Research – Health Care
Tag

Research

Browsing

Viruses are parasites. The only way they can grow is by hijacking their hosts. When they infect a human host, viruses use human proteins to multiply and modify the human cells to sustain the infection. At the same time, the human host activates defense mechanisms to fight the infection.

Most current drugs against viral infections target the virus itself. But scientists are interested in developing therapies that aim for host proteins instead, or the genes that produce them, in part because such therapies are believed less likely to elicit drug resistance. A detailed understanding of virus-host interactions is crucial to the success of this strategy.

A team of Gladstone Institutes scientists led by Senior Investigator Nevan Krogan, PhD, has been cataloging host proteins that physically bind to virus proteins. These physical interactions identify human proteins that the virus can use to infect cells and propagate. However, they don't reveal how host proteins work together to facilitate infection.

To address this gap, Krogan and staff scientist David Gordon, PhD, with colleagues at UC San Francisco (UCSF), University College Dublin, and the Mount Sinai School of Medicine, have developed a new way to understand how host cells control HIV infection in human cells.

Their approach entails disrupting host genes rather than proteins. It is based on the idea, pioneered by Krogan, that you obtain richer information about the functions of genes–and the proteins they encode–when you disable the genes in pairs, instead of one by one. In a paper published in Molecular Cell, the team describes a map of the genes controlling HIV infection in human cells, which they built by assessing more than 63,000 combinations of human genes associated with HIV infection.

HIV is a major public health concern, with an estimated 36.7 million people living with chronic infection, and over 20.9 million people receiving continuous treatment. Studying the impact of gene disruptions in pairs rather than one by one yields important information on how genes work together to mediate virus infection, highlighting processes we can target with drugs to inhibit infection."

Nevan Krogan, Ph.D., senior investigator, professor of Cellular and Molecular Pharmacology at UCSF, and the director of the UCSF Quantitative Biosciences Institute

The map, which the team refers to as a viral epistasis map (vE-MAP), is an essential advance for HIV research in several other ways. For one thing, it uncovers a previously unsuspected set of genes required for the growth of the virus in human cells. For another, the vE-MAP can be used to analyze how different HIV mutants affect host cells or to test drugs that disrupt HIV-host interactions.

Strength in numbers

The vE-MAP is an adaptation of the E-MAP, which Krogan and his colleagues pioneered and refined over the past 15 years to identify genes that control how cells grow. At the core of this approach is the Krogan lab's ability to disrupt a large number of genes, test them in pairs, and analyze the results via sophisticated computational methods.

"The principle behind E-MAPs is that when you disrupt two genes at once and examine the impact on a cell, you sometimes see effects that are significantly larger or smaller than you would have predicted from the effect of disrupting either gene alone," said Krogan.

These unexpected effects suggest that the functions of the two genes are related. Moreover, by carrying out these pairwise disruptions across hundreds of genes, scientists can find groups of genes with similar patterns of interactions, a sign that they are likely to take part in the same molecular process.

"And so, instead of finding important genes one at a time, you can all at once identify multiple, distinct networks of genes affecting the process you are studying," said Gordon.

Related Stories

  • Promising HIV vaccine fails in a large-scale clinical trial
  • Vitamin E can safely treat fatty liver disease in patients with HIV
  • HIV antibody therapy improves immune function

The E-MAP approach has mostly been used to study cell growth. Gordon, in collaboration with a student from University College Dublin, Ariane Watson, had to modify it to study virus infection. The most tricky part was to implement a sophisticated data acquisition and scoring system, which allowed them to measure HIV infection accurately across hundreds of thousands of samples, and compare the effect of pairwise and single-gene disruptions.

It would be an overwhelming effort to test all combinations of the over 20,000 protein-coding genes in the human genome. Instead, the scientists focused on genes already suspected to influence HIV biology. In particular, they used the genes encoding a large number of human proteins that the Krogan lab had previously found to bind to HIV proteins. In all, they included over 350 genes in their analysis and tested over 63,000 pairwise disruptions.

New players at the HIV-host interface

Although HIV is one of the best-studied human viruses and is now well-controlled by antiretroviral therapy, there is no cure for HIV/AIDS. Moreover, antiretroviral therapy is costly, which can make it impractical in resource-poor countries. The search for new means of halting or eradicating the virus is, therefore, still a priority.

Among the genes that stood out in the vE-MAP were several members of the CNOT family, whose role in HIV biology had never before been established. The authors demonstrated that the CNOT complex promotes HIV infection by suppressing innate immunity in CD4+ T cells, the type of immune cells that HIV preferentially targets in humans. Innate immunity is a defense mechanism by which host cells can fight infection.

"The impact of CNOT on innate immunity is a key, yet previously unrecognized, host pathway critical to HIV infection. It will serve as a potential novel therapeutic target in future studies," said Krogan.

For instance, scientists can now study if targeting the CNOT complex with drugs could be a way to help HIV patients fight the infection more effectively.

Furthermore, the vE-MAP uncovered genes that had little impact when disrupted individually, but a great effect when tested together.

"These genes would be overlooked in classic, single-gene disruption experiments," said Gordon. "They confirm the potential of the vE-MAP to uncover new mechanisms by which HIV interacts with human cells."

Combining drugs that target two of these genes at the same time might thus be a promising therapeutic strategy, especially for a virus such as HIV/AIDS, which has evolved multiple ways of tapping its hosts' resources.

The vE-MAP was also able to pick up genes that specifically interact with a known HIV mutant. This observation bodes well for the ability of the vE-MAP to identify distinct host factors affecting the various forms of HIV, or the virus mutants that arise in response to currently available drugs.

Additional testing with a drug known to interfere with HIV-associated human proteins gives the authors confidence that their vE-MAP approach could, in the future, be used to screen for novel anti-HIV drugs and to understand their mode of action.

"This vE-MAP provides an unprecedented view of how HIV hijacks and rewires the cellular machinery in human cells during infection," said Krogan. "It will generate many new ideas and avenues to identify and test novel therapies."

And the benefits may not be limited to HIV research.

"Our work is proof-of-principle that the vE-MAP approach is a powerful way to map out the interface between HIV and human cells, and to uncover new therapeutic avenues," said Gordon. "We now look forward to testing it on other pathogens."

Source:

Gladstone Institutes

A University of Houston researcher is working to increase health literacy among Hispanics/Latinos (H/Ls) when it comes to Alzheimer's disease (AD). The largest ethnic minority in the U.S., at 18% of the population, H/Ls are 50% more likely to develop Alzheimer's disease than non-Hispanic whites. H/Ls also live longer, develop AD symptoms earlier, are diagnosed at later stages and are less likely to be treated.

Given those statistics, it's startling that Hispanics/Latinos comprise less than 1% of clinical trials for Alzheimer's disease.

"From a social justice perspective, in order to help reduce health disparities we need to involve these communities in the decision-making process," said Luis D. Medina, assistant professor of psychology. He will use a $2.35 million grant from the National Institute on Aging to build his "Engaging Communities of Hispanics for Aging Research Network."

Related Stories

  • New multiplexed electrical biosensor for accurate detection of Alzheimer's disease
  • Bruker announces fully validated NMR module for metabolite quantification in urine (research use only)
  • Dementia prevalence falling but the number of cases will double by 2050

"There are various barriers to getting involved in research, including health literacy or what people actually know about Alzheimer's disease. In the Hispanic/Latino communities, it is often thought of as just a part of aging," said Medina, who believes the solution begins with education.

The network will launch in two pilot cities, Houston and Denver. Step one is "boot camp translation" wherein community stakeholders are immersed in learning about the disease, and then the tables turn – the community members educate the trainers on how to speak to their communities.

In boot camp translation we break down the medical jargon to consumable, understandable lay language and the community tells us how to do that. The communities have a lot of strengths that we, as researchers, may or may not have. We are hoping to put more seats at the table so that the communities are involved in research infrastructure and help drive research projects."

Luis D. Medina, assistant professor of psychology, University of Houston

Steven Woods, UH professor of psychology and Jennifer Vardeman, UH associate professor of communication, are assisting on the project in collaboration with Baylor College of Medicine, University of Colorado School of Medicine, University of Nevada, Las Vegas and the Lou Ruvo Center for Brain Health at the Cleveland Clinic in Las Vegas.

Medina plans to expand the project to Las Vegas next as he creates a template for other cities to follow.

"This is about lifting all of us up and improving brain health. The more representative our research samples are, the better we can understand the disease," said Medina, who was recently invited to serve on the Alzheimer's Association International Research Grant Program Council to help craft funding opportunity requests for applications, provide expertise during grant review and make funding recommendations. The association is especially interested in Medina's input on issues related to the recruitment of underrepresented populations.

Source:

University of Houston

A new study published in February 2020 in the journal JAMA Otolaryngology-Head and Neck Surgery shows that using mainstream media to depict rare diseases in a realistic manner can prompt greater public awareness and support for such conditions.

Rare diseases have a very small presence in this world, affecting about 400 million people around the globe. Despite the very few cases of each kind of disease, they often cause a lot of suffering and require significant treatment and rehabilitation. In other words, they create a heavy burden in financial terms as well as the amount of care they need, both on the patients and the health care system. Yet it is challenging to mobilize funds for research, prevention, and treatment, to raise awareness about the condition, or to get sufficient manpower.

Increasing the level of awareness is an urgent necessity, therefore. One possible way out is to show television shows focusing on these conditions as part of widely seen programs. One is the Netflix series, Stranger Things, which showcases the life of Dustin Henderson, a fictional individual born with the rare disease cleidocranial dysplasia (CCD). Henderson is portrayed by actor Gaten Matarazzo III who himself has this condition.

LOS ANGELES – JUN 28: Cast at the "Stranger Things" Season 3 World Premiere at the Santa Monica High School on June 28, 2019 in Santa Monica, CA. Image Credit: Kathy Hutchins / Shutterstock

CCD is a genetic condition in which the clavicles, or collar bones, and the teeth fail to grow or grow abnormally. These features are emphasized in scenes where Dustin is explaining the condition to his friends and colleagues.

However, symptoms vary between patients, even in the same family. CCD currently affects 1 in a million children the world over, both boys and girls.

The early features of abnormal bone development include a prolonged period of open fontanelles when the bones of the skull remain separate at the front and back of the head for more than the usual length of time. The absence of complete collarbones may make the chest appear narrow, and the shoulders are sloping. In fact, many of these children can make their shoulders touch in front.

Bone density is low, the pelvis is narrow, and the height shorter than expected. Baby teeth are lost early, and the secondary teeth arrive late, which may cause the jaw to be crowded with teeth and the jaw misaligned.

The disease is due to an abnormality of the RUNX2 gene, mostly due to a de novo mutation, that is, one which arises at random in the developing embryo rather than being inherited from the parents. If one of the two copies of this gene is affected, the condition will manifest itself.

Related Stories

  • Heart Research UK supports King’s College London project to eliminate 'zombie cells'
  • Cleaning products may raise the risk of childhood asthma finds study
  • Research looks at prenatal cannabis use

Treatment could include dental replacements, speech therapy, treatment of sinus and ear infections, supplementation with vitamin D and calcium, and protecting the head from trauma until the bones are fused.

The study

The current study uses Google Trends and data from websites related to CCD to examine the link between how the condition is portrayed on television shows and the resulting increase in public interest and awareness of CCD.

Google Trends was used to look at the trends for searches focusing on CCD after the show Stranger Things was released. The researchers did a worldwide search for searches with this keyword, over a 5-year period from 2014 to 2019. Also, they asked several foundations dealing with CCD, such as the Children’s Craniofacial Foundation, about any increase in the number of calls or website hits after each season’s release of Stranger Things. This was compared with the expected traffic.

The findings

The researchers found that search interest surged by over 94% after the third season’s release of Stranger Things. In comparison, an increase of about 11% and almost 13% was seen after season 1 and season 2.

Public interest in CCD was reported to increase by all websites related to this topic. However, quantifiable data were obtained only from the foundation About KidsHealth, which had, on average, 5 to 80 views of the CCD page each week, but in the week succeeding the third season’s release of the show, 10,000 visits.

Implications

The portrayal of the condition on the popular television show has helped spark interest in many individuals. Each season has seen a spurt in weekly searches above the predicted number. Meanwhile, Matarazzo has participated in setting up the new foundation CCD Smiles, which is focused on raising awareness of this condition around the world, helping affected people with their dental work, and helping research.

The importance of harnessing celebrity power is vast reach it can offer via already existing links to the public and the media.

And when public awareness increases, funding goes up, early diagnosis is more likely, treatment becomes more broad-based, and people learn to understand and cope with the disorder. This, in turn, helps those affected by it to develop more coping strategies, feel a greater sense of integration into the broader community, and have a better quality of life.

The media also has a catalytic role in helping hundreds of thousands of people to understand such conditions better and to make sure they are correctly represented. Accurate artistic depiction of such conditions is guided by the Entertainment Industries Council, which develops material to help writers and producers understand the disease better so they can present it correctly.

However, at present, there is no guide material for CCD and many other rare diseases. Therefore, the study concludes, “Although writers need to exercise caution when portraying characters with rare disorders, the inclusion of such characters in the mainstream media may be a beneficial strategy to raise awareness of them.”

Journal reference:

Johnson AL, Torgerson T, Cooper C, Khojasteh J, Vassar M. Public Awareness of Cleidocranial Dysplasia After Season Releases of Stranger Things. JAMA Otolaryngol Head Neck Surg. Published online February 20, 2020. doi:10.1001/jamaoto.2019.4791

Proactive outreach, including knocking on the doors of individuals who recently overdosed on opioids, can be an effective way to engage more people who have opioid use disorder with long-term care, according to researchers at The University of Texas Health Science Center at Houston (UTHealth).

In a pilot study, the UTHealth research team measured results of a clinical research program, HEROES, that they created to curb opioid use disorder (OUD) in Houston. Findings were recently published in the Journal of Substance Abuse Treatment. HEROES is one of only a handful of programs in the country engaged in large-scale, door-to-door outreach and tracking results.

According to data from the Harris County Institute of Forensic Sciences, there were 325 opioid-related deaths from January through November of 2019 in Houston, up from 295 in all of 2018. The risk of overdose deaths is rising due to the increased availability of fentanyl and synthetic opioids. Federal data shows nearly 90% of people who have substance use disorder in the U.S. are not currently in treatment.

People with OUD don't always voluntarily seek treatment like you would with any other disease. Even if they recognize they need help, there are few places for them to turn, especially if they don't have insurance. We want to remove all those barriers and bring help directly to them at a time when they are more likely to accept it."

James Langabeer, PhD, EdD, MBA, professor at UTHealth who leads the HEROES program

Theories suggest that people have greater readiness for behavioral change during critical periods or life events, and surviving an overdose could represent such an event, said Langabeer, who was the lead author on the study.

Langabeer and his team at HEROES designed an intervention strategy to identify survivors of overdose through secured data from Memorial Hermann-Texas Medical Center and the Houston Fire Department Emergency Medical Services. Using a motivational interview guide, a trained recovery support coach and a paramedic knock on their doors. If the survivors are home and willing to talk, the team uses motivational interviewing techniques to encourage them to enroll in the HEROES program at no cost to them.

"This type of engagement is important because it helps to emphasize compassion and collaboration with each patient. We use it to have the person feel autonomy in their own decisions and not to be led or forced to a conclusion, but to reach a choice on their own and to feel accountable for it. We find that if they are engaged, they are more likely to follow through in the long run," Langabeer said.

Related Stories

  • Research provides new insights into molecular basis of X-chromosome inactivation
  • Bruker announces fully validated NMR module for metabolite quantification in urine (research use only)
  • Heart Research UK supports King’s College London project to eliminate 'zombie cells'

The peer recovery coaches are people who are in long-term recovery from opioid use disorder themselves.

"We've been through the fire and came out with buckets of water to fight this disease," said Jessica Yeager, a coach with HEROES. "Now people can look at me and say 'You're just like me – you can help me!' If someone had knocked on my door when I was at my worst, my life would be different today."

Between April and December 2018, the team visited 103 people, and 33% chose to engage in the treatment program. After 30 days, 88% of those participants were still active in the program, and 56% were still active after 90 days.

"Having one third of people we reached out to agree to a major step in their recovery while we are in their doorway is a huge accomplishment and much better than we expected, since other studies have shown far lower results," Langabeer said. "Recognizing that major life decisions require time, we are extremely satisfied with the results. Also, we've seen people choose to come into treatment weeks or even months later, so the information we provide during outreach can also help shape future choices."

Treatment through the HEROES program includes access to opioid overdose reversal medication, a recovery coach available 24/7, behavioral counseling with an addiction therapist, weekly support group meetings, and help connecting to county resources.

Another study Langabeer's team just published, which appeared in Substance Abuse Treatment, Prevention, and Policy, found evidence that engaging individuals through nontraditional routes such as community outreach, the criminal justice system, and emergency departments can be effective in engaging more people in medication-assisted treatment.

"We have to find more proactive ways to identify and locate these individuals in order to offer choices and paths for recovery that fit their unique situation," said Langabeer, who was the senior author of the study.

The HEROES program currently has more than 500 participants.

Source:

University of Texas Health Science Center at Houston

Sepsis hospitalizations cost Medicare $41.8 billion in 2018 alone, a new study from the Department of Health and Human Services (HHS) shows. 

The rate of Medicare beneficiaries hospitalized with sepsis has increased by 40% over the past seven years, the HHS study found. The researchers analyzed more than 9.5 million inpatient admissions between 2012 and 2018, making for one of the largest studies into the impact of sepsis. 

The growing sepsis infection rate isn’t related to ballooning Medicare enrollment, the study says, as enrollment grew by 22% even as infection rates grew by 40%. 

Case Study

Across-the-Board Impact of an OB-GYN Hospitalist Program

A Denver facility saw across-the-board improvements in patient satisfaction, maternal quality metrics, decreased subsidy and increased service volume, thanks to the rollout of the first OB-GYN hospitalist program in the state.

See how

“Sepsis is a lethal and costly health threat affecting Americans’ lives and our economy, yet many Americans may never have heard of it,” Robert Kadlec, M.D., HHS assistant secretary for preparedness and response, said in a statement. 

“Any infection can lead to sepsis, including infections caused by influenza or emerging diseases like coronaviruses, which makes sepsis a significant concern in public health emergencies,” Kadlec said. 

A study released last month by the University of Pittsburgh estimates that sepsis is responsible for one in every five deaths worldwide, double previous projections. And while high-income countries have plenty of work to do to address sepsis rates, middle- and low-income countries disproportionately bear the burden of the disease, the Pitt study found.

HHS’ analysis dug into sepsis’ impact on outcomes for Medicare beneficiaries and found that 10% of those with non-severe sepsis died while hospitalized or within a week of discharge, and 60% died within three years of contracting the infection. 

Of those diagnosed with severe sepsis, or septic shock, 40% died in the hospital or within a week of discharge, and 75% died within three years, according to the study. 

Mortality risks were highest among beneficiaries with comorbid chronic conditions, HHS said. 

Medicare patients were more likely to arrive at the hospital with the infection rather than contracting it while hospitalized, the study found. However, two-thirds had a medical encounter in the week before their hospitalization, emphasizing the need for earlier detection. 

The study suggests the cost burden of sepsis isn’t likely to decrease anytime soon. HHS projects that in 2019 the cost for inpatient and skilled nursing care related to sepsis could exceed $69 billion. 

Costs increased by 12% to 14% every two years, the study found. 

Centers for Medicare & Medicaid Services (CMS) Administrator Seema Verma said in a statement that the study highlights the “urgent need” for continued action to mitigate sepsis and said the agency is moving full speed ahead with efforts to eliminate regulatory hurdles that can inhibit access to lifesaving drugs. 

“This groundbreaking study sheds light on the sepsis-related challenges faced by patients, providers, and taxpayers alike,” Verma said. 

“CMS continues to clear away regulatory obstacles and financial disincentives that have long inhibited the development of life-saving antibiotics capable of treating sepsis patients,” she added. “Patients suffering from sepsis deserve to see America’s full innovative potential mobilized to address this devastating condition.” 

Researchers at the University of California, Riverside, have completed a cross-sectional human study that compares biomarkers and metal concentrations in the urine of e-cigarette users, nonsmokers, and cigarette smokers.

They found that the biomarkers, which reflect exposure, effect, and potential harm, are both elevated in e-cigarette users compared to the other groups and linked to metal exposure and oxidative DNA damage.

Our study found e-cigarette users are exposed to increased concentrations of potentially harmful levels of metals — especially zinc — that are correlated to elevated oxidative DNA damage.”

Prue Talbot, professor of cell biology, University of California, Riverside

Zinc, a dietary nutrient, plays key roles in growth, immune function, and wound healing. Too little of this essential trace element can cause death; too much of it can cause disease. Its deficiency, as well as its excess, cause cellular oxidative stress, which, if unchecked, can lead to diseases such as atherosclerosis, coronary heart disease, pulmonary fibrosis, acute lymphoblastic leukemia, and lung cancer.

Electronic cigarettes consist of a battery, atomizing unit, and refill fluid. Metals in e-cigarette aerosols come mainly from the metal components in the atomizer– nichrome wire, tin solder joints, brass clamps, insulating sheaths, and wicks — as well as the e-fluids that the atomizers heat.

The study, which appears in BMJ Open Respiratory Research, marks the first time researchers have examined and quantified urinary biomarkers of effect and potential harm in relation to metals in e-cigarette users.

A biomarker is a quantifiable characteristic of a biological process. Biomarkers allow researchers and physicians to measure a biological or chemical substance that is indicative of a person’s physiological state. Previous e-cigarette studies with humans have examined biomarkers of exposure — for example, nicotine or nicotine metabolites — but none have studied biomarkers of potential harm or shown how this harm correlates with metal exposure.

Related Stories

  • DNA topological problems may cause lymphoma, study shows
  • DNA misfolding linked to heightened risk for Type 1 diabetes
  • Health officials may be underestimating the prevalence of teen e-cigarette use

The biomarkers studied by the UC Riverside researchers were 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage; 8-isoprostane, an indicator of the oxidative degradation of lipids; and metallothionein, a metal response protein. All three biomarkers were significantly elevated in e-cigarette users compared to the concentrations in cigarette smokers.

“Our findings reaffirm that e-cigarette use is not harm free,” said Shane Sakamaki-Ching, a graduate student in the Cell, Molecular and Developmental Biology Graduate Program and the research paper’s first author. “Indeed, prolonged use may lead to disease progression.”

The researchers advise physicians to exercise caution when recommending e-cigarettes to their patients. Electronic cigarette aerosols contain potentially harmful chemicals, cytotoxic flavor chemicals, metals, ultrafine particles, and reaction products. E-cigarette use has been linked to adverse health effects such as respiratory diseases, increased risk for cardiovascular disease, and impaired wound healing following surgery.

“Pregnant women, especially, should not be encouraged to use e-cigarettes,” Talbot said. “Excess of zinc in their bodies can lead to nausea and diarrhea. Given the recent deaths and pulmonary illnesses related to e-cigarette usage, everyone should be made aware of the potential health risks linked to e-cigarette usage.”

Source:

University of California – Riverside

Journal reference:

Sakamaki-Ching, S., et al. (2020) Correlation between biomarkers of exposure, effect and potential harm in the urine of electronic cigarette users. BMJ Open Respiratory Research. doi.org/10.1136/bmjresp-2019-000452.

The 7th annual Metastatic Breast Cancer Research Conference will be hosted by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) in partnership with Baylor College of Medicine and Theresa's Research Foundation on September 10 and 11, 2020. Participants from around the world are invited to discuss metastatic breast cancer including ongoing research and new ideas from early career scientists.

Conference attendees include clinicians, researchers, advocates, and patients who hope to share information and shed light on the need for improved research focus and funding toward metastatic breast cancer, also known as stage IV breast cancer.

The 2020 conference will be held in Salt Lake City under the leadership of Alana Welm, PhD, breast cancer researcher at HCI and professor of oncological sciences at the U of U. "This is one of the most important conferences every year for those of us who focus on metastatic breast cancer research," says Welm. "The unique medley between state-of-the-art clinical and laboratory research, along with incorporation of important patient perspectives, makes it a stimulating and motivating experience for all of us."

The conference will feature sessions on metastatic breast cancer therapy, predictive models, drug development, and more. Invited speakers from around the world will bring their knowledge and expertise to the conference and seek to inspire conversation and collaboration to new approaches to address this challenging disease. Daily keynote address will focus on systemic regulation of metastasis and immunotherapy.

A cure for metastatic breast cancer requires a dedicated, long-term effort to find curative approaches. This conference helps to benchmark these efforts and create the collaborative research environment that is essential for success."  

Matthew Ellis, MB, BCHIR, BSC., PHD, FRCP , professor and director of the Lester and Sue Smith Breast Center at Baylor College of Medicine and Conference Co-Chair

Abstract submissions are encouraged. Limited travel stipends are available for early career investigators who have an abstract accepted. The poster session will be held in partnership with the Metastasis Research Society and GRASP (Guiding Researchers and Advocates to Scientific Partnerships), so that scientists and advocates can view and discuss posters together.

The Metastatic Breast Cancer Research Conference was established as a medical conference in 2014 by Theresa's Research Foundation. Past host institutions include Baylor College of Medicine, Johns Hopkins School of Medicine, the University of Kansas Medical Center, and the Mayo Clinic. The conference received philanthropic support from The Breast Cancer Research Foundation and Huntsman Cancer Foundation.

Source:

Huntsman Cancer Institute

After 50 years of research and the testing of over 1,000 drugs, there is new hope for preserving brain cells for a time after stroke. Treating acute ischemic stroke patients with an experimental neuroprotective drug, combined with a surgical procedure to remove the clot improves outcomes as shown by clinical trial results published today in The Lancet.

The multi-center, double-blinded, randomized trial, led by a team at the Cumming School of Medicine's (CSM) Hotchkiss Brain Institute and Alberta Health Services, investigates the use of the neuroprotective drug nerinetide, developed by NoNO Inc, in two scenarios in the same trial. In one scenario, nerinetide is given to patients in addition to the clot-busting drug alteplase. In the second scenario, patients who were not suitable for alteplase received only nerinetide. Both groups of patients had concurrent endovascular treatment (EVT) to remove the clot.

"Compared to placebo, almost 20 per cent more patients who received nerinetide along with endovascular treatment, but did not receive alteplase, recovered from a devastating stroke – a difference between paralysis and walking out of the hospital," says Dr. Michael Hill, MD, a neurologist at Foothills Medical Centre (FMC) and professor in the departments of Clinical Neurosciences and Radiology at the CSM. "In the patients who received both drugs, the alteplase negated the benefits of the nerinetide."

Hill says the study provides evidence of a biological pathway that protects brain cells from dying when they are deprived of blood flow. Nerinetide targets the final stage of the brain cell's life by stopping the production of nitric oxide within the cell.

"We really believe this is a new scientific observation," says Hill. "There is evidence nerinetide promotes brain cell survival, offering neuroprotection until we can extract the clot. It opens the door to a new way of treating stroke."

Images of patients' brains from the study show the expected size of the damage from the stroke is sizeably reduced when nerinetide is administered and EVT is performed among patients not concurrently receiving alteplase.

After so many studies investigating neuroprotective drugs failed, we are extremely excited by these results. While nerinetide is not approved for use yet, it shows the potential of a new tool to promote recovery from stroke."

Dr. Mayank Goyal, MD, PhD, neuroradiologist at the FMC, and clinical professor in the Department of Radiology at the CSM

Related Stories

  • Researchers design new drug cocktail to kill brain and soft tissue cancers
  • What the western diet is doing to your brain
  • Research looks at prenatal cannabis use

Worldwide, 15 million people suffer a stroke each year – that's one every nine minutes in Canada and every 90 seconds in the United States. The results can be devastating. Ischemic stroke, the most common, is caused by a clot in a blood vessel in the brain. The sudden loss of blood flow causes brain cells to die, which can permanently affect speech, vision, balance and movement.

The international trial enrolled 1,105 patients between March 2017 and August 2019 at centres in North America, Europe, Australia, and Asia – a global academic collaboration bringing together scientists, clinicians, funding agencies, and industry.

"The collaboration between NoNO Inc., the University of Calgary and investigators at 48 leading stroke hospitals around the world has shown how effective such an academic-industry partnership can be in running high-quality, foundational stroke trials that can lead to positive changes in clinical practice," says Dr. Michael Tymianski, MD, PhD, CEO of NoNO Inc. and the inventor of nerinetide.

The results in the current study, called the ESCAPE-NA1 Trial, build on the success of the ESCAPE trial, in which the Calgary Stroke Program proved that a clot retrieval procedure known as EVT can dramatically improve patient outcomes after an acute ischemic stroke. During the procedure, a catheter is inserted in the groin and guided through blood vessels into the brain. A tiny metal mesh device is used to grab the clot and pull it out. The current study investigates whether administering nerinetide in addition to clot retrieval improves the patient's ability to recover.

Source:

University of Calgary

Journal reference:

Hill, M.D, et al. (2020) Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. The Lancet. doi.org/10.1016/S0140-6736(20)30258-0.

Research from Rutgers Cancer Institute of New Jersey shows administering the immunotherapy drug pembrolizumab together with chemotherapy given at the same time as radiation treatment (chemoradiation) is safe and tolerable as a first-line therapy for patients with stage 3 non-small cell lung cancer (NSCLC). The work, stemming from a multi-center phase 1 clinical trial led by Rutgers Cancer Institute, is published in the February 20 online edition of JAMA Oncology.

“Locally advanced NSCLC accounts for 20 to 25 percent of all new diagnoses of NSCLC, with five-year overall survival rates of between 25 to 30 percent when standard therapy is given. Current standard treatment in which an immunotherapy drug is administered after chemoradiaton offers a 57 percent progression-free survival rate compared to 43.5 percent when chemoradiation is given alone. Our team wanted to examine the safety and tolerability of the immunotherapy drug pembrolizumab when administered concurrently with chemoradiation, as we’ve learned from first-line treatment of stage 4 disease that we see better patient outcomes the earlier immunotherapy is given,” shares Rutgers Cancer Institute radiation oncologist Salma Jabbour, MD, who is the lead and corresponding author of the current work.

Typically, the human body’s immune system recognizes abnormal cells in the body and destroys them. Cancer cells frequently create proteins (PD-L1, programmed cell death ligand-1) on the cell surface that act as signals to turn off this part of the immune system. Pembrolizumab is a drug approved by the Food and Drug Administration to treat melanoma and other forms of cancer that targets PD-1 receptors, which act as a signaling ‘switch.’ Pembrolizumab blocks this action and turns the ‘switch’ back on, allowing the immune system to recognize cancer cells as foreign and attack them.

For a 27 month period between 2016 and 2018, 23 participants were enrolled (52 percent were women; median age 69 years). Five cohorts evaluating different timing and dosing of pembrolizumab combined with chemotherapy (carboplatin and paclitaxel weekly) and definitive radiation therapy (60 Gy in 2 Gy/day x 30 fractions) for unresectable, locally advanced, stage 3 disease were examined. Median follow-up time was 16 months.

Related Stories

  • New biomarkers for diagnosis and prognosis of lung cancer identified
  • Updated colorectal cancer screening recommendations released
  • UT Dallas scientists awarded CPRIT grants for lung, kidney cancer research

Results show the combined treatment is feasible and well tolerated with a 12-month progression-free survival of 69.7 percent. Clinical benefit accounted for 94.6 percent at a median of 12.6 months. Of 19 evaluable patients (those who received 2 or more cycles of pembrolizumab) for response, the best response to therapy was a partial response seen in 73.7 percent, followed by 15.8 percent with a complete response, and 5.3 percent with stable disease. Local progression occurred in one patient, and of the six who developed metastatic disease, the median time to metastatic disease was 14.7 months. While there was an increased rate of pneumonitis, the authors note that patients with this form of lung inflammation responded to high-dose steroid treatment.

This study demonstrates that the combination of immunotherapy with chemoradiation has the potential to improve cure rates for patients with stage 3 non-small cell lung cancer.”

Dr. Salma Jabbour, professor of radiation oncology at Rutgers Robert Wood Johnson Medical School

Given the risk of pneumonitis when pembrolizumab is given with chemoradiation, the authors note further evaluation of the treatment combination through clinical trials is warranted, where careful radiation design to limit key lung parameters and biomarkers can be implemented. They add study limitations include the small sample size and limited follow-up duration.

Source:

Rutgers Cancer Institute of New Jersey

Journal reference:

Jabbour, S.K, et al. (2020) Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer. JAMA Oncology. doi.org/10.1001/jamaoncol.2019.6731.

Two grants will fund interdisciplinary research at the Beckman Institute for Advanced Science and Technology, including a look at how neurons and muscle cells communicate with each other and also to develop a drug delivery system for treatment of Alzheimer's disease.

The grant from the National Science Foundation will facilitate the study of how neurons and muscle cells communicate with each other.

My group is interested in engineering functional muscle and using it to assemble autonomous bioactuator systems.

The muscle engineered in vitro is not the same as the muscles in our body because the system does not have any innervating motor neurons. This project is to understand how we can facilitate the innervation of the neurons into the muscle."

Hyunjoon Kong, a Robert W. Schafer professor of chemical and biomolecular engineering

Kong's lab will collaborate with Gabriel Popescu, a professor of electrical and computer engineering, and Martha Gillette, a professor of cell and developmental biology. All are affiliated with the Beckman Institute.

In addition to studying how the neurons and muscle cells communicate, the Kong group will also look at the interaction between neurons and glial cells, which influence neuronal activity. "Although glial cells are not well characterized, they are known to provide certain signals that make the neurons transmit their electrical signals," Kong said.

"I will be working with Martha Gillette's group, who are experts in neurobiology and can guide us in what type of neural cells to look at," Kong said. "Popescu group members are experts at imaging intracellular events and we want to use their imaging techniques to demonstrate the interaction between the neurons and the muscle cells."

Related Stories

  • Research looks at prenatal cannabis use
  • Bruker announces fully validated NMR module for metabolite quantification in urine (research use only)
  • Heart Research UK supports King’s College London project to eliminate 'zombie cells'

Members of the Kong group hope that the study will enable them to understand how neurons can be reactivated in injured muscle, which can help improve the treatment of various neuromuscular disorders and acute muscle injuries.

The second grant, from the Alzheimer's Foundation, will fund research by the Kong group in collaboration with Hee Jung Chung, an associate professor of molecular and integrative physiology and Beckman Institute faculty member.

The grant will study how a drug that has the potential to treat Alzheimer's disease can be delivered into the body. The drug was developed to target tau proteins that, along with β-amyloid proteins, cause the disease. "Historically, researchers have been focused on treatments that reduce the β-amyloid proteins. However, a large group of patients do not respond to those treatments because the tau proteins are also responsible," Kong said.

The Kong group hopes to join the research effort that is now focusing on synthesizing nano-sized drug carriers that can target the tau protein. "The drug that targets tau proteins cannot be currently used because it is hydrophobic and therefore cannot dissolve in water," Kong said. "As a result, you cannot deliver it orally or through injection." The group will try to solve the problem by encapsulating the drug in a nanoparticle system that can be used to target the diseased regions of the brain.

Source:

Beckman Institute for Advanced Science and Technology