Body

The immune system establishes "forward operating bases", or lymph node-like structures, inside the tumors of some patients with kidney and other urologic cancers, researchers at Winship Cancer Institute of Emory University have discovered.

Patients with well-supported immune cells in their tumors are more likely to control their cancers' growth for a longer time -- findings that could guide treatment decisions after surgery for kidney cancer. In addition, ongoing work has found the observation is broadly applicable to many cancer types, and could help researchers expand the dramatic but sparse benefits of cancer immunotherapy to more people.

The results are scheduled for publication in Nature.

"We knew that if there are more T cells in a tumor, the patient is likely to respond better to cancer immunotherapy," says lead author Haydn Kissick, PhD. "But we were looking at a more basic question: why do some tumors have lots of T cells in them, and others don't?"

Kissick is assistant professor of urology and microbiology and immunology at Emory University School of Medicine, Emory Vaccine Center and Winship Cancer Institute. His lab collaborated with surgeons and oncologists at Winship to examine tumor samples removed from patients with kidney, prostate and bladder cancer.

CD8 T cells hunt down and eliminate intruders - in this case, cancer cells. In patients with high levels of CD8 T cells residing in their tumors, their immune systems appeared to be better trained to suppress cancer growth after surgery, when small numbers of cancer cells (micrometastases) may be lurking elsewhere in the body. The cancers of those who had lower levels of CD8 T cells tended to progress four times more quickly after surgery than those with higher levels.

The finding has important implications, says Viraj Master, MD, who performed many of the kidney cancer surgeries. In this situation, additional treatments are not performed unless or until kidney cancer reappears, says Master, who is professor of urology at Emory University School of Medicine and Winship's Director of Integrative Oncology and Survivorship.

“Even after potentially curative surgery for aggressive kidney cancers, a significant fraction of patients will experience cancer recurrence,” he says. “But with this information, we could predict more confidently that some people won’t need anything else, thus avoiding overtreatment. However, on the basis of these findings, for others who are at higher risk of recurrence, we could potentially scan at more regular intervals, and ideally, design adjuvant therapy trials.”

The findings also provide insights for scientists interested in how the immune system successfully controls some cancers, but with others, the T cells become increasingly exhausted and ineffective.

"This study may lead to new insights into why immunotherapy can be so effective in some cancer types, but rarely works in others such as prostate cancer, and may highlight a path forward for developing more effective immunotherapy treatments," says Howard Soule, PhD, executive vice president and chief science officer for the Prostate Cancer Foundation, which supported the Winship team's work.

Kissick and his colleagues were surprised to find "stem-like" T cells, or precursors of exhausted cells, inside tumor samples. Stem-like T cells are the ones that proliferate in response to cancer immunotherapy drugs, which can revive the immune system's ability to fight the cancer.

"Lymph nodes are like 'home base' for the stem-like T cells," says Carey Jansen, an MD/PhD student who is the first author of the Nature paper. "We had expected that the stem-like cells would stay in lymphoid tissue and deploy other T cells to infiltrate and fight the cancer. But instead, the immune system seems to set up an outpost, or a forward base, inside the tumor itself."

The researchers found that other immune cells called "antigen-presenting cells" or APCs, which are usually found within lymph nodes, can also be seen within tumors. APCs help the T cells figure out when and what to attack. Like high numbers of CD8 T cells, high numbers of APCs in tumors were also a predictor of longer progression-free survival in kidney cancer patients.

The APCs and the stem-like cells were usually together within the same "nests," in a way that resemble how the two types of cells interact in lymph nodes. This relationship was apparent in kidney cancers and also in samples from prostate and bladder cancers.

"The question of how the stem-like cells get into a tumor was not answered, but we do think that the APCs support the stem-like cells and are necessary for their maintenance," Kissick says. "Given that these are the cells responsive to cancer immunotherapy agents, focusing on the relationship between the APCs and the T cells within the tumors could be valuable."

Patients with chronic pain caught between cardiovascular concerns about non-opioid analgesics and addiction risks of opioids, likely causing significant unmet need for pain relief.

A new Boston University School of Public Health (BUSPH) study published in JAMA Network Open shows that the decline in prescriptions of non-opioid analgesics--largely NSAIDs and COX-2 inhibitors--in the early 2000s coincided with a marked increase in opioid prescribing. The authors surmise that, after the cardiovascular side effects of COX-2 inhibitors came to light in the early 2000s, opioid prescriptions increased to fill the gap for people with chronic musculoskeletal pain.

"While the opioid epidemic is complex and has many possible causes, our findings suggest that health risks associated with NSAIDs were one factor that led to increased prescribing of opioids," says lead study author Dr. Andrew Stokes, assistant professor of global health at BUSPH.

The study also found that the growing recognition of the opioid crisis between 2013 and 2016 led to decreases in opioid and non-opioid analgesic prescriptions for people with chronic musculoskeletal pain, especially among those of low socioeconomic status. "Care is needed to ensure that our response to the opioid crisis does not leave people living with chronic pain behind. The abrupt decline in prescribing to those of low socioeconomic status is concerning given that these same individuals also face the greatest barriers to accessing alternative pain treatments, such as physical therapy," Dr. Stokes says.

With support from the Robert Wood Johnson Foundation, the researchers used 1999-2016 data from the National Health and Nutrition Examination Study on 7,256 adults with functional limitations due to back or neck pain and/or arthritis or other rheumatic disease. They found that increases in opioid prescriptions approximately matched decreases in non-opioid analgesics (predominantly NSAIDs and COX-2 inhibitors) beginning between 2003 and 2006. They then saw significant decreases in opioid prescriptions between 2013 and 2016, particularly among men and people with less education.

"We realized that the point at which increasing opioid prescriptions crossed over with the decrease in non-opioid prescriptions occurred when the cardiovascular risks of COX-2 inhibitors led to rofecoxib (Vioxx) coming off the market. The gastrointestinal risks of NSAIDs were also well-recognized by then. Thus it appeared to us that an increase in opioid prescribing during that time was, at least in part, an unintended consequence of COX-2 inhibitors coming off the market and concerns about NSAID risk," says study senior author Dr. Tuhina Neogi, professor of epidemiology at BUSPH, professor of medicine at the Boston University School of Medicine, and Chief of Rheumatology at Boston Medical Center.

Dr. Neogi says it is important to continue working to reduce opioid prescribing and use, but there needs to be equal attention and effort toward providing a comprehensive, multimodal approach to pain, including proven but under-utilized non-pharmaceutical strategies such as physical therapy.

"There's so much talk now about transitioning people away from opioids. But if that's happening without considering the barriers to non-pharmacologic treatments, there may be a significant problem of under-treatment of pain," adds study co-author Mx. Dielle Lundberg, a research fellow at BUSPH.

According to a new study led by a team from The University of New Mexico, centuries-old laws about the behavior of gas mixtures do not apply in the presence of shock waves.

This finding could have potential impact on everything that involves mixtures of gases exposed to a shock wave, for example, during combustion in an engine. This is also relevant for conventional and nuclear explosions, supersonic jets, gas-cooled nuclear reactor plants and inertially-confined fusion.

The results were published recently in the paper "Dalton's and Amagat's Laws Fail in Gas Mixtures with Shock Propagation" in Science Advances. Authors on the paper are Patrick Wayne, Daniel Freelong, Gregory Vigil, Timothy Clark, Peter Vorobieff and C. Randall Truman from the Department of Mechanical Engineering at UNM; Sean Cooper, J. Mike Walker '66 Department of Mechanical Engineering, Texas A&M University; Dylan Simons, Department of Aeronautics and Astronautics, Air Force Institute of Technology; Ignacio Trueba-Monje, Aerospace Engineering Department, The Ohio State University; and Vladimir Vorob'ev, Joint Institute for High Temperatures, Russian Academy of Science.

The study, conducted at UNM, involved pre-mixing two gases with dramatically different properties: light helium and heavy and viscous sulfur hexafluoride. The team characterized the properties of the resulting mixture, which agreed well with classical theory, then a shock wave was introduced, and the temperature and pressure of the shock-accelerated medium were measured over several milliseconds - a short time to think of in normal terms, but a long interval compared with the time scales associated with the shock wave passage. The researchers found that the temperature and pressure after the shock compression did not line up with what would have been expected from the predictions of either of the two classical theoretical laws - Dalton's or Amagat's.

French physicist Emile Hilaire Amagat's law of partial volumes from 1880 states that the total volume of a gas mixture is equal to the sum of the partial volumes each gas would occupy if it existed alone at the temperature and pressure of the mixture. And in 1802, scientist John Dalton stated that the total pressure in a non-reactive gas mixture - at constant temperature and volume - is equal to the sum of the partial pressures of the component gases.

"Our study found that classical laws used to predict gas mixture properties fail to work in a fairly common and practically important situation," Vorobieff said.

The reason for disagreements is that neither classical law can accurately describe what happens on the molecular level, he said. Simple considerations of time scales from kinetic molecular theory, and how they are affected by shock acceleration, appear to provide at least a qualitative explanation of the experimental observations. Vorobieff said that although this is a solid first step, the ultimate implications have not yet been determined, and much further study is required. Possible impacts could mean a design change in mechanisms like engines that take into account how shock waves affect the gas mixture properties.

"Our work has shown that classical gas mixture theory does not work in shock-accelerated and possibly other compressible flows," Vorobieff said. "We must conduct experiments with more gas mixtures and a broader range of conditions to explore the scope of the problem and develop a theory explaining our observations."

Phase III clinical trial results reported today in the New England Journal of Medicine and presented concurrently at the San Antonio Breast Cancer Symposium (SABCS) 2019 show the combination of the investigational drug tucatinib with standard of care treatment including the drugs trastuzumab and capecitabine nearly tripled one-year progression-free survival (33 percent vs. 12 percent), and nearly doubled the two-year overall survivor (45 percent vs. 27 percent) in women with HER2+ metastatic breast cancer. The international, multi-center trial, named HER2CLIMB (NCT02614794), builds on early development and clinical trials involving the University of Colorado Cancer Center.

"Tucatinib is one of the most promising new drugs that we have brought forward for women with stage IV HER2-positive breast cancer, especially those with brain metastases," says Virginia Borges, MD, MMSc, director of the Breast Cancer Research Program and Young Women's Breast Cancer Translational Program at CU Cancer Center.

Traditionally, clinical trials have excluded patients with brain metastases due to the likelihood that the poor prognosis of these patients could undermine the appearance of a drug's effectiveness. The current study is the first phase III trial that enrolled women whose breast cancer had metastasized to the brain and whose brain metastasis were progressing. "The data are striking," Borges says, showing 25 percent one-year survival for this patient population with tucatinib, compared with zero percent survival for patients treated with standard-of-care.

"I'm really excited to see this data presented after working with this drug since it entered phase I clinical trials as ARRAY-380, and because it's a local product made originally in Boulder at Array BioPharma! Now, based on all the data, including this trial, we expect Seattle Genetics will likely receive FDA approval for the drug. I'm just incredibly happy to see this drug getting to where we expect it will soon be made available to more patients who can benefit," Borges says.

Tucatinib is an oral medication known as a tyrosine kinase inhibitor that directly blocks the action of the HER2 gene. Side effects included diarrhea and manageable changes in liver function levels in the blood. The study enrolled patients who had progressed after at least two rounds of previous therapy, including therapies targeting HER2.

In addition to the trial HER2CLIMB, studies at CU Cancer Center continue to test tucatinib in other settings, including one of the few trials currently accruing patients that is testing tucatinib combined with standard of care against breast cancer that is positive for both HER2 and estrogen receptors, known as ER+/HER2+ cancer (NCT03054363). Borges and colleagues also recently earned approval for further clinical trials of tucatinib combined with the drug TDM-1 (trastuzumab emtansine) against HER2+ breast cancer (NCT03975647).

"This is a fantastic drug," Borges says. "It has really lived up to the promise we've shown in prior publications."

Efforts to prevent new HIV transmissions in the United States must be accompanied by advances in addressing HIV-associated comorbidities to improve the health of people already living with HIV, National Institutes of Health experts assert in the third of a series of JAMA commentaries. Previous commentaries detailed the proposed Ending the HIV Epidemic: A Plan for America, which aims to reduce new HIV transmissions in the United States by 75% in five years and 90% in 10 years, and discussed the challenges posed by the emerging opioid injection epidemic in rural areas.

Assuming the aspirational goals of Ending the HIV Epidemic are achieved, at least one million people in the United States still will be living with the virus. With effective antiretroviral therapy (ART), people with HIV can expect a near-normal lifespan. But even when treated with ART, people living with HIV are at heightened risk for numerous comorbidities, including heart disease, kidney disease, osteoporosis, liver disease, certain cancers and neurocognitive disease.

Successfully addressing HIV-associated comorbidities will require research advances to better understand how these conditions develop, write Anthony S. Fauci, M.D., director of NIH's National Institute of Allergy and Infectious Diseases (NIAID), and colleagues. Clinical trials to assess treatments for HIV-associated comorbidities and efforts to reduce health care disparities also must be prioritized.

Insight into the mechanisms underlying the chronic immune activation and dysfunction associated with HIV could lead to new therapies to manage numerous HIV-associated comorbidities, including heart disease. In this regard, the REPRIEVE clinical trial is investigating whether a statin medication can reduce the risk of cardiovascular disease among people with HIV. Other factors involved in driving HIV-associated comorbidities include side effects of long-term ART use, such as lowered bone mineral density, and coinfections, such as viral hepatitis. Establishing a better understanding of these comorbidities and how to manage them will be essential to reduce the burden these conditions place on individuals and the health care system, the authors conclude.

DALLAS, Dec. 11, 2019 -- Low-dose aspirin was not associated with a reduced risk of a fatal heart attack among African Americans, according to an observational study published in the Journal of the American Heart Association, the open access journal of the American Heart Association.

"Most available data shows that African Americans have a higher risk of having a heart attack, stroke or other heart diseases compared to whites; however, previous studies didn't include enough black participants to determine if taking a low-dose aspirin for primary prevention of heart disease was useful for this group of people," said Rodrigo Fernandez-Jimenez, M.D., Ph.D., the lead author of the study and a cardiologist and researcher at Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, Spain, and former researcher at the Icahn School of Medicine at Mount Sinai in New York.

Results of the 11-year follow-up study showed that low-dose aspirin appeared not to reduce the risk of a fatal heart attack among African American participants, even when the analysis was restricted to people at the highest risk of cardiovascular disease (10-year cardiovascular risk greater than 10% according to the Framingham Risk Score). The study did show an association of low-dose aspirin with a trend toward decreased risk of fatal heart attacks in whites, particularly among women.

Researchers used data from the Southern Community Cohort Study, an ongoing initiative coordinated by Vanderbilt University that is tracking the risk factors for cancer and other major diseases of more than 65,000 predominantly low-income men and women, ages 40 to 79, who live in the Southeastern United States. More than two-thirds of the study participants are African American and approximately two-thirds of the participants were at high risk of having a heart attack or stroke at the start of the study, according to the Framingham Risk Score.

"We think the reason aspirin use did not have a beneficial effect for African Americans could involve a different genetic response to aspirin therapy and poor control of other risk factors," Fernandez-Jimenez said. "The need to better understand the association between aspirin use, race/ethnicity and socioeconomic status and how these factors play a role in cardiovascular disease are important in light of these findings." This was an observational study, not designed to prove cause and effect.

The American Heart Association does not recommend taking an aspirin to prevent cardiovascular disease without talking with a health care provider. If a person is at low risk for having a heart attack or stroke according to the American Heart Association/American College of Cardiology Atherosclerotic Cardiovascular Disease Risk Calculator, aspirin therapy is generally not advised for everyone because the possible benefits do not offset the risk of increased bleeding. Aspirin therapy may be appropriate for some people who are at higher risk of cardiovascular disease, however, decisions about aspirin use must be individualized to a patient's specific health status in consultation with their physician.

DURHAM, N.C. -- Biomedical engineers at Duke University have developed a system that allows for real-time observations of individual cells in the colon of a living mouse.

Researchers expect the procedure to allow new investigations into the digestive system's microbiome as well as the causes of diseases such as inflammatory bowel disease and colon cancer and their treatments.

The procedure described online on December 11 in Nature Communications involves surgically implanting a transparent window into a mouse's abdominal skin above the colon. Similar setups are already being used to allow live looks into the detailed inner workings of the brain, spinal cord, liver, lungs and other organs. Imaging a live colon, however, is a slipperier proposition.

"A brain doesn't move around a lot, but the colon does, which makes it difficult to get detailed images down to a single cell," said Xiling Shen, the Hawkins Family Associate Professor of Biomedical Engineering at Duke University. "We've developed a magnetic system that is strong enough to stabilize the colon in place during imaging to obtain this level of resolution, but can quickly be turned off to allow the colon to move freely."

Immobilizing the colon for imaging is a tricky task for traditional methods such as glue or stitches. At best they can cause inflammation that would ruin most experiments. At worst they can cause obstructions, which can quickly kill the mouse being studied.

To skirt this issue, Shen developed a magnetic device that looks much like a tiny metal nasal strip and can be safely attached to the colon. A magnetic field snaps the colon into place and keeps it stable during imaging, but once turned off, leaves the colon free to move and function as normal.

A vital organ that houses much of the digestive system's microbiome, the colon can be afflicted by diseases such as inflammatory bowel disease, functional gastrointestinal disorders and cancer. It also plays a key role in regulating the immune system, and can communicate directly with the brain through sacral nerves.

"There is a great need to better understand the colon, because it can suffer from so many diseases and plays so many roles with significant health implications," Shen said.
In the study, Shen and his colleagues conducted several proof-of-principle experiments that provide starting points for future lines of research.

The researchers first colonized a living mouse colon with E. coli bacteria, derived from Crohn's disease patients, that had been tagged with fluorescent proteins. The researchers then showed they could track the migration, growth and decline of the bacteria for more than three days. This ability could help researchers understand not only how antagonistic bacteria afflict the colon, Shen says, but the positive roles probiotics can play and which strains can best help people with gastrointestinal disorders.

In the next experiment, mice were bred with several types of fluorescent immune cells. The researchers then induced inflammation in the colon and carefully watched the activation of these immune cells. Shen says, this approach could be used with various types of immune cells and diseases to gain a better understanding of how the immune system responds to challenges.

Shen and his colleagues then showed that they could tag and track colon epithelial stem cells associated with colorectal cancer throughout radiation treatment. They also demonstrated that they could watch nerves throughout the colon respond to sacral nerve stimulation, an emerging therapy for treating motility and immune disorders such as functional gastrointestinal disorders and irritable bowel disorder.

"While we know electrically stimulating the sacral nerves can alleviate the symptoms of these gastrointestinal disorders, we currently have no idea why or any way to optimize these treatments," Shen said. "Being able to see how the colon's neurons respond to different waveforms, frequencies and amplitudes of stimulation will be invaluable in making this approach a better option for more patients."

WHAT:

Nano-sized vesicles released by certain bacteria that inhabit the vagina may protect against HIV infection, suggests a study of human cells and tissues by researchers at the National Institutes of Health and the University of Bologna, Italy. Known as extracellular vesicles, these bubble-like particles are produced by many kinds of cells and are thought to transport molecules from one cell to another. The study was led Leonid Margolis, Ph.D., of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in Nature Communications.

The researchers conducted a series of experiments showing that vesicles isolated from four strains of Lactobacillus bacteria interfere with the ability of HIV to infect cells. In one experiment, researchers added vesicles to cultures of immune cells known as T lymphocytes and infected the cultures with HIV. HIV infection in the treated cells was much lower than in the untreated cells. When the researchers increased the quantity of vesicles, a much smaller proportion of cells were infected.

Similarly, treatment with vesicles reduced HIV infection in human lymph and uterine cervix and vaginal tissues. The researchers found that bacterial vesicles suppressed the binding of viruses to the cell surface, an essential step before the virus can infect a cell. Further experiments showed that bacterial vesicles directly affect HIV rather than cells. Exposing the viruses to vesicles reduced the appearance of surface molecules on the virus' outer covering, which it needs to attach to cells.

SAN ANTONIO -- Researchers from The University of Texas MD Anderson Cancer Center today reported study results showing the addition of tucatinib to capecitabine (Xeloda) and trastuzumab (Herceptin) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced HER2-positive breast cancer, with and without brain metastasis according to results of the HER2CLIMB clinical trial.

The trial results published in the New England Journal of Medicine and were presented by Rashmi K. Murthy, M.D., assistant professor of Breast Medical Oncology, during the 2019 San Antonio Breast Cancer Symposium.

The trial met its primary endpoint and showed that the treatment combination reduced the risk of death by 46% compared with trastuzumab and capecitabine alone. The trial also met its secondary endpoints at interim analysis, showing tucatinib prolonged OS, reduced the risk of death by 34% and extended PFS by 52% among patients with brain metastasis. The overall response rate was higher in the tucatinib group at 41% compared with 23% in the standard of care treatment.

"This is a uniquely designed trial in that it allowed patients to enroll if they had untreated, treated stable or previously treated, but progressive brain metastasis," said Murthy. "Brain metastasis is a common clinical problem developing in up to half of patients during the disease course, but there are limited systemic treatment options as most drugs have difficulty crossing the blood brain barrier."

HER2-positive breast cancer tumors have high levels of human epidermal growth factor receptor 2 (HER2). This type of breast cancer has been associated with shorter survival times as well as a higher risk of recurrence and brain metastasis. Approximately 25% of breast cancers are HER2-positive and as many as half of patients with HER2-positive disease will develop brain metastasis over the course of their lifetime. Tucatinib is a tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The international randomized trial enrolled 612 patients with locally advanced or metastatic HER2-positive breast cancer who received prior treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine. Researchers randomly assigned patients 2:1 to trastuzumab and capecitabine with or without tucatinib. Nearly half (47.5%) of patients had brain metastasis at baseline.

The triplet combination was generally well tolerated with no unexpected toxicities. The most frequent adverse events in the tucatinib arm included diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, all mostly low grade. There was a low drug discontinuation rate, 5.7% in the triplet arm compared with 3% in the control arm.

"This trial verified that tucatinib is both a safe and effective treatment," said Murthy. "These results are unprecedented for late line therapy in advanced breast cancer, and are a major advance for patients who have significant unmet medical need. Tucatinib in combination with trastuzumab and capecitabine should be the new standard of care for patients pretreated with multiple anti-HER2 agents including patients with brain metastasis."

These positive trial results led to the decision to unblind the study so that all patients can benefit from the combination. There are plans to submit a New Drug Application to the Food and Drug Administration in the first quarter of 2020.

The HER2CLIMB trial is ongoing but is no longer recruiting patients. Completion of the trial is expected in September 2020. The Phase III HER2CLIMB-02 clinical trial began in October 2019. A similar study assessing the safety and efficacy of the combination of tucatinib and trastuzumab with capecitabine for the treatment of leptomeningeal metastases currently is recruiting patients.

High Intensity Focused Ultrasound (HIFU) treatment is a non-invasive method that removes unhealthy tissues and tumors by delivering high intensity ultrasound waves from outside of the body to the lesion. It does only a minimal damage to the normal tissues around the lesion and allows fast recovery of a patient which is why this innovative treatment has been called as the "ultrasound of the next generation." Recently, a research team from Korea developed a photoacoustic (PA) thermometry system for HIFU treatment guidance, and demonstrated real-time monitoring of temperature increase at the tumor in living subjects during the HIFU treatment. With this new finding, further development for an exquisite HIFU treatment is anticipated.

Professor Chulhong Kim of the Department of Creative IT Engineering with his post-doctoral researcher Jeesu Kim and a PhD student Wonseok Choi suggested real-time PA thermometry system that was seamlessly integrated with the HIFU treatment system. This new system allows ultrasound imaging, PA imaging and PA thermometry simultaneously during the therapeutic HIFU wave being delivered.

Their research establishment was published in Transactions on Biomedical Engineering of IEEE (Institute of Electrical and Electronics Engineering) and selected as a feature article and the front cover of the issue.

HIFU treatment delivers intense ultrasound energy to the focal site to induce high temperature rise ranging from 65 to 100 degree Celsius. By this principle, HIFU is able to treat internal lesions without using a knife or needle, or even ionizing radiations.

Measuring the temperatures of normal tissue and lesion helps identify location and status of the lesion precisely during the HIFU treatment. It is also crucial in controlling the safety and accurately planning a treatment. In this aspect, medical imaging techniques such as MRI and ultrasound has been necessary to support the non-invasive treatment monitoring.

While there were several previous researches regarding the PA thermometry to monitor HIFU treatment process, none of them were able to image while HIFU is turned on, to provide two-dimensional monitoring, or to show the feasibility for clinical usage.

The research team demonstrated the PA thermometry by studying the relation between the intensity of the PA signal and the temperature using a tumor-bearing laboratory mouse. They successfully tested the feasibility of the real-time PA thermometry by verifying that there was a strong correlation between the PA signal strength and the temperature at the site of lesion that was treated with HIFU. Also, they were able to distinguish the location of lesion according to the level of optical absorption which was impossible with the conventional ultrasound imaging.

Professor Chulhong Kim who led the research said, "This new development of photoacoustic thermometry system allows temperature measurement during HIFU treatment in real time and we are now able to establish an efficient plan of a HIFU treatment. Moreover, it can be clinically used promptly because we only need to combine laser with the conventional HIFU treatment system that uses ultrasound imaging."

Edith Cowan University researchers have found that a chronic disease affecting up to 80 per cent of overweight people may be causing an iron deficiency that simply leaves them too tired to get off the couch.

Fatty liver disease affects about one in three Australians and is often associated with being overweight or obese. If left untreated, it can lead to liver cirrhosis, liver cancer and increase the risk of a heart attack.

But the remedy - to lose weight through diet or exercise - is often difficult to achieve for affected individuals.

In other words, it may not be laziness but lack of iron which is important for energy production that is stopping people with non-alcoholic liver disease from addressing their condition. -

This research indicates that people with the condition may be physiologically incapable of exercise due to iron not being available for the body to use normally, which is very similar to the effects observed in people who have a true iron deficiency.

The new research, under the direction of lead researcher Professor John Olynyk, will help guide future treatment for people with non-alcoholic fatty liver disease.

The body is like a car

ECU researchers measured the cardiovascular fitness of 848 17-year-old West Australians enrolled in the well known Raine Study and found that those with non-alcoholic fatty liver disease had lower physical work capacity independent of their weight.,

This reduced physical work capacity was also strongly related to parameters suggesting that iron is not being made available to the body for normal metabolism.

Professor John Olynyk said the study showed that people with non-alcoholic-fatty-liver disease had lower cardiovascular fitness, which was likely caused by a functional iron deficiency.

"We know that an iron deficiency can cause lethargy and fatigue, making it harder for people to exercise," he said.

"What is likely happening is that non-alcoholic fatty liver disease is impeding the body's ability to provide adequate iron into the blood to fuel processes such as energy and blood cell production.

"To use an analogy, if you imagine the body as a car and iron as its fuel, what is likely happening is that there is plenty of iron, or fuel in the tank, but the non-alcoholic fatty liver disease has caused the fuel line to shrink, so there's not enough fuel can get to the engine."

Diet before exercise

Professor Olynyk said the findings were useful for guiding the treatment of non-alcoholic fatty liver disease.

"The main treatment is lifestyle change aimed at reducing weight, primarily achieved through exercise and a modified diet," he said.

"In particular, there is evidence published by other investigators in the field that the Mediterranean diet can reduce the severity of non-alcoholic fatty liver disease. This is because it is high in foods like fruit and vegetables and whole grains, which have anti-inflammatory properties.

"This research shows that it may be more effective to first focus on new ways to improve the availability of iron to the body, enabling diet and physical activity to have better and more sustained effects on weight and the severity of their non-alcoholic fatty liver disease."

Newborn babies, elderly people, sick hospital patients and sports enthusiasts all stand to gain from a breakthrough in the development of wearable technology using nanomaterials from the University of Sussex.

Physicist Dr Conor Boland at the University of Sussex has published a 'blueprint' to help scientists understand how to optimise the effectiveness of the nanomaterials which are used in health sensors. Nanomaterials promise to provide the key to wearable technology which tracks blood pressure, pulse, breathing and joint movement in real time, and wirelessly. But how to make these flexible materials both more sensitive and to stretch further has stumped researchers until now. Dr Boland's paper "Stumbling Through the Research Wilderness, Standard Methods to Shine Light on Electrically Conductive Nanocomposites for Future Health-Care Monitoring" is published in the prestigious journal ACS Nano on Thursday 13 December.

Having analysed data from 200 publications on the subject, Dr Conor Boland's paper uncovers for the first time the dilemma that the further a material can be stretched, the less sensitive it is.

However, by introducing a new way for researchers to interpret their data, Dr Boland presents a method for researchers to understand how sensitivities and flexibilities can be optimised. These health monitoring nano-based materials need to be sensitive enough to measure a pulse with its subtle low strain stimuli, but also to maintain that sensitivity when measuring the large strains of a bending joint. The publication of this blueprint unleashes huge potential for all researchers in this field. Dr Boland hopes it will lead to a new golden age of healthcare, ushered in by wearable real-time health monitoring devices based on nanomaterials.

Dr Conor Boland, Lecturer in Materials Physics in the School or Mathematical and Physical Sciences at the University of Sussex, said:

"The goal of our research is to create soft, wearable health sensors using cost-efficient nanomaterials which are capable of real-time health monitoring. The potential of these materials would be invaluable to doctor surgeries and hospitals.

"But until now, researchers have been unable to compare our own successes with those of others. We've been making progress in a way which is akin to wandering into a dark wood with no torch. Our blueprint now shows researchers the way, unleashing the potential for many applications to follow.

"I hope these products will bring about the next golden age of healthcare, by allowing medics to be alerted remotely to changes in a patient's health. The devices we're working towards could provide early warning systems for a range of people: poorly patients on busy hospital wards; elderly people in care homes at risk of falling or sudden illness; those at risk of anaphylactic shock, characterised by a sudden drop in blood pressure.

"By spotting changes in pulse, blood pressure, joint movement and respiration rates, these products could potentially identify sickness before external symptoms reveal themselves. In that way, a patient could be helped sooner.

"There's scope for private commercial use too. Professional and amateur sport enthusiasts should in time see more effective health monitors coming to market. They may provide more accurate diagnostic sensors for rugby players or boxers at risk of concussion, which are sorely needed. And health sensors using nanomaterials could help worried parents too, whether that's by alerting them to a newborn at risk of cot-death or a toddler with soaring temperatures and respiration rates.

"This blueprint we've published paves the way all of that."

This research paper in particular looks materials known as nanocomposites, a blend of a nanomaterial and a stretchy polymer, used as non-invasive sensors worn on the body. They either sit on the skin or are built into wireless devices similar to current commercial fitness devices. To measure a bending joint the material would be attached across the knuckle in the hand or knee; and to measure pulse or blood pressure, it would sit across the skin above the artery in the neck or wrist.

The paper looks at the relationship between three things: sensitivity (gauge factor), how far a material can stretch while making a measurement (working factor) and a material's stiffness (Young's modulus) and provides benchmarks for each which would describe the performance of an optimum sensing material.

While graphene is the best known nanomaterial, there are hundreds of others including Transition Metal Dichalcogenides, Carbon Nanotubes, Metallic Nanowires and MXenes.

New research published today in the Journal of Physiology shows that breastfeeding is crucial in preventing diabetes.

The World Health Organization recommends breastfeeding as the sole source of nutrition for infants until six months of age, as this helps reduce child morbidity and mortality. In contrast, early weaning is associated with both the development of obesity and Type 2 diabetes in adulthood.

Researchers at Rio de Janeiro State University, led by Patricia Lisboa, showed that weaning rat pups early increased insulin secretion in adolescent male pups and in both genders as adults.

By adolescence in male pups, the scientists mean an age in pups that is considered equivalent to adolescence in humans. In rats, adolescence is defined as ranging from age 35 to 55 days.

This increased insulin secretion is indicative of developing insulin resistance, which means a reduced responsiveness to insulin. To try to compensate for this reduced responsiveness of the body, it secretes more insulin. This is one sign of diabetes, a disease characterised by high blood sugar levels. Blood sugar levels are normally regulated by insulin, so high blood sugar levels mean the body creates more insulin to try to regulate this.

The result of increased insulin secretion indicates that adolescent pups might be more susceptible to Type 2 diabetes, as will all the offspring in adulthood.

Patricia Lisboa, one of the authors on the study said:

"There are many causes of Type 2 diabetes, but not breastfeeding for long enough, is one we can guard against. Understanding the increased susceptibility to Type 2 diabetes as a result of early weaning will help us develop the best public health guidance."

A team led by researchers at Baylor College of Medicine and Harvard Medical School has unveiled a novel mechanism that helps explain how endocrine-resistant breast cancer acquires metastatic behavior, opening the possibility of new therapeutic strategies.

Published in the Proceedings of the National Academy of Sciences, the study shows that hyperactive FOXA1 signaling, which previously was reported in endocrine-resistant metastatic breast cancer, triggers genome-wide reprogramming that results in enhanced resistance to treatment and metastatic behaviors.

The researchers also identified HIF-2a as a key mediator of FOXA1-directed reprogramming and showed that an inhibitor of HIF-2a, currently under clinical development for treatment of advanced renal cell carcinoma and recurrent glioblastoma, can effectively reduce migration and invasion of endocrine-resistant breast cancer cells expressing high FOXA1 activity.

"About 75 percent of breast cancers have estrogen receptors, hence they are called estrogen receptor positive (ER+). Original ER+ breast cancer cells depend on estrogen to grow, and therapies that make the estrogen unavailable to cells, called hormone therapies, can result in long-term remission in some patients. Tamoxifen, one of several types of hormone therapy, works by binding to and blocking the estrogen receptor on cancer cells," said co-corresponding author Dr. Rachel Schiff, associate professor of medicine and the Lester and Sue Smith Breast Center at Baylor.

However, most patients with metastatic disease, including those whose tumors responded initially to hormone therapy, eventually relapse and die due to the tumors' acquired resistance to hormone therapy.

In previous work, Schiff and her colleagues discovered that tumor cells resistant to hormone therapies make more FOXA1 than susceptible cells, and this abundance of FOXA1 plays an active role in conferring resistance to the therapy. In the current study, the researchers took a genome-wide approach to dig deeper into how FOXA1 accomplishes the complex task of triggering metastatic behavior.

"Working with breast cancer cell lines in the laboratory, we discovered that FOXA1 reprograms endocrine therapy-resistant breast cancer cells by turning on certain genes that were turned off before and turning off other genes. The new gene expression program mimics an early embryonic developmental program that endows cancer cells with new capabilities, such as being able to migrate to other tissues and invade them aggressively, hallmarks of metastatic behavior," said first and co-corresponding author Dr. Xiaoyong Fu, assistant professor of molecular and cellular biology and part of the Lester and Sue Smith Breast Center at Baylor.

The researchers also discovered that FOXA1 does not act alone. Along with other factors, it activates a large number of enhancers that work together to synchronize genome-wide cell reprogramming. HIF-2a is the top enhancer working with FOXA1 mediating the activation of pro-metastatic gene sets and pathways associated with poor clinical outcome.

Importantly, the researchers showed in laboratory cell experiments that an inhibitor of HIF-2a reduced migration and invasion of endocrine-resistant breast cancer cells expressing high FOXA1 activity.

"In collaboration with our colleagues from Harvard Medical School, we explored the possibility of transferring these findings to the clinic. We analyzed clinical metastatic breast cancer datasets and found reprogramming events that were similar to those found in our endocrine-resistant breast cancer cell models," said Schiff, who also is a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

Taken together, these findings reveal details of the intricate mechanism FOXA1 triggers to induce metastatic behavior in endocrine-resistant breast cancer, which other reports have suggested also is present in other types of cancer, such as prostate and pancreatic cancer. In addition, the findings support further exploration of the possibility that inhibiting HIF-2a or other enhancer that controls the expression of many genes in endocrine therapy-resistant breast cancer could be translated into effective therapeutic strategies.

In the last decade, scientists discovered that blocking a key regulator of the immune system helped unleash the body's natural defenses against several forms of cancer, opening up a new era of cancer immunotherapy. Now Yale scientists have essentially flipped this script and found that when impaired a molecularly similar regulator can cause the damaging immune system attacks on skin and organs that are the hallmark of the autoimmune disease lupus, they report Dec. 11 in the journal Science Translational Medicine.

The study results help explain the origins of lupus and suggest novel ways researchers might be able to restore function of this inhibitor and provide much needed new therapy to treat the disease, the scientists said.

The immune system has a series of regulators designed to prevent it from attacking tissues in its host, a system that goes awry in autoimmune diseases. Yale researchers found that mice lacking an immune system inhibitor called programmed death-1 homolog, or PD-1H, spontaneously developed symptoms that resemble two forms of lupus -- systemic, in which the immune system attacks multiple organs; and cutaneous, which is marked by pronounced skin deformities.

"This molecule is clearly involved in inhibiting lupus, but it seems to be selective because it does not have the same effect in several other autoimmune diseases," said senior author Lieping Chen, the United Technologies Corporation Professor in Cancer Research, and professor of immunobiology, dermatology, and medicine.

PD-1H is molecularly similar to the more commonly known PD-1 molecule, which also helps suppress immune system response. Chen was a pioneer in identifying and developing inhibitors to PD-1, which freed T cells to attack several forms of cancer. Several labs have also tried to use PD-1H as a cancer treatment but so far have been unsuccessful.

Chen said his findings suggest that in people with lupus the function of PD-1H is critical. When it is impaired, they are vulnerable to the immune system attacks on skin and multiple organs that are the hallmark of the disease.

Lupus patients currently have very limited options for treatment, but the new findings suggest a novel approach called protein fusion might mimic PD-1H and help control the immune system and combat the disease, Chen said.