed-cells predominantly survive depending on their integration site.
The movement of HERV-K on the genome might cause cancer and neurological diseases by altering the gene expression profile. The researchers believe that the risk of HERV-K transposition is low in iPS cells but suggest that monitoring HERV-K integration sites should be seriously considered to improve the safety of regenerative medicine using iPS cells.
This research was published online on 14 April 2022 in the Journal of Virology.
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Materials provided by Kumamoto University. Note: Content may be edited for style and length.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesMonkeypox patients should avoid any contact with their pets for 21 days, according to new advice from the UK Health Security Agency (UKHSA). So far, 106 people in the UK have been confirmed as infected with the virus.Gerbils, hamsters and other rodents could be particularly susceptible to the disease and the concern is it could spread in the animal population. The government said no cases have been detected in pets so far and the risk is still low.”The worry is the virus could get into domestic animals and essentially ping-pong between them and humans,” said Prof Lawrence Young, a virologist at the University of Warwick.”If you are not careful you might create an animal reservoir for the disease that could result in it spreading back into humans, and we’ll be in a loop of infection.”What is monkeypox and how do you catch it?How to tell if a rash is monkeypoxMonkeypox: Handing out health advice without stigmaThe guidance from the UKHSA and other health authorities recommends that pet guinea pigs, rats, mice and other rodents should be removed from the household of someone infected with monkeypox for 21 days, and be tested for the disease. There are thought to be two million households in the UK with a pet rodent of some kind, according to sales data.Other pets like dogs and cats should be placed under household isolation with regular vet checks to “ensure no clinical signs are observed”.Related advice from the Department for Environment, Food and Rural Affairs (Defra) says that “where possible” the patient should avoid preparing food or grooming their pet if this can be done by someone else in the household. England’s chief veterinary officer Christine Middlemiss said: “No cases of monkeypox have ever been suspected or reported in pets in the UK and the risk remains low. “We will continue to monitor the situation closely and work with veterinary and public health colleagues, both in the UK and across the world, to manage the animal health associated risks with monkeypox.”Reservoir riskSeparate advice published by the European Centre for Disease Control (ECDC) this week said that rodent pets belonging to monkeypox patients should “ideally” be isolated in monitored facilities and tested for the disease before their quarantine period ends.The animals should only be put down as a last resort in situations where isolation is not feasible, the document said. Larger pets, such as dogs, could quarantine at home with regular checks on their health status. Image source, Getty ImagesScientists say little is currently known about how monkeypox might behave in the domestic pet population. But rodents and a particular species of squirrel are likely to be capable of catching and spreading the disease more easily than humans. The ECDC says a “spillover” event, where a human infects a pet animal, could potentially lead to the virus establishing itself in European wildlife, although it describes the risk as “very low”.The concern is that monkeypox could become what’s known as an endemic zoonoses, where a disease jumps between animal species and is constantly present in that new population. More on this storyMonkeypox: Handing out health advice without stigmaMonkeypox: Time to worry or one to ignore?Got a new rash? How to tell if it is monkeypox

Drinking a small amount of whey protein before meals has been shown to help people with type 2 diabetes control their blood sugars.
In a study, which holds potential for dietary management of the condition, people with type 2 diabetes drank a pre-made shot before meals which contained a low dose of whey protein. They were monitored for a week as they went about normal daily life.
To compare the potential benefits of whey protein, the same participants also spent a week drinking a control shot that contained no protein in order to measure the results against each other.
Results from continuous glucose monitoring revealed that glucose levels were much better controlled when taking the whey supplement before meals. On average, they had two hours extra per day of normal blood sugar levels compared to the no protein week. In addition, their daily blood glucose levels were 0.6 mmol/L lower compared to when they consumed the supplement without any protein.
Dr Daniel West, Senior Lecturer and Principal Investigator working within the Human Nutrition Research Centre and Diabetes Research Group at Newcastle University, UK said: “While previous studies for a few hours in the lab have shown the potential for this dietary intervention, this is the first time that people have been monitored as they go about normal life.
“We believe the whey protein works in two ways, firstly, by slowing down how quickly food passes through the digestive system and secondly, by stimulating a number of important hormones that prevent the blood sugars climbing so high.
“As we see growing numbers of people around the world developing diabetes, investigating the potential of alternatives to drugs such as food supplements becomes more important.”
18 people with type 2 diabetes consumed a small drink — in a 100 ml shot- with 15 grams of protein 10 minutes before breakfast, lunch and dinner over seven days and remained on their prescribed diabetes medication. Continuous glucose monitoring automatically tracked blood glucose levels over the course of the week.
Newcastle University PhD student, Kieran Smith, who oversaw the glucose monitoring and analysed the data, said: “People were able to stick to the regime and liked the idea of having a convenient, tasty, small pre-made drink that could be carried with them and taken before meals.”
The team intend to further explore the benefits of non-medical interventions running the study on a larger scale and for a longer period of up to six months. They also plan to look at alternative proteins, such as those that come from plant sources like peas, fungi and potatoes to open up options for vegan and religious dietary needs.
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Materials provided by Newcastle University. Note: Content may be edited for style and length.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesAnother 25 children have been diagnosed with unexplained hepatitis in the UK, bringing the total number affected to 222, health officials say.Of those cases, 158 live in England, 31 in Scotland, 17 in Wales and 16 in Northern Ireland.Most are under five years old and had diarrhoea and nausea followed by jaundice – yellowing of the skin or eyes.A surge in cases has also been detected in countries around the world.The UK Health Security Agency (UKHSA) is investigating a strong link with a common virus, called adenovirus.It has been detected in many samples taken from children, but health experts are also looking at other factors including the effect of previous infections, such as Covid, or two infections occurring at the same time.A formal study of the causes and factors involved is under way, UKHSA said.Mum’s fear for girl, four, in hepatitis outbreak The UK first reported an unexpected rise in cases of severe liver inflammation, or acute hepatitis, in previously healthy children in mid-April.It said there was no evidence of any link to coronavirus vaccines because the majority of infected children are too young to have received the jab.More than 20 countries have since found children affected in a similar way.Dr Renu Bindra, senior medical adviser and incident director at UKHSA, said: “We are working with other countries who are also seeing new cases to share information and learn more about these infections.”The likelihood of children developing hepatitis remains extremely low. “Maintaining normal hygiene measures, including making sure children regularly wash their hands properly, helps to reduce the spread of many common infections, including adenovirus.”We continue to remind everyone to be alert to the signs of hepatitis – particularly jaundice, look for a yellow tinge in the whites of the eyes – and contact your doctor if you are concerned.”A small number of children over the age of 10 with hepatitis are also being investigated. Some children in the UK have needed a liver transplant.No children have died from the illness in the UK, but there have been deaths overseas.More on this storyHepatitis detected in nearly 300 children worldwideHepatitis in children mystery still unsolvedChild hepatitis cases falsely linked to Covid jab