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Genetic risk factor for equine eye cancer identified

Squamous cell carcinoma (SCC) is the most common cancer found in equine eyes and the second most common tumor of the horse overall. Thanks to a recent genetic study led by UC Davis, horse owners can now identify horses at risk for ocular SCC and make informed breeding decisions.

In the cover article for the International Journal of Cancer, scientists announced the discovery of a genetic mutation in horses that is hypothesized to impact the ability of damage specific DNA binding protein 2 (DDB2) to carry out its standard role. Normally, the protein conducts DNA surveillance, looking for UV damage and then calling in other proteins to help repair the harm.

“The mutation is predicted to alter the shape of the protein so it can’t recognize UV-damaged DNA,” said Dr. Rebecca Bellone, an equine geneticist at the Veterinary Genetics Laboratory and associate adjunct professor at UC Davis School of Veterinary Medicine. “We believe this is a risk factor because cells can’t repair the damage and accumulate mutations in the DNA that lead to cancer.”

Several equine breeds, including Haflingers, have a higher occurrence of limbal SCC, the form of the disease that originates in the junction between the cornea–the clear surface of the eyeball–and the conjunctiva that covers the white of the eye. A former study, conducted by Bellone and one of her research partners, Dr. Mary Lassaline, found that about 26 percent of SCC-affected horses in a retrospective study were Haflingers.

“The fact that we see this type of cancer in a relatively small breed with a narrow pedigree makes it a good model to study,” said Lassaline, associate professor of clinical equine ophthalmology at the UC Davis School of Veterinary Medicine.

Ocular SCC can lead to vision loss and even loss of the eye. In advanced cases, SCC can be locally invasive and spread to the orbit and eat away at bone and eventually the brain–leading to loss of life. These recent study results offer a huge application in identifying horses at risk for developing SCC on two fronts.

“One, it’s important for the individual horse with a known risk and we can be more vigilant about exams as well as protecting their eyes from UV exposure,” Lassaline said. “If detected early, we can remove the tumor and save the eye. Secondly, that knowledge is important for making informed breeding decisions.”

Scientists at the UC Davis Veterinary Genetics Laboratory were able to develop a genetic test for horses based on the research. The test determines if a horse carries the mutation or has two copies of the risk variant, putting it at highest risk for cancer.

In addition to improving the health of horses, this study may have implications for human health as well. The gene found to be associated with equine SCC is also linked in humans to xeroderma pigmentosum complementation group E–a disease characterized by sun sensitivity and increased risk of cutaneous SCC and melanoma.

“There is an interesting parallel in humans with mutation in this protein,” Bellone said. “Now we have the ability to understand why it’s affecting the eyes of horses as well as the skin of humans.”

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‘Sticky’ Particles Promise More Precise Drug Delivery for Brain Cancer

A Yale research team has found that by tinkering with the surface properties of drug-loaded nanoparticles, they can potentially direct these particles to specific cells in the brain.

By making nanoparticles bioadhesive, or “sticky,” the researchers have answered a long-standing question: Once you get the particles to the brain, how do you get them to interact with the cancer cells there? Their findings are published May 19 in Nature Communications.

“Until now, research has focused on whether you can load the nanoparticles with drugs and whether we can get them into the brain at all, without thinking too much about what cells they go to,” said senior author W. Mark Saltzman, the Goizueta Foundation Professor of Chemical and Biomedical Engineering, professor of cellular and molecular physiology, and member of the Yale Cancer Center. “This is the first exploration of the particles’ affinity for different cells.”

The ability for nanoparticles to deliver drugs to specific areas of the body holds great promise for fighting cancer and other diseases while minimizing the side effects of drugs that are often very toxic, according to scientists. Their use in treating brain cancer, though, has been particularly challenging. That’s partly due to the blood-brain barrier, which acts to keep foreign elements out of the brain. Researchers have been able to get nanoparticles to penetrate the brain in recent years with help from a polymer coating that gives the particles “stealth” properties, allowing the particles to hide from the body’s immune system. Those same stealth properties, however, also keep cells from recognizing the particles.

“So they’re just kind of in the space between the cells, and not really doing what they’re supposed to be doing,” said co-lead author Eric Song, a graduate student at the Yale School of Medicine.

The Yale researchers found that they could correct for this by altering the chemistry of the nanoparticles. In two groups of rats — ones with brain tumors and ones with healthy brains — the researchers found that differences in the particles’ surface chemistry played a significant role in whether the particles were internalized by cells in the brain.

They covered one group of particles with polymers rich in aldehydes, which chemically bind to amines — a compound found in most proteins. These bioadhesive particles were most likely to be taken up by cells of all types in the brain: Tumor cells were among those that internalized the bioadhesive particles at a particularly high rate.

These results suggest that tailoring the chemical properties of particles provides an opportunity to control the distribution of the drugs they’re carrying, said the researchers. Further, they believe that the particles could be tailored for specific therapies to improve efficacy in target cells, and minimize toxicity to the cells they’re not targeting.

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Bronchial Thermoplasty Helps Asthma Patients Reduce Severe Attacks, Hospitalizations and ER Visits

In a new study presented at the 2017 American Thoracic Society International Conference, adult asthma patients treated with bronchial thermoplasty (BT) had fewer severe exacerbations and were able to reduce their ER visits and hospitalizations in the two years following treatment.  Approved by the FDA in 2010, BT is a new device-based therapy that uses a series of three radio-frequency treatments to open the airways of adults with severe, persistent asthma whose symptoms are not adequately controlled by inhaled corticosteroids or long-acting beta-agonists.

To date, more than 6,800 patients in 33 countries have been treated with BT.

The “Post-FDA Approval Clinical Trial Evaluating BT in Severe Persistent Asthma” (PAS2 study), which involves hundreds of patients at dozens of research centers, looks at the long-term effects and safety of BT.

“The results of the PAS2 study suggest that after a single series of BT procedures, patients experience long-term improvement in their asthma control,” said lead author Geoffrey Chupp, MD, from Yale School of Medicine.  “These results indicate that BT works across the spectrum of severe asthma patients. We believe BT should be more widely considered as a treatment option in patients with poorly controlled severe asthma.”

Two-hundred eighty four patients were enrolled in the study at 27 centers in the U.S. and Canada.  Two-hundred seventy-nine study subjects had at least one BT procedure, and 271 had all three procedures.  In the 12 months prior to the first BT procedure, 78 percent of subjects had at least one severe exacerbation, 16 percent required hospitalization and 29 percent had ER visits.  In the first year follow up, 50.6 percent had severe exacerbations; 45.4 percent had exacerbations in the second year follow up.  Asthma-related hospitalizations and ER visits also saw significant, continuing reductions:  14.4 percent and 12.7 percent of subjects had hospitalizations, respectively, in

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Cancer-cardiac connection illuminates promising new drug for heart failure

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved drugs, approximately 40% of patients with heart failure die within 5 years of their initial diagnosis.

“The current standard of care is clearly not sufficient, which highlights the urgent need for new therapeutic approaches,” said Saptarsi Haldar, MD, an associate investigator at Gladstone and senior author of a new study featured on the cover of the scientific journal Science Translational Medicine. “In our previous work, we found that a drug-like small molecule called JQ1 can prevent the development of heart failure in mouse models when administered at the very onset of the disease. However, as the majority of patients requiring treatment already have longstanding cardiac dysfunction, we needed to determine if our strategy could also treat established heart failure.”

As part of an emerging treatment strategy, drugs derived from JQ1 are currently under study in early-phase human cancer trials. These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET bromodomains, which directly influences heart failure. With this study, the scientists found that JQ1 can effectively treat severe, pre-established heart failure in both small animal and human cell models by blocking inflammation and fibrosis (scarring of the heart tissue).

“It has long been known that inflammation and fibrosis are key conspirators in the development of heart failure, but targeting these processes with drugs has remained a significant challenge,” added Haldar, who is also a practicing cardiologist and an associate professor in the Department of Medicine at the University of California, San Francisco. “By inhibiting the function of the protein BRD4, an approach that simultaneously blocks both of these processes, we are using a new and different strategy altogether to tackle the problem.”

Currently available drugs used for heart failure work at the surface of heart cells. In contrast, Haldar’s approach goes to the root of the problem and blocks destructive processes in the cell’s command center, or nucleus.

“We treated mouse models of heart failure with JQ1, similarly to how patients would be treated in a clinic,” said Qiming Duan, MD, PhD, postdoctoral scholar in Haldar’s lab and co-first author of the study. “We showed that this approach effectively treats pre-established heart failure that occurs both after a massive heart attack or in response to persistent high blood pressure (mechanical overload), suggesting it could be used to treat a wide array of patients.”

Using Gladstone’s unique expertise, the scientists then used induced pluripotent stem cells (iPSCs), generated from adult human skin cells, to create a type of beating heart cell known as cardiomyocytes.

“After testing the drug in mice, we wanted to check whether JQ1 would have the same effect in humans,” explained co-first author Sarah McMahon, a UCSF graduate student in Haldar’s lab. “We tested the drug on human cardiomyocytes, as they are cells that not only beat, but can also trigger the processes of inflammation and fibrosis, which in turn make heart failure progressively worse. Similar to our animal studies, we found that JQ1 was also effective in human heart cells, reaffirming the clinical relevance of our results.”

The study also showed that, in contrast to several cancer drugs that have been documented to cause cardiac toxicity, BRD4 inhibitors may be a class of anti-cancer therapeutics that has protective effects in the human heart.

“Our study demonstrates a new therapeutic approach to successfully target inflammation and fibrosis, representing a major advance in the field,” concluded Haldar. “We also believe our current work has important near-term translational impact in human heart failure. Given that drugs derived from JQ1 are already being tested in cancer clinical trials, their safety and efficacy in humans are already being defined. This key information could accelerate the development of a new heart failure drug and make it available to patients more quickly.”

Photo caption: Saptarsi Haldar (right), Qiming Duan (left) and Sarah McMahon (center) find a new strategy to treat heart failure. [Photo: Chris Goodfellow, Gladstone Institutes]

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Discovery may offer hope to Parkinson’s disease patients

The finding of a common protein abnormality in these degenerative diseases supports a hypothesis among experts that abnormal deposition of proteins in many neurodegenerative disorders reflects an early change in these proteins.

“We have pinpointed a protein abnormality known as the ‘SOD1 fingerprint’ in regions of neuronal loss in the Parkinson’s disease brain,” said Associate Professor Kay Double who led the research published in Acta Neuropathologica.

“We believe this loss of neurons results from a combination of oxidative stress and a regional deficiency in copper, both of which occur specifically in vulnerable regions of the Parkinson’s disease brain.”

This new finding may offer hope to Parkinson’s disease patients, since therapies targeting abnormal SOD1 protein have resulted in substantial improvements in motor function and survival time in models of ALS, prompting their progression into human clinical trials in this disease. This new finding suggests that such therapies may also be useful to treat Parkinson’s disease.

The discovery that the abnormal SOD1 protein is also linked to nerve cell loss in the Parkinson’s disease brain, suggests coincident degenerative pathways in Parkinson’s disease and ALS.

Alterations in the anti-oxidant enzyme superoxide dismutase (SOD1) underlie around 20 percent of familial (f)ALS cases, where mutations to the sod1 gene result in functional and/or structural defects, including misfolding of the protein and loss of copper binding capacity. The aggregation of mutant SOD1 is believed to underlie motor neuron death in these ALS patients.

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Study redefines HPV-related head and neck cancers

Much of what we thought we knew about the human papilloma virus (HPV) in HPV-related head and neck cancers may be wrong, according to a newly published study by Virginia Commonwealth University (VCU) researchers that analyzed data from The Human Cancer Genome Atlas. Head and neck cancers involving HPV are on the rise, and many experts believe we are seeing the start of an epidemic that will only get worse in the coming years.

The Cancer Genome Atlas is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research (NHGR) Institute that makes publicly available genomic information on tumor samples from 33 different types of cancers. Its aim is to help the cancer research community improve the prevention, diagnosis and treatment of cancer.

It is thought that there are two main forms of HPV-related cancers, episomal and integrated. In episomal variants, the HPV genome replicates independently. Integrated HPV has become part of the DNA of the host cell and relies on it for replication. Previously, it was believed that most HPV-related head and neck cancers had integrated HPV, as is what is believed with HPV-related cervical cancers. However, Windle’s study, recently published in the journal Oncotarget, found that HPV DNA is maintained separate from the human genome in the majority of HPV-related head and neck cancers, though, in many cases, the HPV genome can acquire a small piece of human DNA making it look like integrated HPV. This viral-human hybrid represents a new category of episomal HPV in HPV-related cancers.

“Our work challenges the idea that finding HPV DNA joined to human DNA means that HPV is integrated. With this new view of the state of HPV, we conclude that episomal HPV is the predominant state in HPV-related head and neck cancers,” says Brad Windle, member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, professor at the Philips Institute for Oral Health Research at the VCU School of Dentistry and co-principle investigator on the study. “This is an important distinction because patients with episomal HPV cancer respond better to therapy than patients with integrated HPV cancer.”

Windle’s team analyzed the genomes of all 520 HNC samples in The Cancer Genome Atlas and found that 72 were HPV positive. The large majority of these cancers had a common type of the virus known as HPV16 present, so they focused on that virus type. The data showed that 75 percent of the HPV16 samples had the HPV genome in the episomal state, and about half of the genomes contained a piece of human DNA within their circular structure.

The researchers also found that 73 percent of the tumor samples were still dependent on proteins known as E1 and E2 for replication. This is important because when the HPV genome integrates with human DNA, expression of the HPV E2 protein–essential for independent replication–is lost. The presence of E2, or lack thereof, in tumor biopsies could be a reliable way for physicians to determine the cancer type and provide a more accurate prognosis.

“Perhaps our most striking outcome is the potential to target the E1 and E2 proteins for diagnosis and treatment,” says Windle. With nearly three quarters of these cancers dependent on E1 and E2 for replication, we could develop drugs that target these proteins and promote cell death.”

Windle’s team plans to continue studying the integration of HPV in HPV-related head and neck cancers, and suggests that viral-human DNA hybrid HPV should be further explored in HPV-related cervical cancers. His team is currently working with Massey clinicians in order to use this information to assess patients’ prognosis in the clinic.

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Diagnostic biomarkers in saliva show promise in recognizing early Alzheimer’s disease

Your spit may hold a clue to future brain health. Investigators at the Beaumont Research Institute, part of Beaumont Health in Michigan, are hopeful that their study involving small molecules in saliva will help identify those at risk of developing Alzheimer’s disease – a neurologic condition predicted to reach epidemic proportions worldwide by 2050.

Their study, “Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva using 1H NMR-Based Metabolomics” was published in the Journal of Alzheimer’s Disease 58(2) on May 16.

Investigators found salivary molecules hold promise as reliable diagnostic biomarkers. The study exemplifies the quest by scientists to combat Alzheimer’s disease, a degenerative brain disorder with no cure and few reliable diagnostic tests. In the United States, Alzheimer’s is a health epidemic affecting more than 5 million Americans. Investigators seek to develop valid and reliable biomarkers, diagnosing the disease in its earliest stages before brain damage occurs and dementia begins.

Researcher Stewart Graham, Ph.D., said, “We used metabolomics, a newer technique to study molecules involved in metabolism. Our goal was to find unique patterns of molecules in the saliva of our study participants that could be used to diagnose Alzheimer’s disease in the earliest stages, when treatment is considered most effective. Presently, therapies for Alzheimer’s are initiated only after a patient is diagnosed and treatments offer modest benefits.”

Metabolomics is used in medicine and biology for the study of living organisms. It measures large numbers of naturally occurring small molecules, called metabolites, present in the blood, saliva and tissues. The pattern or fingerprint of metabolites in the biological sample can be used to learn about the health of the organism.

“Our team’s study demonstrates the potential for using metabolomics and saliva for the early diagnosis of Alzheimer’s disease,” explained Dr. Graham. “Given the ease and convenience of collecting saliva, the development of accurate and sensitive biomarkers would be ideal for screening those at greatest risk of developing Alzheimer’s. In fact, unlike blood or cerebrospinal fluid, saliva is one of the most noninvasive means of getting cellular samples and it’s also inexpensive.”

The study participants included 29 adults in three groups: mild cognitive impairment, Alzheimer’s disease and a control group. After specimens were collected, the researchers positively identified and accurately quantified 57 metabolites. Some of the observed variances in the biomarkers were significant. From their data, they were able to make predictions as to those at most risk of developing Alzheimer’s. Said Dr. Graham, “Worldwide, the development of valid and reliable biomarkers for Alzheimer’s disease is considered the No. 1 priority for most national dementia strategies. It’s a necessary first step to design prevention and early-intervention research studies.”

As Americans age, the number of people affected by Alzheimer’s is rising dramatically. According to the Alzheimer’s Association, by 2050, it’s estimated the number of Americans living with Alzheimer’s disease will triple to about 15-16 million.

Alzheimer’s disease is a type of dementia affecting a person’s ability to think, communicate and function. It greatly impacts their relationships, their independence and lifestyle. The condition’s toll not only affects millions of Americans, but in 2017, it could cost the nation $259 billion.

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Long Term Survival Indicated for Advanced Stage Colorectal Cancer Patients who Survive at Least Two Years

Improvements in chemotherapy and liver surgery have resulted in increased overall survival in patients with advanced stage colorectal cancer in recent decades. In order to better predict outcomes for these patients, researchers at Rutgers Cancer Institute of New Jersey conducted a retrospective analysis and found that stage IV colorectal cancer patients who survived at least two years have a better prognosis than originally thought. Results of the work will be presented as part of a poster presentation at the American Society of Clinical Oncology Annual Meeting being held in Chicago early next month.

“With patients in this population living longer, it is imperative we refine prognostic information to more accurately predict survival.  This data will assist multi-disciplinary cancer management teams in making treatment decisions that ultimately will impact a patient’s quality of life,” notes Darren Carpizo, MD, PhD, surgical oncologist and director of the Hepatobiliary Program at Rutgers Cancer Institute and senior investigator of the work (pictured).

Investigators examined data on more than a thousand stage IV colorectal cancer patients seen at Rutgers Cancer Institute between 2005 and 2015. This included patients who had their cancer removed through surgery and were treated with follow-up therapies, as well as those patients who were not eligible for surgery. Complete data was available for 125 patients who survived for more than two years (75 had surgical removal of their cancer; 50 did not).  Median overall survival of patients who underwent surgery was not reached, while median overall survival for those who were not eligible for surgery was six years and three months.

“For those patients not eligible for initial surgery who survive two years, these findings indicate they may benefit from future surgery, if feasible, to treat remaining disease. For those patients who initially had surgery, this information may be helpful to identify patients who might benefit from repeat surgery to resect any recurrent metastatic disease,” adds Dr. Carpizo, who is also an associate professor of surgery and pharmacology at Rutgers Robert Wood Johnson Medical School.

Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, Rutgers Cancer Institute is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention both at its flagship New Brunswick location and at its Newark campus at Rutgers Cancer Institute of New Jersey at University Hospital. Physician-scientists across Rutgers Cancer Institute also engage in translational research, transforming their laboratory discoveries into clinical practice that supports patients on both campuses.

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Researchers take an important step toward an HIV vaccine

Vaccines are an essential tool for preventing and treating serious infectious diseases such as polio, chicken pox and measles. But so far it has not been possible to develop vaccines capable of contributing to the treatment and prevention of chronic infectious diseases such as HIV and hepatitis C.

This new research paves the way for vaccines that, as opposed to conventional methods, boosting the parts of the immune system attacking the viral genes, which are the least active during the infection. This prolongs the resistance of the immune system to the virus.

Traditional vaccines typically cause a strong stimulation of the parts of the immune system, that are most responsive to the specific virus. But the reaction to the vaccine and the infection is often so intense that the immune system ‘loses momentum’ and consequently is not able to completely eliminate the virus. Researchers have therefore designed a vaccine which boosts the cells of the immune system responsible for the less exposed parts of the virus. As a result, the cells are able to distribute the ‘work load’ and retain the defense against the virus attack for a longer period of time. This gives the immune system time to build a more efficient defense, which may then defeat the remaining of the virus.

“We’re presenting an entirely new vaccine solution. Our vaccine supports the work of the immune system in developing an effective combating mechanism against the virus, rather than immediately combating the toughest parts of the virus. In combination with other vaccines, this approach can prove to have a highly efficient effect,” says Research Team Leader and Associate Professor Peter Holst of the Department of Immunology and Microbiology.

In 2008, the research team decided to develop a new vaccine strategy, which generates so-called strong immune responses against weak immunostimulatory parts of viruses. Research initially focused on experiments on mice and later on monkeys.

Now, the results of the research team show, that this technology can control the SIV virus infection (simian immunodefiency virus) in monkeys. SIV is a chronic infectious disease and a highly realistic representation of HIV. The results are an important step toward developing a vaccine against HIV and other chronic infections.

“The next phase of our work is to build virus control in all infected animals and later in humans. We’re convinced that it’s possible to identify further improvements in our experiments and thus achieve a well-functioning vaccine, initially against HIV, but also against other chronic infections,” says Peter Holst.

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Epilepsy drug therapies to be improved by new targeted approach

New research from the University of Liverpool, in collaboration with the Mario Negri Institute in Milan, published today in the Journal of Clinical Investigation, has identified a protein that could help patients with epilepsy respond more positively to drug therapies.

Epilepsy continues to be a serious health problem and is the most common serious neurological disease. Despite 30 years of drug development, approximately 30% of people with epilepsy do not become free of fits (also called seizures) with currently available drugs.

New, more effective drugs are therefore required for these individuals. We do not fully understand why some people develop seizures, why some go onto develop epilepsy (continuing seizures), and most importantly, why some patients cannot be controlled with current drugs.

Inflammation

There is now increasing body of evidence suggesting that local inflammation in the brain may be important in preventing control of seizures. Inflammation refers to the process by which the body reacts to insults such as having a fit. In most cases, the inflammation settles down, but in a small number of patients, the inflammation continues.

The aim of the research, undertaken by Dr Lauren Walker while she was a Medical Research Council (MRC) Clinical Training Fellow, was to address the important question of how can inflammation be detected by using blood samples, and whether this may provide us with new ways of treating patients in the future to reduce the inflammation and therefore improve seizure control.

The research focused on a protein called high mobility group box-1 (HMGB1), which exists in different forms in tissues and bloodstream (called isoforms), as it can provide a marker to gauge the level of inflammation present.

Predicting drug response

The results showed that there was a persistent increase in these isoforms in patients with newly-diagnosed epilepsy who had continuing seizure activity, despite anti-epileptic drug therapy, but not in those where the fits were controlled.

An accompanying drug study also found that HMGB1 isoforms may predict how an epilepsy patient’s seizures will respond to anti-inflammatory drugs.

Dr Lauren Walker, said: “Our data suggest that HMGB1 isoforms represent potential new drug targets, which could also identify which patients will respond to anti-inflammatory therapies. This will require evaluation in larger-scale prospective trials.”

Innovative scheme

Professor Sir Munir Pirmohamed, Director of the MRC Centre for Drug Safety Science and Programme lead for the MRC Clinical Pharmacology scheme, said: “The MRC Clinical Pharmacology scheme is a highly successful scheme to train “high flyers” who are likely to become future leaders in academia and industry.

“Dr Walker’s research is testament to this and shows how this innovative scheme, which was jointly funded by the MRC and Industry, can tackle areas of unmet clinical need, and identify new ways of treating patients with epilepsy using a personalised medicine approach”.

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Skin cancer on the rise

New diagnoses for two types of skin cancer increased in recent years, according to a Mayo Clinic-led team of researchers.

Their paper, published today in Mayo Clinic Proceedings, uses medical records from the Rochester Epidemiology Project to compare diagnoses of basal cell carcinoma and squamous cell carcinoma — both nonmelanoma skin cancers — between 2000 and 2010 to diagnoses in prior years. The Rochester Epidemiology project is a medical records linkage system and research collaborative in Minnesota and Wisconsin.

Age, sex lead to different diagnoses

The researchers report that, between 2000 and 2010, squamous cell carcinoma (also called cutaneous squamous cell carcinoma) diagnoses increased 263 percent, and basal cell carcinomas increased 145 percent. They compared the 2000-2010 period to two other segments of time: 1976-1984 and 1985-1992.

Women 30-49 experienced the greatest increase in basal cell carcinoma diagnoses; whereas, women 40-59 and 70-79 experienced the greatest increase in squamous cell carcinomas.

Men had an increase in squamous cell carcinomas between the first and second time period studied (1976-1984 and 1985-1992), but experienced a slight decline in the 2000-2010 period. However, for basal cell carcinomas, men over 29 showed similar increases in diagnoses in the 2000-2010 period then the two earlier periods.

Tanning: Beautifying or death-defying?

“We know that the sun and some artificial sunlight sources give off skin-damaging ultraviolet, or UV, rays,” says Christian Baum, M.D., a Mayo Clinic dermatologist and the study’s senior author. “This skin damage accumulates over time and can often lead to skin cancer.”

“Despite the fact that sunscreens and cautionary information have been widely available for more than 50 years, we saw the emergence of tanning beds in the 1980s, and tanning – indoors or out – was a common activity for many years.”

Although Dr. Baum notes that tanning has slowed, tanning beds still exist, and beaches will never be empty. But what people should remember is that the damage accumulates, he says, and “eventually those blistering sunburns of your youth and hot, reddened skin, and peeling shoulders of your adulthood can add up to one or more skin cancers.”

The authors also reported that shifts in exposure to UV light may be the reason for a location shift in where the cancer tumors are found. In the earlier time periods, both basal cell and squamous cell carcinomas were diagnosed more often on the head and neck. But, in the most recent time period, the records showed that basal cell tumors on the torso increased, as did squamous cell carcinomas on the arms and legs.

Dr. Baum says that the risk of cancer should provide the ultimate argument for using sunscreen – every day, year-round on all exposed skin.

“Use sunscreen,” says Dr. Baum. “This includes on your left arm for those who do a lot of driving. UV rays can penetrate car windows and exposed skin — even when the sun isn’t shining. UV rays bounce around under the clouds, off the snow, buildings, and more, causing damage — even on gray days.

More on the data

Using the Rochester Epidemiology Project medical records linkage system, the research team was able to identify nearly all of the Olmsted County, Minnesota, adult residents who received an initial diagnosis of the most common nonmelanoma skin cancers — basal or squamous cell carcinoma (or both), during the 2000-2010 period and the comparison years.

“There is no tumor registry for these types of cancer,” says Dr. Baum, “So it is difficult to have accurate estimates of the national or worldwide impact of these cancers. However, because the Rochester Epidemiology Project contains health care information for virtually all residents of Olmsted County since 1966, it provides a good proxy for information on many global population health concerns.”

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Stem Cell Trial for Stroke Patients Suffering Chronic Motor Deficits Begins at UTHealth

A clinical trial to evaluate the safety and efficacy of a stem cell product injected directly into the brain to treat chronic motor deficits from ischemic stroke has begun at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth).

McGovern Medical School at UTHealth is the only site in Texas and the central south portion of the country to open enrollment for the multi-institutional, phase 2B study – the first in the U.S. for chronic stroke. Surgeries will be conducted at Memorial Hermann-Texas Medical Center.

“This trial is one of the first randomized, sham-controlled studies to test the efficacy of administering adult-derived stem cells in patients disabled with a chronic stroke,” said Sean I. Savitz, M.D., professor and the Frank M. Yatsu Chair in Neurology at McGovern Medical School and director of the UTHealth Institute for Stroke and Cerebrovascular Disease. “We were chosen as one of only a handful of referral centers in the nation and patients from all over the country will be referred to our center for this trial. Overall, the study adds to our growing regenerative medicine program for patients with neurological disorders.”

In the double-blind, sham-surgery controlled study, patients randomized to the study intervention will receive a stem cell product made by SanBio and patients must have chronic motor deficits from an ischemic stroke to be eligible for the study. The product, administered through tiny holes bored into the skull and placed near the site of the damage, came from the bone marrow of two healthy adult donors. Enrollment is limited to patients who are between six and 60 months post-stroke and have a chronic motor neurological deficit.

Results of a phase 1/2A study of the stem cell product, presented at the International Society of Stem Cell Research Meeting and published in the journal, Stroke, showed statistically significant improvements in motor function and no safety concerns.

The UTHealth Stroke Program at McGovern Medical School, led by Savitz, is one of the most active research and clinical programs in the country. It was one of the lead sites in the National Institute of Neurological Disease and Stroke’s (NINDS) tPA stroke study; was one of eight centers in the country funded by the NIH to conduct specialized translational research to develop novel acute stroke therapies; and receives NINDS fellowship funding to train the next generation of academic leaders in cerebrovascular disease.

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Scientists confirm correlation between malignant hyperthermia and exertional heat stroke

New research published online in The FASEB Journal may ultimately help athletes and trainers better understand who may be more at risk for heat stroke. In the report, scientists use animals to show that there is a link between the susceptibility to malignant hyperthermia (MH) and exertional heat stroke.

“Global warming and increasing frequency of heat waves, which are particularly dangerous in large urban areas, in future years will represent a reason of concern for human health,” said Feliciano Protasi, Ph.D., a researcher involved in the work at the Department of Neuroscience, Imaging and Clinical Sciences, University G. d’Annunzio, Chieti, Italy. “However, in spite of the increased incidence, severity and life-threatening nature of heat stroke, there are currently no safe and effective drug interventions to protect or reverse this deadly syndrome. We hope that our study will contribute to develop preventive measures and/or acute treatments for heat stroke caused by environmental heat and physical exertion.”

Scientists used three groups of mice to reach their conclusion. The first two groups (RYR1Y522S/WT and CASQ1-null mice) had altered genes that made them susceptible to lethal hyperthermic crises when exposed to anesthetics, while the third group was normal (wild-type mice). When the three sets of mice were exposed to a protocol of exertional stress (incremental running at 34 degrees Celsius and 40 percent humidity) the MH-susceptible mice (but not the normal mice) suffered lethal overheating episodes.

“This work addresses a dangerous, often lethal, physiological maladjustment that animals and humans can undergo,” said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. “The door now stands open to finding effective preventative drugs.”

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Forge Therapeutics Raises $15M Series A Financing to Develop First Novel Gram-Negative Antibiotic in Decades

Forge Therapeutics, Inc., a biotechnology company discovering first-in-class antibiotics using a breakthrough drug discovery platform, announced today the completion of a $15M Series A financing. The round is led by MagnaSci Ventures, with participation from Evotec AG, Alexandria Venture Investments, MP Healthcare Venture Management, Red Apple Group, and WS Investments. Forge has used its enabling technology to identify a novel LpxC inhibitor effective against multi-drug resistant bacteria ‘superbugs,’ and the funding will support the program into clinical studies.

“This financing is an important step forward to solving the ‘superbug’ epidemic, an urgent global health issue in desperate need of innovation. We’ve been impressed with the strength of the Forge team, their technologies and their commitment to innovating the antibiotic space,” said Brian T. Dorsey, Founding Partner at MagnaSci Ventures. “With our investment and resources, we look forward to working together on developing the first novel antibiotic against Gram-negative bacteria in decades.” In connection with the Series A financing, Mr. Dorsey will be joining Forge’s Board of Directors.

“We are pleased to have such quality investors join us in our pursuit to eradicate deadly ‘superbug’ infections with novel antibiotics stemming from our robust drug discovery engine,” said Zachary A. Zimmerman, Ph.D., CEO of Forge. “The proceeds from this financing, coupled with the non-dilutive monies received from government agencies CARB-X and NIH/NIAID, will advance our LpxC inhibitor into clinical studies.”

With its proprietary chemistry approach, Forge develops small molecule inhibitors targeting metalloenzymes.  Forge’s lead effort is focused on LpxC, a zinc metalloenzyme found only in Gram-negative bacteria and which is essential for bacteria to grow. Forge has discovered novel small molecule inhibitors of LpxC that are potent in vitro, efficacious in vivo, and effective against drug resistant Gram-negative bacteria ‘superbugs.’

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Sangamo Therapeutics and Pfizer Announce Collaboration for Hemophilia A Gene Therapy

Sangamo Therapeutics, Inc. and Pfizer Inc. announced this week, an exclusive, global collaboration and license agreement for the development and commercialization of gene therapy programs for Hemophilia A, including SB-525, one of Sangamo’s four lead product candidates, which Sangamo expects will enter the clinic this quarter.

“Sangamo brings deep scientific and technical expertise across multiple genomic platforms, and we look forward to working together to advance this potentially transformative treatment for patients living with Hemophilia A,” said Mikael Dolsten, MD, PhD, President of Worldwide Research and Development at Pfizer. “Pfizer has made significant investments in gene therapy over the last few years and we are building an industry-leading expertise in recombinant adeno-associated virus (rAAV) vector design and manufacturing. We believe SB-525 has the potential to be a best-in-class therapy that may provide patients with stable and durable levels of Factor VIII protein with a single administration treatment.”

“With a long-standing heritage in rare disease, including hemophilia, Pfizer is an ideal partner for our Hemophilia A program,” said Dr. Sandy Macrae, Sangamo’s Chief Executive Officer. “We believe Pfizer’s end-to-end gene therapy capabilities will enable comprehensive development and commercialization of SB-525, which could potentially benefit Hemophilia A patients around the world. This collaboration also marks an important milestone for Sangamo as we continue to make progress in the translation of our ground-breaking research into new genomic therapies to treat serious, genetically tractable diseases.”

Under the terms of the collaboration agreement, Sangamo will receive a $70 million upfront payment from Pfizer. Sangamo will be responsible for conducting the SB-525 Phase 1/2 clinical study and certain manufacturing activities. Pfizer will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for SB-525 and additional products, if any. Sangamo is eligible to receive potential milestone payments of up to $475 million, including up to $300 million for the development and commercialization of SB-525 and up to $175 million for additional Hemophilia A gene therapy product candidates that may be developed under the collaboration. Sangamo will also receive tiered double-digit royalties on net sales. Additionally, Sangamo will be collaborating with Pfizer on manufacturing and technical operations utilizing viral delivery vectors.

Gene therapy is a potentially transformational technology for patients, focused on highly specialized, one-time, treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patient’s cells to compensate for a defective one. The genetic material can be delivered to the cells by a variety of means, most frequently using a viral vector such as rAAV. There have been no gene therapy products approved in the U.S. to date.

Hemophilia A is a rare blood disorder caused by a genetic mutation resulting in insufficient activity of Factor VIII, a blood clotting protein the body uses to stop bleeding. There are approximately 16,000 patients in the U.S. and more than 150,000 worldwide with Hemophilia A. SB-525 is comprised of a rAAV vector carrying a Factor VIII gene construct driven by a proprietary, synthetic, liver-specific promoter. The U.S. Food and Drug Administration has cleared initiation of human clinical trials for SB-525, which also has been granted orphan drug designation. Sangamo is on track this quarter to start a Phase 1/2 clinical trial to evaluate safety and to measure blood levels of Factor VIII protein and other efficacy endpoints.

 

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Trigger for autoimmune disease identified

Researchers at National Jewish Health have identified a trigger for autoimmune diseases such as lupus, Crohn’s disease and multiple sclerosis. The findings, published in the April 2017 issue of Journal of Clinical Investigation, help explain why women suffer autoimmune disease more frequently than men, and suggest a therapeutic target to prevent autoimmune disease in humans.

“Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease,” said Kira Rubtsova, PhD, an instructor in biomedical science at National Jewish Health. “We demonstrated that the transcription factor T-bet inside B cells causes ABCs to develop. When we deleted T-bet inside B cells, mice prone to develop autoimmune disease remained healthy. We believe the same process occurs in humans with autoimmune disease, more often in elderly women.”

Autoimmune diseases occur when the immune system attacks and destroys the organs and tissue of its own host. Dozens of autoimmune diseases afflict millions of people in the United States. Several autoimmune diseases, including lupus, rheumatoid arthritis and multiple sclerosis strike women two to 10 times as often as men. Overall, about 80 percent of autoimmune patients are women. There is no cure for autoimmune disease.

B cells are important players in autoimmune disease. The National Jewish Health research team, led by Chair of Biomedical Science Philippa Marrack, PhD, previously identified a subset of B cells that accumulate in autoimmune patients, autoimmune and elderly female mice. They named the cells Age-associated B cells, or ABCs. Subsequent research showed that the transcription factor T-bet plays a crucial role in the appearance of ABC.

Transcription factors bind to DNA inside cells and drive the expression of one or several genes. Researchers believe that T-bet appears inside cells when a combination of receptors on B-cell surfaces — TLR7, Interferon-gamma and the B-cell receptor — are stimulated.

Through breeding and genetic techniques the research team eliminated the ability of autoimmune-prone mice to express T-bet inside their B cells. As a result, ABCs did not appear and the mice remained healthy. Kidney damage appeared in 80 percent of mice with T-bet in the B cells and in only 20 percent of T-bet-deficient mice. Seventy-five percent of mice with T-bet in their B cells died by 12 months, while 90 percent of T-bet-deficient mice survived 12 months.

“Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it,” said Dr. Rubtsova.

ABCs have attracted increasing interests since their discovery in 2011. Dr. Rubtsova and her colleagues at National Jewish Health have expanded their study of ABCs beyond autoimmune disease and are looking at their involvement in sarcoidosis, hypersensitivity pneumonitis and chronic beryllium disease.

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Researchers Uncover Key Role for MicroRNA in Inflammatory Bowel Disease

An international team of researchers has discovered that a microRNA produced by certain white blood cells can prevent excessive inflammation in the intestine. The study, “Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome,” which will be published May 9 in The Journal of Experimental Medicine, shows that synthetic versions of this microRNA can reduce intestinal inflammation in mice and suggests a new therapeutic approach to treating patients with Crohn’s disease or ulcerative colitis.

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, affects almost 2 million people in the US. Although IBD is caused by a complex mix of genetic and environmental factors, it is thought to be initiated by an excessive immune response against bacteria in the gut. This immune response involves the recruitment of various white blood cells, such as neutrophils and monocytes, into the intestine and the activation of a protein complex in these cells known as the inflammasome. The inflammasome, in turn, activates the proinflammatory signaling molecules IL-1β and IL-18, which stimulate the further influx of white blood cells.

MicroRNAs are small RNA molecules that can bind and repress protein-coding messenger RNAs. An international team of researchers led by Eóin McNamee at the University of Colorado-Anschutz Medical Campus found that IBD patients showed increased levels of a microRNA called miR-223 during active bouts of inflammation. This microRNA was also elevated in laboratory mice with colitis.

miR-223 is produced by neutrophils and monocytes and has previously been shown to repress the messenger RNA encoding NLRP3, a key component of the inflammasome. McNamee and colleagues found that mice lacking miR-223 expressed higher levels of NLRP3, causing increased IL-1β production and enhanced susceptibility to intestinal inflammation.

In contrast, mice treated with lipid nanoparticles containing synthetic RNA molecules that mimic miR-223 showed lower levels of NLRP3 and IL-1β and were accordingly protected from experimentally induced colitis.

“Our study highlights the miR-223–NLRP3–IL-1β regulatory circuit as a critical component of intestinal inflammation,” McNamee says. “miR-223 serves to constrain the level of NLRP3 inflammasome activation and provides an early brake that limits excessive inflammation. Genetic or pharmacologic stabilization of miR-223 may hold promise as a future novel therapy for active flares in IBD.”

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First-In-Human Clinical Trial Aims to Extend Remission for Children and Young Adults With Leukemia Treated With T-Cell Immunotherapy

Phase 1 pilot study utilizes T-cell antigen presenting cells to prolong the persistence of cancer-fighting chimeric antigen receptor (CAR) T cells, reduce the relapse rate

After phase 1 results of Seattle Children’s Pediatric Leukemia Adoptive Therapy (PLAT-02) trial have shown T-cell immunotherapy to be effective in getting  93 percent of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) into complete initial remission, researchers have now opened a first-in-human clinical trial aimed at reducing the rate of relapse after the therapy, which is about 50 percent. The new phase 1 pilot study, PLAT-03, will examine the feasibility and safety of administering a second T-cell product intended to increase the long-term persistence of the patient’s chimeric antigen receptor (CAR) T cells that were reprogrammed to detect and destroy cancer.

The research team, led by Dr. Mike Jensen at the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute, is exploring this strategy after discovering that of the patients who relapse in the PLAT-02 trial, about half of them have lost their CAR T cells. Lasting persistence of the CAR T cells is critical in combating a recurrence of cancer cells.

“While it’s promising that we’re able to get these patients who are very sick back into remission, we’re also seeing that the loss of the CAR T cells in some patients may be opening the door for the cancer to return,” said Dr. Colleen Annesley, an oncologist at Seattle Children’s and the lead investigator of the PLAT-03 trial. “We’re pleased to now be able to offer patients who have lost or are at risk of losing their cancer-fighting T cells an option that will hopefully lead to them achieving long-term remission.”

In the PLAT-03 trial, patients will receive “booster” infusions of a second T-cell product, called T antigen-presenting cells (T-APCs). The T-APCs have been genetically modified to express the CD19 target for the cancer-fighting CAR T cells to recognize. Patients will receive a full dose of T-APCs every 28 days for at least one and up to six doses. By stimulating the CAR T cells with a steady stream of target cells to attack, researchers hope the CAR T cells will re-activate, helping to ensure their persistence long enough to put patients into long-term remission.

PLAT-03 is now open to patients who first enroll in phase 2 of Seattle Children’s PLAT-02 trial and who are also identified as being at risk for early loss of their reprogrammed CAR T cells, or those who lose their reprogrammed CAR T cells within six months of receiving them.

The PLAT-03 trial is one of several trials that Seattle Children’s researchers are planning to open within the next year aimed at further improving the long-term efficacy of T-cell immunotherapy. In addition to the current T-cell immunotherapy trial that is open for children with neuroblastoma, researchers also hope to expand this promising therapy to other solid tumor cancers.

“We are pleased to be at a pivotal point where we are now looking at several new strategies to further improve CAR T-cell immunotherapy so it remains a long-term defense for all of our patients,” said Dr. Rebecca Gardner, Seattle Children’s oncologist and the lead investigator of the PLAT-02 trial. “We’re also excited to be working to apply this therapy to several other forms of pediatric cancer beyond ALL, with the hope that T-cell immunotherapy becomes a first line of defense, reducing the need for toxic therapies and minimizing the length of treatment to only weeks.”

To read about the experience of one of the patients in the PLAT-02 trial, please visit Seattle Children’s On the Pulse blog.

The T-cell immunotherapy trials at Seattle Children’s are funded in part by Strong Against Cancer, a national philanthropic initiative with worldwide implications for potentially curing childhood cancers. If you are interested in supporting the advancement of immunotherapy and cancer research, please visit Strong Against Cancer’s donation page.

For more information on immunotherapy research trials at Seattle Children’s, please call (206) 987-2106 or email immunotherapy@seattlechildrens.org.

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Biomarker Test for Lou Gehrig’s Disease Useful in Diagnosing Canine Neurodegenerative Disease

Mizzou researchers seek clinical trial participants for further treatment study

In 2009, Joan Coates, a veterinary neurologist, along with other researchers at the University of Missouri and the Broad Institute at MIT/Harvard, found a genetic link between degenerative myelopathy (DM) in dogs and amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease in people. Now, MU researchers Coates and Michael Garcia, an associate professor in the Division of Biological Sciences, have found that a biomarker test that helps diagnose ALS also can assist with determining a diagnosis for degenerative myelopathy.

Coates is seeking clinical trial participants to evaluate a treatment for canine DM.

In dogs, DM is an older adult onset disease that can eventually lead to paralysis. The neurodegenerative disease has been confirmed in more than 30 pure bred dog breeds, such as Pembroke Welsh corgis, German Shepherd Dogs and boxers, as well as mixed breed dogs. The current genetic test for DM can be useful to breeders and veterinarians in identifying risk for the disease; however, it has limitations when diagnosing DM.

“DM is a diagnosis of exclusion, meaning that veterinarians must rule out all other diseases that mimic it before coming to a final diagnosis,” said Coates, a professor in the MU Department of Veterinary Medicine and Surgery. “This requires expensive diagnostic procedures such as MRIs of the spinal cord. Now that we know that DM and ALS are related, we are studying ways to diagnose and measure disease progression with similar diagnostic modalities used in ALS patients.”

ALS can be tested using phosphorylated neurofilament heavy proteins (pNF-H) that are released into spinal fluid and blood in humans with ALS. These biomarkers are released during the degeneration of spinal tissues making them a good indicator that ALS is present. Coates and co-principal investigator Garcia tested whether the diagnostic tool could be used in canines.

“I was very excited by the idea that there could be another model that might have many more strength than the existing models,” Garcia said. “So this was a natural fit for me.”

Cerebrospinal fluid and blood samples were collected from DM-affected dogs, including dogs that had a confirmed diagnosis as well as dogs in early stages of the disease. pNF-H concentrations from those samples were compared to samples from age-matched normal dogs and dogs with mimicking diseases.

“We found a significant difference in the DM affected dogs,” Coates said. “pNF-H levels were increased in the cerebrospinal fluid of the DM-affected dogs relative to the control groups, indicating that the human ALS test could be used to diagnose DM. These results will enable us to ‘scale up’ the test to make it more accessible to veterinary community.”

Collecting cerebrospinal fluid from patients is more complicated than a blood test, but is less expensive compared to an MRI to make a presumptive DM diagnosis, Coates said. Nonetheless, pNF-H may serve as a diagnostic tool for diagnosis of DM.

Coates also is conducting clinical trial research for treatment of DM. The goals of the therapies being tested is to slow the progression of neurologic signs of DM and improve quality of life. These therapies are in collaborations with other ALS researchers and funded by the ALS Association and National Institutes of Health. The clinical trials are taking place at the MU Veterinary Health Center (VHC) Small Animal Hospital. To inquire about enrolling a dog, contact Coates at coatesj@missouri.edu.

Collaborations among human health and veterinary clinicians and researchers highlights the multidisciplinary, One Health/One Medicine initiative at Mizzou. The concept is a worldwide strategy for expanding interdisciplinary collaborations and communications in all aspects of healthcare for humans and animals where biomedical research discoveries and expanding the scientific knowledge base lead to faster improvements benefitting both humans and our pets.

The study, “Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy,” was published in the Journal of Veterinary Internal Medicine. Christine Toedebusch, a veterinary neurology resident and doctoral candidate, was lead author on the study. The study was funded in part by the American Boxer Charitable Foundation and the American Kennel Club Canine Health Foundation (Grant #2165). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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Penn Study Identifies New Target to Fight Prostate, Lung Cancer

A newly identified molecular chain of events in a mouse model of prostate cancer highlights novel targets to treat it and other cancers. A team led by Marcelo Kazanietz, PhD, a professor of Systems Pharmacology and Translational Therapeutics, published in Cell Reports that the overexpression of a protein called PKCε with the loss of the tumor suppressor Pten causes the progression of prostate cancer.

This deadly combination produces an uptick in the levels of the cancer-promoting molecule CXCL13. When the team purposely disrupted CXCL13, or CXCR5, the cell-surface receptor it attaches to, the metastatic and tumor-forming characteristics of the mouse prostate cancer cells were impaired.

“In addition to providing evidence for a vicious cancer cycle driven by PKCε, our studies identified a compelling rationale for blocking the CXCL13-CXCR5 molecules as a new cancer treatment,” Kazanietz said. He and colleagues plan to identify compounds to block CXCR5 or CXCL13 with potential to be developed as anti-cancer agents. The researchers also suggested that CXCL13 levels in blood could be used as a biomarker to measure the precise state of prostate cancer progression in a patient.

The team’s next step will be to interfere with CXCR5/CXCL13 signals not only from the cancer cells but also from other cells in the tumor microenvironment that contribute to cancer growth.

Pulmonologists and oncologists have also observed that PKCε is overexpressed in lung cancer patients, but they do not fully understand its exact molecular consequences. In general, a high level of PKCε is associated with a poor prognosis.

“We are in the midst of extending these findings to lung cancer,” said Kazanietz, who is collaborating with Penn Medicine researchers David Feldser, PhD, an assistant professor of Cancer Biology, Steven M. Albelda, MD, a professor of Pulmonary, Allergy and Critical Care, and Evgeniy Eruslanov, PhD, a research assistant professor of Thoracic Surgery.